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Perioperative thrombocytopenia
Abstract
Purpose of review:
In this review, we discuss recent developments and trends in the perioperative management of thrombocytopenia.
Recent findings:
Large contemporary data base studies show that preoperative thrombocytopenia is present in about 8% of asymptomatic patients, and is associated with increased risks for bleeding and 30-day mortality. Traditionally specific threshold platelet counts were recommended for specific procedures. However, the risk of bleeding may not correlate well with platelet counts and varies with platelet function depending on the underlying etiology. Evidence to support prophylactic platelet transfusion is limited and refractoriness to platelet transfusion is common. A number of options exist to optimize platelet counts prior to procedures, which include steroids, intravenous immunoglobulin, thrombopoietin receptor agonists, and monoclonal antibodies. In addition, intraoperative alternatives and adjuncts to transfusion should be considered. It appears reasonable to use prophylactic desmopressin and antifibrinolytic agents, whereas activated recombinant factor VII could be considered in severe bleeding. Other options include enhancing thrombin generation with prothrombin complex concentrate or increasing fibrinogen levels with fibrinogen concentrate or cryoprecipitate.
Summary:
Given the lack of good quality evidence, much research remains to be done. However, with a multidisciplinary multimodal perioperative strategy, the risk of bleeding can be decreased effectively.
Immune thrombocytopenia (ITP) is a common hematological manifestation of systemic lupus erythematosus (SLE). The heterogeneity of its clinical characteristics and therapeutic responses reflects a complex pathogenesis. A better understanding of its pathophysiological mechanisms and employing an optimal treatment regimen is therefore important to improve the response rate and prognosis, and avoid unwanted outcomes. Besides glucocorticoids, traditional immunosuppressants (i.e. cyclosporine, mycophenolate mofetil) and intravenous immunoglobulins, new therapies are emerging and promising for the treatment of intractable SLE-ITP, such as thrombopoietin receptor agonists (TPO-RAs), platelet desialylation inhibitors(i.e. oseltamivir), B-cell targeting therapy(i.e. rituximab, belimumab), neonatal Fc receptor(FcRn) inhibitor, spleen tyrosine kinase(Syk) inhibitor and Bruton tyrosine kinase(BTK) inhibitor et al., although more rigorous randomized controlled trials are needed to substantiate their efficacy. In this review, we update our current knowledge on the pathogenesis and treatment of SLE-ITP.
Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2. Primarily an infection of the lower respiratory tract, it is now well known to cause multisystem abnormalities. Hematologic manifestations constitute a significant area of concern. Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis. Coronavirus disease 2019 causes lymphopenia, neutrophilia, and thrombocytopenia. Prophylactic anticoagulation is vital in patients with coronavirus disease 2019, as its effect on the coagulation system is associated with significant morbidity and mortality. The disease can cause both arterial and venous thromboses, especially pulmonary embolism and pulmonary microthrombi. A high index of suspicion is indispensable in recognizing these complications, and timely institution of therapeutic anticoagulation is vital in treating them. Virus-induced disseminated intravascular coagulation is uncommon but shares some similarities to sepsis-induced disseminated intravascular coagulation. Marked elevations in hematologic biomarkers such as lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein are associated with worse outcomes. Understanding the pathophysiology and recognizing factors associated with poor prognosis are crucial in improving patient outcomes with coronavirus disease 2019.
IgG‐specific and polyspecific PF4‐dependent enzyme‐immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin‐induced thrombocytopenia (HIT), a drug reaction caused by platelet‐activating antibodies detectable by serotonin‐release assay (SRA). The IgG‐specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis‐à‐vis polyspecific EIAs. We investigated the frequency of SRA‐positive/EIA‐negative (SRA+/EIA−) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient (“index case”) with false‐negative IgG‐specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG‐specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near‐fatal cardiac arrest, indicating likely post‐heparin HIT‐associated anaphylactoid reaction. Further investigations revealed a strong‐positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor‐blocking monoclonal antibody (indicating IgG‐mediated platelet activation); however, five different IgG‐specific immunoassays yielded primarily negative (or weak‐positive) results. To investigate the frequency of SRA+/EIA− HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6‐year period in which our reference laboratory investigated for HIT using both SRA and IgG‐specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA− profile, further review of 15 such cases indicated clerical/laboratory misclassification or false‐positive SRA in all, with no SRA+/EIA− HIT case identified. We conclude that while SRA+/EIA− HIT is possible—as shown by our index case—this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false‐positive SRA result.
Background:
Preoperative laboratory studies are often obtained as part of the workup for surgeries such as total hip arthroplasty (THA). An increasing need exists to be able to identify patients at risk for adverse outcomes. Thus, metrics that correlate with postoperative adverse events and readmissions are increasingly important to optimize patient care. The implications of varying abnormal platelet counts, especially on the high end of the spectrum, have yet to be assessed in large, multicenter patient populations. This study aims to risk stratify THA patients with varying preoperative platelet counts to address these questions. The purposes of this study were to (1) evaluate cutoffs for normal versus abnormal platelet counts for patients undergoing THA by using postoperative complications data and (2) assess the correlation of such values with readmission data using the National Surgical Quality Improvement Program database.
Methods:
Patients who underwent elective primary THA were identified in the 2011 to 2015 National Surgical Quality Improvement Program database. Risk of 30-day perioperative complications was calculated as a function of preoperative platelet counts. Based on the risk criteria, patients were categorized into the following three groups: normal platelet counts, abnormally low platelet counts, and abnormally high platelet counts. Multivariate analyses were performed to compare 30-day postoperative complications, readmissions, surgical time, and length of hospital stay between these populations.
Results:
The current study identified 86,845 THA patients. Using the relative risk threshold of 1.5, platelets counts were divided into abnormally low (≤142,000/mL) and abnormally high (≥417,000/mL) categories. Higher rates of any, major, and minor adverse events and hospital readmission were associated with both the abnormally low and high platelet cohorts.
Conclusion:
This study suggests that preoperative high, as well as low, platelet counts are correlated with perioperative complications after THA, including hospital readmissions. Patients with these laboratory findings warrant further attention with possible preoperative and postoperative optimization.
Heavily transfused patients frequently develop human leukocyte antigen (HLA) allo‐immunization resulting in platelet transfusion refractoriness and a high risk for life‐threatening thrombocytopenia. Data suggest complement activation leading to the destruction of platelets bound by HLA allo‐antibodies may play a pathophysiologic role in platelet refractoriness. Here we conducted a pilot trial to investigate the use of eculizumab, a monoclonal antibody that binds and inhibits C5 complement, to treat platelet transfusion refractoriness in allo‐immunized patients with severe thrombocytopenia. A single eculizumab infusion was administered to 10 eligible patients, with four (40%) patients overcoming platelet refractories assessed measuring the corrected platelet count increment (CCI) 10–60 min and 18–24 h post transfusion. Responding patients had a reduction in the requirement for subsequent platelet transfusions and had higher post‐transfusion platelet increments for 14 days following eculizumab administration. Remarkably, three of the four responders met CCI criteria for response despite receiving HLA‐incompatible platelets. Our results suggest that eculizumab has the ability to overcome platelet transfusion refractoriness in patients with broad HLA allo‐immunization. This study establishes proof of principle that complement inhibition can treat platelet transfusion refractoriness, laying the foundation for a large multicentre trial to assess the overall efficacy of this approach (ClinicalTrials.gov, identifier: NCT02298933).
Background:
Impaired thrombin generation (TG) in patients with acquired coagulopathy, is due to low coagulation factors and thrombocytopenia. The latter is typically treated with platelet transfusions and the former with plasma and occasionally with prothrombin complex concentrates (PCCs). We hypothesized that manipulating the concentrations of coagulation factors might result in restoration of platelet-dependent TG over and above that of simple replacement therapy.
Objective:
To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia.
Methods:
TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20-300 × 109/L) were spiked with PCCs (25%-150% increase in plasma PCC levels).
Results:
PCCs and platelets significantly increased TG in a dose-dependent manner in vitro. Two-way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combination with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG.
Conclusions:
Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to moderate thrombocytopenia and abnormal coagulation.
Background:
Patients with haematological malignancies often develop thrombocytopenia as a consequence of either their disease or its treatment. Platelet transfusions are commonly given to raise a low platelet count and reduce the risk of clinical bleeding (prophylaxis) or stop active bleeding (therapy). Recent studies have shown that many patients continue to experience bleeding despite the use of prophylactic platelet transfusions. Tranexamic acid is an anti-fibrinolytic, which reduces the breakdown of clots formed in response to bleeding. Anti-fibrinolytics have been shown to prevent bleeding, decrease blood loss and use of red cell transfusions in elective and emergency surgery, and are used widely in these settings. The aim of this trial is to test whether giving tranexamic acid to patients receiving treatment for haematological malignancies reduces the risk of bleeding or death and the need for platelet transfusions.
Methods:
This is a multinational randomised, double-blind, placebo-controlled, parallel, superiority trial. Patients will be randomly assigned to receive tranexamic acid (given intravenously or orally) or a matching placebo in a 1:1 ratio, stratified by site. Patients with haematological malignancies receiving intensive chemotherapy or stem cell transplantation (or both) who are at least 18 years of age and expected to become severely thrombocytopenic for at least 5 days will be eligible for this trial. The primary outcome of the trial is the proportion of patients who died or had bleeding of World Health Organization grade 2 or above during the first 30 days of the trial. We will measure the rates of bleeding daily by using a short, structured assessment of bleeding, and we will record the number of transfusions given to patients. We will assess the risk of arterial and venous thrombosis for 120 days from the start of trial treatment.
Discussion:
This trial will assess the safety and efficacy of using prophylactic tranexamic acid during a period of intensive chemotherapy and associated thrombocytopenia in people with haematological disorders.
Trial registration:
This study was prospectively registered on Current Controlled Trials on 25 March 2015 (ISRCTN73545489) and is also registered on ClinicalTrials.gov (NCT03136445).
Bleeding is the most common clinical symptom and the leading cause of death in patients with primary immune thrombocytopenia (ITP). Our research intends to verify the role of fibrinogen levels as independent determinants of bleeding. We retrospectively analyzed the relationship between fibrinogen levels and bleeding events in 463 patients. Additionally, we confirmed the impact of fibrinogen level on clot firmness in 25 patients via thrombelastography (TEG). Fibrinogen levels (median and inter-quartile range, IQR) were significantly different (p < .001) between bleeding and non-bleeding patients [258(207–314) mg/dL vs. 315(262–407) mg/dL, respectively]. Further analyzes in three subgroups based on platelet (PLT) count showed that non-bleeding patients still had higher fibrinogen levels than bleeding patients. The optimal discriminant threshold of fibrinogen in bleeding was 288.5 mg/dL according to receiver operating characteristic (ROC) curves. Patients were divided into low (LF, 230[193–258] mg/dL) and high (HF, 349[313–424] mg/dL) fibrinogen groups based on this threshold. Bleeding event rates were significantly different (LF: 84.6% vs. HF: 60.4%, P < .001) between the two groups. Multivariable analyses further confirmed these differences. Moreover, TEG parameters showed elevated clot firmness in the HF group. Our data suggest that high fibrinogen levels are associated with reduced bleeding events.
Background
Desmopressin is used to reduce bleeding complications for kidney biopsies with azotemia but little is known about desmopressin-induced hyponatremia in these individuals. We aimed to evaluate the impact of desmopressin prophylaxis on severe hyponatremia and bleeding after kidney biopsies in individuals with renal impairment.
Method
This is a single-center retrospective cohort study of consecutive adults with serum creatinine ≥ 150 µmol/L and had ultrasound-guided percutaneous native or transplant kidney biopsies between June 2011 and July 2015. Data were retrieved from electronic medical records. Primary outcomes were the use of desmopressin prophylaxis and severe hyponatremia (serum sodium ≤ 125 mmol/L) within 7 days post-biopsy. Secondary outcome was post-biopsy bleeding.
Results
240 native kidney and 196 allograft biopsies were performed. Median age was 51 (IQR 42.3, 60) years and eGFR was 21.9 (12.9, 30.1) ml/min/1.73 m². Although patients prescribed desmopressin prophylaxis (n = 226) had higher serum creatinine [279 (201, 392) vs. 187 (160, 241), p < 0.001], bleeding (15.0% vs. 13.3%, p = 0.60) was not significantly different with and without desmopressin. Severe hyponatremia occurred in 30 biopsies (6.9%) with nadir serum sodium level of 122 (119, 124) mmol/L at 3 (2, 5) days after biopsy, more frequently among those with desmopressin prophylaxis (10.7% vs. 3.0%, p = 0.002). Multi-variate analysis found that pre-biopsy serum sodium level [adjusted OR 0.80 (95% CI 0.72, 0.90), p < 0.001] and desmopressin prophylaxis [adjusted OR 4.02 (95% CI 1.58, 10.21), p = 0.003] were independently associated with severe hyponatremia after kidney biopsy.
Conclusion
Pre-biopsy desmopressin was associated with severe hyponatremia in individuals with renal impairment; hence, susceptible patients given desmopressin should be closely monitored.
Background
Thrombocytopenia is the most common hematologic complication associated with chronic liver disease (CLD) with important clinical implications. While the mechanisms for thrombocytopenia are multifactorial, platelet sequestration in the spleen and decreased thrombopoietin (TPO) production are the main mechanisms in patients with CLD.
Aim
This review outlines the current treatment options for thrombocytopenia in patients with CLD, explores their limitations, and proposes a revised treatment algorithm for the management of thrombocytopenia in this patient group.
Methods
A PubMed search of the literature was undertaken with search terms focused on CLD and thrombocytopenia.
Results
Until now, the standard-of-care treatment in these patients has been the use of platelet transfusions either prophylactically or periprocedurally to control bleeding. Treatment options, such as splenic artery embolization and splenectomy, are invasive, and their utility is limited by significant complications. The US Food and Drug Administration recently approved 2 s-generation TPO-receptor agonists, avatrombopag and lusutrombopag, as safe and effective therapies for the treatment of thrombocytopenia in patients with CLD scheduled to undergo a procedure.
Conclusions
The addition of avatrombopag and lusutrombopag offers physicians an alternative to platelet transfusions in patients with CLD who have to undergo medical/dental procedures that could potentially put them at an increased risk of bleeding. There are several other drugs in the research pipeline at various stages of development, including a new class of monoclonal antibodies that can bind to and activate TPO-receptor agonists. The outlook for treatment choices for thrombocytopenia in patients with liver disease is promising.
Background:
Anemia and transfusion of blood in the peri-operative period have been shown to be associated with increased morbidity and mortality across a wide variety of non-cardiac surgeries. While tests of coagulation, including the platelet count, have frequently been used to identify patients with an increased risk of peri-operative bleeding, results have been equivocal. The aim of this study was to assess the effect of platelet level on outcomes in patients undergoing elective surgery.
Materials and methods:
Retrospective cohort analysis of prospectively-collected clinical data from American College of Surgeons National Surgical Quality Improvement Program (NSQIP) between 2006-2016.
Results:
We identified 3,884,400 adult patients who underwent elective, non-cardiac surgery from 2006-2016 at hospitals participating in NSQIP, a prospectively-collected, national clinical database with established reproducibility and validity. After controlling for all peri- and intraoperative factors by matching on propensity scores, patients with all levels of thrombocytopenia or thrombocytosis had higher odds for perioperative transfusion. All levels of thrombocytopenia were associated with higher mortality, but there was no association with complications or other morbidity after matching. On the other hand, thrombocytosis was not associated with mortality; but odds for postoperative complications and 30-day return to the operating room remained slightly increased after matching.
Conclusions:
These findings may guide surgeons in the appropriate use and appreciation of the utility of pre-operative screening of the platelet count prior to an elective, non-cardiac surgery.
Background
The thrombopoietin receptor agonist (TPO‐RA) avatrombopag has recently been FDA‐approved for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) scheduled for a procedure. The TPO receptor c‐mpl is expressed on the platelet surface and TPO lowers the threshold for platelet activation. TPO‐RAs may therefore also lead to platelet activation.
Objectives
To evaluate the effects of avatrombopag on platelet activation.
Patients/Methods
CLD patients with thrombocytopenia participated in a randomized, double‐blind, placebo‐controlled, parallel‐group study. No patient received a platelet transfusion within 10 days of study blood draws. Platelet activation was evaluated by whole blood flow cytometry (which, unlike other methods, is accurate in thrombocytopenic samples).
Results
Avatrombopag, but not placebo, increased platelet counts. As measured by platelet surface P‐selectin and activated GPIIb‐IIIa: 1) Circulating activated platelets were not increased in avatrombopag‐treated patients compared with placebo‐treated patients. 2) Platelet reactivity to low and high concentrations of ADP and thrombin receptor activating peptide was not increased in avatrombopag‐treated patients compared with placebo‐treated patients.
Conclusions
In this randomized, double‐blind, placebo‐controlled, parallel‐group study of CLD patients with thrombocytopenia, avatrombopag increased platelet counts but did not increase platelet activation in vivo or platelet reactivity in vitro.
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Beyond haemostasis, platelets have emerged as versatile effectors of the immune response. The contribution of platelets in inflammation, tissue integrity and defence against infections has considerably widened the spectrum of their role in health and disease. Here, we propose a narrative review that first describes these new platelet attributes. We then examine their relevance to microcirculatory alterations in multi-organ dysfunction, a major sepsis complication. Rapid progresses that are made on the knowledge of novel platelet functions should improve the understanding of thrombocytopenia, a common condition and a predictor of adverse outcome in sepsis, and may provide potential avenues for management and therapy.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count or platelet dysfunction (inherited or acquired). © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Bleeding remains a significant problem for many thrombocytopenic hematology/oncology patients in spite of platelet transfusions. Factors that might contribute to bleeding were analyzed for 16 320 patient-days on or after their first platelet transfusion in 1077 adult patients enrolled in the Platelet Dose (PLADO) trial. All patients had a greatly increased risk of bleeding at platelet counts of ≤5 × 109/L (odds ratio [OR], 3.1; 95% confidence interval [CI], 2.0-4.8) compared with platelet counts ≥81 × 109/L. Platelet counts between 6 × 109/L and 80 × 109/L were also associated with a somewhat elevated bleeding risk in patients receiving allogeneic stem cell transplants (SCTs) or chemotherapy but not in those undergoing autologous SCTs. Other significant laboratory predictors of bleeding were hematocrit ≤25% (OR, 1.29; 95% CI, 1.11-1.49), activated partial thromboplastin time (aPTT) 30 to ≤50 seconds (OR, 1.40; 95% CI, 1.08-1.81; P = .01), aPTT >50 seconds (OR, 2.34; 95% CI, 1.54-3.56), international normalized ratio (INR) 1.2 to 1.5 (OR, 1.46; 95% CI, 1.17-1.83), and INR >1.5 (OR, 2.05; 95% CI, 1.43-2.95). Transfusion of either platelets or red blood cells (RBCs) on days with bleeding was often not sufficient to change bleeding outcomes on the following day. Because bleeding occurred over a wide range of platelet counts among patients undergoing allogeneic SCT or chemotherapy and because platelet transfusions may not prevent bleeding, other risk factors may be involved. These may include low hematocrit and coagulation abnormalities. This trial was registered at www.clinicaltrials.gov as #NCT00128713.
Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders (IPD), however very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a multicentric, retrospective worldwide study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted and their efficacy in patients with IPDs by rating the outcome of 829 surgical procedures carried out in 423 patients with well defined forms of IPD (238 inherited platelet function disorders -IPFD- and 185 inherited platelet number disorders-IPND-). Frequency of surgical bleeding was high in patients with IPD (19.7%), with a significantly higher bleeding incidence in IPFDs (24.8%) than in IPNDs (13.4%). The frequency of bleeding varied according to the type of IPD, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%), and was predicted by a preoperative WHO bleeding score >/-2. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urologic surgery. The use of preoperative prohemostatic treatments was associated with a lower bleeding frequency in patients with IPFD but not in IPNDs. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in IPD is substantial, especially in IPFDs, and bleeding history, type of disorder, type of surgery and female gender are associated with higher bleeding frequency. Prophylactic preoperative prohemostatic treatments appear to be required and associated with a lower bleeding incidence.
Background:
Thrombocytopenia has been considered a relative or even absolute contraindication to neuraxial techniques due to the risk of epidural hematoma. There is limited literature to estimate the risk of epidural hematoma in thrombocytopenic parturients. The authors reviewed a large perioperative database and performed a systematic review to further define the risk of epidural hematoma requiring surgical decompression in this population.
Methods:
The authors performed a retrospective cohort study using the Multicenter Perioperative Outcomes Group database to identify thrombocytopenic parturients who received a neuraxial technique and to estimate the risk of epidural hematoma. Patients were stratified by platelet count, and those requiring surgical decompression were identified. A systematic review was performed, and risk estimates were combined with those from the existing literature.
Results:
A total of 573 parturients with a platelet count less than 100,000 mm who received a neuraxial technique across 14 institutions were identified in the Multicenter Perioperative Outcomes Group database, and a total of 1,524 parturients were identified after combining the data from the systematic review. No cases of epidural hematoma requiring surgical decompression were observed. The upper bound of the 95% CI for the risk of epidural hematoma for a platelet count of 0 to 49,000 mm is 11%, for 50,000 to 69,000 mm is 3%, and for 70,000 to 100,000 mm is 0.2%.
Conclusions:
The number of thrombocytopenic parturients in the literature who received neuraxial techniques without complication has been significantly increased. The risk of epidural hematoma associated with neuraxial techniques in parturients at a platelet count less than 70,000 mm remains poorly defined due to limited observations.
The volume fraction of red blood cells (RBCs) in a capillary affects the degree to which platelets are promoted to marginate to near a vessel wall and form blood clots. In this work we investigate the relationship between RBC hematocrit and platelet adhesion activity. We perform experiments flowing blood samples through a microfluidic channel coated with type 1 collagen and observe the rate at which platelets adhere to the wall. We compare these results with three-dimensional boundary integral simulations of a suspension of RBCs and platelets in a periodic channel where platelets can adhere to the wall. In both cases, we find that the rate of platelet adhesion varies greatly with the RBC hematocrit. We observe that the relative decrease in platelet activity as hematocrit falls shows a similar profile for simulation and experiment.
Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. The majority of the included procedures were endoscopic. TPO-RAs were significantly more likely to result in a preoperative platelet count greater than 50 x 10⁹/L (72.1% vs 15.6%, RR 4.8, 95% CI 3.6–6.4 p < .00001. NNT 1.8) and reduced the incidence of platelet transfusions (22.5% vs 67.8%, RR 0.33, 95% CI 0.3–0.4 p < .00001. NNT 2.2). Total periprocedural bleeding was decreased in patients who received TPO-RAs (11.6% vs 15.6%, RR 0.64, 95% CI 0.5–0.9 p = .01. NNT 24.7) and there was no increase in the rate of thrombosis (2.2% vs 1.8% RR 1.25, 95% CI 0.6–2.9 p = .60. NNH 211.1). In patients with CLD the use of preprocedural TPO-RAs resulted in significant increased platelet counts, and decreased the incidence of platelet transfusions as compared to placebo. TPO use likewise decreased the incidence of total periprocedural bleeding without increasing the rate of thrombosis.
Refractoriness to platelet transfusion is a common clinical problem encountered by the transfusion medicine specialist. It is well recognized that most causes of refractoriness to platelet transfusion are not a consequence of alloimmunization to human leukocyte, platelet-specific, or ABO antigens, but are a consequence of platelet sequestration and consumption. This review summarizes the clinical factors that result in platelet refractoriness and highlights recent data describing novel biological mechanisms that contribute to this clinical problem.
Despite significant advancements in the production of platelet products, storage, and transfusion, transfusion refractoriness remains a significant clinical problem, affecting up to 14% of hematological patients receiving platelet transfusions. Human leukocyte antigen (HLA) alloimmunization is a major cause of immune platelet refractoriness, and its rate can be significantly reduced by implementation of leukoreduction. Despite promising preclinical results, pathogen reduction does not reduce HLA alloimmunization. Patients with HLA alloimmune refractoriness are usually managed with HLA-selected platelet transfusions. In this review, we describe the pathophysiology of HLA alloimmunization and alloimmune refractoriness, as well as options to prevent and treat these transfusion complications. We discuss the evidence supporting these options and point out the outstanding gaps. Finally, we review the possible future directions for prevention and treatment of alloimmune refractoriness.
Background
Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin.
Methods
We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 10 ⁹ cells per L before major surgery or less than 50 × 10 ⁹ cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 10 ⁹ cells per L before major surgery or 45 × 10 ⁹ cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of –10%. This trial is registered with ClinicalTrials.gov, NCT01621204.
Findings
Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49–55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; p non-inferiority=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI –2·1%; p non-inferiority=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred.
Interpretation
Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles.
Funding
GlaxoSmithKline and Novartis.
Thrombocytopenia is one of the most common hematologic complications in cirrhosis. Despite limited data linking platelet count and bleeding risk in patients with cirrhosis, the use of platelets transfusions for invasive procedures has been a common practice. Recently, thrombopoietin (TPO) receptor agonists have been approved for use in patients with chronic liver disease (CLD) undergoing invasive procedures. The aim of this study was to review current literature on bleeding risk in patients with cirrhosis and the use of platelet transfusions and TPO receptor agonists in the context of invasive procedures. PubMed search was conducted to find articles relating to cirrhosis, thrombocytopenia, and new novel treatments for this condition. Search terms included CLD, cirrhosis, thrombocytopenia, bleeding, thrombosis, coagulopathy, hemostasis, and TPO receptor agonists. Romiplostim, eltrombopag, avatrombopag, and lusutrombopag are approved TPO receptor agonists, with avatrombopag and lusutrombopag specifically approved for use in patients with CLD undergoing invasive procedures. In patients with platelet counts < 50,000/mm3, avatrombopag and lusutrombopag increased the platelet counts above this threshold in the majority of treated patients and reduced the frequency of platelet transfusions. At the approved doses, incidence of thrombosis was not increased and therapies were well tolerated. Studies were not powered to assess whether risk of bleeding complications was reduced and the fundamental question of whether correction of thrombocytopenia is warranted in patients undergoing invasive procedures remains unanswered. The use of TPO receptor agonists has resulted in less requirement for platelet transfusions. In patients with cirrhosis undergoing invasive procedures for whom platelet transfusion is planned, TPO receptor agonists are an alternative and avoid the risks associated with transfusions. However, there is need for a thoughtful approach to manage bleeding risk in patients with cirrhosis undergoing procedures, with the consideration of a comprehensive hemostatic profile, the severity of portal hypertension, and the complexity of the invasive procedure to guide decisions regarding transfusions or use of TPO receptor agonists.
Background
Blood transfusion is a well-established independent risk factor for mortality in patients undergoing cardiac surgery but the impact of platelet transfusion is less clear. We performed a systematic review and meta-analysis of observational studies comparing outcomes of patients who received platelet transfusion following cardiac surgery.
Methods
We searched MEDLINE and EMBASE databases to January 2019 for studies comparing peri-operative outcomes in patients undergoing cardiac surgery with and without platelet transfusion.
Results
There were 9 observational studies reporting on 101,511 patients: 12% with and 88% without platelet transfusion. In unmatched/unadjusted studies, patients who received platelet transfusion were older with greater incidence of renal, peripheral and cerebrovascular disease, myocardial infarction, left ventricular dysfunction, and anemia. They were more likely to have non-elective, combined surgery; pre-operative hemodynamic instability and endocarditis; and more likely to be on clopidogrel preoperatively. Perioperative complications were significantly increased without adjusting for these baseline differences. After pooling only matched/adjusted data, differences were not found in patients who did vs did not receive platelets for operative mortality (risk ratio [RR] 1.26, 95%CI:0.69-2.32, p=0.46, 5 studies), stroke (RR 0.94, 95%CI:0.62-1.45, p=0.79, 5 studies), myocardial infarction (RR1.29, 95%CI:0.95-1.77, p=0.11, 3 studies), reoperation for bleeding (RR1.20, 95%CI:0.46-3.18, p=0.71, 3 studies), infection (RR1.02, 95%CI:0.86-1.20, p=0.85, 6 studies), and peri-operative dialysis (RR0.91, 95%CI:0.63-1.32, p=0.62, 3 studies).
Conclusions
After accounting for baseline differences, platelet transfusion was not linked with perioperative complications in cardiac surgery patients. Given the small number of observational studies, these findings should be considered hypothesis generating.
Thrombocytopenia is a consequence of portal hypertension and is the most common hematological manifestation of chronic liver disease (CLD) (ie, cirrhosis). Data indicates the rates of CLD are increasing and, as a result, so will the incidence of this complication. Although bleeding risks are only relevant when elective procedures are performed, this is a frequent concern as these procedures are commonly part of the spectrum of care for patients with cirrhosis. As such, thrombocytopenia remains a pertinent issue. Fortunately, we now have effective and accurate treatment modalities to raise platelet counts before scheduled procedures, known as thrombopoietin receptor agonists. Two drugs in this therapeutic class (avatrombopag and lusutrombopag) are now approved for the treatment of thrombocytopenia in adults with CLD undergoing a procedure and have revolutionized how this is managed. Although there is progress in the field, peer-reviewed literature and expert guidance are lacking. Recognizing these unmet needs, a group of expert hepatologists comprised this review, which summarizes the most current and relevant peer-reviewed literature on thrombocytopenia in CLD and provides clinical expertise on this timely topic.
Platelet transfusions aim to improve primary hemostasis and to prevent or treat bleeding in patients with reduced platelet numbers and/or platelet function. In this review, the authors address the role of platelet transfusions with a focus on perioperative medicine. They summarize different causes of thrombocytopenia in perioperative patients, describe general characteristics and potential adverse effects of different platelet concentrates, describe principles of perioperative platelet transfusion strategies, and highlight specific perioperative scenarios, for example, in patients undergoing antiplatelet therapy. The evidence for any transfusion threshold in perioperative patients based on platelet numbers is low. The evidence supporting prophylactic platelet transfusions in the perioperative setting is very low, and all recommended thresholds for preintervention platelet transfusions are based on weak evidence or expert opinion. Besides the platelet count, platelet function, additional risk factors for bleeding, and the pharmacokinetic properties of concomitant antiplatelet drugs are important criteria for the decision to transfuse or not to transfuse platelets. The few available prospective trials give at least a signal that a liberal platelet transfusion strategy might be associated with poorer outcomes compared with a restrictive platelet transfusion strategy in critically ill patients. Given the unknown risks for adverse outcomes, a therapeutic transfusion strategy during surgery (eventually guided by point of care testing in cardiac surgery, major liver surgery, and major trauma) may be most appropriate for interventions, in which intraoperative bleeding can be controlled until platelets are available, and during the postsurgery period.
Introduction:
There is currently no consensus regarding the minimum threshold platelet count to ensure safe neuraxial procedures. Numerous reports describe the safe performance of lumbar punctures in severely thrombocytopenic patients but reports of neuraxial anesthetic procedures in thrombocytopenic patients are limited. To date, the focus on specific populations in contemporary reviews has failed to include any actual hematoma cases. This systematic review aggregates reported lumbar neuraxial procedures from diverse thrombocytopenic populations to best elucidate the risk of spinal epidural hematoma.
Methods:
MEDLINE, Embase, Cochrane, CINAHL databases were searched for articles about thrombocytopenic patients (<100,000 × 106/L) who received a lumbar neuraxial procedure (lumbar puncture; spinal, epidural, or combined spinal-epidural analgesia/anesthesia; epidural catheter removal), whether spinal epidural hematoma occurred.
Results:
Of 4167 articles reviewed, 131 met inclusion criteria. 7476 lumbar neuraxial procedures were performed without and 33 procedures with spinal epidural hematoma. Within the platelet count ranges of 1-25,000 × 106/L, 26-50,000 × 106/L, 51-75,000 × 106/L, and 76-99,000 × 106/L there were 14, 6, 9, and 4 spinal epidural hematomas, respectively. An infection point and narrow confidence intervals were observed near 75,000 × 106/L or above, reflecting a low probability of spinal epidural hematoma in this sample. Of the 19 spinal epidural hematoma cases for which the onset of symptoms was reported, 18 (95%) were symptomatic within 48 h of the procedure.
Conclusions:
Spinal epidural hematoma in thrombocytopenic patients is rare. In this sample of patients, an inflection point and narrow confidence intervals are observed near a platelet count of 75,000 × 106/L or above, reflecting an estimated low spinal epidural hematoma event rate with more certainty given a larger sample size and inclusion of spinal epidural hematoma cases. Thrombocytopenic patients should be monitored, particularly in the first 48 h, and educated about symptoms concerning for spinal epidural hematoma.
Thrombocytopenia is a common hematologic finding with variable clinical expression. A low platelet count may be the initial manifestation of infections such as HIV and hepatitis C virus or it may reflect the activity of life-threatening disorders such as the thrombotic microangiopathies. A correct identification of the causes of thrombocytopenia is crucial for the appropriate management of these patients. In this review, we present a systematic evaluation of adults with thrombocytopenia. The approach is clearly different between outpatients, who are frequently asymptomatic and in whom we can sometimes indulge in sophisticated and relatively lengthy investigations, and the dramatic presentation of acute thrombocytopenia in the emergency department or in the intensive care unit, which requires immediate intervention and for which only a few diagnostic tests are available. A brief discussion of the most common etiologies seen in both settings is provided.
The possibility of an acquired platelet function disorder should be considered in patients who present with recent onset muco-cutaneous bleeding. Despite the availability of newer and faster platelet function assays, light transmission aggregometry (LTA) remains the preferred diagnostic test. This review examines and discusses the causes of acquired platelet dysfunction; most commonly drugs, dietary factors, medical disorders and procedures. In addition to well-known antiplatelet therapies, clinicians should be alert for newer drugs which can affect platelets, such as ibrutinib. There is little clinical trial evidence to guide the management of acquired platelet function defects, but we summarise commonly employed strategies, which include addressing the underlying cause, antifibrinolytic agents, desmopressin infusions, and in selected patients, platelet transfusions.
Abstract
Background
Lab studies are routinely performed as a part of the preoperative workup for a total knee arthroplasty (TKA). The ramifications of abnormal preoperative platelet counts remain uncharacterized in large, multicenter patient populations.
Methods
Patients who underwent elective primary TKA were identified in the 2011-2015 National Surgical Quality Improvement Program (NSQIP) database. Risk of 30-day postoperative complications was calculated as a function of pre-operative platelet counts. Patients were characterized as having a normal platelet count, abnormally low platelet count, and abnormally high platelet count based on relative risk calculations. Univariate and multivariate analyses were performed to associate abnormal platelet counts with patient demographics, operative variables, 30-day postoperative complications, and readmissions.
Results
In total, 140,073 patients who underwent elective TKA were identified. Using the relative risk threshold of 1.5 for any adverse event, abnormally low and abnormally high platelet count thresholds were set at ≤116,000/mL and ≥492,000/mL, respectively. Multivariate analyses revealed low platelet counts to be associated with higher rates of any, major, and minor adverse events and longer length of stay. Analogously, high platelet counts were associated with higher rates of any and minor adverse events and longer length of stay.
Discussion
The current study employed a large patient sample size and showed that elective TKA patients with abnormally high, as well as low, platelet counts are at increased risk of post-operative adverse outcomes. Focused attention needs to be paid to TKA patients with preoperative abnormal platelet counts for optimization and postoperative care.
Background
In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor–cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti–von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets.
Methods
In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers.
Results
The median time to normalization of the platelet count was shorter with caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P=0.01), and patients who received caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with caplacizumab than with placebo (12% vs. 49%, P<0.001). The percentage of patients who had a recurrence of TTP at any time during the trial was 67% lower with caplacizumab than with placebo (12% vs. 38%, P<0.001). Refractory disease developed in no patients in the caplacizumab group and in three patients in the placebo group. Patients who received caplacizumab needed less plasma exchange and had a shorter hospitalization than those who received placebo. The most common adverse event was mucocutaneous bleeding, which was reported in 65% of the patients in the caplacizumab group and in 48% in the placebo group. During the trial treatment period, three patients in the placebo group died. One patient in the caplacizumab group died from cerebral ischemia after the end of the treatment period.
Conclusions
Among patients with TTP, treatment with caplacizumab was associated with faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo. (Funded by Ablynx; HERCULES ClinicalTrials.gov number, NCT02553317.)
Thrombocytopenia is a common perioperative clinical problem. While global haemostasis is influenced by many patient- and procedure-related factors, the contribution of thrombocytopenia to bleeding risk is difficult to predict, as platelet count does not linearly correlate with likelihood of bleeding. Thus, the widely used definition of thrombocytopenia and grading of its severity have limited clinical utility. We present a summary and analysis of the current recommendations for invasive procedures in thrombocytopenic patients, although the platelet count at which any given procedure may safely proceed is unknown. The benefits and risks of preoperative platelet transfusions should be assessed on a patient-by-patient basis, and alternatives to platelet transfusion should be considered. In non-emergent surgeries or in postoperative thrombocytopenic patients, haematology consultation should be considered to guide diagnostics and management. We present a pragmatic approach to the evaluation of perioperative thrombocytopenia.
Background:
People with thrombocytopenia often require a surgical procedure. A low platelet count is a relative contraindication to surgery due to the risk of bleeding. Platelet transfusions are used in clinical practice to prevent and treat bleeding in people with thrombocytopenia. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to surgery. Alternatives to platelet transfusion are also used prior surgery.
Objectives:
To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count.
Search methods:
We searched the following major data bases: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), PubMed (e-publications only), Ovid MEDLINE, Ovid Embase, the Transfusion Evidence Library and ongoing trial databases to 11 December 2017.
Selection criteria:
We included all randomised controlled trials (RCTs), as well as non-RCTs and controlled before-and-after studies (CBAs), that met Cochrane EPOC (Effective Practice and Organisation of Care) criteria, that involved the transfusion of platelets prior to surgery (any dose, at any time, single or multiple) in people with low platelet counts. We excluded studies on people with a low platelet count who were actively bleeding.
Data collection and analysis:
We used standard methodological procedures expected by Cochrane for data collection. We were only able to combine data for two outcomes and we presented the rest of the findings in a narrative form.
Main results:
We identified five RCTs, all conducted in adults; there were no eligible non-randomised studies. Three completed trials enrolled 180 adults and two ongoing trials aim to include 627 participants. The completed trials were conducted between 2005 and 2009. The two ongoing trials are scheduled to complete recruitment by October 2019. One trial compared prophylactic platelet transfusions to no transfusion in people with thrombocytopenia in an intensive care unit (ICU). Two small trials, 108 participants, compared prophylactic platelet transfusions to other alternative treatments in people with liver disease. One trial compared desmopressin to fresh frozen plasma or one unit of platelet transfusion or both prior to surgery. The second trial compared platelet transfusion prior to surgery with two types of thrombopoietin mimetics: romiplostim and eltrombopag. None of the included trials were free from methodological bias. No included trials compared different platelet count thresholds for administering a prophylactic platelet transfusion prior to surgery. None of the included trials reported on all the review outcomes and the overall quality per reported outcome was very low.None of the three completed trials reported: all-cause mortality at 90 days post surgery; mortality secondary to bleeding, thromboembolism or infection; number of red cell or platelet transfusions per participant; length of hospital stay; or quality of life.None of the trials included children or people who needed major surgery or emergency surgical procedures.Platelet transfusion versus no platelet transfusion (1 trial, 72 participants)We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on all-cause mortality within 30 days (1 trial, 72 participants; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.41 to 1.45; very-low quality evidence). We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on the risk of major (1 trial, 64 participants; RR 1.60, 95% CI 0.29 to 8.92; very low-quality evidence), or minor bleeding (1 trial, 64 participants; RR 1.29, 95% CI 0.90 to 1.85; very-low quality evidence). No serious adverse events occurred in either study arm (1 trial, 72 participants, very low-quality evidence).Platelet transfusion versus alternative to platelet transfusion (2 trials, 108 participants)We were very uncertain whether giving a platelet transfusion prior to surgery compared to an alternative has any effect on the risk of major (2 trials, 108 participants; no events; very low-quality evidence), or minor bleeding (desmopressin: 1 trial, 36 participants; RR 0.89, 95% CI 0.06 to 13.23; very-low quality evidence: thrombopoietin mimetics: 1 trial, 65 participants; no events; very-low quality evidence). We were very uncertain whether there was a difference in transfusion-related adverse effects between the platelet transfused group and the alternative treatment group (desmopressin: 1 trial, 36 participants; RR 2.70, 95% CI 0.12 to 62.17; very-low quality evidence).
Authors' conclusions:
Findings of this review were based on three small trials involving minor surgery in adults with thrombocytopenia. We found insufficient evidence to recommend the administration of preprocedure prophylactic platelet transfusions in this situation with a lack of evidence that transfusion resulted in a reduction in postoperative bleeding or all-cause mortality. The small number of trials meeting the inclusion criteria and the limitation in reported outcomes across the trials precluded meta-analysis for most outcomes. Further adequately powered trials, in people of all ages, of prophylactic platelet transfusions compared with no transfusion, other alternative treatments, and considering different platelet thresholds prior to planned and emergency surgical procedures are required. Future trials should include major surgery and report on bleeding, adverse effects, mortality (as a long-term outcome) after surgery, duration of hospital stay and quality of life measures.
Background
The aim of this cross‐sectional study was to assess risk factors of bleeding in ITP adults, including the determination of platelet count thresholds.
Methods
We selected all newly diagnosed ITP adults included in the CARMEN register and at the French referral center for autoimmune cytopenias. Frequencies of any bleeding, mucosal bleeding and severe bleeding (gastro‐intestinal, intracranial or macroscopic hematuria) at ITP onset were assessed. Platelet count thresholds were assessed using receiver‐operating characteristics curves. All potential risk factors were included in logistic regression models.
Results
Among the 302 patients, the rates of any, mucosal and severe bleeding were 57.9%, 30.1% and 6.6%, respectively. The best discriminant threshold of platelet count for any bleeding was 20 x10⁹/L. In multivariate analysis, factors associated with any bleeding were the platelet count (<10 x10⁹/L vs. ≥20 x10⁹/L: OR, 48.2, 95% CI: 20.0‐116.3; between 10 and 19 x10⁹/L vs. ≥20 x10⁹/L: OR, 5.2, 95% CI: 2.3‐11.6), female sex (OR, 2.6, 95% CI: 1.3‐5.0) and the exposure to NSAIDs (OR, 4.8, 95% CI: 1.1‐20.7). A low platelet count was also the main risk factor of mucosal bleeding. Exposure to anticoagulant drugs was associated with severe bleeding (OR, 4.3, 95% CI: 1.3‐14.1).
Conclusions
Platelet counts <20 x10⁹/L and <10 x10⁹/L were thresholds with major increased risks of any and mucosal bleeding. Platelet count, female sex and exposure to NSAIDs should be considered to assess the risk of any bleeding. Exposure to anticoagulant drugs was a major risk factor for severe bleeding.
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Background
Platelet counts of less than 150,000 per cubic millimeter during uncomplicated pregnancies are described as gestational thrombocytopenia if no alternative cause is identified. Platelet counts may be even lower in women with pregnancy-related complications. However, the occurrence and severity of thrombocytopenia throughout pregnancy are not defined.
Methods
We evaluated platelet counts throughout pregnancy in women who delivered at Oklahoma University Medical Center between 2011 and 2014. These platelet counts were compared with those of nonpregnant women who were included in the National Health and Nutrition Examination Survey from 1999 through 2012.
Results
Among the 15,723 deliveries that occurred during the study period, 7351 women had sufficient data for our analyses. Of these women, 4568 had uncomplicated pregnancies, 2586 had pregnancy-related complications, and 197 had preexisting disorders associated with thrombocytopenia. Among the women who had uncomplicated pregnancies, the mean platelet count in the first trimester (mean gestation, 8.7 weeks) was 251,000 per cubic millimeter, which was lower than the mean platelet count in the 8885 nonpregnant women (273,000 per cubic millimeter) (P<0.001). At the time of delivery, 9.9% of the women with uncomplicated pregnancies had a platelet count below 150,000 per cubic millimeter. During the course of the uncomplicated pregnancies and deliveries, only 45 women (1.0%) had a platelet count below 100,000 per cubic millimeter. Among the 12 women with uncomplicated pregnancies who had a platelet count below 80,000 per cubic millimeter, only 5 (0.1%, among whom the range of platelet counts was 62,000 to 78,000 per cubic millimeter; median, 65,000) were identified by medical record review as having no alternative cause for the thrombocytopenia. Platelet counts of less than 150,000 per cubic millimeter at the time of delivery were more common among women who had pregnancy-related complications than among women who had uncomplicated pregnancies (11.9% vs. 9.9%, P=0.01). Throughout their pregnancies and deliveries, 59 women (2.3%) with pregnancy-related complications had a platelet count below 100,000 per cubic millimeter, and 31 (1.2%) had a platelet count below 80,000 per cubic millimeter.
Conclusions
Mean platelet counts decreased during pregnancy in all the women, beginning in the first trimester. In women who have a platelet count of less than 100,000 per cubic millimeter, a cause other than pregnancy or its complications should be considered. (Funded by the National Heart, Lung, and Blood Institute.)
Patients with the inherited bleeding disorder Glanzmann thrombasthenia (GT) possess platelets that lack αIIbβ3 integrin and fail to aggregate, and have moderate to severe mucocutaneous bleeding. Many become refractory to platelet transfusions due to the formation of isoantibodies to αIIbβ3 with the rapid elimination of donor platelets and/or a block of function. Epitope characterization has shown isoantibodies to be polyclonal and to recognize different epitopes on the integrin with β3 a major site and αvβ3 on endothelial and vascular cells a newly recognized target. Pregnancy in GT can also lead to isoantibody formation when fetal cells with β3 integrins pass into the circulation of a mother lacking them; a consequence is neonatal thrombocytopenia and a high risk of mortality. Antibody removal prior to donor transfusions can provide transient relief, but all evidence points to recombinant FVIIa as the first choice for GT patients either to stop bleeding or as prophylaxis. Promoting thrombin generation by rFVIIa favors GT platelet interaction with fibrin, and the risk of deep vein thrombosis also associated with prolonged immobilization and catheter use requires surveillance. Although having a high risk, allogeneic bone marrow transplantation associated with different stem cell sources and conditioning regimens has proved successful in many cases of severe GT with antibodies, and often, the associated conditioning and immunosuppressive therapy leads to loss of isoantibody production. Animal models of gene therapy for GT show promising results, but isoantibody production can be stimulated and CRISPR/Cas9 technology has yet to be applied. Up-to-date consensus protocols for dealing with isoantibodies in GT are urgently required, and networks providing patient care should be expanded.
Thrombocytopenic patients requiring invasive surgery have few options to improve their platelet count preoperatively. This is a single‐centre, retrospective review of thrombocytopenic patients receiving the thrombopoietin receptor agonist romiplostim perioperatively to allow for surgical interventions. Patient characteristics, romiplostim use, and surgical and safety outcomes (bleeding, thrombosis, transfusions) were collected and analysed. Forty‐seven patients underwent 51 surgical procedures (ranging from total hip arthroplasty to open cardiac surgery) with romiplostim support. Thrombocytopenia aetiologies included immune thrombocytopenia, chronic liver disease, haematological malignancy, drug‐related thrombocytopenia, and hereditary thrombocytopenia. Median (range) platelet counts improved, from 47 × 109/l (9–120 × 109/l) at romiplostim initiation to 164 × 109/l (28–603 × 109/l) at the time of surgery (P < 0·0001). A dose of 3 μg/kg per week for 2 doses increased the platelet count to >100 × 109/l in 79% of patients within 14 days. In 96% of cases, surgery proceeded on schedule without delay or cancellation. Four patients had bleeding events unrelated to thrombocytopenia and 1 patient developed deep venous thrombosis. Six patients required red cell transfusion and 3 patients required platelet transfusion perioperatively. In conclusion, romiplostim was effective in increasing platelet counts to allow surgery to proceed safely and on schedule. Bleeding and thromboembolic events were within acceptable limits for this surgical population.
Background:
People with a low platelet count (thrombocytopenia) often require lumbar punctures or an epidural anaesthetic. Lumbar punctures can be diagnostic (haematological malignancies, subarachnoid haematoma, meningitis) or therapeutic (spinal anaesthetic, administration of chemotherapy). Epidural catheters are placed for administration of epidural anaesthetic. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to lumbar punctures and epidural anaesthesia, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to these procedures varies significantly from country to country. This indicates significant uncertainty among clinicians regarding the correct management of these patients. The risk of bleeding appears to be low, but if bleeding occurs it can be very serious (spinal haematoma). Consequently, people may be exposed to the risks of a platelet transfusion without any obvious clinical benefit.This is an update of a Cochrane Review first published in 2016.
Objectives:
To assess the effects of different platelet transfusion thresholds prior to a lumbar puncture or epidural anaesthesia in people with thrombocytopenia (low platelet count).
Search methods:
We searched for randomised controlled trials (RCTs), non-randomised controlled trials (nRCTs), controlled before-after studies (CBAs), interrupted time series studies (ITSs), and cohort studies in CENTRAL (the Cochrane Library 2018, Issue 1), MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 13 February 2018.
Selection criteria:
We included RCTs, nRCTs, CBAs, ITSs, and cohort studies involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people of any age with thrombocytopenia requiring insertion of a lumbar puncture needle or epidural catheter.The original review only included RCTs.
Data collection and analysis:
We used standard methodological procedures expected by Cochrane for including RCTs, nRCTs, CBAs, and ITSs. Two review authors independently assessed studies for eligibility and risk of bias and extracted data. Results were only expressed narratively.
Main results:
We identified no completed or ongoing RCTs, nRCTs, CBAs, or ITSs. No studies included people undergoing an epidural procedure. No studies compared different platelet count thresholds prior to a procedure.In this update we identified three retrospective cohort studies that contained participants who did and did not receive platelet transfusions prior to lumbar puncture procedures. All three studies were carried out in people with cancer, most of whom had a haematological malignancy. Two studies were in children, and one was in adults.The number of participants receiving platelet transfusions prior to the lumbar puncture procedures was not reported in one study. We therefore only summarised in a narrative form the relevant outcomes from two studies (150 participants; 129 children and 21 adults), in which the number of participants who received the transfusion was given.We judged the overall risk of bias for all reported outcomes for both studies as 'serious' based on the ROBINS-I tool.No procedure-related major bleeding occurred in the two studies that reported this outcome (2 studies, 150 participants, no cases, very low-quality evidence).There was no evidence of a difference in the risk of minor bleeding (traumatic tap) in participants who received platelet transfusions before a lumbar puncture and those who did not receive a platelet transfusion before the procedure (2 studies, 150 participants, very low-quality evidence). One of the 14 adults who received a platelet transfusion experienced minor bleeding (traumatic tap; defined as at least 500 x 106/L red blood cells in the cerebrospinal fluid); none of the seven adults who did not receive a platelet transfusion experienced this event. Ten children experienced minor bleeding (traumatic taps; defined as at least 100 x 106/L red blood cells in the cerebrospinal fluid), six out of the 57 children who received a platelet transfusion and four out of the 72 children who did not receive a platelet transfusion.No serious adverse events occurred in the one study that reported this outcome (1 study, 21 participants, very low-quality evidence).We found no studies that evaluated all-cause mortality within 30 days from the lumbar puncture procedure, length of hospital stay, proportion of participants who received platelet transfusions, or quality of life.
Authors' conclusions:
We found no evidence from RCTs or non-randomised studies on which to base an assessment of the correct platelet transfusion threshold prior to insertion of a lumbar puncture needle or epidural catheter. There are no ongoing registered RCTs assessing the effects of different platelet transfusion thresholds prior to the insertion of a lumbar puncture or epidural anaesthesia in people with thrombocytopenia. Any future study would need to be very large to detect a difference in the risk of bleeding. A study would need to be designed with at least 47,030 participants to be able to detect an increase in the number of people who had major procedure-related bleeding from 1 in 1000 to 2 in 1000. The use of a central data collection register or routinely collected electronic records (big data) is likely to be the only method to systematically gather data relevant to this population.
Background:
Laboring women with low platelet counts may be denied neuraxial block due to concerns about causing a spinal-epidural hematoma.
Aims:
To assess the anesthetic management, complications and outcome variables of women with low platelet counts, and to expand the existing data regarding the safety of neuraxial blocks in this patient population.
Methods:
This is a retrospective analysis of anesthetic and obstetric data from women with platelet counts <100 000/μL, who were admitted to a single referral center during 2011-2014. The rate of neuraxial block and related complications was examined in relation to the platelet count and the results combined with published data to assess the risk of spinal epidural hematoma.
Results:
During the study period, 471 of 45 462 women (1%) had a low platelet count (<100 000/μL). The rate of neuraxial block was significantly higher in women with platelet counts of 70-99 000/μL (280/394, 71.1%) when compared to women with platelet counts of 50-69 000/μL and 0 to 49 000/μL (23/59, 38.9% and 5/18, 27.8%, respectively, P <0.0001). Women in the lower platelet count ranges had a higher risk of cesarean delivery under general anesthesia and longer hospital stay. No neuraxial hematoma were reported.
Conclusions:
This study contributes a substantial series of neuraxial blocks among women with low platelet counts. The findings support that the risk of hematoma is low if the platelet count is <100 000/μL, specifically between 70 and 99 000/μL. Risk assessment in the lower count ranges requires a much larger sample.
Introduction:
Severe bleeding with platelet transfusion refractoriness (PTR) is a common complication associated with reduced survival in patients with hematologic malignancies. The present study aimed to evaluate the efficacy of recombinant factor VIIa (rFVIIa) for severe bleeding complicated by PTR.
Materials and methods:
Sixty-four patients suffering from severe bleeding with PTR hospitalized in our center between September 2012 and December 2016 were enrolled in this study. Thirty-two patients received rFVIIa (rFVIIa group) and other conventional hemostatic treatments, while the other 32 patients received conventional hemostatic treatments other than rFVIIa (control group).
Results:
The baseline parameters of patients before treatment were similar in both groups. The total response rates to hemostatic treatment at 24h and 48h were significantly higher in the rFVIIa group compared with the control group (p=0.014, p=0.020, respectively). Significantly more patients in the rFVIIa group achieved complete responses (CR) at 24h (p=0.031), 48h (p=0.039), and 72h (p=0.021) compared with the control group. The bleeding score (p=0.029), time to control bleeding (p=0.034), and activated partial thromboplastin time (p=0.021) after hemostatic treatment were significantly lower in the rFVIIa group compared with the control group. Patients who achieved a CR to rFVIIa had a significant survival advantage compared with those with a partial response/no response (p=0.020). No complications with venous or arterial thromboembolism were observed during treatment.
Conclusions:
rFVIIa may provide effective and safe hemostasis in patients suffering from severe bleeding and PTR.
Background:
After cardiopulmonary bypass (CPB) thrombocytopenia is a relatively common pattern which may trigger postoperative bleeding. The purpose of this study is to verify if the endogenous fibrinogen levels are independent determinants of chest drain blood loss and need for allogeneic blood products transfusions in a clinical model of post-CPB thrombocytopenia.
Methods:
Retrospective analysis on 445 consecutive patients having a platelet count <100×1000cells/μL after CPB. Based on the fibrinogen levels the patients were divided into three groups with similar platelet count and low (LF, median 170mg/dL), intermediate (IF, median 215mg/dL), and high (HF, median 280mg/dL), fibrinogen levels. Chest drain blood loss (mL/12h), transfusion rate of red blood cells (RBC), fresh frozen plasma (FFP) and platelet concentrates were assessed and compared between groups.
Results:
There was a significant (P=0.001) difference in chest drain blood loss with higher values in the LF group (487mL/12h, IQR 300-600mL/12h) than in the IF group (350mL/12h, IQR 200-500mL/12h) and the HF group (300mL/12h, IQR 200-475mL/12h). Transfusion rates of FFP significantly (P=0.014) differed between groups (LF: 18.4%, IF: 7.9%, HF: 9.2%) and platelet concentrate transfusions significantly (P=0.020) differed between groups (LF: 23.5%, IF: 16.5%, HF: 10.7%). In multivariable models, these differences were confirmed. Thromboelastography parameters showed an effective compensation of clot firmness in group HF vs. IF and LF.
Conclusions:
Levels of fibrinogen >240mg/dL compensate the decrease in clot firmness observed in thrombocytopenic patients following CPB, and reduce bleeding and transfusion needs.
Background and objectives:
Platelet transfusions are widely administered to restore perioperative haemostasis in haemorrhagic patients; however, the role of platelet transfusion is not well understood and administration is often based on empiric data. This review aims to explore consensus regarding platelet transfusion trigger, dose and how the haemostatic efficacy of platelet transfusion was assessed for the treatment of perioperative bleeding.
Materials and methods:
A literature search was carried out using MEDLINE (PubMed) on 28 February 2017, to identify publications reporting the effect of platelet transfusion in relation to triggers, dose and assessment of haemostatic efficacy in bleeding patients in a perioperative setting.
Results:
Eight publications were identified across a variety of settings, covering both prophylactic and therapeutic platelet transfusion in adult patients; the majority of the reports were in cardiac surgery. A high degree of variability was observed in the published studies, with only 50% of articles specifying a trigger for platelet transfusion. The most commonly used trigger was platelet count (25% of publications), with no consensus identified regarding the platelet count values used as triggers. Doses reported per transfusion varied from 1 to 12 units, and outcome measures were mixed, although the majority of publications (63%) assessed the requirement for transfusion with other blood products.
Conclusion:
The lack of consensus in published studies hinders our ability to draw conclusions regarding platelet transfusion and highlights the need for further studies to assess the appropriate dose and triggers for use in perioperative patients.
Background:
Blood transfusion is administered during many types of surgery, but its efficacy and safety are increasingly questioned. Evaluation of the efficacy of agents, such as desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), that may reduce perioperative blood loss is needed.
Objectives:
To examine the evidence for the efficacy of DDAVP in reducing perioperative blood loss and the need for red cell transfusion in people who do not have inherited bleeding disorders.
Search methods:
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (2017, issue 3) in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1937), the Transfusion Evidence Library (from 1980), and ongoing trial databases (all searches to 3 April 2017).
Selection criteria:
We included randomised controlled trials comparing DDAVP to placebo or an active comparator (e.g. tranexamic acid, aprotinin) before, during, or immediately after surgery or after invasive procedures in adults or children.
Data collection and analysis:
We used the standard methodological procedures expected by Cochrane.
Main results:
We identified 65 completed trials (3874 participants) and four ongoing trials. Of the 65 completed trials, 39 focused on adult cardiac surgery, three on paediatric cardiac surgery, 12 on orthopaedic surgery, two on plastic surgery, and two on vascular surgery; seven studies were conducted in surgery for other conditions. These trials were conducted between 1986 and 2016, and 11 were funded by pharmaceutical companies or by a party with a commercial interest in the outcome of the trial.The GRADE quality of evidence was very low to moderate across all outcomes. No trial reported quality of life. DDAVP versus placebo or no treatmentTrial results showed considerable heterogeneity between surgical settings for total volume of red cells transfused (low-quality evidence) and for total blood loss (very low-quality evidence) due to large differences in baseline blood loss. Consequently, these outcomes were not pooled and were reported in subgroups.Compared with placebo, DDAVP may slightly decrease the total volume of red cells transfused in adult cardiac surgery (mean difference (MD) -0.52 units, 95% confidence interval (CI) -0.96 to -0.08 units; 14 trials, 957 participants), but may lead to little or no difference in orthopaedic surgery (MD -0.02, 95% CI -0.67 to 0.64 units; 6 trials, 303 participants), vascular surgery (MD 0.06, 95% CI -0.60 to 0.73 units; 2 trials, 135 participants), or hepatic surgery (MD -0.47, 95% CI -1.27 to 0.33 units; 1 trial, 59 participants).DDAVP probably leads to little or no difference in the total number of participants transfused with blood (risk ratio (RR) 0.96, 95% CI 0.86 to 1.06; 25 trials; 1806 participants) (moderate-quality evidence).Whether DDAVP decreases total blood loss in adult cardiac surgery (MD -135.24 mL, 95% CI -210.80 mL to -59.68 mL; 22 trials, 1358 participants), orthopaedic surgery (MD -285.76 mL, 95% CI -514.99 mL to -56.53 mL; 5 trials, 241 participants), or vascular surgery (MD -582.00 mL, 95% CI -1264.07 mL to 100.07 mL; 1 trial, 44 participants) is uncertain because the quality of evidence is very low.DDAVP probably leads to little or no difference in all-cause mortality (Peto odds ratio (pOR) 1.09, 95% CI 0.51 to 2.34; 22 trials, 1631 participants) or in thrombotic events (pOR 1.36, 95% CI, 0.85 to 2.16; 29 trials, 1984 participants) (both low-quality evidence). DDAVP versus placebo or no treatment for people with platelet dysfunctionCompared with placebo, DDAVP may lead to a reduction in the total volume of red cells transfused (MD -0.65 units, 95% CI -1.16 to -0.13 units; 6 trials, 388 participants) (low-quality evidence) and in total blood loss (MD -253.93 mL, 95% CI -408.01 mL to -99.85 mL; 7 trials, 422 participants) (low-quality evidence).DDAVP probably leads to little or no difference in the total number of participants receiving a red cell transfusion (RR 0.83, 95% CI 0.66 to 1.04; 5 trials, 258 participants) (moderate-quality evidence).Whether DDAVP leads to a difference in all-cause mortality (pOR 0.72, 95% CI 0.12 to 4.22; 7 trials; 422 participants) or in thrombotic events (pOR 1.58, 95% CI 0.60 to 4.17; 7 trials, 422 participants) is uncertain because the quality of evidence is very low. DDAVP versus tranexamic acidCompared with tranexamic acid, DDAVP may increase the volume of blood transfused (MD 0.6 units, 95% CI 0.09 to 1.11 units; 1 trial, 40 participants) and total blood loss (MD 142.81 mL, 95% CI 79.78 mL to 205.84 mL; 2 trials, 115 participants) (both low-quality evidence).Whether DDAVP increases or decreases the total number of participants transfused with blood is uncertain because the quality of evidence is very low (RR 2.42, 95% CI 1.04 to 5.64; 3 trials, 135 participants).No trial reported all-cause mortality.Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 2.92, 95% CI 0.32 to 26.83; 2 trials, 115 participants). DDAVP versus aprotininCompared with aprotinin, DDAVP probably increases the total number of participants transfused with blood (RR 2.41, 95% CI 1.45 to 4.02; 1 trial, 99 participants) (moderate-quality evidence).No trials reported volume of blood transfused or total blood loss and the single trial that included mortality as an outcome reported no deaths.Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 0.98, 95% CI 0.06 to 15.89; 2 trials, 152 participants).
Authors' conclusions:
Most of the evidence derived by comparing DDAVP versus placebo was obtained in cardiac surgery, where DDAVP was administered after cardiopulmonary bypass. In adults undergoing cardiac surgery, the reduction in volume of red cells transfused and total blood loss was small and was unlikely to be clinically important. It is less clear whether DDAVP may be of benefit for children and for those undergoing non-cardiac surgery. A key area for researchers is examining the effects of DDAVP for people with platelet dysfunction. Few trials have compared DDAVP versus tranexamic acid or aprotinin; consequently, we are uncertain of the relative efficacy of these interventions.
Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate cellular FcγRIIA on platelets and monocytes to propagate a hypercoagulable state culminating in life-threatening thrombosis. It is now recognized that anti-PF4/heparin antibodies develop commonly after heparin exposure, but only a subset of sensitized patients progress to life-threatening complications of thrombocytopenia and thrombosis. Recent scientific developments have clarified mechanisms underlying PF4/heparin immunogenicity, disease susceptibility and clinical manifestations of disease. Insights from clinical and laboratory findings have also been recently harnessed for disease prevention. This review will summarize our current understanding of HIT by reviewing pathogenesis, essential clinical and laboratory features and management.
Background:
Platelet (PLT) transfusion before interventional radiology procedures is commonly performed in patients with thrombocytopenia. However, it is unclear if PLT transfusion is associated with reduced bleeding complications.
Study design and methods:
This is a retrospective cohort study of adults undergoing interventional radiology procedures between January 1, 2009, and December 31, 2013. Baseline characteristics, coagulation variables, transfusion requirements, and procedural details were evaluated. Propensity-matched analyses were used to assess relationships between PLT transfusions and the outcomes of interest, including a primary outcome of periprocedural red blood cell (RBC) transfusion during the procedure or within the first 24 hours after procedure.
Results:
A total of 18,204 participants met inclusion criteria, and 2060 (11.3%) had a PLT count of not more than 100 × 10(9) /L before their procedure. Of these, 203 patients (9.9) received preprocedural PLTs. There was no significant difference in RBC requirements between those receiving or not receiving preprocedural PLTs in propensity-matched analysis (odds ratio [OR], 1.45; 95% confidence interval [CI], 0.95-2.21; p = 0.085). PLT transfusion was associated with increased rates of intensive care unit admission (OR [95% CI], 1.57 [1.07-2.32]; p = 0.022).
Conclusion:
In patients with thrombocytopenia undergoing interventional radiology procedures, preprocedural PLT transfusion was not associated with reduced periprocedural RBC requirements. These findings suggest that prophylactic PLT transfusions are not warranted in nonbleeding patients with preprocedural PLT counts exceeding 50 × 10(9) /L. Future clinical trials are needed to further define relationships between prophylactic PLT administration and bleeding complications, especially at more severe levels of thrombocytopenia or in the presence of PLT dysfunction.
A low platelet count is a frequently encountered haematological abnormality in patients treated in intensive treatment units (ITUs). Although severe thrombocytopenia (platelet count <20 × 10(9) /l) can be associated with bleeding, even moderate-degree thrombocytopenia is associated with organ failure and adverse prognosis. The aetiology for thrombocytopenia in ITU is often multifactorial and correcting one aetiology may not normalise the low platelet count. The classical view for thrombocytopenia in this setting is consumption associated with thrombin-mediated platelet activation, but other concepts, including platelet adhesion to endothelial cells and leucocytes, platelet aggregation by increased von Willebrand factor release, red cell damage and histone release, and platelet destruction by the complement system, have recently been described. The management of severe thrombocytopenia is platelet transfusion in the presence of active bleeding or invasive procedure, but the risk-benefit of prophylactic platelet transfusions in this setting is uncertain. In this review, the incidence and mechanisms of thrombocytopenia in patients with ITU, its prognostic significance and the impact on organ function is discussed. A practical approach based on the authors' experience is described to guide management of a critically ill patient who develops thrombocytopenia.
Importance:
More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are uncertain.
Objective:
To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion.
Evidence review:
Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes.
Findings:
It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence).
Conclusions and relevance:
Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.
Background:
Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review and a meta-analysis of randomised trials to establish the effect of high-dose dexamethasone compared with prednisone for long-term platelet count response.
Methods:
We searched MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Library Database for papers published from 1970 to July, 2016, and abstracts from American Society of Hematology annual meetings published from 2004 to 2015 for randomised trials comparing different corticosteroid regimens for patients with previously untreated immune thrombocytopenia who achieved a platelet count response. Trials that compared corticosteroids exclusively with other interventions were excluded. The primary endpoint was overall (platelets >30 × 10(9)/L) and complete (platelets >100 × 10(9)/L) platelet count response at 6 months with high-dose dexamethasone compared with standard-dose prednisone. Children and adults were analysed separately. Estimates of effect were pooled with a random-effects model.
Findings:
Nine randomised trials (n=1138) were included. Of those, five (n=533) compared one to three cycles of dexamethasone (40 mg per day for 4 days) with prednisone (1 mg per kg) for 14-28 days followed by dose tapering in adults. We found no difference in overall platelet count response at 6 months (pooled proportions 54% vs 43%, relative risk [RR] 1·16, 95% CI 0·79-1·71; p=0·44). At 14 days, overall platelet count response was higher with dexamethasone (79% vs 59%, RR 1·22, 95% CI 1·00-1·49; p=0·048). The dexamethasone group had fewer reported toxicities. Long-term response rates were similar when the data were analysed by cumulative corticosteroid dose over the course of treatment. No difference in initial platelet count response was observed with different high-dose corticosteroid regimens in children.
Interpretation:
In adults with previously untreated immune thrombocytopenia, high-dose dexamethasone did not improve durable platelet count responses compared with standard-dose prednisone. High-dose dexamethasone might be preferred over prednisone for patients with severe immune thrombocytopenia who require a rapid rise in platelet count.
Funding:
Canadian Institutes of Health Research, and Canadian Blood Services, and Health Canada.
The obstetric anesthesiologist must consider the risk of spinal-epidural hematoma in patients with thrombocytopenia when choosing to provide neuraxial anesthesia. There are little data exploring this complication in the parturient. In this single-center retrospective study of 20,244 obstetric patients, the incidence of peripartum thrombocytopenia (platelet count <100,000/mm) was 1.8% (368 patients). Of these patients, 69% (256) received neuraxial anesthesia. No neuraxial hematoma occurred in any of our patients. The upper 95% confidence limit for spinal-epidural hematoma in patients who received neuraxial anesthesia with a platelet count of <100,000/mm was 1.2%.