Figure - available from: Journal of Thrombosis and Thrombolysis
This content is subject to copyright. Terms and conditions apply.
a Hypercoagulable aPTT Clot Waveform tracing and parameters of a 35-year-old male with severe COVID-19 infection complicated by acute right ischaemic limb secondary to extensive thromboembolic disease in the abdominal aorta, right external iliac and right popliteal arteries. *Patient’s clot waveform tracing in black, healthy controls in multicolour (for reference). Patient’s haemostatic and clot waveform parameters: PT 14.2 s (11.7–14.0 s), aPTT 38.7 s (27.0–37.0 s), fibrinogen 5.0 g/L (1.8–4.5 g/L), D-Dimer 2.26 μg/ml (<0.50 μg/ml), Platelets 337 × 10⁹/L (150–360 x10⁹/L). Factor II 122% (70–120%), Factor VIII 196% (60–150%), Factor × 106% (70–120%), vWF 200% (56–160%), anti-thrombin III 74% (80–130%), Protein C 61% (70–150%), Protein S 79% (55–130%). Absent lupus anticoagulant and antiphospholipid antibodies. CWA: Min1 9.715%/s (2.86–6.78%/s), Min2 1.493%/s² (0.46–1.10%/s²), Max2 1.243%/s² (0.37–0.93%/s²), Delta change 81.2% (25.21–63.09%). b aPTT Clot Waveform tracing of a 40-year-old male on mechanical ventilation for severe COVID-19 pneumonia, Day 18 of illness (Day 2 ECMO), with probable pulmonary intravascular coagulopathy with concurrent bacterial pneumonia and sepsis induced coagulopathy, not initiated on anticoagulation yet. Clots were seen in the ECMO oxygenator as well as the dialysis circuit. *Patient’s clot waveform tracing in black, healthy controls in multicolour (for reference). Patient’s haemostatic and clot waveform parameters. PT 18.2 s (11.7–14.0 s), aPTT 53.2 s (27.0–37.0 s), fibrinogen 3.8 g/L (1.8–4.5 g/L), D-Dimer >20 μg /ml (<0.5 μg /ml), Platelets 115 × 10⁹/L (150–360 × 10⁹). Factor II 46% (70–120%), Factor V 68% (70–120%), Factor VIII 196% (60–150%), Factor IX 115% (60–150%) Factor × 68% (70–120%), vWF 387% (56–160%), anti-thrombin III 54% (80–130%), Protein C 28% (70–130%), Protein S 19% (55–130%). Lupus anticoagulant moderately present and anti cardiolipin IgG < 20 (0–20 GPL units), anti cardiolipin IgM 23 (0–20 MPL units), anti B2 glycoprotein-1 < 2 RU/ml (0–20 RU/ml). CWA: Min1 4.123%/s (2.86–6.78%/s), Min2 0.457%/s² (0.46–1.10%/s²), Max2 0.351%/s² (0.37–0.93), Delta change 68.2% (25.21–63.09%). c aPTT Clot Waveform tracing of a 73-year-old male on Day 13 of illness with severe COVID-19 pneumonia with probable pulmonary intravascular coagulopathy and concurrent sepsis induced coagulopathy from stenotrophomonas maltophilia bacteraemia and ventilator associated pneumonia. *Patient’s clot waveform tracing in black, healthy controls in multicolour (for reference). Patient’s haemostatic and clot waveform parameters. PT 15.3 s (11.7–14.0 s), aPTT 41.3 s (27.0–37.0 s), fibrinogen 4.0 g/L (1.8–4.5 g/L), D-Dimer >20 μg/ml (<0.5 μg/ml), Platelets 120 × 10⁹/L. Factor II 56% (70–120%), Factor V 93% (70–120%), Factor VIII 195% (60–150%), Factor IX 105% (60–150%), Factor × 68% (70–120%), Factor XI 47% (60–150%), vWF 200% (56–160%), anti-thrombin III 74% (80–130%), Protein C 61% (70–150%), Protein S 79% (55–130%). Lupus anticoagulant and antiphospholipid antibodies absent. CWA: Min1 5.005%/s (2.86–6.78%/s), Min2 0.641%/s² (0.46–1.10%/s²), Max2 0.512%/s² (0.37–0.93%/s²), Delta change 63.6% (25.21–63.09%)
Source publication
Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic response to the SARS-CoV-2 infection. Overlapping syndromes of COVID-19 associated coagulopathy with consumptive coagulopathy and microangiopathy can be seen in critically ill patients as well. Blo...
Similar publications
Background: A significant proportion of patients with coronavirus disease 19 (COVID-19) suffer from excessive coagulation activation and coagulopathy which is associated with an increased risk of venous and arterial thromboembolism and adverse outcome. Our study investigates coagulation markers and the incidence of thromboembolic events in COVID-19...
Citations
... Our patient had FFT of the descending aorta, most likely caused by COVID-19-related hypercoagulability. Often, patients with a COVID-19 infection who present in a hyperinflammatory state also present with elevated levels of D-dimer, factor VIII fibrinogen, PT/aPTT, IL-6, TNF-alpha, and IL-1beta [10,11]. Additionally, numerous reports have indicated the presence of antiphospholipid antibodies (aPL Ab), predictors of hypercoagulability caused by antiphospholipid syndrome (APS), in COVID-19 infections. ...
... In our study, the most aberrant pathway at baseline that was associated with that development of moderate/ severe vs mild disease was dysfunction in the coagulation system, specifically coagulation factors VII (lower in patients with moderate/severe disease) and IX (higher in patients with moderate/severe disease) (Fig. S4). This suggests the specific aberration associated with the development of severe COVID-19 is an overactive intrinsic pathway early in the disease course 28 . We identified patients with moderate/severe disease had significantly reduced Factor VII at baseline, patients with moderate/severe disease also had increased tissue factor pathway inhibitor (TFPI), an inhibitor of the extrinsic pathway (Fig. S4). ...
Significant progress has been made in preventing severe COVID-19 disease through the development of vaccines. However, we still lack a validated baseline predictive biologic signature for the development of more severe disease in both outpatients and inpatients infected with SARS-CoV-2. The objective of this study was to develop and externally validate, via 5 international outpatient and inpatient trials and/or prospective cohort studies, a novel baseline proteomic signature, which predicts the development of moderate or severe (vs mild) disease in patients with COVID-19 from a proteomic analysis of 7000 + proteins. The secondary objective was exploratory, to identify (1) individual baseline protein levels and/or (2) protein level changes within the first 2 weeks of acute infection that are associated with the development of moderate/severe (vs mild) disease. For model development, samples collected from 2 randomized controlled trials were used. Plasma was isolated and the SomaLogic SomaScan platform was used to characterize protein levels for 7301 proteins of interest for all studies. We dichotomized 113 patients as having mild or moderate/severe COVID-19 disease. An elastic net approach was used to develop a predictive proteomic signature. For validation, we applied our signature to data from three independent prospective biomarker studies. We found 4110 proteins measured at baseline that significantly differed between patients with mild COVID-19 and those with moderate/severe COVID-19 after adjusting for multiple hypothesis testing. Baseline protein expression was associated with predicted disease severity with an error rate of 4.7% (AUC = 0.964). We also found that five proteins (Afamin, I-309, NKG2A, PRS57, LIPK) and patient age serve as a signature that separates patients with mild COVID-19 and patients with moderate/severe COVID-19 with an error rate of 1.77% (AUC = 0.9804). This panel was validated using data from 3 external studies with AUCs of 0.764 (Harvard University), 0.696 (University of Colorado), and 0.893 (Karolinska Institutet). In this study we developed and externally validated a baseline COVID-19 proteomic signature associated with disease severity for potential use in both outpatients and inpatients with COVID-19.
... The virus that causes Coronavirus 2019 (COVID- 19), known as SARS-CoV-2 (for severe acute respiratory syndrome coronavirus 2), was initially discovered in Wuhan, China, in December 2019 before migrating to other countries and infecting Algeria in March 2020 [1][2][3]. According to Wu et al. [4], this illness is connected to an inflammatory condition, suffocating respiratory distress syndrome (SDRA), a multi-visceral insufficiency, and, in severe cases, shock. ...
... In these severely ill or critically ill sepsis patients, this may be attributed to platelet activation, endothelial dysfunction, neutrophil extracellular traps, and activation of the coagulation cascade, which are reflective of an uncontrolled proinflammatory response with immune dysregulation and, rarely, cytokine storm. Tan et al., [18] and a significant incidence of thrombosis [19,20] in critically sick COVID-19 patients. ...
This study’s goal was to identify the haemostatic profile of COVID-19 patients and their relationships to disease severity and death rates. 163 COVID-19 patients were enrolled in the research, and their diagnoses were made using PCR, common symptoms, and radiological findings (CT). Patients that were hospitalized to Ali Boushaba Public Hospitalier Khenchela’s Infectology Service in 2020. Data was gathered between January 1 and June 30, 2021. In the population that was counted, patients with COVID-19 have an average age of 61.44 + 15.4 years. The gender ratio of males to women was in the range of 0.98, therefore there was no discernible male predominance. 20% of the oxygen was desaturated, and 38.6% and 6.8% of patients had significant or serious lung disease, respectively. 16.4% mortality was seen in these individuals. These individuals had a wide spectrum of biochemical anomalies, including hyperglycaemia, which had an average value of 1.94+1.22 g/L. An increase in the mean values of CRP (68.35+58.87 mg/l) was noted. About the haemostatic profile we recorded an increase in the level of D-dimer (730.49+674.87 ng/l), a decrease in prothrombin time (55.54+36.24%). The highest D-dimer value (946.40+ 568.02 ng/l) was recorded in patients with critical parenchymal involvement (≥ 75%), and a significant correlation between the D-dimer value and parenchymal involvement was noted. Furthermore, statistically the relationship of haemostatic profile with COVID-19’s severity and with clinical outcome was insignificant.
... From the earliest efforts to characterize the specific pathogenic features of SARS-CoV-2 infection, it was evident that tropism for infection of ACE2-positive endothelial cells made this, to a large extent, an acute infection involving hypercoagulability, endotheliopathy and potentially widespread microthrombi [103][104][105] . Endothelial cell damage followed by activation are considered key steps in the generation of thrombi. ...
... Clearly, perturbations of the vascular endothelium and occlusion of vessels by microthrombi have the potential to impair oxygen delivery to tissues, thus accounting for many aspects of tissue-specific dysfunction in long COVID. A plethora of studies, often derived from longitudinal follow-up of individuals discharged from hospital following severe infections during the first wave, show long-term dysregulation across a wide range of parameters of coagulation and haemostasis [103][104][105][107][108][109][110][111] . A report of 163 patients discharged from hospital showed a cumulative 2.5% incidence of thrombosis within 1 month 105 . ...
... A systematic review and meta-analysis of thrombo-embolic events over a mean follow-up period of 8.5 months from acute infection showed HRs of 3.16 for pulmonary embolisms and 2.55 for deep venous thrombosis 110 . Follow-up of 39 patients recovering from COVID-19 over a 16-month period showed a significant minority of individuals with raised D-dimer, factor VIII, IL-6 and von Willebrand factor (vWF) 104 . In terms of specific correlation with long COVID symptoms, a similar analysis of sustained endotheliopathy markers showed that vWF levels inversely correlated with performance in the 6-minute walk-test 108 or desaturation and/or an increase in lactate in a 1-minute sit-to-stand test 109 . ...
Long COVID is the patient-coined term for the disease entity whereby persistent symptoms ensue in a significant proportion of those who have had COVID-19, whether asymptomatic, mild or severe. Estimated numbers vary but the assumption is that, of all those who had COVID-19 globally, at least 10% have long COVID. The disease burden spans from mild symptoms to profound disability, the scale making this a huge, new health-care challenge. Long COVID will likely be stratified into several more or less discrete entities with potentially distinct pathogenic pathways. The evolving symptom list is extensive, multi-organ, multisystem and relapsing-remitting, including fatigue, breathlessness, neurocognitive effects and dysautonomia. A range of radiological abnormalities in the olfactory bulb, brain, heart, lung and other sites have been observed in individuals with long COVID. Some body sites indicate the presence of microclots; these and other blood markers of hypercoagulation implicate a likely role of endothelial activation and clotting abnormalities. Diverse auto-antibody (AAB) specificities have been found, as yet without a clear consensus or correlation with symptom clusters. There is support for a role of persistent SARS-CoV-2 reservoirs and/or an effect of Epstein-Barr virus reactivation, and evidence from immune subset changes for broad immune perturbation. Thus, the current picture is one of convergence towards a map of an immunopathogenic aetiology of long COVID, though as yet with insufficient data for a mechanistic synthesis or to fully inform therapeutic pathways.
... There is substantial literature on the application of CWA in the diagnosis of and prognostication in haemophilia [15,16], disseminated intravascular coagulation [17,18] and sepsis [19,20]. CWA has also been used to demonstrate and characterise the hypercoagulability in venous thromboembolism [21,22] and COVID-19-associated coagulopathy [23,24]. However, its role in arterial thrombotic events is uncertain. ...
Background: Activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is a plasma-based global haemostatic assay. Elevated CWA parameters have been associated with hypercoagulability in venous thromboembolism, but its role in arterial thrombotic disease is uncertain. This study aims to explore the relationship between aPTT-based CWA and acute myocardial infarction (AMI) and its complications.
Methods: This is a retrospective case-control study that included patients with AMI who underwent emergency cardiac catheterisation and control patients who underwent elective orthopaedic and urological procedures. The pre-procedural aPTT and CWA parameters – min1, min2 and max2 – of AMI patients were compared against those of controls.
Results: Compared to controls (N=109), patients with AMI (N=214) had shorter aPTT (26.7±3.3s vs 27.9±1.7s, P<0.001) and higher CWA parameters (min1: 6.11±1.40%/s vs 5.58±1.14%/s; min2: 0.98±0.23%/s² vs 0.90±0.19%/s²; max2: 0.81±0.20%/s² vs 0.74±0.16%/s², all P≤0.001). Elevated CWA parameters, defined as having CWA values above their respective reference ranges, were associated with the occurrence of AMI, with odds ratio (OR) of 2.06 [95% confidence intervals (CI):1.10–3.86], 2.23 (95% CI:1.18–4.24) and 2.01 (95% CI:1.07–3.77) for min1, min2 and max2, respectively. Similarly, elevated min1 and min2 were both individually associated with the presence of adverse outcomes of AMI with ORs of 2.63 (95% CI:1.24–5.59).
Conclusions: Patients with AMI had significantly increased CWA parameters. Elevated aPTT-based CWA parameters are significantly associated with the occurrence of AMI and its complications. Potential utility of CWA as risk and prognostic markers for AMI warrants future works.
... However, in both endogenous and exogenous assays, COVID-19 samples degraded significantly faster after desialylation, indicating that SA residues play some role in these multifactorial influences. The degradation assays we performed investigated instantaneous degradation rate; however, these data also support fibrinogen structure as partial explanation for previous findings that overall clot persistence and total time to degrade is higher among COVID-19 plasma.34 Our findings that area under the curve is significantly greater for COVID-19 patients alongside the visualizations of clot degradation(Figures 3A and 5A) are consistent with findings that COVID-19 clots persist for longer than control clots during ex vivo degradation studies.34 ...
... The degradation assays we performed investigated instantaneous degradation rate; however, these data also support fibrinogen structure as partial explanation for previous findings that overall clot persistence and total time to degrade is higher among COVID-19 plasma.34 Our findings that area under the curve is significantly greater for COVID-19 patients alongside the visualizations of clot degradation(Figures 3A and 5A) are consistent with findings that COVID-19 clots persist for longer than control clots during ex vivo degradation studies.34 This work evaluates isolated fibrinogen without the influence of other plasma factors. ...
Background:
Thrombogenicity is a known complication of COVID-19, resulting from SARS-Cov-2 infection, with significant effects on morbidity and mortality.
Objective:
We aimed to better understand the effects of COVID-19 on fibrinogen and the resulting effects on clot structure, formation and degradation.
Methods:
Fibrinogen isolated from COVID-19 patients and uninfected subjects was used to form uniformly concentrated clots (2 mg/mL), which were characterized using confocal microscopy, scanning electron microscopy, atomic force microscopy, and endogenous and exogenous fibrinolysis assays. Neuraminidase digestion and subsequent NANA assay were used to quantify sialic acid residue presence; clots made from the desialylated fibrinogen were then assayed similarly to the original fibrinogen clots.
Results:
Clots made from purified fibrinogen from COVID-19 patients were shown to be significantly stiffer and denser than clots made using fibrinogen from non-infected subjects. Endogenous and exogenous fibrinolysis assays demonstrated that clot polymerization and degradation dynamics were different for purified fibrinogen from COVID-19 patients compared to fibrinogen from non-infected subjects. Quantification of sialic acid residues via the NANA assay demonstrated that SARS-Cov-2-positive fibrinogen samples contained significantly more sialic acid. Desialylation via neuraminidase digestion resolved differences in clot density. Desialylation did not normalize differences in polymerization, but did affect rate of exogenous fibrinolysis.
Discussion:
These differences noted in purified SARS-Cov-2-positive clots demonstrate that structural differences in fibrinogen, and not just differences in gross fibrinogen concentration, contribute to clinical differences in thrombotic features associated with COVID-19. These structural differences are at least in part mediated by differential sialylation.
... This may be attributed to platelet activation, endothelial dysfunction, neutrophil extracellular traps and activation of the coagulation cascade, which are reflective of an uncontrolled proinflammatory response with immune dysregulation and rarely, cytokine storm, in these severe or critically ill patients with sepsis. While hypercoagulability [3] and a high incidence of thrombosis [4,5] in severely ill COVID-19 patients has been well described, less is known about the haemostatic profile in patients with mild COVID-19 infection who are non-hypoxic with normal chest imaging. ...
... In recent studies on CWA and COVID-19 associated hypercoagulability, CWA parameters were significantly higher in severe COVID-19 [3,21] as compared with mild disease [22,23]. The analysis of aPTT and PT clot waveform parameters in our severe patients showed hypercoagulability with elevated delta change, clot velocity and clot acceleration and deceleration. ...
Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 μg/mL (IQR 0.6, 1.4) (p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) (p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) (p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) (p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) (p = 0.02), PT clot acceleration (min 2) 3.6%/s2 (IQR 3.2, 4.5) (p = 0.02) and PT clot deceleration (max2) 2.9%/s2 (IQR 2.5, 3.5) (p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) (p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) (p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) (p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) (p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels.
... Depression of fibrinolysis was reported not only in ICU patients with severe infection and clinical signs of thromboembolism (26) but also in the general unselected ICU cohort (108,109). Viscoelastic testing ([ROTEM, tissue-type plasminogen activator (tPA) ROTEM, TEG] and evaluation of clot formation by Clot Waveworm analysis have demonstrated a hypercoagulable state, characterized by increased clot stiffness and severely impaired fibrinolysis (17,108,111,112). However, no consistent association between abnormal VET (viscoelastometric testing) pattern at COVID-19 and clinical outcome have been demonstrated [rev. ...
Introduction
Coagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity.
Methods
Electronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies.
Results
Overall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD −0.1684 with 95%CI (−0.2826; −0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias.
Conclusions
The hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.
... We demonstrated the lack of hypercoagulability among mildly ill COVID-19 patients who did not require oxygen supplementation, an aspect not well evaluated in existing literature. On the other end of the clinical spectrum, our study reaffirmed that critically ill COVID-19 patients had a hypercoagulable state [3,4] with no hyperfibrinolysis seen on thromboelastography (TEG) profiling and this also correlated well with parameters seen on clot waveform analysis as well as conventional haemostatic tests. ...
... The hypercoagulable state is commonly seen in critically ill patients with COVID-19 [9,10]. In critical ICU patients, venous thromboembolism events (VTE) are more commonly noticed. ...
... In critical ICU patients, venous thromboembolism events (VTE) are more commonly noticed. Arterial thrombosis is considered a rare manifestation; however, arterial and venous thrombosis are considered poor prognostic factors especially in comorbid populations [5,9]. The incidence of acute limb ischemia (ALI) is around five times higher in COVID-19 positive cases when relatively compared to the usual number of 1.5 cases per 10,000 persons per year prior to the pandemic. ...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus that causes multi-systemic manifestations identified as coronavirus disease 2019 (COVID-19). Respiratory tract symptoms are the most commonly seen in infected patients with COVID-19. Hypercoagulability state is the most common coagulopathy disorder associated with critically ill COVID-19 patients. Several inflammatory and coagulation factors such as D-dimers and fibrinogen correlate with the degree of pro-thrombotic state and burden of the disease. We describe a case of a 51-year-old man who presented with respiratory pneumonia and concomitant severe bilateral arterial thrombosis followed by right above knee amputation.
