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The mechanism of onset of disseminated intravascular coagulation (DIC) in patients with malignant tumors and infectious diseases. AT III, antithrombin III; ECs, endothelial cells; IFN-g, interferon; IL-6, interleukin-6; LPS, lipopolysaccharide; MOF, multiple organ failure; PAI-1, plasminogen activator inhibitor-1; PMN, polymorphonuclear cell: TF, tissue factor; TM, thrombomodulin
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Disseminated intravascular coagulation (DIC) is associated with organ failure and it is often fatal condition. The main underlying diseases are infection, hematological malignancy and solid cancer. DIC is subclassified into overt DIC and non-overt DIC. The International Society on Thrombosis and Haemostasis (ISTH) and the Japanese Association for A...
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Context 1
... is a condition caused by continuous activation of the coagulation and fibrinolysis systems within blood vessels due to an increase in "offense factors" or a decrease in "defense factors" (described below). Recently, organ dysfunction has been considered to be more important, and offense factors have been drawing greater attention. Fig. 1 shows the mecha- nism of onset of DIC in patients with malignant tumors and infectious ...
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Haemostasis encompasses a set of strictly regulated actions, such as vasoconstriction, platelet activation and blood coagulation. Endothelial cells play a crucial role in all of these processes and are an integral part of the vascular response to injury resulting in thrombus formation. Healthy endothelium expresses mediators to prevent platelet act...
Citations
... As DIC can arise from a broad spectrum of clinical scenarios, its impact on morbidity and mortality risk is likely influenced by the underlying disease status (Table 1) [6][7][8]. Depending on the clinical context and the extent of platelet and/or coagulation factor consumption, DIC may predominantly lead to widespread thrombosis and/or substantial bleeding. ...
... Despite the clinical significance of DIC, no single diagnostic test can definitively confirm or rule out its presence. DIC is typically diagnosed through a combination of coagulation-related laboratory tests and clinical findings [7]. However, since the Japanese Ministry of Health, Labor and Welfare proposed diagnostic criteria for DIC, numerous research studies and trials have aimed to establish more accurate definitions and diagnostic approaches for this condition [18][19][20][21][22][23][24][25][26]. ...
... Clinical and laboratory data must be used to identify DIC. Some of the investigatory findings include reduced platelet count, elevated prothrombin and thrombin times, and the presence of schistocytes in the peripheral smear [27]. Administering these DIC patients fresh frozen plasma (FFP) may be beneficial if they seem to have an extended prothrombin time (PT) as well as an activated partial thromboplastin time (aPTT) [28]. ...
Red blood cells (RBCs) start to break down early in hemolytic anemia, which can be chronic or life-threatening. It should be considered while determining if normocytic or macrocytic anemia is present. Hemolysis in the reticuloendothelial system may happen intravascularly, extravascularly, or both. It accounts for a broad spectrum of laboratory and clinical situations, both physiological and pathological. Whenever the frequency of RBC breakdown is rapid enough to lower hemoglobin levels below the normal range, hemolytic anemia occurs. Microangiopathic hemolytic anemia (MAHA) is a term used to describe non-immune hemolysis induced by intravascular RBC fragmentation caused by substances in the tiny blood arteries that generate schistocytes in the peripheral circulation. Microvasculature abnormalities, such as small arterioles and capillaries, are usually involved. Furthermore, MAHA can also be brought on by intravascular devices like a prosthetic heart valve or assistive technologies. Poor deformity results in entrapment, phagocytosis, antibody-mediated elimination through phagocytosis or direct complement activation, fragmentation brought about by microthrombi or acute mechanical stress, oxidation, or spontaneous cellular death. Hemolysis may cause acute anemia, jaundice, hematuria, dyspnea, tiredness, tachycardia, and possibly hypotension. This article aims to synthesize existing research, identify therapeutic strategies, and provide insights into current and emerging approaches for managing this complex hematological disorder.
... Although not statistically significant, some control R300-treated mice showed thrombocytopenia ( Figure 4D). Approximately 3.2% to 78.0% of patients with cancer experience disseminated intravascular coagulation [51]. We assume that CLEC-2 depletion control. ...
Background:
Cancer-associated thrombosis (CAT) is the leading cause of morbidity and mortality. Cancer-associated fibroblasts (CAFs) are a prominent component of the tumor microenvironment that contributes to cancer progression through direct cell-cell interactions and the release of extracellular vesicles (EVs). However, the role of CAFs in CAT remains unclear.
Objective:
This study aims to investigate whether CAFs aggravate CAT and the underlying molecular mechanism using a preclinical mouse lung cancer model.
Methods:
We designed a Lewis lung carcinoma (LLC) tumor-bearing mouse model. CAFs were characterized using fluorescence immunohistostaining. The presence of podoplanin, a platelet-activating membrane protein through C-type lectin-like receptor-2 (CLEC-2), in EVs isolated from primary CAFs or LLC tumor tissues was assessed by immunoblotting. The platelet activation and aggregation abilities of the EVs were quantified using flow cytometry. Podoplanin plasma levels were measured by ELISA. Venous thrombosis was induced in the femoral vein using 2.5% ferric chloride. The anti-C type lectin-like receptor 2 (CLEC-2) monoclonal antibody 2A2B10 was used to deplete CLEC-2 on the surface of the platelets.
Results:
CAFs expressing CD90, PDGFRβ, HSP47, CD34, and vimentin, co-expressed podoplanin and induced platelet activation and aggregation in a CLEC-2-dependent manner. Tumor-bearing mice showed elevated podoplanin plasma levels. CAF-EV injection and tumor-bearing mice showed shorter occlusion time in the venous thrombosis model. Although tumor growth was not altered, antibody-induced CLEC-2 depletion suppressed venous thrombosis in the tumor-bearing state but not in the healthy condition.
Conclusions:
CAFs and CAF-derived EVs induce CLEC-2-dependent platelet aggregation and aggravate venous thrombosis.
... [7] DIK'in etiyolojileri arasında ablasyo plasenta ve amniyon sıvı embolisi gibi obstetrik komplikasyonlar, ağır enfeksiyonlar, hematolojik maligniteler ve solid organ tümörleri, ağır doku hasarına neden olan travmalar ve yanıklar, zehirlenmeler (yılan ve artropot zehirleri, ilaçlar), kalp damar hastalıkları ve immunolojik hastalıklar sayılabilir. [8,9] DIK'in tanısında laboratuvar bulgular oldukça önemlidir. Tanıda trombin üretiminin arttığını ve fibrinolitik sistemin hızlandığını göstermek gerekmektedir. ...
Z Koagülasyon sistem bozuklukları, prokoagülan ve antikoagülan aktivite arasındaki dengesizlikten kaynaklanmakta olup, konjenital ve edinilmiş pıhtılaşma bozuklukları şeklinde sınıflandırılmaktadır. Bu başlıklar altında onlarca hastalık mevcut olup, bu hasta-lıklar gözün ön ve arka segment yapılarında ve orbitada ciddi komplikasyonlara neden olabilmektedir. Bu komplikasyonlardan subkonjonktival hemoraji gibi spontan resorbsiyon ile düzelebilen durumlar olabileceği gibi, retino-koroidal hemoraji ve iskemi gibi ciddi görme kaybıyla sonuçlanabilen durumlarda görülebilmektedir. Oftalmoloji pratiğinde kanama bozukluğu şüphesi ile gelen bir hastanın oküler ve orbital komplikasyonlarını değerlendirerek hızlı bir şekilde tedavi etmek, görsel prognoz açısından çok önemlidir. Özellikle vitreoretinal hemorajilerin tedavisinde vitreoretinal cerrahi önemli ve etkin bir tedavi protokolü olarak gö-rülmektedir. Cerrahi sırasında meydana gelebilecek olası komplikasyonları önlemek için multidisipliner bir yaklaşım ile hemoraji riskini azaltacak önlemler alınmalıdır. Bu derlemede kanama ve koagülasyon sistem bozukluklarında orbital komplikasyonlara ve retinal patolojilere yaklaşım tartışılacaktır. Anahtar Kelimeler: Kanama sistemi bozuklukları, Koagülasyon sistem bozuklukları, Retina, Vitreoretinal cerrahi ABSTRACT Coagulation system disorders result from the imbalance between procoagulant and anticoagulant activity and are classified as congenital and acquired coagulation disorders. There are dozens of diseases under these headings, and these diseases can cause serious complications in the anterior and posterior segment structures of the eye and orbit. Among these complications, there may be situations such as subconjunctival hemorrhage, which can be resolved by spontaneous resorption, or it can be seen in cases such as retinal-choroidal hemorrhage and ischemia that may result in severe vision loss. In ophthalmology practice, evaluating and treating ocular complications of a patient with a suspected bleeding disorder is very important in terms of visual prognosis. Especially in the treatment of vitreoretinal hemorrhages, vitreoretinal surgery is seen as an important and effective treatment protocol. To prevent possible complications that may occur during surgery, precautions should be taken to reduce the risk of hemorrhage with a multidisciplinary approach. This review will discuss the approach to orbital complications and retinal pathologies in coagulation system disorders.
... The scoring should be repeated daily if it is greater than or equal to 5.38 Prolonged elevation of PT and platelets has been affiliated with poorer outcomes. 1,39 A gold standard does not exist for the ideal diagnostic criteria, but three are primarily used throughout the world.38,40,41 Patients with DIC can show signs of organ failure.8,9 ...
Disseminated intravascular coagulation (DIC) is linked with severe COVID-19, prompting considerable concern. DIC can be a devastating systemic disorder. It is often markedly manifest on the skin as acrocyanosis or as petechiae and purpura with progression to hemorrhagic bullae. Subcutaneous hematomas may occur, as may thrombotic findings including necrosis and gangrene. The most common cause is infection, with special emphasis now on COVID-19. We have reviewed the medical literature under the search terms "Disseminated intravascular coagulation" and "consumption coagulopathy" for the past two decades in the English language using Medline and Google Scholar to update special concerns and considerations, focusing on those with COVID-19. Skin findings with DIC may be prominent. The severity of cutaneous lesions often correlates with the gravity of systemic disease. DIC is most effectively treated by addressing the underlying cause and resuscitating the patient using supportive measures. It is pivotal to recognize and treat DIC early, before deadly complications, such as multiple organ failure, arise.
... substances are sufficient and can promote the formation of a stable thrombus. 14 In this study, we observed that PT and APTT levels were significantly increased while the FIB level was significantly decreased in the LPS-induced mouse DIC model (Figure 3a-c). These data indicate that the coagulation and fibrinolytic systems in the LPS-induced mouse DIC model had been severely disrupted, which was an important typical symptom of DIC. ...
Objectives:
The aim of this study was to determine the therapeutic effects of tetrahydropalmatine (Tet) on disseminated intravascular coagulation (DIC) by exploring the role of Tet using a lipopolysaccharide (LPS)-induced DIC model. Methods/Materials: We established a mouse DIC model by injecting LPS. Hematoxylin-eosin (HE) staining was performed to detect liver and kidney damage. Blood samples were obtained to determine liver and kidney injury indexes, coagulation indexes, and inflammatory cytokines. An in vitro cell inflammation model was also established. Tumor necrosis factor-α (TNF-α) levels and nuclear factor kappa B (NF-κB) signaling pathway activation were determined by western blot.
Result:
Tet ameliorated the damage to organ tissues, improved coagulation indexes, and reduced the inflammatory cytokine production in LPS-induced mouse DIC. Tet also inhibited TNF-α expression by suppressing NF-κB signaling pathway activation in an in vitro LPS model using RAW 264.7 macrophages.
Conclusions:
Tet has a mitigating and therapeutic effect on the LPS-induced DIC model via anticoagulant and anti-inflammatory effects, showing its potential as an adjunct to DIC treatment.
... First, the International Society on Thrombosis and Hemostasis (ISTH) has introduced the "DIC" scoring system to better establish the diagnosis of "DIC" [102]. It has not been used as a primary diagnostic tool, but has been applied to confirm the diagnosis using hematologic parameters only after predetermined as "DIC" with a clinical disorder known to cause "DIC". ...
... It has not been used as a primary diagnostic tool, but has been applied to confirm the diagnosis using hematologic parameters only after predetermined as "DIC" with a clinical disorder known to cause "DIC". The scoring system has shown low specificity [102]. It should be emphasized that no single laboratory test or set of tests is sensitive or specific enough to allow a definitive diagnosis of "DIC" [103]. ...
... Additionally, this profile oddly develops only in some patients with "DIC". Therefore, the "chronic/compensated/covert" concept [102,112,113], including "low grade DIC", has been introduced if the coagulation profile is normal or mildly abnormal in "DIC". This description also cannot explain inexplicably extensive microthrombosis in the absence of depleted coagulation factors. ...
TTP is characterized by microangiopathic hemolytic anemia and thrombocytopenia associated with brain and kidney dysfunction. It occurs due to ADAMTS13 deficiency. TTP-like syndrome occurs in critically ill patients with the similar hematologic changes and additional organ dysfunction syndromes. Vascular microthrombotic disease (VMTD) includes both TTP and TTP-like syndrome because their underlying pathology is the same disseminated intravascular microthrombosis (DIT). Microthrombi are composed of platelet-unusually large von Willebrand factor multimers (ULVWF) complexes. TTP occurs as a result of accumulation of circulating ULVWF secondary to ADAMTS13 deficiency. This protease deficiency triggers microthrombogenesis, leading to “microthrombi” formation in microcirculation. Unlike TTP, TTP-like syndrome occurs in critical illnesses due to complement activation. Terminal C5b-9 complex causes channel formation to endothelial membrane, leading to endotheliopathy, which activates two different molecular pathways (i.e., inflammatory and microthrombotic). Activation of inflammatory pathway triggers inflammation. Activation of microthrombotic pathway promotes platelet activation and excessive endothelial exocytosis of ULVWF from endothelial cells (ECs). Overexpressed and uncleaved ULVWF become anchored to ECs as long elongated strings to recruit activated platelets, and assemble “microthrombi”. In TTP, circulating microthrombi typically be lodged in microvasculature of the brain and kidney, but in TTP-like syndrome, microthrombi anchored to ECs of organs such as the lungs and liver as well as the brain and kidneys, leading to multiorgan dysfunction syndrome. TTP occurs as hereditary or autoimmune disease and is the phenotype of ADAMTS13 deficiency-associated VMTD. But TTP-like syndrome is hemostatic disorder occurring in critical illnesses and is the phenotype of endotheliopathy-associated VMTD. Thus, this author’s contention is TTP and TTP-like syndrome are two distinctly different disorders with dissimilar underlying pathology and pathogenesis.
... Of note, it has been shown that the platelet transfusions may not necessarily aggravate the course of the disease. 21,22 Given the prothrombic nature of HUS, 8,23,24 the fact that our patient showed abnormal coagulation profiles including elevated plasma levels of fibrinogen degradation product, d-dimer, and prolonged PT, as well as thrombocytopenia, which met the proposed criteria of DIC, 25 is not surprising, and it might also be unnecessary to list DIC as a separate diagnosis. However, an association between HUS and DIC has been described anecdotally, [26][27][28][29] and Vashakidze et al 30 reported their experience, showing that up to 14% of patients with E coli-mediated HUS experience DIC during the course of the disease. ...
A 28-year-old man was referred and admitted to our hospital due to Escherichia coli O157–mediated hemorrhagic colitis with severe thrombocytopenia. A systemic workup concluded that the patient had acute pancreatitis as well as hemolytic uremic syndrome. The patient was ultimately discharged, with his platelet count having recovered. Our case serves an illustrative example of potentially serious complications of an increasingly recognized public health problem. Systemic studies on this topic are insufficient, and we strongly recommend the further accumulation of more experiences like ours. Several diagnostic and management concerns that emerged in this case are also discussed.
... Disseminated intravascular coagulopathy (DIC) is characterized by massive microthrombi appearing through various mechanisms. 1 Enhanced thrombolysis and consumption of coagulation factors in DIC lead to bleeding tendency, thrombocytopenia, hypofibrinogenemia, and increased circulating fibrinogen degradation product (FDP). 1 Although DIC is frequently accompanied by severe infection, leukemia, and cancer cell invasion of the bone marrow, some cases are caused by tumors of vascular origin, such as cavernous hemangioendothelioma. 1 Hepatic angiosarcoma is an uncommon malignant vascular tumor of the liver that is very rarely accompanied with DIC. 2 We herein report a case of hepatic angiosarcoma showing Kasabach-Merritt phenomenon (KMP), review its clinical features, and compare it with existing cases in the literature. ...
... Disseminated intravascular coagulopathy (DIC) is characterized by massive microthrombi appearing through various mechanisms. 1 Enhanced thrombolysis and consumption of coagulation factors in DIC lead to bleeding tendency, thrombocytopenia, hypofibrinogenemia, and increased circulating fibrinogen degradation product (FDP). 1 Although DIC is frequently accompanied by severe infection, leukemia, and cancer cell invasion of the bone marrow, some cases are caused by tumors of vascular origin, such as cavernous hemangioendothelioma. 1 Hepatic angiosarcoma is an uncommon malignant vascular tumor of the liver that is very rarely accompanied with DIC. 2 We herein report a case of hepatic angiosarcoma showing Kasabach-Merritt phenomenon (KMP), review its clinical features, and compare it with existing cases in the literature. ...
... Disseminated intravascular coagulopathy (DIC) is characterized by massive microthrombi appearing through various mechanisms. 1 Enhanced thrombolysis and consumption of coagulation factors in DIC lead to bleeding tendency, thrombocytopenia, hypofibrinogenemia, and increased circulating fibrinogen degradation product (FDP). 1 Although DIC is frequently accompanied by severe infection, leukemia, and cancer cell invasion of the bone marrow, some cases are caused by tumors of vascular origin, such as cavernous hemangioendothelioma. 1 Hepatic angiosarcoma is an uncommon malignant vascular tumor of the liver that is very rarely accompanied with DIC. 2 We herein report a case of hepatic angiosarcoma showing Kasabach-Merritt phenomenon (KMP), review its clinical features, and compare it with existing cases in the literature. ...
A 76-year-old woman was referred to our hospital due to massive gingival bleeding following teeth extraction. Laboratory findings suggested disseminated intravascular coagulopathy (DIC). Enhanced computed tomography and magnetic resonance imaging disclosed multiple hypervascular liver masses of 2-6 cm in diameter, the largest of which displaying an irregular enhancement pattern. We considered that her DIC was caused by the multiple liver masses and commenced repeated erythrocyte/fresh frozen plasma infusión and gabexate mesilate administration. However, the DIC proved uncontrollable and trans-arterial embolization could not be attempted. The patient eventually died 4 months after admission due to spontaneous hepatic tumor rupture and hepatic failure. Post-mortem hepatic tumor biopsy led to a final diagnosis of hepatic angiosarcoma with Kasabach-Merritt phenomenon (KMP). Among the 7 cases of hepatic angiosarcoma representing KMP found in the literature, mortality occurred within 4 months of the appearance of bleeding tendency primarily due to abdominal bleeding and hepatic failure. The possibility of hepatic angiosarcoma should be considered in patients with DIC and hypervascular liver tumors. Since treatment is uncertain and prognosis is poor, novel diagnostic and therapeutic advances are needed for angiosarcoma.
... EZR is a modified version of R commander (version 1.6-3) that includes statistical functions that are frequently used in biostatistics. 23 ...
Background:
Several noninvasive biomarkers are available for diagnosing liver fibrosis stage and predicting hepatocellular carcinoma (HCC) development in patients with chronic hepatitis and liver cirrhosis. However, these biomarkers are not sufficiently accurate. Recently, von Willebrand factor (VWF) has been related to angiogenesis and apoptosis. Furthermore, VWF is associated with hepatic spare ability and HCC.
Objective:
We aimed to determine whether VWF is a potential biomarker for liver fibrosis and HCC development.
Methods:
Two hundred and twelve patients with chronic hepatitis B and C were recruited. VWF antigen (VWF: Ag) levels in each patient were determined via enzyme-linked immunosorbent assay. Univariable and multivariable analyses were used to determine the risk factor of HCC.
Results:
The VWF: Ag levels were higher in patients with severe liver fibrosis stage and/or HCC development than in those without. The area under the curve of VWF: Ag for diagnosis of severe liver fibrosis stage was 0.721. Multivariable analysis showed that only VWF: Ag was a predictive biomarker for HCC development.
Conclusions:
VWF: Ag is related to liver fibrosis and may be useful for predicting HCC development. VWF is a potentially useful biomarker to diagnose severe liver fibrosis and predict HCC development.
