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Journal of Hepatology Jun 2022Patients with cirrhosis frequently acquire complex changes in their haemostatic system including a decreased platelet count and decreased levels of various haemostatic... (Review)
Review
Patients with cirrhosis frequently acquire complex changes in their haemostatic system including a decreased platelet count and decreased levels of various haemostatic proteins. Although historically patients with cirrhosis were thought to have a haemostasis-related bleeding tendency, it is now widely accepted that the haemostatic system of patients with cirrhosis remains in balance as a result of simultaneous changes in pro- and anti-haemostatic systems. The concept of rebalanced haemostasis has led to changes in clinical management, although firm evidence from well-designed clinical studies is largely lacking. For example, many invasive procedures in patients with cirrhosis and a prolonged prothrombin time are now performed without prophylaxis with fresh frozen plasma. Conversely, clinicians have become more aware of the need for anti-thrombotic therapy, even in those patients with abnormal routine coagulation tests. This paper will outline recent advances in pathogenesis, prevention and treatment of both bleeding and thrombotic complications in patients with cirrhosis. Among other topics, we will discuss the haemostatic status of acutely ill patients with cirrhosis, the various causes of bleeding in patients with cirrhosis, and how best to prevent or treat bleeding. In addition, we will discuss the hypercoagulable features of patients with cirrhosis, new insights into the pathogenesis of portal vein thrombosis, and how best to prevent or treat thromboses.
Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Fibrosis; Hemorrhage; Hemostasis; Hemostatics; Humans; Liver Cirrhosis
PubMed: 35589251
DOI: 10.1016/j.jhep.2021.11.004 -
Seminars in Liver Disease Feb 2002The liver plays a central role in the clotting process, and acute and chronic liver diseases are invariably associated with coagulation disorders due to multiple causes:... (Review)
Review
The liver plays a central role in the clotting process, and acute and chronic liver diseases are invariably associated with coagulation disorders due to multiple causes: decreased synthesis of clotting and inhibitor factors, decreased clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis, and accelerated intravascular coagulation. The bleeding tendency accounts for increased risk of morbidity and mortality in patients with liver disease undergoing diagnostic or therapeutic invasive procedures. Peculiar coagulation disorders are prevalent in patients with acute fatty liver of pregnancy or undergoing liver transplantation. Emerging evidence shows that sepsis further impairs hemostasis in patients with liver cirrhosis bleeding from esophageal varices. Thrombotic events, even if rare in cirrhotic patients, occur mainly in the portal and mesenteric veins. The therapeutic approach to coagulative disorders is also discussed.
Topics: Bacterial Infections; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Fibrinolysis; HELLP Syndrome; Hemostasis; Humans; Liver; Liver Cirrhosis; Liver Diseases; Pregnancy; Thrombocytopenia; Vitamin K Deficiency
PubMed: 11928081
DOI: 10.1055/s-2002-23205 -
Anesthesiology May 2020
Review
Topics: Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Humans; Inflammation Mediators; Sepsis
PubMed: 32044801
DOI: 10.1097/ALN.0000000000003122 -
Nihon Rinsho. Japanese Journal of... Aug 2012
Topics: Antithrombins; Aspirin; Blood Coagulation Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Humans; Receptors, Cytoplasmic and Nuclear; Thrombocytopenia; Vitamin K
PubMed: 23156554
DOI: No ID Found -
Journal of Thrombosis and Haemostasis :... Sep 2020The COVID-19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated... (Review)
Review
The COVID-19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID-19. The clinical presentation of COVID-19-associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D-dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial-sepsis-associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID-19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID-19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.
Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; COVID-19; Cytokines; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Inflammation; Lung; Lymphocytes; Partial Thromboplastin Time; Protease Inhibitors; Prothrombin Time; Sepsis; Thrombosis
PubMed: 32558075
DOI: 10.1111/jth.14975 -
Hamostaseologie Nov 2020Factor XI (FXI) is a serine protease involved in the propagation phase of coagulation and in providing clot stability. Several mutations in the gene lead to FXI... (Review)
Review
Factor XI (FXI) is a serine protease involved in the propagation phase of coagulation and in providing clot stability. Several mutations in the gene lead to FXI deficiency, a rare mild bleeding disorder. Current laboratory methods are unable to assess bleeding risk in FXI-deficient patients, because the degree of bleeding tendency does not correlate with plasma FXI activity as measured by routine coagulometric aPTT-based assays. Bleeding manifestations are highly variable among FXI-deficient patients and FXI replacement therapy can be associated with an increased thrombotic risk. A correct evaluation of the patient hemostatic potential is crucial to prevent under- or overtreatment. In recent years, different research groups have investigated the use of global coagulation assays as alternative for studying the role of FXI in hemostasis and identifying the clinical phenotype of FXI deficiency. This brief review article summarizes the main features of coagulation factor XI and its deficiency and resumes the principle axes of research and methods used to investigate FXI functions.
Topics: Blood Coagulation Disorders; Factor XI Deficiency; Fibrinolysis; Phenotype; Thrombin
PubMed: 33003209
DOI: 10.1055/a-1227-8122 -
Blood Dec 1956
Topics: Blood Coagulation Disorders; Hemorrhagic Disorders; Uremia
PubMed: 13373925
DOI: No ID Found -
The New England Journal of Medicine Oct 1957
Topics: Blood Coagulation Disorders; Hemorrhagic Disorders; Humans; Uremia
PubMed: 13477393
DOI: 10.1056/NEJM195710242571704 -
Blood Reviews May 2023Rare bleeding disorders (RBDs), including factor (F) I, FII, FV, FVII, combined FV and FVIII (CF5F8), FXI, FXIII and vitamin-K dependent coagulation factors (VKCF)... (Review)
Review
Rare bleeding disorders (RBDs), including factor (F) I, FII, FV, FVII, combined FV and FVIII (CF5F8), FXI, FXIII and vitamin-K dependent coagulation factors (VKCF) deficiencies, are a heterogeneous group of hemorrhagic disorder with a variable bleeding tendency. RBDs are due to mutation in underlying coagulation factors genes, except for CF5F8 and VKCF deficiencies. FVII deficiency is the most common RBD with >330 variants in the F7 gene, while only 63 variants have been identified in the F2 gene. Most detected variants in the affected genes are missense (>50% of all RBDs), while large deletions are the rarest, having been reported in FVII, FX, FXI and FXIII deficiencies. Most were located in the catalytic and activated domains of FXI, FX, FXIII and prothrombin deficiencies. Understanding the proper molecular basis of RBDs not only can help achieve a timely and cost-effective diagnosis, but also can help to phenotype properties of the disorders.
Topics: Humans; Blood Coagulation Disorders; Blood Coagulation Disorders, Inherited; Blood Coagulation Factors; Hemorrhagic Disorders; Hemorrhage; Coagulation Protein Disorders; Vitamin K
PubMed: 36369145
DOI: 10.1016/j.blre.2022.101029 -
Journal of Thrombosis and Haemostasis :... Jun 2021Mild to moderate bleeding disorders are a diagnostic challenge. Many patients remain undiagnosed despite thorough and repeated laboratory testing. Thrombin generation...
BACKGROUND
Mild to moderate bleeding disorders are a diagnostic challenge. Many patients remain undiagnosed despite thorough and repeated laboratory testing. Thrombin generation (TG) is an overall assay measuring the functionality of the hemostatic system and may be a useful tool in diagnosing patients with bleeding tendency.
OBJECTIVES
We examined the added value of TG in patients with mild bleeding tendency with and without diagnosis after classical laboratory testing. Further, we investigated the role of different expressions of results, between-method variation, and reference ranges.
METHODS
TG of patients and controls was measured in parallel by two TG platforms (ST Genesia and calibrated automated thrombogram [CAT]). All TG parameters in patient and control groups were compared by statistical analysis (Mann-Whitney U tests) including visual representation with box-and-whisker plots. Results were expressed as normalized ratios (ST Genesia and CAT) or corrected values (ST Genesia). Reference intervals were calculated to which patient results were compared. We studied lot-to-lot reagent variability for both platforms.
RESULTS
In 62.7% (ST Genesia) to 69.5% (CAT) of patients undiagnosed with a traditional laboratory work-up, abnormal TG parameters (lag time and endogenous thrombin potential expressed as normalized ratio and/or corrected value) were detected. In the group of previously diagnosed patients, abnormal parameters were found in 58.1% of patients for both TG assays. No relevant lot-to-lot reagent variability was observed.
CONCLUSIONS
Adding TG helps with diagnosing patients with mild bleeding disorder. TG seems a promising tool in diagnosis of bleeding tendency, but further evaluation is necessary before application in diagnostic laboratory testing.
Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Hemostasis; Humans; Reference Values; Thrombin
PubMed: 33724649
DOI: 10.1111/jth.15292