Enhanced thrombin generation in patients with cirrhosis‐induced coagulopathy

Gatt, Alex; Riddell, Anne; Calvaruso, Vincenza; Tuddenham, Edward G. D.; Makris, Michael; Burroughs, A K

doi:10.1111/j.1538-7836.2010.03937.x

Cited by 181 publications

(209 citation statements)

References 28 publications

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“…13 The TGT was used to demonstrate that plasma from patients with stable cirrhosis generates thrombin at a normal or even increased rate despite prolonged PT/INR and PTT values. 13,23 The TGT is still primarily a research tool and not validated for predicting bleeding risk in patients with liver disease. Early studies showed that TEG guided factor replacement reduced red cell transfusions and the volume of plasma infused during liver transplantation.…”

Section: Global Tests Of Hemostasismentioning

confidence: 99%

Coagulopathy in liver disease: a balancing act

Kujovich

2015

Hematology

114

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Liver disease results in complex alterations of all 3 phases of hemostasis. It is now recognized that hemostasis is rebalanced in chronic liver disease. The fall in clotting factor levels is accompanied by a parallel fall in anticoagulant proteins. High von Willebrand factor levels counteract defects in primary hemostasis. Conventional coagulation tests do not fully reflect the derangement in hemostasis and do not accurately predict the risk of bleeding. Global coagulation assays (thrombin generation, thromboelastography) reflect the interaction between procoagulant factors, anticoagulant factors, platelets, and the fibrinolytic system and show promise for assessing bleeding risk and guiding therapy. These assays are not yet commercially approved or validated. Prevention of bleeding should not be aimed at correcting conventional coagulation tests. Thrombopoietin receptor agonists were shown to increase the platelet count in cirrhotic patients undergoing invasive procedures

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Section: Global Tests Of Hemostasismentioning

confidence: 99%

Coagulopathy in liver disease: a balancing act

Kujovich

2015

Hematology

114

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“…More recently, it was proposed that TGA, performed in the presence or absence of thrombomodulin and with results expressed as a ratio between the 2 measurements, could be a sensitive parameter to detect hypercoagulability (18 ). This approach was instrumental to show that patients with cirrhosis possess a certain degree of hypercoagulability (31)(32)(33). This observation paved the way to the treatment of patients with cirrhosis and portal vein thrombosis with low molecular weight heparin (LMWH) (34 ), a treatment that was until recently considered a contraindication in these patients because of the perceived risk of bleeding.…”

Section: Application Of Tga To Increase Understanding Of Coagulation mentioning

confidence: 99%

Thrombin Generation Assay and Its Application in the Clinical Laboratory

2016

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BACKGROUND A gap exists between in vivo and ex vivo coagulation when investigated by use of the coagulation tests prothrombin time (PT) and activated partial thromboplastin time (APTT). The thrombin generation assay (TGA) has been developed to fill this gap. CONTENT TGA evaluates thrombin generation (resulting from the action of the procoagulant driver) and decay (resulting from the action of the anticoagulant driver), thus assessing the balance between the two. Coagulation of the test plasma (platelet poor or platelet rich) is activated by small amounts of tissue factor and phospholipids, and the reaction of thrombin generation is continuously monitored by means of a thrombin-specific fluorogenic substrate. Among the parameters derived from the thrombin-generation curve, the most important is the endogenous thrombin potential, defined as the net amount of thrombin that test plasmas can generate on the basis of the relative strength of the pro- and anticoagulant drivers. TGA is therefore the candidate assay to investigate hypo- or hypercoagulability. SUMMARY From my analysis of the literature, I draw the following conclusions. There is strong evidence that TGA is helpful to elucidate coagulation mechanisms in various clinical conditions that until recently were poorly understood (chronic liver disease; diabetes; inflammatory bowel disease, myeloproliferative neoplasms, nonalcoholic fatty liver disease). TGA is a promising laboratory tool for investigating hemorrhagic coagulopathies and monitoring replacement therapy in hemophiliacs, predicting the risk of recurrent venous thromboembolism after a first event, and monitoring patients on parenteral or oral anticoagulants. These applications require clinical trials in which TGA results are combined with specific clinical end points.

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“…Patients with advanced fibrosis have significantly lower levels of protein C and antithrombin (Tripodi et al, 2005). Furthermore, this partial deficiency of anticoagulant proteins in those with advanced chronic liver disease is accompanied by enhanced thrombin generation within these patients (Gatt et al, 2010), together resulting in a procoagulant state. This could in part explain why the historical assumption that cirrhotics are 'auto-anticoagulated' and therefore protected against developing peripheral thromboembolic disease has now been demonstrated to be untrue.…”

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confidence: 99%