Global coagulation in myeloproliferative neoplasms

Tripodi, Armando; Chantarangkul, Veena; Gianniello, Francesca; Clerici, Marigrazia; Lemma, Laura; Padovan, Lidia; Gatti, Loredana; Mannucci, Pier Mannuccio; Peyvandi, Flora

doi:10.1007/s00277-013-1834-x

Cited by 29 publications

(42 citation statements)

References 20 publications

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“…Among these the most important are diabetes, nonalcoholic fatty liver diseases, myeloproliferative neoplasms, inflammatory bowel diseases, and others for which plasma hypercoagulability was surmised, but never substantiated by laboratory tests. Investigations showed that in these clinical conditions there are distinct biochemical signs of hypercoagulability that can be detected by TGA (35)(36)(37)(38). In conclusion, TGA gave an unprecedented opportunity to investigate mechanisms of coagulation that were until recently poorly known.…”

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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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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“…There was a direct correlation between ETP and platelet counts and an inverse one between ETP and antithrombin, protein C, and free protein S levels 11 . ETP ratios were lower in patients treated with hydroxycarbamidum versus those treated with other drugs.…”

Section: The Relationship Between Thrombin Generation and Plateletsmentioning

confidence: 80%

“…The prophylaxis with antiplatelet drugs is indicated in subjects with arterial thrombosis risk (if the platelet count is not over 1500000/mm 3 ), while anticoagulant prophylaxis of venous thrombosis is recommended in those found in high-risk situations or after the first event 7 . Unfortunately, the traditional tests used in order to explore the coagulation do not accurately reflect the balance between pro-and anti-coagulant factors, nor the effects of platelet or other blood cells 11 . A feasible solution could be the study of thrombin generation with calibrated automated thrombography, as thrombin generation reflects more correctly the balance between pro-and anticoagulant factors.…”

Section: The Thrombotic Risk Of Patients With Philadelphia-negative Mmentioning

confidence: 99%

Thrombin generation - a potentially useful biomarker of thrombotic risk in Philadelphia-negative myeloproliferative neoplasms

Mihăilă¹

2017

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The diagnosis of essential thrombocythemia and polycythemia vera is often made during a thrombotic event which can be serious. Philadelphia-negative chronic myeloproliferative neoplasia patients have an increased thrombotic risk. This is assessed using various scoring systems but these are far from ideal and individual risk. The currend trend to personalised medicine requires finding the most useful thrombotic risk biomarker in these patients. Routine tests for coagulation do not take account of both pro-and anti-coagulant factors which is why these tests are not useful in patients with Philadelphia-negative myeloproliferative neoplasms. Thrombin generation reflects more accurately the balance between pro-and anti-coagulant factors. Some parameters of thrombin generation such as the endogenous thrombin potential are higher in Philadelphia-negative myeloproliferative neoplasm patients, especially in JAK2 V617F carriers than in healthy controls. They are even higher in those with reactive thrombocytosis. The JAK2 V617F allele burden correlates more with a higher thrombin generation potential in patients who are not treated with hydroxycarbamidum. Instead, JAK2 V617F-positive patients with Philadelphia-negative myeloproliferative neoplasms were the most sensitive to hydroxycarbamidum, as was reflected in lower values of platelet thrombin generation potential. The use of thrombin generation examination in these patients would enable detection of imminent thrombosis and personalised prophylactic management.

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“…These tests are unable to reflect and integrate all pro-and anticoagulant reactions that regulate the formation and inhibition of thrombin and the effect of platelets and other blood cells [8].…”

Section: Introductionmentioning

confidence: 99%

“…Thrombin generation assays measure the ability of a plasma sample to generate thrombin following in vitro activation of coagulation with tissue factor or another trigger, and then the concentration of thrombin formed over the time is monitored [8,9].…”

Section: Introductionmentioning

confidence: 99%