Prospective assessment of thrombin generation test for dose monitoring of bypassing therapy in hemophilia patients with inhibitors undergoing elective surgery

Dargaud, Yesim; Lienhart, Anne; Négrier, Claude

doi:10.1182/blood-2010-06-291906

Cited by 121 publications

(165 citation statements)

References 12 publications

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“…The logical conclusion is that thrombin generation in these patients is a more sensitive parameter than factor VIII. Other observations showed that thrombin generation, which is low in patients with hemophilia, increased substantially after infusion of bypassing agents (40 ). The above observations paved the way to investigate TGA as a reliable laboratory tool to monitor hemophiliacs during replacement therapy.…”

Section: Application Of Tga To Manage Patients With Hemorrhagic Coagumentioning

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 Manage Patients With Hemorrhagic Coagumentioning

confidence: 99%

Thrombin Generation Assay and Its Application in the Clinical Laboratory

2016

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“…Data have been published with the CAT method, consistent with a potentially high added value in clinical practice, in settings such as diagnosis and management of bleeding disorders [6][7][8], detection of hypercoagulability [9,10], characterization/monitoring of anticoagulant drugs including non-vitamin K antagonist oral anticoagulants [11,12] or even in acquired complex coagulation disorders [13]. Most of the data come from single-centre studies and must be confirmed in prospective, large, multicentre studies.…”

Section: Introductionmentioning

confidence: 99%

Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma

Perrin

Depasse

Lecompte

et al. 2015

Thrombosis Research

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Calibrated Automated Thrombography (CAT) has been widely used to assess in vitro thrombin generation as an informative intermediary phenotype of coagulation. Interlaboratory exercises have documented a worrisome poor reproducibility. There are some data on the normalisation with an appropriate external reference plasma (RP). This multicentre study of the French-speaking CAT Club aimed at providing further evidence for the usefulness of such a normalisation

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“…25,26 There is also a relationship between bleeding and failure to normalize ETP in hemophilia patients with inhibitors treated with inhibitor bypass agents at the time of surgery. 27 We therefore studied thrombin generation in patients with discrepant factor FVIII:C assays and compared it to that in patients with non-discrepant assays and normal subjects given suggestions in the literature that two-stage assays and chromogenic assays may correlate than one-stage assays with the clinical phenotype. 4 Gilmore et al reported on the effect of three mutations linked to lower two-stage discrepancy (p.Arg550His/Cys and p.Arg717Trp) on CAT, demonstrating impaired thrombin generation in this group similar to non-discrepant patients with the mean ETP being 58-67% of normal and peak thrombin generation being 27-30% of normal.…”

Section: Calibrated Automated Thrombographymentioning

confidence: 99%

Specific and global coagulation assays in the diagnosis of discrepant mild hemophilia A

Bowyer¹,

Veen²,

Goodeve

et al. 2013

Haematologica

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The activity of the factor VIII coagulation protein can be measured by three methods: a one or two-stage clotting assay and a chromogenic assay. The factor VIII activity of most individuals with mild hemophilia A is the same regardless of which method is employed. However, approximately 30% of patients show marked discrepancies in factor VIII activity measured with the different methods. The objective of this study was to investigate the incidence of assay discrepancy in our center, assess the impact of alternative reagents on factor VIII activity assays and determine the usefulness of global assays of hemostasis in mild hemophilia A. Factor VIII activity was measured in 84 individuals with mild hemophilia A using different reagents. Assay discrepancy was defined as a two-fold or greater difference between the results of the one-stage and two-stage clotting assays. Rotational thromboelastometry and calibrated automated thrombography were performed. Assay discrepancy was observed in 31% of individuals; 12% with lower activity in the two-stage assay and 19% with lower activity in the one-stage assay. The phenotype could not always be predicted from the individual's genotype. Chromogenic assays were shown to be a suitable alternative to the two-stage clotting assay. Thromboelastometry was found to have poor sensitivity in hemophilia. Calibrated automated thrombography supported the results obtained by the two-stage and chromogenic assays. The current international guidelines do not define the type of assay to be used in the diagnosis of mild hemophilia A and some patients could be misclassified as normal. In our study, 4% of patients would not have been diagnosed on the basis of the one-stage factor VIII assay. Laboratories should use both one stage and chromogenic (or two-stage) assays in the diagnosis of patients with possible hemophilia A.

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Prospective assessment of thrombin generation test for dose monitoring of bypassing therapy in hemophilia patients with inhibitors undergoing elective surgery

Cited by 121 publications

References 12 publications

Thrombin Generation Assay and Its Application in the Clinical Laboratory

Thrombin Generation Assay and Its Application in the Clinical Laboratory

Large external quality assessment survey on thrombin generation with CAT: further evidence for the usefulness of normalisation with an external reference plasma

Specific and global coagulation assays in the diagnosis of discrepant mild hemophilia A

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