Thrombin generation abnormalities in commonly encountered platelet function disorders

Sharma, Tanmya; Brunet, Justin; Tasneem, Subia; Smith, Stephanie A.; Morrissey, James H.; Hayward, Catherine P.M.

doi:10.1111/ijlh.13638

Cited by 7 publications

(19 citation statements)

References 40 publications

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“…Platelets provide primary hemostasis and regulate thrombin generation by exposure of procoagulant phospholipids and secretion of FV as well as TFPIα. 31 It should be noted that alterations in platelets and/or blood cells are not considered in the present study, while these could contribute to major bleeding. Excitingly, thrombin generation evaluation is now possible in whole blood and may provide additional info on bleeding risk.…”

Section: Discussionmentioning

confidence: 90%

“…Another limitation of our study is that the effects of platelets and other blood cells are lacking in the TG measurements. Platelets provide primary hemostasis and regulate thrombin generation by exposure of procoagulant phospholipids and secretion of FV as well as TFPIα 31 . It should be noted that alterations in platelets and/or blood cells are not considered in the present study, while these could contribute to major bleeding.…”

Section: Discussionmentioning

confidence: 96%

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Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa

Maag

Rein

Schuijt

et al. 2022

Journal of Thrombosis and Haemostasis

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 96%

Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa

Maag

Rein

Schuijt

et al. 2022

Journal of Thrombosis and Haemostasis

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“… 5 Among persons with these PFD, those with poor wound healing have significantly lower PRP peak thrombin concentrations and longer times to peak TG than those without this symptom 5 . Additionally, those with prolonged wound bleeding have longer times to peak TG and longer lag times than those without this symptom 5 . This study noted abnormalities in both PRP and PPP TG among PFD cases, and very strong correlations between PRP and PPP TG endpoints for both controls and PFD cases, and recommended testing both PRP and PPP when evaluating TG in bleeding disorders 5 .…”

Section: Platelet Procoagulant Function In Bleeding Disordersmentioning

confidence: 99%

“…20 Platelets contain an important, releasable pool of polyP in F I G U R E 2 Thrombin generation with platelets present. Panels show previously unpublished platelet rich plasma (PRP) thrombograms from References [5,6]. Panel A shows a control sample to illustrate the endpoints of lag time, time to peak thrombin generation (TG), peak TG and endogenous thrombin potential (ETP, the area under the curve).…”

Section: Platelet Dense Granule Polyphosphate As a Modulator Of Coagu...mentioning

confidence: 99%

“…[1][2][3][4] Recent studies of TG with both platelets and plasma present, using calibrated automated thrombograms (CAT) to study platelet rich plasma (PRP) (see Figure 2) provide evidence that platelet procoagulant function influences the bleeding phenotype of severe factor deficiencies and the symptoms of some platelet function disorders (PFD). 5,7 This review highlights recent advances in our understanding of platelet-dependent procoagulant mechanisms, including updated information on platelet procoagulant activity in bleeding disorders.…”

mentioning

confidence: 99%

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Update on platelet procoagulant mechanisms in health and in bleeding disorders

Bourguignon

Tasneem

Hayward

2022

Int J Lab Hematology

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Platelet procoagulant mechanisms are emerging to be complex and important to achieving haemostasis. The mechanisms include the release of procoagulant molecules from platelet storage granules, and strong agonist-induced expression of procoagulant phospholipids on the outer platelet membrane for tenase and prothrombinase assembly. The release of dense granule polyphosphate is important to platelet procoagulant function as it promotes the activation of factors XII, XI and V, inhibits tissue factor pathway inhibitor and fibrinolysis, and strengthens fibrin clots. Platelet procoagulant function also involves the release of partially activated factor V from platelets. Scott syndrome has provided important insights on the mechanisms that regulate procoagulant phospholipids expression on the external platelet membrane, which require strong agonist stimulation that increase cystolic calcium levels, mitochondrial calcium uptake, the loss of flippase function and activation of the transmembrane scramblase protein anoctamin 6. There have been advances in the methods used to directly and indirectly assess platelet procoagulant function in health and disease. Assessments of thrombin generation with platelet rich plasma samples has provided new insights on how platelet procoagulant function is altered in inherited platelet disorders, and how platelets influence the bleeding phenotype of a number of severe coagulation factor deficiencies. Several therapies, including desmopressin and recombinant factor VIIa, improve thrombin generation by platelets.There is growing interest in targeting platelet procoagulant function for therapeutic benefit. This review highlights recent advances in our understanding of plateletdependent procoagulant mechanisms in health and in bleeding disorders.

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Bleeding phenotype and hemostatic evaluation by thrombin generation in children with Noonan syndrome: A prospective study

Barg,

Yeshayahu,

Avishai

et al. 2023

Pediatric Blood & Cancer

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BackgroundThis study aimed to evaluate the bleeding phenotype and to conduct a comprehensive hemostatic evaluation in individuals with Noonan syndrome (NS), a dominantly inherited disorder caused by pathogenic variants in genes associated with the Ras/MAPK signaling pathway.MethodsChildren with a genetically confirmed diagnosis of NS underwent clinical evaluation, routine laboratory tests, platelet function testing, and thrombin generation (TG) assessment.ResultsThe study included 24 children. The most frequently reported bleeding symptoms were easy bruising and epistaxis, while bleeding complications were observed in 15% of surgical procedures. Various hemostatic abnormalities were identified, including platelet dysfunction, von Willebrand disease, and clotting factor deficiencies. Abnormal platelet function was observed in 50% of the patients, and significantly lower TG parameters were found compared to controls. However, no significant correlation was observed between bleeding symptoms and TG results.ConclusionsThe study suggests that the bleeding diathesis in NS is multifactorial, involving both platelet dysfunction and deficiencies of plasma coagulation factors. The potential role of TG assay as an ancillary tool for predicting bleeding tendencies in individuals with NS undergoing surgery warrants further investigation.

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Thrombin generation abnormalities in commonly encountered platelet function disorders

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 7 publications

References 40 publications

Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa

Major bleeding during oral anticoagulant therapy associated with factor V activation by factor Xa

Update on platelet procoagulant mechanisms in health and in bleeding disorders

Bleeding phenotype and hemostatic evaluation by thrombin generation in children with Noonan syndrome: A prospective study

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