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Impaired platelet-dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro

Chowdary, P; Hamid, C; Slatter, D; Morris, R; Foley, JH; Gomez, K; Brodkin, E; ... McVey, JH; + view all (2020) Impaired platelet-dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro. Research and Practice in Thrombosis and Haemostasis , 4 (2) pp. 334-342. 10.1002/rth2.12310. Green open access

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Abstract

BACKGROUND Impaired thrombin generation (TG) in patients with acquired coagulopathy, is due to low coagulation factors and thrombocytopenia. The latter is typically treated with platelet transfusions and the former with plasma and occasionally with prothrombin complex concentrates (PCCs). We hypothesized that manipulating the concentrations of coagulation factors might result in restoration of platelet‐dependent TG over and above that of simple replacement therapy. OBJECTIVE To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia. METHODS TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20‐300 × 109/L) were spiked with PCCs (25%‐150% increase in plasma PCC levels). RESULTS PCCs and platelets significantly increased TG in a dose‐dependent manner in vitro. Two‐way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combination with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 109/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 109/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG. CONCLUSIONS Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to moderate thrombocytopenia and abnormal coagulation.

Type: Article
Title: Impaired platelet-dependent thrombin generation associated with thrombocytopenia is improved by prothrombin complex concentrates in vitro
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/rth2.12310
Publisher version: https://doi.org/10.1002/rth2.12310
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: acquired coagulopathy, blood coagulation disorders, blood platelets, prothrombin complex concentrates, thrombin, thrombocytopenia
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10093034
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