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Thrombin generation abnormalities in Quebec platelet disorder
Author(s) -
Brunet Justin G.,
Sharma Tanmya,
Tasneem Subia,
Liang Minggao,
Wilson Michael D.,
Rivard Georges E.,
Hayward Catherine P. M.
Publication year - 2020
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.13302
Subject(s) - platelet , plasmin , thrombin , plasminogen activator , medicine , platelet rich plasma , platelet poor plasma , endocrinology , platelet activation , immunology , chemistry , biochemistry , enzyme
Calibrated automated thrombograms (CAT) with platelet‐poor (PPP) and platelet‐rich plasma (PRP) have provided useful insights on bleeding disorders. We used CAT to assess thrombin generation (TG) in Quebec platelet disorder (QPD)—a bleeding disorder caused by a PLAU duplication mutation that increases platelet (but not plasma) urokinase plasminogen activator (uPA), leading to intraplatelet (but not systemic) plasmin generation that degrades α‐granule proteins and causes platelet (but not plasma) factor V (FV) deficiency. Methods Calibrated automated thrombograms was used to test QPD (n = 7) and control (n = 22) PPP and PRP, with or without added tranexamic acid (TXA). TG endpoints were evaluated for relationships to platelet FV and uPA, plasma FV and tissue factor pathway inhibitor (TFPI) levels, and bleeding scores. Results Quebec platelet disorder PPP TG was normal whereas QPD PRP had reduced endogenous thrombin potential and peak thrombin concentrations ( P values < .01), proportionate to the platelet FV deficiency ( R 2 ≥ 0.81), but unrelated to platelet uPA, plasma FV, or bleeding scores. QPD TG abnormalities were not associated with TFPI abnormalities and were not reproduced by adding uPA to control PRP. TXA increased QPD and control PRP TG more than PPP TG, but it did not fully correct QPD PRP TG abnormalities or improve TG by plasminogen‐deficient plasma. Conclusion Quebec platelet disorder results in a platelet‐specific TG defect, proportionate to the loss of platelet FV, that is improved but not fully corrected by TXA. Our study provides an interesting example of why it is important to assess both PRP and PPP TG in bleeding disorders.