Absence of hyperfibrinolysis may explain lack of efficacy of tranexamic acid in hypoproliferative thrombocytopenia

被引:4
作者
Ilich, Anton [1 ,2 ]
Gernsheimer, Terry B. [3 ,4 ]
Triulzi, Darrell J. [5 ]
Herren, Heather [6 ]
Brown, Siobhan P. [6 ]
Holle, Lori A. [2 ,7 ]
Lucas, Andrew T. [8 ]
de Laat, Bas [9 ]
El Kassar, Nahed [10 ]
Wolberg, Alisa S. [2 ,7 ]
May, Susanne [6 ]
Key, Nigel S. [1 ,2 ,7 ,11 ]
机构
[1] Univ N Carolina, Dept Med, Div Hematol, Sch Med, Chapel Hill, NC USA
[2] Univ N Carolina, UNC Blood Res Ctr, Sch Med, Chapel Hill, NC USA
[3] Univ Washington, Dept Med Hematol, Seattle, WA USA
[4] Univ Washington, Seattle Canc Care Alliance, Seattle, WA USA
[5] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA
[6] Univ Washington, Dept Biostat, Seattle, WA USA
[7] Univ N Carolina, Dept Pathol & Lab Med, Sch Med, Chapel Hill, NC USA
[8] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Eshelman Sch Pharm, Chapel Hill, NC USA
[9] Synapse Res Inst, Maastricht, Netherlands
[10] NHLBI, Div Blood Dis & Resources, Washington, DC USA
[11] Univ N Carolina, Sch Med, 8008B Mary Ellen Jones Bldg,CB 7035,116 Manning Dr, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
VASCULAR OCCLUSIVE EVENTS; FIBRINOLYTIC ACTIVATION; PLATELET TRANSFUSIONS; NORMAL MENSTRUATION; CONTROLLED-TRIAL; TRAUMA PATIENTS; CRASH-2; WOMEN; DIAGNOSIS; DEATH;
D O I
10.1182/bloodadvances.2022008255
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT, NCT02578901) demonstrated no superiority of TXA over placebo in preventing World Health Organization (WHO) grade 2 or higher bleeding in patients with severe thrombocytopenia requiring supportive platelet transfusion following myeloablative therapy for hematologic disorders. In this ancillary study, we sought to determine whether this clinical outcome could be explained on the basis of correlative assays of fibrinolysis. Plasma was collected from A-TREAT participants (n = 115) before the initiation of study drug (baseline) and when TXA was at steady-state trough concentration (follow-up). Global fibrinolysis was measured by 3 assays: euglobulin clot lysis time (ECLT), plasmin generation (PG), and tissue-type plasminogen activator (tPA)-challenged clot lysis time (tPA-CLT). TXA was quantified in follow-up samples by tandem mass spectrometry. Baseline samples did not demonstrate fibrinolytic activation by ECLT or tPA-CLT. Furthermore, neither ECLT nor levels of plasminogen activator inhibitor-1, tPA, plasminogen, alpha2-antiplasmin, or plasmin-antiplasmin complexes were associated with a greater risk of WHO grade 2+ bleeding. TXA trough concentrations were highly variable (range, 0.7-10 mu g/mL) and did not correlate with bleeding severity, despite the fact that plasma TXA levels correlated strongly with pharmacodynamic assessments by PG (Spearman r, -0.78) and tPA-CLT (r, 0.74). We conclude that (1) no evidence of fibrinolytic activation was observed in these patients with thrombocytopenia, (2) trough TXA concentrations varied significantly between patients receiving the same dosing schedule, and (3) tPA-CLT and PG correlated well with TXA drug levels.
引用
收藏
页码:900 / 908
页数:9
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