Platelets and platelet-derived factor Va confer hemostatic competence in complete factor V deficiency
Platelets and platelet-derived factor Va confer hemostatic competence in complete factor V deficiency
复制标题
DOI：
10.1182/blood-2014-07-589580
复制
发表时间：
2015-06-04
期刊：
影响因子：
20.3
通讯作者：
Tracy, Paula B.
中科院分区：
文献类型：
--
作者：
Bouchard, Beth A.;Chapin, John;Tracy, Paula B.
对一个完全没有血浆和血小板衍生因子V(FV)的个体进行全基因组测序，发现他的F5基因有167个变异，包括先前发现的rs6027和Leu90Ser的破坏性错义突变。由于新鲜冰冻血浆(FFP)可预防患者的胃肠道出血，因此评估了其对血浆和血小板衍生的Fv浓度的影响。患者的血浆FV水平在注射FFP后2小时达到峰值，96小时后检测不到。相反，血小板源Fv/Va浓度在6小时内升高，24小时达到高峰，7天后缓慢下降，并源于巨核细胞内吞和血浆Fv的细胞内处理。输血10天后，在组织因子启动的全血凝固试验中，除非加入外源性FV，否则不会产生凝血酶，这与完全没有血浆FV是一致的。与此形成鲜明对比的是，在血小板激活后，患者的血小板衍生Fv/Va(正常的7%)的释放导致了强劲的凝血酶生成，与血浆和血小板衍生Fv浓度正常的个体相似。因此，总的Fv不足可以通过血浆给药来纠正，这部分地补充和维持了血小板辅助因子池，从而突出了血小板衍生的Fv/Va在确保止血能力方面的关键作用。
Whole genome sequencing of an individual completely devoid of plasma-and platelet-derived factor V (FV) identified 167 variants in his F5 gene including previously identified and damaging missense mutations at rs6027 and Leu90Ser. Because the administration of fresh frozen plasma (FFP) prevents gastrointestinal bleeding in this individual, its effects on his plasma-and platelet-derived FV concentrations were assessed. The patient's plasma FV levels peaked by 2 hours following FFP administration and were undetectable 96 hours later. In contrast, increased platelet-derived FV/Va concentrations were observed within 6 hours, peaked at 24 hours, decreased slowly over 7 days, and originated from megakaryocyte endocytosis and intracellular processing of plasma FV. Ten days after transfusion, no thrombin was generated in a tissue factor-initiated whole blood clotting assay unless exogenous FV was added, consistent with the complete absence of plasma FV. In marked contrast, release of the patient's platelet-derived FV/Va (7% of normal) following platelet activation resulted in robust thrombin generation, similar to that in an individual with normal plasma-and platelet-derived FV concentrations. Thus, total FV deficiency can be corrected by plasma administration, which partially repletes and sustains the platelet cofactor pool, thereby highlighting the critical role of platelet-derived FV/Va in ensuring hemostatic competence.