Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands.
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
PLoS One. 2022 Jul 15;17(7):e0271527. doi: 10.1371/journal.pone.0271527. eCollection 2022.
Decreased platelet count is an early phenomenon in asexual Plasmodium falciparum parasitemia, but its association with acute or long-term functional changes in platelets and coagulation is unknown. Moreover, the impact of gametocytemia on platelets and coagulation remains unclear. We investigated the changes in platelet number and function during early asexual parasitemia, gametocytemia and convalescence in 16 individuals participating in a controlled human malaria infection study, and studied its relationship with changes in total and active von Willebrand factor levels (VWF) and the coagulation system. Platelet activation and reactivity were determined by flow cytometry, and the coagulation system was assessed using different representative assays including antigen assays, activity assays and global functional assays. Platelet count was decreased during asexual blood stage infection but normalized during gametocytemia. Platelet P-selectin expression was slightly increased during asexual parasitemia, gametocytemia and at day 64. In contrast, platelet reactivity to different agonists remained unchanged, except a marked decrease in reactivity to low dose collagen-related peptide-XL. Thrombin generation and antigen assays did not show a clear activation of the coagulation during asexual parasitemia, whereas total and active VWF levels were markedly increased. During gametocytemia and on day 64, the endogenous thrombin potential, thrombin peak and velocity index were increased and prothrombin conversion and plasma prothrombin levels were decreased. We conclude that the decreased platelet count during asexual parasitemia is associated with increased active VWF levels (i.e. endothelial activation), but not platelet hyperreactivity or hypercoagulability, and that the increased platelet clearance in asexual parasitemia could cause spontaneous VWF-platelet complexes formation.
血小板计数减少是无性疟原虫寄生虫血症的早期现象，但它与血小板和凝血的急性或长期功能变化的关系尚不清楚。此外，配子体血症对血小板和凝血的影响仍不清楚。我们研究了 16 名参与对照人体疟疾感染研究的个体在早期无性寄生虫血症、配子体血症和恢复期期间血小板数量和功能的变化，并研究了其与总和活性血管性血友病因子（VWF）水平和凝血系统变化的关系。通过流式细胞术测定血小板活化和反应性，并用不同的代表性测定法（包括抗原测定法、活性测定法和整体功能测定法）评估凝血系统。血小板计数在无性血期感染期间减少，但在配子体血症期间正常化。血小板 P-选择素表达在无性寄生虫血症、配子体血症和第 64 天期间略有增加。相比之下，血小板对不同激动剂的反应性保持不变，除了对低剂量胶原蛋白相关肽-XL 的反应性明显降低。在无性寄生虫血症期间，凝血酶生成和抗原测定法均未显示出凝血的明显激活，而总和活性 VWF 水平显著增加。在配子体血症和第 64 天期间，内源性凝血酶潜能、凝血酶峰值和速度指数增加，凝血酶原转化率和血浆凝血酶原水平降低。我们得出结论，无性寄生虫血症期间血小板计数减少与活性 VWF 水平（即内皮细胞活化）增加有关，但与血小板高反应性或高凝状态无关，无性寄生虫血症期间血小板清除增加可能导致自发性 VWF-血小板复合物的形成。
