Büchsel Martin, Geisen Ulrich, Beckenkamp Clara, Wengenmayer Tobias, Zieger Barbara, Westermann Dirk, Siegel Patrick M
Institute for Clinical Chemistry and Laboratory Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
Interdisciplinary Medical Intensive Care (IMIT), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Thromb J. 2023 Jan 10;21(1):4. doi: 10.1186/s12959-022-00448-1.
Extracorporeal membrane oxygenation (ECMO) is applied in patients with respiratory or cardiopulmonary failure, but bleeding is a frequent complication contributing to the high mortality rates in this patient collective. A major factor predisposing patients to bleeding events is an acquired von Willebrand syndrome (aVWS). So far, specific treatment options for this phenomenon are lacking. In hereditary von Willebrand disease (VWD), treatment with recombinant or plasma-derived von Willebrand factor (rVWF or pVWF) is common practice. Closure time measured by the Platelet Function Analyser-200 (PFA-200) is an established assay to detect defects in primary hemostasis and the method is useful to monitor the effect of hemostatic therapy. The aim of this study was to assess the effect of recombinant (rVWF) vs. plasma-derived von Willebrand factor (pVWF) on closure times measured by PFA in blood obtained from ECMO patients with aVWS.
Blood was sampled from thirteen patients receiving extracorporeal membrane oxygenation and three patients with hereditary VWD. Diagnosis of aVWS was made by conventional coagulation parameters and by multimeric structure analysis. PFA analysis of blood spiked with rVWF or pVWF was performed.
Thirteen patients receiving ECMO were recruited. Ten patients survived and three patients suffered major bleeding complications. PFA closure times in ECMO patients with aVWS spiked with rVWF were significantly shorter at all concentrations than with pVWF (e.g., rVWF vs. pVWF: 1 U/ml: 150.4 ± 21.7 s vs. 263.8 ± 11.7 s; 4 U/ml: 97.8 ± 9.8 s vs. 195.8 ± 15.4 s, p<0.001). PFA closure times were also significantly shorter in three patients with hereditary VWD treated with rVWF compared to pVWF (e.g., 1 U/ml rVWF vs. pVWF: 73.7±1.33 s vs. 231.3±43.4 s, p<0.01) CONCLUSION: In summary, this study shows that rVWF compared to pVWF more effectively reduced PFA closures times in blood samples of ECMO patients with aVWS. Higher doses of VWF are needed to normalize PFA closure time in blood samples of patients with ECMO-induced aVWS compared to hereditary VWD. These data support the use of PFA-200 to monitor hemostatic effects in a future clinical trial involving ECMO patients with aVWS.
体外膜肺氧合（ECMO）应用于呼吸或心肺功能衰竭患者，但出血是常见并发症，导致该患者群体死亡率较高。导致患者发生出血事件的一个主要因素是获得性血管性血友病综合征（aVWS）。到目前为止，针对这一现象缺乏具体的治疗选择。在遗传性血管性血友病（VWD）中，使用重组或血浆来源的血管性血友病因子（rVWF或pVWF）进行治疗是常见做法。通过血小板功能分析仪-200（PFA-200）测量的闭合时间是一种用于检测初级止血缺陷的既定检测方法，该方法有助于监测止血治疗的效果。本研究的目的是评估重组血管性血友病因子（rVWF）与血浆来源的血管性血友病因子（pVWF）对从患有aVWS的ECMO患者获得的血液中通过PFA测量的闭合时间的影响。
从13例接受体外膜肺氧合的患者和3例遗传性VWD患者中采集血液。通过传统凝血参数和多聚体结构分析诊断aVWS。对添加了rVWF或pVWF的血液进行PFA分析。
招募了13例接受ECMO的患者。10例患者存活，3例患者发生严重出血并发症。添加rVWF的患有aVWS的ECMO患者在所有浓度下的PFA闭合时间均显著短于添加pVWF的患者（例如，rVWF与pVWF：1 U/ml：150.4±21.7秒对263.8±11.7秒；4 U/ml：97.8±9.8秒对195.8±15.4秒，p<0.001）。与pVWF相比，3例接受rVWF治疗的遗传性VWD患者的PFA闭合时间也显著缩短（例如，1 U/ml rVWF与pVWF：73.7±1.33秒对231.3±43.4秒，p<0.01）。结论：总之，本研究表明，与pVWF相比，rVWF能更有效地缩短患有aVWS的ECMO患者血样中的PFA闭合时间。与遗传性VWD相比，需要更高剂量的VWF才能使患有ECMO诱导的aVWS患者的血样中的PFA闭合时间正常化。这些数据支持在未来涉及患有aVWS的ECMO患者的临床试验中使用PFA-200来监测止血效果。
