Enhanced VWF clearance in low VWF pathogenesis: limitations of the VWFpp/VWF:Ag ratio and clinical significance.
Enhanced VWF clearance in low VWF pathogenesis: limitations of the VWFpp/VWF:Ag ratio and clinical significance.
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VWF低发病机理中增强的VWF清除率：VWFPP/VWF的局限性：Ag比率和临床意义。
DOI：
10.1182/bloodadvances.2022007340
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发表时间：
2023-02-14
期刊：
影响因子：
7.5
通讯作者：
O'Donnell, James S.
中科院分区：
文献类型：
--
作者：
Doherty, Dearbhla;Lavin, Michelle;Byrne, Mary;Nolan, Margaret;O'Sullivan, Jamie M.;Ryan, Kevin;O'Connell, Niamh M.;Haberichter, Sandra L.;Christopherson, Pamela A.;Di Paola, Jorge;James, Paula D.;O'Donnell, James S.
在20%的低VWF患者中，VWF清除率存在轻微增强，并与出血表型减轻有关。在低VWF患者中，去氨加压素脱落率与稳态VWFpp/VWF:Ag比值相关性较差。血管性血友病因子（VWF）清除率增高在1型和2型血管性血友病（VWD）的发病机制中起关键作用。然而，轻度至中度血浆VWF:Ag降低（范围，30-50 IU/dL；低VWF）患者的病理机制仍然知之甚少。在本研究中，我们研究了VWF清除增强可能有助于低VWF病理生物学的假设。低VWF患者在伦理批准和知情同意后被招募到LoVIC研究中。75例患者静脉给予去氨加压素，并在基线、1小时和4小时时间点采血。根据最近的ASH/ISTH/NHF/WFH指南的定义，20%的低VWF队列显示VWF清除率显着提高。重要的是，从临床角度来看，在大多数情况下，去氨加压素输注后VWF清除率增强，但不影响VWF前肽（VWFpp）与VWF抗原（VWF:Ag）的稳态比值（VWFpp/VWF:Ag）。轻度定量VWD患者VWFpp/VWF:Ag比值和去氨加压素脱落率之间的差异可能反映了VWFpp清除动力学的改变。最后，与以VWF生物合成减少为主要致病机制的患者相比，VWF清除率增强的低VWF患者的出血评分显著降低。该试验在http://www.clinicaltrials.gov注册为#NCT03167320。
Subtle enhanced VWF clearance is present in 20% of patients with low VWF and is associated with an attenuated bleeding phenotype. In patients with low VWF, there is poor correlation between desmopressin fall-off rates and steady-state VWFpp/VWF:Ag ratios. Increased von Willebrand factor (VWF) clearance plays a key role in the pathogenesis of type 1 and type 2 von Willebrand disease (VWD). However, the pathological mechanisms involved in patients with mild to moderate reductions in plasma VWF:Ag (range, 30-50 IU/dL; low VWF) remain poorly understood. In this study, we investigated the hypothesis that enhanced VWF clearance may contribute to the pathobiology of low VWF. Patients with low VWF were recruited to the LoVIC study after ethics approval and receipt of informed consent. Desmopressin was administered IV in 75 patients, and blood samples were drawn at baseline and at the 1-hour and 4-hour time points. As defined by recent ASH/ISTH/NHF/WFH guidelines, 20% of our low-VWF cohort demonstrated significantly enhanced VWF clearance. Importantly, from a clinical perspective, this enhanced VWF clearance was seen after desmopressin infusion, but did not affect the steady-state VWF propeptide (VWFpp)-to-VWF antigen (VWF:Ag) ratio (VWFpp/VWF:Ag) in most cases. The discrepancy between the VWFpp/VWF:Ag ratio and desmopressin fall-off rates in patients with mild quantitative VWD may have reflected alteration in VWFpp clearance kinetics. Finally, bleeding scores were significantly lower in patients with low VWF with enhanced VWF clearance, compared with those in whom reduced VWF biosynthesis represented the principle pathogenic mechanism. This trial was registered at http://www.clinicaltrials.gov as #NCT03167320.
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