Platelet secretion defects and acquired von Willebrand syndrome in patients with Ventricular Assist Devices

Abstract

Background--The number of implanted ventricular assist devices (VADs) has increased significantly recently. Bleeding, the most frequent complication, cannot be solely attributed to anticoagulation therapy. Acquired von Willebrand syndrome (AVWS) caused by increased shear stress is frequent in VAD patients and can increase the bleeding risk. The HeartMate III (HM III) is a novel left VAD featuring potential improvements over the HeartMate II.Methods and Results--In this study, we investigated the prevalence and onset of AVWS in 198 VAD patients. To our knowledge, this is the largest cohort of VAD patients whose longitudinal data on AVWS have been collected. We also analyzed whether AVWS is less severe in HM III patients than in HeartMate II patients. Because platelet dysfunction can raise the bleeding risk, we investigated platelet function in a subset of patients. In total, 198 VAD patients and 60 patients with heart transplants as controls were included in this study. The ratio of von Willebrand factor collagen binding capacity to von Willebrand factor:antigen, multimer analyses, and platelet function (especially secretion of aand d-granules) were investigated. All 198 VAD patients developed AVWS. As soon as the VAD was explanted, the AVWS disappeared within hours. AVWS was less severe in the HM III patients than in the HeartMate II patients. The HM III patients had fewer bleeding symptoms. In addition, VAD patients exhibited a platelet aand d-granule secretion defect.Conclusions--AVWS develops in VAD patients and may increase the bleeding risk. The HM III device causes less severe AVWS. Platelet secretion defects should be investigated in VAD patients because they also raise the bleeding risk.Clinical Trial Registration--https://www.drks.de/drks_web.

Effect of ex vivo extracorporeal membrane oxygenation flow dynamics on immune response

“…As illuminated in previous CPB and ventricular assist device (VAD) studies, two main factors are associated with blood trauma: intensity (high-flow dynamics/shear stress) and duration (prolonged exposure time). [5][6][7][8][9][10] Akin to these mechanical circulatory devices, laboratory and clinical ECMO studies have reported induction of haemolysis, 11 von Willebrand factor degradation, [12][13][14] platelet dysfunction 15 and peripheral blood leukocyte activation. [16][17][18][19] These are in spite of the technological advancements in developing more biocompatible pump and oxygenator systems.…”

Acquired bleeding disorders

“…VAD patients exhibit a high bleeding risk at multiple sites including pulmonary and intracranial bleeding, and an increased rate of gastrointestinal (GI) bleeds during long‐term VAD support which may be caused by arteriovenous malformations 19 . Anticoagulation is necessary; however, non‐surgical haemorrhage cannot be attributed to anticoagulation alone 20 …”

“…Elevated shear stress due to pathological blood flow remains an issue in MCS, because these haemodynamic changes lead to AVWS in VAD and ECMO patients 20,21 . AVWS exacerbates bleeding symptoms due to the loss of high molecular weight (HMW) multimers of VWF resulting in impaired haemostatic activity 22 …”

Hemostatic complications associated with ventricular assist devices

“…26 Studies reveal that decreased or absent HMW multimers are very common, occurring in virtually all patients with a VAD. 33 However, the level of VWF activity of protein is not the only explanation for clinical bleeding seen in patients with VADs. 35 In one prospective study, 27% of patients with loss of HMW multimers had bleeding complications.…”