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 α- and δ-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 α- and δ-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. Unique identifier: DRKS00000649.

Keywords: platelet; ventricular assist device; von Willebrand factor.

Figure 1

Study diagram of the investigated patients. BVAD indicates biventricular assist device; HM II, HeartMate II; HM III, HeartMate III; HTX, heart transplantation; preOP, preoperative; RVAD, right ventricular assist device.

Figure 2

A, VWF:CB/VWF:Ag ratio of patients with VAD (n=198) and of HTX patients (n=60). B, Longitudinal progression of VWF:CB/VWF:Ag ratios in patients (n=24) before HM II implantation, with HM II, and after HTX. HM II indicates HeartMate II; HTX, heart transplantation; pre‐OP, preoperative; VWF:Ag indicates VWF antigen; VWF:CB, VWF collagen binding capacity.

Figure 3

A, VWF:CB/VWF:Ag ratios in patients with HM II, HM III, BVAD, and HM II and RVAD (HM II+RVAD). Significance symbols are based on multiplicity corrected P values. B, Percentage of patients with pathological and normal VWF multimers in HM II and HM III patients pre‐OP and on days 1, 3, 7, 30, and 90 after implantation. Significance markings relate to differences between the HM II and HM III groups. *P<0.05, ***P<0.001. BVAD indicates biventricular assist device; HM II, HeartMate II; HM III, HeartMate III; HTX, heart transplantation; NS indicates not significant; pre‐OP, preoperative; RVAD, right ventricular assist device; VWF:Ag, VWF antigen; VWF:CB, VWF collagen binding capacity.

Figure 4

CD62 expression (α‐granule secretion) in VAD patients. A, Representative IgG‐corrected CD62 expression on platelets from a VAD patient and a healthy control at increasing thrombin concentrations. B, CD62 expression on platelets of VAD patients (n=22) in relation to paired healthy controls at increasing thrombin concentrations (data depicted in percentage of respective fluorescence from a healthy control). FITC indicates fluorescein isothiocyanate; VAD, ventricular assist device.

Figure 5

CD63‐expression (δ‐granule secretion) in VAD‐patients. A, Representative IgG corrected CD63‐expression on platelets of a VAD‐patient and of a healthy control at increasing thrombin concentrations. B, CD63‐expression on platelets of VAD patients (N=22) in relation to paired healthy controls at increasing thrombin concentrations (data depicted in % of respective fluorescence from a healthy control). FITC indicates fluorescein isothiocyanate; VAD, ventricular assist device.

Figure 6

Distribution of (A) hemoglobin levels and (B) creatinine levels in patients with HM II, HM III, HTX, BVAD, and HM II and RVAD (HM II+RVAD). BVAD indicates biventricular assist device; HM II, HeartMate II; HM III, HeartMate III; HTX, heart transplantation; RVAD, right ventricular assist device.