Acquired von Willebrand Syndrome in Patients With an Axial Flow Left Ventricular Assist Device

Abstract

Background-Rotary blood pumps used as left ventricular assist devices (LVADs) allow for long-term support and may become suitable alternatives to heart transplantation. Effects of this technology on the coagulation system are not completely understood, leading to controversial anticoagulation protocols. Thus, we investigated the primary hemostasis in patients with chronic LVAD therapy. Methods and Results-Twenty-six outpatients received axial flow LVAD (HeartMate II; Thoratec) for a median support time of 4.5 months. In a cross-sectional protocol, platelet aggregation in response to ADP and epinephrine, von Willebrand antigen (vWF:AG), and collagen-binding capacity (vWF:CB) were obtained. Von Willebrand factor (vWF) multimer analyses were performed, and patients were screened for bleeding events. This analysis was repeated after removal of the device for transplantation or recovery (nϭ12) and after a median of 15.5 months in ongoing patients (nϭ11). In all patients on devices, severe impairment of platelet aggregation as well as a loss of large vWF multimers were found. In 10 patients, a decreased vWF:CB/vWF:AG ratio was observed. Bleeding episodes occurred with an incidence of 0.17 per patient-year. After removal of the device, normal patterns of platelet aggregation, multimer analysis, and vWF:CB/vWF:AG ratio were recorded. In the second analysis of ongoing patients, impairment of platelet aggregation and loss of large vWF multimers were verified. Conclusions-A diagnosis of von Willebrand syndrome type 2 was established in all patients after LVAD implantation, and bleeding events confirmed this finding. Reversibility of this condition was found after removal of the device. (Circ Heart Fail. 2010;3:675-681.)

Pulsatility and the Risk of Nonsurgical Bleeding in Patients Supported With the Continuous-Flow Left Ventricular Assist Device HeartMate II

“…In addition, bleeding events occurred even in the absence of supratherapeutic anticoagulation, 30,32 a fact also seen in our study where 82% of the patients with bleeding had an INR within the desired therapeutic range. Other factors have been implicated in the increased incidence of bleeding in CF-LVADs, including the development of acquired von Willebrand syndrome, 14,16,17,33,34 impairment in platelet aggregation, 15 and the lack of pulsatility. The potential role of the first 2 factors in the bleeding diathesis observed in patients with CF-LVADs has been investigated; however, the role of pulsatility in this setting is less clear.…”

Acquired von Willebrand Syndrome

“…Usually, AvWS is associated with complete loss of HMW vWF or decreased level thereof [19]. Owing that HMW vWF deficiency may be also observed in some patients with normal levels of vWF:RCo, vWF:Ag and vWF:CB, as well as in persons with normal vWF:RCo/ vWF:Ag and vWF:CB/vWF:Ag ratios, all subjects with suspected AvWS should be subjected to multimer analysis [9,35,39]. Although most patients with AvWS present with type 2 vWD [19], type 1 or type 3 vWD can be also detected in individuals in whom AvWS is associated with abnormal synthesis of vWF (e.g.…”

Trends, predictors and outcomes of ischemic stroke and intracranial hemorrhage in patients with a left ventricular assist device

“…Although, data regarding abnormal coagulation profile is available in the NIS database, the information about anticoagulation time in therapeutic range at the time of IS is not available and it is difficult to ascertain from this administrative database if the stroke occurred due to subtherapeutic INR or other reasons. We tested several patient factors with whom an association was seen in previous studies, such as diabetes (11,12,20), hypertension (13,20), female gender (11,21) and tobacco use (20). Our study failed to find any significant association with these factors.…”

“…The pathophysiology of increased stroke in LVAD implantation is related to the intrinsic propensity towards thrombogenicity as the LVAD foreign object encounters blood in circulation (8) and increased risk of bleeding which is expected with the use of chronic anticoagulation. Although, medications use that increases bleeding propensity is the most obvious etiology for bleeding in LVAD patients, several other mechanisms play a role in bleeding including, including the acquired Von Willebrand syndrome due to the effect of shear forces on clotting factors and platelet activation and aggregation (21).…”