Acquired von Willebrand Syndrome After Continuous-Flow Mechanical Device Support Contributes to a High Prevalence of Bleeding During Long-Term Support and at the Time of Transplantation

Department of Medicine, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, NY 10032, USA.
Journal of the American College of Cardiology (Impact Factor: 16.5). 10/2010; 56(15):1207-13. DOI: 10.1016/j.jacc.2010.05.016
Source: PubMed


The objective of the study was to determine the prevalence of bleeding during continuous-flow left ventricular assist device support and to identify potential mechanisms for those bleeding events.
Bleeding is frequently reported with continuous-flow left ventricular assist devices and may result from anticoagulation coupled with bleeding diathesis such as acquired von Willebrand syndrome. Accordingly, the prevalence of coagulation abnormalities including laboratory assessment for von Willebrand syndrome, bleeding events during device support, and at heart transplantation were evaluated.
A retrospective study in all HeartMate II (HM II) (Thoratec Corp., Pleasanton, California) patients who underwent implantation between April 1, 2004, and August 1, 2009, was performed. Bleeding was defined as the need for transfusion >7 days after device insertion of 1 U of packed red blood cells. Transfusion at heart transplantation was compared with that in HeartMate XVE patients.
Seventy-nine HM II devices were implanted. Anticoagulation included warfarin in 68.3%, aspirin in 55.7%, and dipyridamole in 58.2% of the patients. Of the patients, 44.3% had bleeding episodes at 112 ± 183 days after left ventricular assist device implantation, with 50% experiencing an event within 2 months. Gastrointestinal bleeding was the most frequent event. At the index event, the international normalized ratio averaged 1.67 ± 0.53, and the platelet count was 237 ± 119 × 10(9)/l. Comparison of the transfusion requirements at heart transplantation of 35 HM II patients with 62 HeartMate XVE patients demonstrated twice the transfusion requirements in HM II patients (packed red blood cells, 6.3 ± 0.8 U vs. 3.8 ± 0.5 U; platelets, 12.5 ± 5.4 U vs. 8.6 ± 6.4 U; fresh frozen plasma, 9.6 ± 4.9 U vs. 4.9 ± 3.6 U; and cryoprecipitate, 4.3 ± 3.6 U vs. 2.2 ± 3.5 U; p < 0.05 for all). High molecular weight von Willebrand factor multimers were measured in 31 HM II patients and were reduced in all patients; 18 of these 31 (58%) patients had bleeding.
Patients with the HM II had a high incidence of bleeding events during device support and at heart transplantation. All HM II patients had reduced high molecular weight von Willebrand factor multimers. The role of these abnormalities in the high incidence of bleeding deserves further investigation. Furthermore, alterations in anticoagulation should be considered during device support and before surgery in patients supported with the HM II.

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Available from: Pierre Vladimir Ennezat, Aug 14, 2014
    • "disease, vWF – von Willebrand factor, vWF:Ag – vWF antigen, vWF:RCo – vWFristocetin cofactor, FVIII:C – FVIII coagulant activity, vWF:CB – vWF collagen binding, N – normal, A – absent, ↓ – low, ↓↓↓ – very low, HMWM – high-molecular-weight multimersBoth, retrospective and prospective studies, report that LVAD implantation leads to substantial reductions in HMWM of vWF[14,15]. The triad: angiodysplasia, aVS2A, and GI bleeding (Fig. 1) share a striking resemblance with Heyde's syndrome. "
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    ABSTRACT: Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short-and longterm management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2-to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-Threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-Time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF.
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    • "Whether these bleeding events are solely a consequence of anticoagulation therapy has been questioned. LVADs expose blood to shear stress that may contribute to breakdown of von Willebrand factor (vWF) multimers, compromising platelet aggregation [5]. Several studies have shown that LVADs can alter hemostatic factors and cause acquired von Willebrand syndrome [6] analogous to the bleeding diathesis observed in aortic stenosis [7]. "
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    ABSTRACT: Background Intracranial hemorrhages associated with new generation left ventricular assist devices (LVAD) are increasingly reported as the use of these life saving devices is becoming more common, but few data are currently available to guide the acute management of these critically ill patients. Methods This is a case presentation of a 33-year-old woman status post LVAD implantation on therapeutic anticoagulation who developed acute headache followed by rapidly progressive impairment of consciousness secondary to spontaneous subarachnoid hemorrhage and hydrocephalus. Results After discontinuation of heparin infusion, the patient underwent external ventricular drain placement(EVD)and her mental status fully recovered. Her work-up was negative for aneurysmal sources of bleeding. She received daily aspirin for 7 days for antiplatelet effect during which she did not experience any thromboembolic events related to the LVAD. At day 6 the EVD was clamped for 24 hours and her neurological exam remained intact. The EVD was removed and she was restarted on heparin infusion without further complications. Conclusions Our experience suggests that in case of subarachnoid hemorrhage in patients with LVADs, temporary suspension of anticoagulation and EVD placement is safe and can lead to good neurological outcome.
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    ABSTRACT: A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether there is an optimal antithrombotic management for patients supported with axial-flow left ventricular assist devices (LVADs). Altogether, more than 758 papers were found using the reported search, of which 17 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. These included seven prospective and three retrospective cohort studies with a total of 538 patients with axial-flow left ventricular assist device (LVAD) (HeartMate II, Jarvik 2000, INCOR, Thoratec assist device) implanted across the world as destination therapy or bridge to transplantation. We conclude that there is a substantial alteration of the prothrombotic profile in patients with axial-flow LVADs. These abnormalities appeared to be reversible with the removal of the device and are likely to be responsible for the high incidence of non-surgical bleeding episodes reported. Warfarin seems to offer a lower thromboembolic risk compared with unfractioned heparin or low molecular weight heparin. There are reports that suggest that managing axial-flow LVAD without anticoagulation, after major bleeding complications, is possible but in all probability, these papers are subject to publication bias as poor outcomes are unlikely to have been reported. All patients with axial-flow LVAD, showed severely impaired platelet function at point of care tests. The use of warfarin (INR target 2.5), in association with aspirin at 100 mg/day, or with point-of-care tests titrated antiplatelet therapy to inhibit 70%, seems to have the best bleeding-thrombosis, and in many cases a very small dose of aspirin of 25 mg twice a day and a dose of clopidogrel of 35 mg/day, were sufficient to achieve a reduction of the maximum aggregation to less than 30%. Finally, we would like to emphasize that such recommendations are addressed only to patients with axial-flow LVAD.
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