High Molecular Weight von Willebrand Factor Multimer Loss and Bleeding in Patients with Short-Term Mechanical Circulatory Support Devices: A Case Series.

Acquired von Willebrand syndrome (VWS) due to loss of high-molecular-weight multimers (HMWMs) has been reported with longer term mechanical devices and is associated with mucosal bleeding, a primary hemostasis type of bleeding. However, little is known whether a similar defect occurs in patients with short-term mechanical circulatory support (STMCS) devices. We reviewed von Willebrand factor (VWF) profiles in patients with STMCS devices who underwent VWS workup from December 2015 to March 2017 at an academic quaternary care hospital. There were a total of 18 patients (57.0 ± 12.7 years old; 83.3% male) including nine with mucosal bleeding and nine with decreasing hemoglobin. The STMCS devices included Impella (n = 11), Impella and right ventricular assist device (n = 2), and an extracorporeal membrane oxygenator (n = 5). The mean HMWM by quantitative VWF multimer analysis was 3.6% ± 1.3% (normal cutoff: 18-34%). In all 10 cases in which VWF activity, fibrinogen, factor VIII, or VWF antigen level were obtained, they were either normal or elevated. All cases demonstrated high normal or elevated levels of low molecular weight multimers (LMWMs). These findings are consistent with type 2 VWS (qualitative defect). This is the first study that quantitatively describes STMCS device-associated HMWM loss, which may contribute to mucosal bleeding. This finding may have implications for intraoperative management during implantation of longer term devices or heart transplantation or other surgery while on STMCS.

[1]  J. Bauersachs,et al.  Acquired von Willebrand syndrome in cardiogenic shock patients on mechanical circulatory microaxial pump support , 2017, PloS one.

[2]  D. Ramzy,et al.  Comparative analysis of von Willebrand factor profiles after implantation of left ventricular assist device and total artificial heart , 2017, Journal of thrombosis and haemostasis : JTH.

[3]  Jessica L. Howard,et al.  Left Ventricular Assist Device Design Reduces von Willebrand Factor Degradation: A Comparative Study Between the HeartMate II and the EVAHEART Left Ventricular Assist System. , 2017, The Annals of thoracic surgery.

[4]  M. Mehra,et al.  Evaluation of von Willebrand factor with a fully magnetically levitated centrifugal continuous-flow left ventricular assist device in advanced heart failure. , 2016, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[5]  J. Moake,et al.  Acquired von Willebrand syndrome associated with left ventricular assist device. , 2016, Blood.

[6]  Robert L Kormos,et al.  Seventh INTERMACS annual report: 15,000 patients and counting. , 2015, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[7]  M. Acker,et al.  Inhibition of ADAMTS-13 by Doxycycline Reduces von Willebrand Factor Degradation During Supraphysiological Shear Stress: Therapeutic Implications for Left Ventricular Assist Device-Associated Bleeding. , 2015, JACC. Heart failure.

[8]  E. Belle,et al.  Circulatory support devices: fundamental aspects and clinical management of bleeding and thrombosis , 2015, Journal of thrombosis and haemostasis : JTH.

[9]  B. Zieger,et al.  Early diagnosis of acquired von Willebrand Syndrome (AVWS) is elementary for clinical practice in patients treated with ECMO therapy. , 2015, Journal of atherosclerosis and thrombosis.

[10]  M. Stark,et al.  Shear stress‐associated acquired von Willebrand syndrome in patients with mitral regurgitation , 2014, Journal of thrombosis and haemostasis : JTH.

[11]  Ranjit John,et al.  Gastrointestinal bleed after left ventricular assist device implantation: incidence, management, and prevention. , 2014, Annals of cardiothoracic surgery.

[12]  M. Keebler,et al.  Development of acquired von Willebrand syndrome during short-term micro axial pump support: implications for bleeding in a patient bridged to a long-term continuous-flow left ventricular assist device. , 2014, ASAIO journal.

[13]  C. Bara,et al.  Acquired von Willebrand syndrome in patients with a centrifugal or axial continuous flow left ventricular assist device. , 2014, JACC. Heart failure.

[14]  X. Zheng Structure–function and regulation of ADAMTS‐13 protease , 2013, Journal of thrombosis and haemostasis : JTH.

[15]  H. Tsai von Willebrand Factor, Shear Stress, and ADAMTS13 in Hemostasis and Thrombosis , 2012, ASAIO journal.

[16]  N. Uriel,et al.  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. , 2010, Journal of the American College of Cardiology.

[17]  Dong Chen,et al.  Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients. , 2010, The Annals of thoracic surgery.

[18]  C. Schlensak,et al.  Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart , 2010, Thrombosis and Haemostasis.

[19]  L. Nielsen,et al.  Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II). , 2009, Journal of the American College of Cardiology.

[20]  Christoph Benk,et al.  Non-surgical bleeding in patients with ventricular assist devices could be explained by acquired von Willebrand disease. , 2008, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[21]  P. Mannucci,et al.  Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor , 2006, Journal of thrombosis and haemostasis : JTH.

[22]  J. Webb,et al.  Heyde's syndrome: a review. , 2004, The Journal of heart valve disease.

[23]  J. Shults,et al.  Prevalence of von Willebrand disease in children: a multiethnic study. , 1993, The Journal of pediatrics.

[24]  F Rodeghiero,et al.  Epidemiological investigation of the prevalence of von Willebrand's disease. , 1987, Blood.

[25]  H. Schima,et al.  Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent. , 2016, Thrombosis research.

[26]  Ulrich Budde,et al.  Ambient hemolysis and activation of coagulation is different between HeartMate II and HeartWare left ventricular assist devices. , 2014, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[27]  M. Shimizu,et al.  Occult gastrointestinal bleeding due to acquired von Willebrand syndrome in a patient with hypertrophic obstructive cardiomyopathy. , 2007, Internal medicine.