Download PDF
Thorac Cardiovasc Surg 2020; 68(03): 200-211
DOI: 10.1055/s-0038-1673670
Review
Georg Thieme Verlag KG Stuttgart · New York

Diagnosis and Management of Acquired von Willebrand Disease in Heart Disease: A Review of the Literature

Mate Petricevic   ∗
1   Department of Cardiac Surgery, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia
,
Jadranka Knezevic   ∗
2   Department of Transfusion Medicine, University Hospital Center Mostar, Mostar, Bosnia and Herzegovina
,
Gordan Samoukovic
3   Divisions of Cardiac Surgery and Critical Care, Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
,
Bozena Bradaric
4   Merkur University Hospital, Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Disease, Zagreb, Croatia
,
Ivica Safradin
1   Department of Cardiac Surgery, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia
,
Marija Mestrovic
1   Department of Cardiac Surgery, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia
,
Vasil Papestiev
1   Department of Cardiac Surgery, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia
,
Alen Hodalin
1   Department of Cardiac Surgery, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia
,
Tomislav Madzar
5   University of Osijek School of Medicine, Osijek, Croatia
,
Mario Mihalj
6   Department of Neurology, University of Split School of Medicine, University Hospital Center Split, Split, Croatia
,
Ante Rotim
5   University of Osijek School of Medicine, Osijek, Croatia
,
Bojan Biocina
1   Department of Cardiac Surgery, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, Croatia
› Author Affiliations
Further Information

Publication History

29 April 2018

05 September 2018

Publication Date:
20 November 2018 (online)

   Buy Article Permissions and Reprints All articles of this category

Abstract

The incidence of acquired von Willebrand syndrome (AvWS) in patients with heart disease is commonly perceived as rare. However, its occurrence is underestimated and underdiagnosed, potentially leading to inadequate treatment resulting in increased morbidity and mortality.

In patients with cardiac disease, AvWS frequently occurs in patients with structural heart disease and in those undergoing mechanical circulatory support (MCS).

The clinical manifestation of an AvWS is usually characterized by apparent or occult gastrointestinal (GI) or mucocutaneous hemorrhage frequently accompanied by signs of anemia and/or increased bleeding during surgical procedures. The primary change is loss of high-molecular weight von Willebrand factor multimers (HMWM). Whereas the loss of HMWM in patients with structural heart disease is caused by increased HMWM cleavage by von Willebrand factor (vWF)-cleaving protease, ADAMTS13, AvWS in MCS patients is predominantly a result of a high shear stress coupled with mechanical destruction of vWF itself.

This manuscript provides a comprehensive review of the evidence regarding both diagnosis and contemporary management of AVWS in patients with heart disease.

Keywords

cardiac - cardiopulmonary bypass - CPB - hematology - surgery - complications - vascular science

∗ Both authors contributed equally to this work.


 

  • References

  • 1 Dixon B, Santamaria JD, Reid D. , et al. The association of blood transfusion with mortality after cardiac surgery: cause or confounding? (CME). Transfusion 2013; 53 (01) 19-27
    CrossrefPubMedGoogle Scholar
  • 2 Despotis G, Avidan M, Eby C. Prediction and management of bleeding in cardiac surgery. J Thromb Haemost 2009; 7 (Suppl. 01) 111-117
    PubMedGoogle Scholar
  • 3 Smilowitz NR, Gupta N, Guo Y, Bangalore S, Berger JS. Perioperative bleeding and thrombotic risks in patients with Von Willebrand disease. J Thromb Thrombolysis 2017; 44 (01) 67-70
    CrossrefPubMedGoogle Scholar
  • 4 Natorska J, Mazur P, Undas A. Increased bleeding risk in patients with aortic valvular stenosis: From new mechanisms to new therapies. Thromb Res 2016; 139: 85-89
    CrossrefPubMedGoogle Scholar
  • 5 Stockschlaeder M, Schneppenheim R, Budde U. Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis. Blood Coagul Fibrinolysis 2014; 25 (03) 206-216
    CrossrefPubMedGoogle Scholar
  • 6 Gadisseur A, Hermans C, Berneman Z, Schroyens W, Deckmyn H, Michiels JJ. Laboratory diagnosis and molecular classification of von Willebrand disease. Acta Haematol 2009; 121 (2-3): 71-84
    CrossrefPubMedGoogle Scholar
  • 7 Dassanayaka S, Slaughter MS, Bartoli CR. Mechanistic pathway(s) of acquired von willebrand syndrome with a continuous-flow ventricular assist device: in vitro findings. ASAIO J 2013; 59 (02) 123-129
    CrossrefPubMedGoogle Scholar
  • 8 Tiede A, Rand JH, Budde U, Ganser A, Federici AB. How I treat the acquired von Willebrand syndrome. Blood 2011; 117 (25) 6777-6785
    CrossrefPubMedGoogle Scholar
  • 9 Federici AB, Rand JH, Bucciarelli P. , et al; Subcommittee on von Willebrand Factor. Acquired von Willebrand syndrome: data from an international registry. Thromb Haemost 2000; 84 (02) 345-349
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Federici AB. Acquired von Willebrand syndrome: is it an extremely rare disorder or do we see only the tip of the iceberg?. J Thromb Haemost 2008; 6 (04) 565-568
    CrossrefPubMedGoogle Scholar
  • 11 Tiede A, Priesack J, Werwitzke S. , et al. Diagnostic workup of patients with acquired von Willebrand syndrome: a retrospective single-centre cohort study. J Thromb Haemost 2008; 6 (04) 569-576
    CrossrefPubMedGoogle Scholar
  • 12 Kumar SPR, Nichols WL. Estimation of prevalence and natural history of acquired von Willebrand disease. Haemophilia 2000; 6: 213
    PubMedGoogle Scholar
  • 13 Simone JV, Cornet JA, Abildgaard CF. Acquired von Willebrand's syndrome in systemic lupus erythematosus. Blood 1968; 31 (06) 806-812
    CrossrefPubMedGoogle Scholar
  • 14 Budde U, Bergmann F, Michiels JJ. Acquired von Willebrand syndrome: experience from 2 years in a single laboratory compared with data from the literature and an international registry. Semin Thromb Hemost 2002; 28 (02) 227-238
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Budde U, Pieconka A, Will K, Schneppenheim R. Laboratory testing for von Willebrand disease: contribution of multimer analysis to diagnosis and classification. Semin Thromb Hemost 2006; 32 (05) 514-521
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Sadler JE, Budde U, Eikenboom JC. , et al; Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 4 (10) 2103-2114
    CrossrefPubMedGoogle Scholar
  • 17 Heilmann C, Geisen U, Beyersdorf F. , et al. Acquired Von Willebrand syndrome is an early-onset problem in ventricular assist device patients. Eur J Cardiothorac Surg 2011; 40 (06) 1328-1333 , discussion 1233
    PubMedGoogle Scholar
  • 18 Sucker C, Feindt P, Zotz RB, Stockschlaeder M, Scharf RE. Functional von Willebrand Factor assays are not predictive for the absence of highest-molecular weight von Willebrand Factor multimers in patients with aortic-valve stenosis. Thromb Haemost 2005; 94 (02) 465-466
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Mohri H. Acquired von Willebrand syndrome: features and management. Am J Hematol 2006; 81 (08) 616-623
    CrossrefPubMedGoogle Scholar
  • 20 Geisen U, Heilmann C, Beyersdorf F. , et al. Non-surgical bleeding in patients with ventricular assist devices could be explained by acquired von Willebrand disease. Eur J Cardiothorac Surg 2008; 33 (04) 679-684
    CrossrefPubMedGoogle Scholar
  • 21 Stone ME, Mazzeffi M, Derham J, Korshin A. Current management of von Willebrand disease and von Willebrand syndrome. Curr Opin Anaesthesiol 2014; 27 (03) 353-358
    CrossrefPubMedGoogle Scholar
  • 22 Fressinaud E, Veyradier A, Truchaud F. , et al. Screening for von Willebrand disease with a new analyzer using high shear stress: a study of 60 cases. Blood 1998; 91 (04) 1325-1331
    CrossrefPubMedGoogle Scholar
  • 23 Cattaneo M, Federici AB, Lecchi A. , et al. Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease. Thromb Haemost 1999; 82 (01) 35-39
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Quiroga T, Goycoolea M, Muñoz B. , et al. Template bleeding time and PFA-100 have low sensitivity to screen patients with hereditary mucocutaneous hemorrhages: comparative study in 148 patients. J Thromb Haemost 2004; 2 (06) 892-898
    CrossrefPubMedGoogle Scholar
  • 25 Würtz M, Hvas AM, Wulff LN, Kristensen SD, Grove EL. Shear-induced platelet aggregation in aspirin-treated patients: initial experience with the novel PlaCor PRT device. Thromb Res 2012; 130 (05) 753-758
    CrossrefPubMedGoogle Scholar
  • 26 Valarche V, Desconclois C, Boutekedjiret T, Dreyfus M, Proulle V. Multiplate whole blood impedance aggregometry: a new tool for von Willebrand disease. J Thromb Haemost 2011; 9 (08) 1645-1647
    CrossrefPubMedGoogle Scholar
  • 27 Blackshear JL, Wysokinska EM, Safford RE. , et al. Shear stress-associated acquired von Willebrand syndrome in patients with mitral regurgitation. J Thromb Haemost 2014; 12 (12) 1966-1974
    CrossrefPubMedGoogle Scholar
  • 28 Pickering NJ, Brody JI, Barrett MJ. von Willebrand syndromes and mitral-valve prolapse; linked mesenchymal dysplasias. N Engl J Med 1981; 305 (03) 131-134
    CrossrefPubMedGoogle Scholar
  • 29 Yoshida K, Tobe S, Kawata M, Yamaguchi M. Acquired and reversible von Willebrand disease with high shear stress aortic valve stenosis. Ann Thorac Surg 2006; 81 (02) 490-494
    CrossrefPubMedGoogle Scholar
  • 30 Massyn MW, Khan SA. Heyde syndrome: a common diagnosis in older patients with severe aortic stenosis. Age Ageing 2009; 38 (03) 267-270 , discussion 251
    PubMedGoogle Scholar
  • 31 ED H. Gastrointestinal bleeding in aortic stenosis. N Eng J Med 1958; 196
    PubMedGoogle Scholar
  • 32 Ledingham D. Heyde's syndrome: exploring the link between aortic stenosis and an acquired bleeding disorder. BMJ Case Rep 2013; 2013
    PubMedGoogle Scholar
  • 33 Blackshear JL, Schaff HV, Ommen SR, Chen D, Nichols WL. Hypertrophic obstructive cardiomyopathy, bleeding history, and acquired von Willebrand syndrome: response to septal myectomy. Mayo Clin Proc 2011; 86 (03) 219-224
    CrossrefPubMedGoogle Scholar
  • 34 Schödel J, Obergfell A, Maass AH. Severe aortic valve stenosis and nosebleed. Int J Cardiol 2007; 120 (02) 286-287
    CrossrefPubMedGoogle Scholar
  • 35 Kapila A, Chhabra L, Khanna A. Valvular aortic stenosis causing angiodysplasia and acquired von Willebrand's disease: Heyde's syndrome. BMJ Case Rep 2014; 2014
    PubMedGoogle Scholar
  • 36 Tsuji A, Tanabe M, Onishi K. , et al. Intravascular hemolysis in aortic stenosis. Intern Med 2004; 43 (10) 935-938
    CrossrefPubMedGoogle Scholar
  • 37 Vincentelli A, Susen S, Le Tourneau T. , et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 2003; 349 (04) 343-349
    CrossrefPubMedGoogle Scholar
  • 38 Blackshear JL, Wysokinska EM, Safford RE. , et al. Indexes of von Willebrand factor as biomarkers of aortic stenosis severity (from the Biomarkers of Aortic Stenosis Severity [BASS] study). Am J Cardiol 2013; 111 (03) 374-381
    CrossrefPubMedGoogle Scholar
  • 39 Le Tourneau T, Susen S, Caron C. , et al. Functional impairment of von Willebrand factor in hypertrophic cardiomyopathy: relation to rest and exercise obstruction. Circulation 2008; 118 (15) 1550-1557
    CrossrefPubMedGoogle Scholar
  • 40 Bailly DK, Boshkov LK, Zubair MM. , et al. Congenital cardiac lesions involving systolic flow abnormalities are associated with platelet dysfunction in children. Ann Thorac Surg 2014; 98 (04) 1419-1424
    CrossrefPubMedGoogle Scholar
  • 41 Loeffelbein F, Funk D, Nakamura L. , et al. Shear-stress induced acquired von Willebrand syndrome in children with congenital heart disease. Interact Cardiovasc Thorac Surg 2014; 19 (06) 926-932
    CrossrefPubMedGoogle Scholar
  • 42 Arslan MT, Ozyurek R, Kavakli K. , et al. Frequency of acquired von Willebrand's disease in children with congenital heart disease. Acta Cardiol 2007; 62 (04) 403-408
    CrossrefPubMedGoogle Scholar
  • 43 Tatebe S, Kanazawa H, Yamazaki Y, Aoki E, Sakurai Y, Miyamura H. Closure of a ventricular septal defect in a patient with von Willebrand disease. Surg Today 1997; 27 (07) 661-663
    CrossrefPubMedGoogle Scholar
  • 44 Gill JC, Wilson AD, Endres-Brooks J, Montgomery RR. Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects. Blood 1986; 67 (03) 758-761
    CrossrefPubMedGoogle Scholar
  • 45 Onimoe G, Grooms L, Perdue K, Ruymann F. Acquired von Willebrand Syndrome in congenital heart disease: does it promote an increased bleeding risk?. Br J Haematol 2011; 155 (05) 622-624
    CrossrefPubMedGoogle Scholar
  • 46 Zubair MM, Hohimer AR, Bailly DK. , et al. High flow velocity through congenital cardiac lesions predicts preoperative platelet dysfunction. Ann Thorac Surg 2015; 99 (04) 1379-1385
    CrossrefPubMedGoogle Scholar
  • 47 Suarez J, Patel CB, Felker GM, Becker R, Hernandez AF, Rogers JG. Mechanisms of bleeding and approach to patients with axial-flow left ventricular assist devices. Circ Heart Fail 2011; 4 (06) 779-784
    CrossrefPubMedGoogle Scholar
  • 48 Slaughter MS, Rogers JG, Milano CA. , et al; HeartMate II Investigators. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med 2009; 361 (23) 2241-2251
    CrossrefPubMedGoogle Scholar
  • 49 Crow S, John R, Boyle A. , et al. Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices. J Thorac Cardiovasc Surg 2009; 137 (01) 208-215
    CrossrefPubMedGoogle Scholar
  • 50 Genovese EA, Dew MA, Teuteberg JJ. , et al. Incidence and patterns of adverse event onset during the first 60 days after ventricular assist device implantation. Ann Thorac Surg 2009; 88 (04) 1162-1170
    CrossrefPubMedGoogle Scholar
  • 51 Pal JD, Piacentino V, Cuevas AD. , et al. Impact of left ventricular assist device bridging on posttransplant outcomes. Ann Thorac Surg 2009; 88 (05) 1457-1461 , discussion 1461
    CrossrefPubMedGoogle Scholar
  • 52 Uriel N, Pak SW, Jorde UP. , 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. J Am Coll Cardiol 2010; 56 (15) 1207-1213
    CrossrefPubMedGoogle Scholar
  • 53 Heilmann C, Geisen U, Beyersdorf F. , et al. Acquired von Willebrand syndrome in patients with ventricular assist device or total artificial heart. Thromb Haemost 2010; 103 (05) 962-967
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Steinlechner B, Dworschak M, Birkenberg B. , et al. Platelet dysfunction in outpatients with left ventricular assist devices. Ann Thorac Surg 2009; 87 (01) 131-137
    CrossrefPubMedGoogle Scholar
  • 55 Klovaite J, Gustafsson F, Mortensen SA, Sander K, Nielsen LB. Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II). J Am Coll Cardiol 2009; 53 (23) 2162-2167
    CrossrefPubMedGoogle Scholar
  • 56 Bartoli CR, Dassanayaka S, Brittian KR. , et al. Insights into the mechanism(s) of von Willebrand factor degradation during mechanical circulatory support. J Thorac Cardiovasc Surg 2014; 147 (05) 1634-1643
    CrossrefPubMedGoogle Scholar
  • 57 Crow S, Chen D, Milano C. , et al. Acquired von Willebrand syndrome in continuous-flow ventricular assist device recipients. Ann Thorac Surg 2010; 90 (04) 1263-1269 , discussion 1269
    CrossrefPubMedGoogle Scholar
  • 58 Crow S, Milano C, Joyce L. , et al. Comparative analysis of von Willebrand factor profiles in pulsatile and continuous left ventricular assist device recipients. ASAIO J 2010; 56 (05) 441-445
    CrossrefPubMedGoogle Scholar
  • 59 Davis ME, Haglund NA, Tricarico NM, Matafonov A, Gailani D, Maltais S. Immediate recovery of acquired von Willebrand syndrome after left ventricular assist device explantation: implications for heart transplantation. ASAIO J 2015; 61 (01) e1-e4
    CrossrefPubMedGoogle Scholar
  • 60 Goda M, Jacobs S, Rega F. , et al. Time course of acquired von Willebrand disease associated with two types of continuous-flow left ventricular assist devices: HeartMate II and CircuLite Synergy Pocket Micro-pump. J Heart Lung Transplant 2013; 32 (05) 539-545
    CrossrefPubMedGoogle Scholar
  • 61 Rastan AJ, Dege A, Mohr M. , et al. Early and late outcomes of 517 consecutive adult patients treated with extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. J Thorac Cardiovasc Surg 2010; 139 (02) 302-311 , 311.e1
    CrossrefPubMedGoogle Scholar
  • 62 Wang J, Han J, Jia Y. , et al. Early and intermediate results of rescue extracorporeal membrane oxygenation in adult cardiogenic shock. Ann Thorac Surg 2009; 88 (06) 1897-1903
    CrossrefPubMedGoogle Scholar
  • 63 Heilmann C, Geisen U, Beyersdorf F. , et al. Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS). Intensive Care Med 2012; 38 (01) 62-68
    CrossrefPubMedGoogle Scholar
  • 64 Henne S, Denzer U, Seitz U, Göttsche J, Soehendra N, Lohse A. [Recurrent gastrointestinal bleeding and aortic valve stenosis (Heyde syndrome): need for valve replacement?]. Z Gastroenterol 2007; 45 (03) 245-249
    Article in Thieme ConnectPubMedGoogle Scholar
  • 65 Pate GE, Mulligan A. An epidemiological study of Heyde's syndrome: an association between aortic stenosis and gastrointestinal bleeding. J Heart Valve Dis 2004; 13 (05) 713-716
    PubMedGoogle Scholar
  • 66 Love JW. The syndrome of calcific aortic stenosis and gastrointestinal bleeding: resolution following aortic valve replacement. J Thorac Cardiovasc Surg 1982; 83 (05) 779-783
    CrossrefPubMedGoogle Scholar
  • 67 King RM, Pluth JR, Giuliani ER. The association of unexplained gastrointestinal bleeding with calcific aortic stenosis. Ann Thorac Surg 1987; 44 (05) 514-516
    CrossrefPubMedGoogle Scholar
  • 68 Saad RA, Lwaleed BA, Kazmi RS. Gastrointestinal bleeding and aortic stenosis (Heyde syndrome): the role of aortic valve replacement. J Card Surg 2013; 28 (04) 414-416
    CrossrefPubMedGoogle Scholar
  • 69 Riis Hansen P, Hassager C. Septal alcohol ablation and Heyde's syndrome revisited. J Intern Med 2003; 253 (04) 490-491
    CrossrefPubMedGoogle Scholar
  • 70 Pate GE, Chandavimol M, Naiman SC, Webb JG. Heyde's syndrome: a review. J Heart Valve Dis 2004; 13 (05) 701-712
    PubMedGoogle Scholar
  • 71 Franchini M, Veneri D, Lippi G. The use of recombinant activated factor VII in congenital and acquired von Willebrand disease. Blood Coagul Fibrinolysis 2006; 17 (08) 615-619
    CrossrefPubMedGoogle Scholar
  • 72 Schwartz J, Rozenfeld V, Habot B. Cessation of recurrent bleeding from gastrointestinal angiodysplasia, after beta blocker treatment in a patient with hypertrophic subaortic stenosis--a case history. Angiology 1992; 43 (3 Pt 1): 244-248
    CrossrefPubMedGoogle Scholar
  • 73 Shimizu M, Masai H, Miwa Y. Occult gastrointestinal bleeding due to acquired von Willebrand syndrome in a patient with hypertrophic obstructive cardiomyopathy. Intern Med 2007; 46 (08) 481-485
    CrossrefPubMedGoogle Scholar
  • 74 John R, Kamdar F, Liao K. , et al. Low thromboembolic risk for patients with the Heartmate II left ventricular assist device. J Thorac Cardiovasc Surg 2008; 136 (05) 1318-1323
    CrossrefPubMedGoogle Scholar
  • 75 Pereira NL, Chen D, Kushwaha SS, Park SJ. Discontinuation of antithrombotic therapy for a year or more in patients with continuous-flow left ventricular assist devices. Interact Cardiovasc Thorac Surg 2010; 11 (04) 503-505
    CrossrefPubMedGoogle Scholar