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Journal of Thrombosis and Thrombolysis
Published in: Journal of Thrombosis and Thrombolysis 1/2019

01-07-2019 | Thrombosis

Acquired Von Willebrand Syndrome (AVWS) in cardiovascular disease: a state of the art review for clinicians

Authors: Radha Mehta, Muhammad Athar, Sameh Girgis, Atif Hassan, Richard C. Becker

Published in: Journal of Thrombosis and Thrombolysis | Issue 1/2019

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Abstract

Von Willebrand Factor (vWF) is a large glycoprotein with a broad range of physiological and pathological functions in health and disease. While vWF is critical for normal hemostasis, vascular integrity and repair, quantitative and qualitative abnormalities in the molecule can predispose to serious bleeding and thrombosis. The heritable form of von Willebrand Disease was first described nearly a century ago, but more recently, recognition of an acquired condition known as acquired von Willebrand Syndrome (AVWF) has emerged in persons with hematological, endocrine and cardiovascular diseases, disorders and conditions. An in-depth understanding of the causes, diagnostic approach and management of AVWS is important for practicing clinicians.
Literature
1.
2.
Ruggeri ZM (2000) Role of von Willebrand factor in platelet thrombus formation. Ann Med 32(Suppl 1):2–9PubMed
3.
Huisman B et al (2017) Modeling the cleavage of von Willebrand factor by ADAMTS13 protease in shear flow. Med Eng Phys 48:14–22PubMedCrossRef
4.
5.
6.
Favaloro EJ, Pasalic L, Curnow J (2016) Type 2 M and Type 2A von Willebrand disease: similar but Different. Semin Thromb Hemost 42(5):483–497PubMedCrossRef
7.
Xu ER, Blythe EE (2017) Structural analyses of von Willebrand factor C domains of collagen 2A and CCN3 reveal an alternative mode of binding to bone morphogenetic protein-2. J Biol Chem 292(30):12516–12527PubMedPubMedCentralCrossRef
8.
9.
Lynch CJ, Lane DA, Luken BM (2014) Control of VWF A2 domain stability and ADAMTS13 access to the scissile bond of full-length VWF. Blood 123(16):2585–2592PubMedPubMedCentralCrossRef
10.
11.
12.
Dayananda KM et al (2010) von Willebrand factor self-association on platelet GpIbalpha under hydrodynamic shear: effect on shear-induced platelet activation. Blood 116(19):3990–3998PubMedPubMedCentralCrossRef
13.
Rack K, Huck V (2017) Margination and stretching of von Willebrand factor in the blood stream enable adhesion. 7(1):14278
14.
Coenen DM, Mastenbroek TG (2017) Cosemans, J, Platelet interaction with activated endothelium: mechanistic insights from microfluidics. Blood. 130(26):2819–2828PubMedCrossRef
15.
Meyer D et al (2001) Type 2 von Willebrand disease causing defective von Willebrand factor-dependent platelet function. Best Pract Res Clin Haematol 14(2):349–364PubMedCrossRef
16.
Sutherland JJ et al (2004) Molecular modeling of the von Willebrand factor A2 Domain and the effects of associated type 2A von Willebrand disease mutations. J Mol Model 10(4):259–270PubMedCrossRef
17.
Dong JF et al (2003) ADAMTS-13 metalloprotease interacts with the endothelial cell-derived ultra-large von Willebrand factor. J Biol Chem 278(32):29633–29639PubMedCrossRef
18.
Brown SA et al (2003) Increased clearance of von Willebrand factor antigen post-DDAVP in Type 1 von Willebrand disease: is it a potential pathogenic process? J Thromb Haemost 1(8):1714–1717PubMedCrossRef
19.
Sztukowska M et al (2008) Von Willebrand factor propeptide makes it easy to identify the shorter Von Willebrand factor survival in patients with type 1 and type Vicenza von Willebrand disease. Br J Haematol 143(1):107–114PubMedCrossRef
20.
Gallinaro L et al (2008) A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor. Blood 111(7):3540–3545PubMedCrossRef
21.
Gill JC et al (1987) The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 69(6):1691–1695PubMed
22.
van Schooten CJ et al (2008) Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo. Blood 112(5):1704–1712PubMedCrossRef
23.
Casari C et al (2013) Accelerated uptake of VWF/platelet complexes in macrophages contributes to VWD type 2B-associated thrombocytopenia. Blood 122(16):2893–2902PubMedCrossRef
24.
25.
26.
Christodoulides N et al (2001) Glycoprotein Ib/IX/V binding to the membrane skeleton maintains shear-induced platelet aggregation. Thromb Res 102(2):133–142PubMedCrossRef
27.
Jy W et al (2005) Endothelial microparticles induce formation of platelet aggregates via a von Willebrand factor/ristocetin dependent pathway, rendering them resistant to dissociation. J Thromb Haemost 3(6):1301–1308PubMedCrossRef
28.
Yuan, Y., et al., Calpain regulation of cytoskeletal signaling complexes in von Willebrand factor-stimulated platelets. Distinct roles for glycoprotein Ib-V-IX and glycoprotein IIb-IIIa (integrin alphaIIbbeta3) in von Willebrand factor-induced signal transduction. J Biol Chem, 1997. 272(35): p. 21847-54
29.
30.
Zimmerman TS, Ratnoff OD, Powell AE (1971) Immunologic differentiation of classic hemophilia (factor 8 deficiency) and von Willebrand’s dissase, with observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and on an acquired circulating anticoagulant against antihemophilic factor. J Clin Invest 50(1):244–254PubMedPubMedCentralCrossRef
31.
Boender, J., et al., Clinically relevant differences between assays for von Willebrand factor activity. J Thromb Haemost, 2018
32.
Just S (2017) Laboratory Testing for von Willebrand Disease: the Past, Present, and Future State of Play for von Willebrand Factor Assays that Measure Platelet Binding Activity, with or without Ristocetin. Semin Thromb Hemost 43(1):75–91PubMed
33.
Nichols WL et al (2008) von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia 14(2):171–232PubMedCrossRef
34.
35.
Favaloro EJ et al (2018) Differential sensitivity of von Willebrand factor activity assays to reduced VWF molecular weight forms: a large international cross-laboratory study. Thromb Res 166:96–105PubMedCrossRef
36.
37.
Deconinck S et al (2018) Differences in von Willebrand factor function in type 2A von Willebrand disease and left ventricular assist device-induced acquired von Willebrand syndrome. Res Pract Thromb Haemost 2(4):762–766PubMedPubMedCentralCrossRef
38.
Waldow HC et al (2014) Acquired von Willebrand syndrome in adult patients with congenital heart disease. Int J Cardiol 176(3):739–745PubMedCrossRef
39.
40.
Massyn, M.W. and S.A. Khan, Heyde syndrome: a common diagnosis in older patients with severe aortic stenosis. Age Ageing, 2009. 38(3): p. 267-70; discussion 251
41.
Warkentin TE, Moore JC (2010) Heyde’s syndrome: from controversy to mainstream. Thromb Haemost 103(2):251–253PubMedCrossRef
42.
Vincentelli A et al (2003) Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 349(4):343–349PubMedCrossRef
43.
Ibrahim H, Rondina MT, Kleiman NS (2018) Von Willebrand factor and the aortic valve: concepts that are important in the transcatheter aortic valve replacement era. Thromb Res 170:20–27PubMedCrossRef
44.
Van Belle E et al (2016) Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement. N Engl J Med 375(4):335–344PubMedCrossRef
45.
Froom P et al (1988) Von Willebrand factor and mitral valve prolapse. Thromb Haemost 60(2):230–231PubMedCrossRef
46.
Blackshear JL et al (2011) Hypertrophic obstructive cardiomyopathy, bleeding history, and acquired von Willebrand syndrome: response to septal myectomy. Mayo Clin Proc 86(3):219–224PubMedPubMedCentralCrossRef
47.
Onimoe G et al (2011) Acquired von Willebrand Syndrome in congenital heart disease: does it promote an increased bleeding risk? Br J Haematol 155(5):622–624PubMedCrossRef
48.
Federici AB et al (2013) Current diagnostic and therapeutic approaches to patients with acquired von Willebrand syndrome: a 2013 update. Semin Thromb Hemost 39(2):191–201PubMedCrossRef
49.
Bongers TN et al (2006) High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability. Stroke 37(11):2672–2677PubMedCrossRef
50.
Pedrazzini G et al (2016) Acquired intracoronary ADAMTS13 deficiency and VWF retention at sites of critical coronary stenosis in patients with STEMI. Blood 127(23):2934–2936PubMedCrossRef
51.
Jacquemin M, Peerlinck K (2015) Free hemoglobin: a boost to platelet thrombi. Blood 126(20):2262–2263PubMedCrossRef
52.
Muslem R, Caliskan K, Leebeek FWG (2018) Acquired coagulopathy in patients with left ventricular assist devices. J Thromb Haemost 16(3):429–440PubMedCrossRef
53.
Da Q et al (2014) Platelet adhesion involves a novel interaction between vimentin and von Willebrand factor under high shear stress. Blood 123(17):2715–2721PubMedPubMedCentralCrossRef
54.
Selvam SN et al (2017) Abnormal angiogenesis in blood outgrowth endothelial cells derived from von Willebrand disease patients. Blood Coagul Fibrinolysis 28(7):521–533PubMedPubMedCentralCrossRef
55.
Bartoli CR et al (2018) Clinical and In Vitro Evidence That Left Ventricular Assist Device-Induced von Willebrand Factor Degradation Alters Angiogenesis. Circ Heart Fail 11(9):e004638PubMedCrossRef
56.
Starling RC et al (2014) Unexpected abrupt increase in left ventricular assist device thrombosis. N Engl J Med 370(1):33–40PubMedCrossRef
57.
Zhou Z et al (2009) Haemoglobin blocks von Willebrand factor proteolysis by ADAMTS-13: a mechanism associated with sickle cell disease. Thromb Haemost 101(6):1070–1077PubMedCrossRef
58.
Arkebauer MR et al (2011) Carbon monoxide and nitric oxide modulate alpha(2)-antiplasmin and plasmin activity: role of heme. Blood Coagul Fibrinolysis 22(8):712–719PubMedCrossRef
59.
Meyer AL et al (2014) Acquired von Willebrand syndrome in patients with a centrifugal or axial continuous flow left ventricular assist device. JACC Heart Fail 2(2):141–145PubMedCrossRef
60.
Shankaran H, Neelamegham S (2004) Hydrodynamic forces applied on intercellular bonds, soluble molecules, and cell-surface receptors. Biophys J 86(1 Pt 1):576–588PubMedPubMedCentralCrossRef
61.
62.
Letsou GV et al (2005) Gastrointestinal bleeding from arteriovenous malformations in patients supported by the Jarvik 2000 axial-flow left ventricular assist device. J Heart Lung Transplant 24(1):105–109PubMedCrossRef
63.
Uriel N et al (2014) Device thrombosis in HeartMate II continuous-flow left ventricular assist devices: a multifactorial phenomenon. J Heart Lung Transplant 33(1):51–59PubMedCrossRef
64.
Vincent F et al (2018) Arterial Pulsatility and Circulating von Willebrand Factor in Patients on Mechanical Circulatory Support. J Am Coll Cardiol 71(19):2106–2118PubMedCrossRef
65.
Brehm MA et al (2014) von Willebrand disease type 2A phenotypes IIC, IID and IIE: a day in the life of shear-stressed mutant von Willebrand factor. Thromb Haemost 112(1):96–108PubMed
66.
Keesler DA, Flood VH (2018) Current issues in diagnosis and treatment of von Willebrand disease. Research and Practice in Thrombosis and Haemostasis 2(1):34–41PubMedCrossRef
67.
Draper K et al (2015) Thalidomide for treatment of gastrointestinal angiodysplasia in patients with left ventricular assist devices: case series and treatment protocol. J Heart Lung Transplant 34(1):132–134PubMedCrossRef
68.
Borel-Derlon A et al (2007) Treatment of severe von Willebrand disease with a high-purity von Willebrand factor concentrate (Wilfactin): a prospective study of 50 patients. J Thromb Haemost 5(6):1115–1124PubMedCrossRef
69.
Grosman-Rimon L et al (2018) The Physiological Rationale for Incorporating Pulsatility in Continuous-Flow Left Ventricular Assist Devices. Cardiol Rev 26(6):294–301PubMed
70.
Edwards AL et al (2018) Association of Pulsatility with Gastrointestinal Bleeding in a Cohort of HeartMate II Recipients. ASAIO J 64(4):472–479PubMedCrossRef
71.
Halder LC et al (2017) Time in Therapeutic Range for Left Ventricular Assist Device Patients Anticoagulated With Warfarin: a Correlation to Clinical Outcomes. ASAIO J 63(1):37–40PubMedCrossRef
72.
Molina TL et al (2018) Gastrointestinal Bleeding in Left Ventricular Assist Device: octreotide and Other Treatment Modalities. ASAIO J 64(4):433–439PubMedCrossRef
73.
Hollis IB et al (2017) Inhaled Desmopressin for Refractory Gastrointestinal Bleeding in a Patient With a HeartMate II Left Ventricular Assist Device. ASAIO J 63(4):e47–e49PubMedCrossRef
74.
Goudemand J et al (2005) Pharmacokinetic studies on Wilfactin, a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods. J Thromb Haemost 3(10):2219–2227PubMedCrossRef
75.
Tsai HM et al (1997) Proteolytic cleavage of recombinant type 2A von Willebrand factor mutants R834 W and R834Q: inhibition by doxycycline and by monoclonal antibody VP-1. Blood 89(6):1954–1962PubMed
76.
Rauch A et al (2014) Antibody-based prevention of von Willebrand factor degradation mediated by circulatory assist devices. Thromb Haemost 112(5):1014–1023PubMedCrossRef
77.
Lenting PJ, Christophe OD, Denis CV (2015) von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends. Blood 25(13):2019–2028CrossRef
Metadata
Title
Acquired Von Willebrand Syndrome (AVWS) in cardiovascular disease: a state of the art review for clinicians
Authors
Radha Mehta
Muhammad Athar
Sameh Girgis
Atif Hassan
Richard C. Becker
Publication date
01-07-2019
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 1/2019
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-019-01849-2

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