Erworbenes von-Willebrand-Syndrom Typ 2A als Begleiterscheinung eines Dialyseshunts?

Summary

Acquired von Willebrand’s disease (aVWD) is considered to be an underestimated cause of unexplained bleeding. Adsorption of von Willebrand factor (VWF) to tumour cells or hydroxyethyl starch and elimination of VWF by autoantibodies as well as shear stress-induced mechanical alteration of VWF with concomitant cleavage by enzymes may lead to an acquired deficiency of VWF and a bleeding disorder.

We report a 39-year-old woman who developed spontaneous bleeding five years after surgical creation of an arteriovenous fistula (AVF) for haemodialysis treatment. AVWD type 2A was diagnosed after successful renal transplantation. One year after surgical closure of the AVF, the aVWD could not be verified again. Thus, the aVWD may have developed because of altered blood flow and shear stress inside the arteriovenous fistula.

Zusammenfassung

Das erworbene von-Willebrand-Syndrom (VWS) gilt als unterschätzte Ursache vermeintlich unerklärlicher Blutungsneigungen. Neben der Adsorption des von-Willebrand-Faktors (VWF) an Tumorzellen oder Hydroxyethylstärke sowie der Elimination von VWF durch Autoantikörper kann eine Scherkraft-induzierte mechanische Alterierung des VWF mit nachfolgender enzymatischer Spaltung zu einem erworbenen VWF-Mangel und einer entsprechenden Blutungsneigung führen.

Wir berichten über eine 39-jährige ehemals dialysepflichtige Patientin, bei der es fünf Jahre nach Anlage eines Dialyseshunts zu spontanen Blutungen kam. Die Diagnose eines erworbenen VWS Typ 2A wurde nach erfolgreicher Nierentransplantation gestellt. Ein Jahr nach operativem Shuntverschluss war das VWS nicht mehr nachweisbar. Es kann somit vermutet werden, dass das VWS durch veränderte Strömungsverhältnisse und Scherkräfte im Bereich des Dialyseshunts entstanden war.

Keywords

Acquired von Willebrand’s disease - arteriovenous fistula - bleeding - shear stress

Schlüsselwörter

Blutung - Dialyseshunt - erworbenes von-Willebrand-Syndrom - Scherkräfte

• Literatur

• 1 Allon M. Current management of vascular access. Clin J Am Soc Nephrol 2007; 02: 786-800.
• 2 Bowen DJ, Collins PW. Insights into von Willebrand factor proteolysis: clinical implications. Br J Haematol 2006; 133: 457-467.
• 3 Brescia MJ, Cimino JE, Appel K. et al. Chronic hemodialysis using venipuncture and a surgically created arteriovenous fistula. N Engl J Med 1966; 275: 1089-1092.
• 4 Brittinger WD, Twittenhoff WD. Anschlussverfahren an die künstliche Niere. Stuttgart: Thieme; 2005. 08
• 5 Brown JE, Bosak JO. An ELISA test for the binding of von Willebrand antigen to collagen. Thromb Res 1986; 43: 303-311.
• 6 Casonato A, Pontara E, Doria A. et al. Lack of multimer organization of von Willebrand factor in an acquired von Willebrand syndrome. Br J Haematol 2002; 116: 899-904.
• 7 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: 35-39.
• 8 Cuker A, Connors JM, Katz JT. et al. Bloody mystery. N Engl J Med 2009; 361: 1887-1894.
• 9 Favaloro EJ, Grispo L, Exner T. et al. Development of a simple collagen based ELISA assay aids in the diagnosis of, and permits sensitive discrimination between type I and type II, von Willebrand’s disease. Blood Coagul Fibrinolysis 1991; 02: 285-291.
• 10 Federici AB, Rand JH, Bucciarelli P. et al. Acquired von Willebrand syndrome: data from an international registry. Thromb Haemost 2000; 84: 345-349 739.
• 11 Federici AB. Acquired von Willebrand syndrome: an underdiagnosed and misdiagnosed bleeding complication in patients with lymphoproliferative and myeloproliferative disorders. Semin Hematol 2006; 43: (Suppl. 01) S48-S58.
• 12 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: 962-967.
• 13 Hepp W, Koch M, Konner K. Dialyseshunts. Grundlagen, Chirurgie, Komplikationen. Darmstadt: Steinkopff; 2009: 119-134.
• 14 Huijbregts HJT, Bots ML, Wittens CHA. et al. on behalf of the CIMINO study group. Hemodialysis Arteriovenous Fistula Patency Revisited: Results of a Prospective, Multicenter Initiative. Clin J Am Soc Nephrol 2008; 03: 714-719.
• 15 Jonville-Béra AP, Autret-Leca E, Gruet Y. Acquired type I von Willebrand’s disease associated with highly substituted hydroxyethyl starch. N Engl J Med 2001; 345: 622-623.
• 16 Macfarlane DE, Stibbe J, Kirby EP. et al. A method for assaying von Willebrand factor (ristocetin cofactor). Thromb Diath Haemorrh 1975; 34: 306-308.
• 17 Manucci PM. Treatment of von Willebrand’s disease. N Engl J Med 2004; 351: 683-694.
• 18 Mohri H. Acquired von Willebrand syndrome: features and management. Am J Hematol 2006; 81: 616-623.
• 19 Nishino M, Girma JP, Rothschild C. et al. New variant of von Willebrand disease with defective binding to factor VIII. Blood 1989; 74: 1591-1599.
• 20 Reininger AJ, Angerer J, Napoleone M. et al. High shear dependent, reversible VWF network assembly and concomitant reversible platelet aggregation. Hämostaseologie 2010; 30: A8.
• 21 Ruggeri ZM, Zimmerman TS. The complex multimeric composition of factor VIII/von Willebrand factor. Blood 1981; 57: 1140-1143.
• 22 Ruggeri ZM, Zimmerman TS. Variant von Willebrand’s disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/ von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65: 1318-1325.
• 23 Sadler JE. Aortic stenosis, von Willebrand factor, and bleeding. N Engl J Med 2003; 349: 323-325.
• 24 Sadler JE. Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 1998; 67: 395-424.
• 25 Sadler JE. A revised classification of von Willebrand disease. Thromb Haemost 1994; 71: 520-525.
• 26 Schneppenheim R, Budde U. Angeborenes und erworbenes von-Willebrand-Syndrom. Hämostaseologie 2008; 28: 312-319.
• 27 Siediecki CA, Lestini BJ, Kottke-Marchant KK. et al. Shear-dependent changes in the threedimensional structure of human von Willebrand factor. Blood 1996; 88: 2939-2950.
• 28 Tsai HM, Sussman II, Nagel RL. Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. Blood 1994; 83: 2171-2179.
• 29 Turner NA, Nolasco L, Ruggeri ZM. et al. Endothelial cell ADAMTS-13 and VWF: Production, release, and VWF string cleavage. Blood 2009; 114: 5102-5111.
• 30 Van Haren B, Wouters N, Brouwer M. et al. Correction of von Willebrand factor multimer abnormalities in severe aortic valve stenosis after percutaneous aortic valve replacement. Hämostaseologie 2010; 30: A67.
• 31 Vincentelli A, Susen S, Le Tourneau T. et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med 2003; 349: 343-349.
• 32 Weiss HJ, Hoyer LW, Rickles FR. et al. Quantitative assay of a plasma factor deficient in von Willebrand’s disease that is necessary for platelet aggregation: relationship to factor VIII procoagulant activity and antigen content. J Clin Invest 1973; 52: 2708-2716.
• 33 Zimmerman TS, Ratnoff OD, Powell AE. Immunologic differentiation of classic hemophilia (factor 8 deficiency) and von Willebrand’s disease, with observations on combined deficiencies of antihemophilic factor and proaccelerin (factor V) and on an acquired circulating anticoagulant against anti-hemophilic factor. J Clin Invest 1971; 50: 244-254.