Acquired von Willebrand disease--hemostatic management of major orthopedic surgery with high-dose immunoglobulin, desmopressin, and continuous factor concentrate infusion.
Acquired von Willebrand disease (aVWD) is a rare bleeding disorder that mimics congenital VWD in previously healthy individuals; it is most frequently associated with monoclonal gammopathy. Hemostatic therapy of aVWD is challenging due to the extremely shortened half-life of endogenous and exogenous VWF. High-dose intravenous immunoglobulin (ivIG) is recommended as the treatment of choice, usually rapidly normalizing coagulation; but in case of failure, alternative treatment options are not well explored. We report successful major orthopedic surgery in a 61-year-old woman with multiple myeloma IgG lambda and aVWD. IvIG alone failed to correct hemostasis. However, ivIG pretreatment improved the VWF ristocetin cofactor (VWF:RCo) half-life from only 1.5 hr to more than 4 hr, allowing desmopressin infusions twice daily to maintain sufficient VWF:RCo levels. Because of diminishing desmopressin effect, we attempted for the first time in aVWD a continuous VWF/FVIII infusion (Haemate HS), 2.1-2.7 FVIII U/kg/hr or 51-64 U/kg/day, respectively 4.6-6.0 VWF:RCo U/kg/hr or 110-145 U/kg/day) to reach constant factor levels. The steady-state clearance was 2.4 mL/kg/hr for FVIII:C and 13.5 mL/kg/hr for VWF:RCo. During surgery, VWF:RCo, FVIII:C, and PFA-100 closure time were normalized. Until day 5, VWF:RCo was kept above 50%, from day 6 to 10 at least 30% activity were attained. FVIII:C levels were always >70%. The clinical course was uneventful without bleeding. Two weeks after hip surgery the patient was discharged from the hospital without complaints. The therapy described can be recommended as safe and feasible for further evaluation in aVWD patients who are hyporesponsive to ivIG treatment alone. Continuous VWF/FVIII infusion can improve substitution therapy in aVWD.
Frank
Rolf Dario
RD
Department of Nephrology and Clinical Immunology, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany. dario.frank@ukaachen.de
Kunz
Dagmar
D
Wirtz
Dieter Christian
DC
D019644:Arthroplasty, Replacement, Hip; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005169:Factor VIII / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006487:Hemostasis; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D008875:Middle Aged; D016896:Treatment Outcome; D014842:von Willebrand Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D014841:von Willebrand Factor / Q000008:administration & dosage* / Q000627:therapeutic use
D004338:Drug Combinations; D006490:Hemostatics; D016756:Immunoglobulins, Intravenous; D014841:von Willebrand Factor; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin