Hemostatic Outcomes of Hip and Knee Joint Replacement Surgery in Von Willebrand Disease (VWD) Patients: A Single Center Study

Abstract ²²⁷⁹

Surgery for patients with von Willebrand disease (VWD) is increasingly common, however there is a paucity of data on hemostatic outcomes for VWD patients undergoing joint replacement surgery when compared to patients without bleeding disorders. The aim of this study was to evaluate hemostatic prophylaxis and outcomes in VWD patients who underwent hip or knee joint replacement, with comparison to matched case control patients. Methods: We retrospectively reviewed medical records of VWD patients who underwent total hip (THA) or total knee (TKA) arthroplasty between February 1993 and January 2011 at Mayo Clinic Rochester. Outcomes for each VWD patient were compared with two case controls matched for age, gender, surgeon and surgery. For VWD patients the hemostatic prophylaxis regimen during and following surgical procedures was evaluated including results of serial monitoring of plasma levels of VWF:RCo, VWF:Ag and FVIII:C. We compared VWD and control cases for bleeding complications (major and minor), transfusion requirements, DVT (deep vein thrombosis) prophylaxis and occurrence, duration of hospitalization, and other complications. Results: Twelve VWD patients (7 female) underwent 12 TKA and 7 THA surgeries; the median age was 62 (range 42–76) years. Seven had Type 1 VWD, one had Type 3 and four had Types 2A, 2B or 2M VWD. The 19 surgical episodes were matched to 38 control surgeries. Indications for arthroplasties were mainly degenerative joint disease in both subject groups. The median BMI was 30 (range 21–45) in the VWD patients and 31.9 (20–53) in controls. Three patients with mild Type 1 VWD received during 5 surgeries only one preoperative dose of DDAVP (desmopressin 0.3μg/kg body weight). Infusions of VWF/FVIII concentrates (Humate-P or occasionally Koate-DVI) were prescribed for twelve procedures, with median preoperative dose 52 IU/kg (range 19–71). Postoperative maintenance doses were infused once or twice daily usually for up to 7 days (more than 7 days only for one Type 3 and one Type 2A VWD patient), with median ranges 22 to 38 IU/kg, and highest dose 90 IU/kg and lowest dose 11 IU/kg (typically when treatment was administrated twice daily). These substantial ranges may be explained by dose adjustments based on monitoring postoperative plasma levels of VWF:RCo and FVIII:C. The median number of infusions per procedure was 5.5 (range 1–13). One hour after the preoperative dose the median of all factors was more than 110 IU/dL, specifically VWF:RCo 154 UI/dL (range 72–277), VWF:Ag 178 IU/dL (range 101–307), and FVIII:C 114 IU/dL (range 64–290). The lowest factor levels measured during daily postoperative follow-up are represented in Figure 1. Assessment of red blood cell transfusion requirements showed no difference between baseline and D1 blood hemoglobin levels for VWD and control groups (decline of 3.0 g/dL). During follow-up, hemoglobin levels and total blood losses were also not different between both groups. However, the number of patients transfused was twice as high for the VWD group (63% vs 32% for controls, respectively), and the mean number of RBC units transfused was higher in VWD patients than in controls (1.5 vs. 0.6 units, respectively). DVT prophylaxis (low molecular weight heparin (LMWH) injections or warfarin), was administrated to 58% of VWD patients vs. 97% of controls. No postoperative thrombotic events were identified in either group. Finally, the median duration of hospitalization for VWD patients and controls was not different: 5 days (range 3–13) and 5 days (range 3–7) respectively. Conclusions: Few data are available in published literature analyzing treatment regimens and hemostatic outcomes for patients with VWD undergoing THA or TKA, a relatively common treatment for advanced degenerative joint disease. This is the first large retrospective study which reports the effectiveness of prophylactic regimens specifically in joint replacement for patients with VWD. Our results support that, as recommended in the 2008 NHLBI/NIH treatment guidelines, monitoring of plasma VWF and FVIII levels at least once daily allows for efficient and relatively low dose maintenance administration. Further, our study helps identify an adequate duration of treatment for these major surgeries, without substantively increased blood loss for VWD patients compared with controls.