Quantification of perioperative changes in von Willebrand factor and factor VIII during elective orthopaedic surgery in normal individuals

Abstract

Summary von Willebrand’s disease (VWD) patients undergoing major surgery are prophylactically treated to promote haemostasis. There is variability in perioperative clinical practice; however, most guidelines suggest replacing the deficient factor to a level of 1.0 IU mL−1 (or 100%). A review of the literature reveals a paucity of well constructed descriptive data quantifying the changes in coagulation that occur in response to surgical stress. The aim of this study was to quantify the changes in haemostatic variables occurring in response to elective orthopaedic surgery in normal individuals. Eligible subjects >18 years of age undergoing total hip or knee replacement were recruited. Blood samples were drawn at five time points: baseline, preoperatively, 30 min after surgical incision, 30 min postoperatively, postoperative day (POD) 1. Analyses included t-tests and repeated measures anova. Overall 30 patients, 21 women and 9 men, with a mean age of 65 were included in the final analysis. All von Willebrand factor (VWF) variables were seen to significantly decrease intraoperatively and increase postoperatively. VWF multimers showed a statistically significant decrease in high molecular weight multimers intraoperatively and an increase postoperatively. On subgroup analysis, age, gender and anaesthesia type were significantly correlated with changes in VWF parameters. Data presented in the current study establish a physiological baseline for VWF parameters in the normal population and demonstrate mean VWF/factor VIII levels greater than 1.0 IU mL−1 intraoperatively. As such, current management in VWD patients does not appear to mimic the normal physiological response to surgery.

Analysis of current perioperative management with Haemate® P/Humate P® in von Willebrand disease: Identifying the need for personalized treatment

“…In our study, 8% of trough levels of FVIII were above 2.70 IU mL. Also, observed postoperative VWF:Act and FVIII levels were increased for only a brief period of time and coincide with physiological levels in healthy individuals without a bleeding disorder . Mannucci et al.…”

“…Increasing FVIII levels, due to concomitant increase in both endogenous and exogenous FVIII, were significantly higher than VWF:Act levels ( P < .01). This may be partly explained by findings by Kahlon et al . who observed an intraoperative decrease and postoperative increase in VWF and FVIII levels in 30 individuals without a bleeding disorder undergoing surgery.…”

A population pharmacokinetic model for perioperative dosing of factor VIII in hemophilia A patients

“…43,44 In addition, it has been shown that, in healthy individuals undergoing orthopedic surgery, VWF decreases significantly intraoperatively and rises immediately after surgery. 39 Therefore, we suspected a time-dependent FVIII clearance in the presented PK model, with an increased clearance during the surgical procedure itself and a decrease in clearance directly after surgery. However, no time-dependent clearance could be established.…”

“…36,37 We hypothesized that an extra intravascular component resulting in a large V2 may be the result of the high affinity and stoichiometry of FVIII to VWF, 38 combined with the significant increase of VWF after surgery due to inflicted endothelial damage and its role in the acute phase reaction. 39 In addition, Deitcher et al have shown that volume of distribution increases after desmopressin administration, which, of course, results in an overall increase in VWF levels. 40 Moreover, we believe that VWF may play a crucial role in the perioperative setting with regard to FVIII PK parameters, as previous studies have demonstrated a clear association between VWF plasma concentrations and FVIII halflife.…”

Pharmacokinetic-guided dosing of factor VIII concentrate in a patient with haemophilia during renal transplantation

“…Most probably this under prediction is caused by high postsurgical VWF levels due to inflicted endothelial damage due to the intensity of the surgical procedure. VWF prolongs FVIII presence in the circulation, due to the decrease in clearance by protection from proteolysis, resulting in higher FVIII plasma concentrations 4 10 11. In the ongoing prospective randomised controlled ‘OPTI-CLOT’ trial, which is described in more detail elsewhere,12 we hope to gain more insight into the relationship between VWF levels and PK parameter estimates.…”