Perioperative substitution therapy with plasma-derived factor VIII concentrate in patients with von Willebrand disease

Abstract

Von Willebrand (vW) disease is a common hemorrhagic disorder characterized by various clinical manifestations and a variety of bleeding symptoms. By classification 3 types of vW disease are described concerning synthesis and multimeric constitution of vW factor. Especially the type 3 disorder is often complicated by perioperative hemorrhages. vW factor may be released from endothelial depots due to hormonal regulation or stress. Therefore, patients (pts) with vW disease type 1 or 2 may suffer from haemorrhagic complications after major surgery even if preoperative coagulation tests had found to be normal. Especially in pts with combined plasmatic disorders as coagulation factor (F) V or F XI deficiency bleeding may start once more after initial haemostasis. Until now, recombinant vW factor is not available. There are no clear dosage regimens of plasma derived FVIII concentrate. Substitution therapy with plasmatic F VIII / vW factor concentrates usually has to be adjusted to plasma concentrations of vW ristocetin cofactor. We report 5 pts with vW disease type 1 and 1 patient type 2 and history of bleeding disorders who received F VIII / vW factor concentrate (Immunate) meanwhile surgery. In 2 pts there was evidence of additional F XI or F V deficiency. After initial bolus administration (80 – 120 IU / kg body weight) we started continuous infusion (3.4 – 9.8 IU / kg body weight) for 48 h. The initial dose of continuous infusion was reduced to 50% after 24 h and to 25% after 36 h, respectively. In type 1 pts we saw a 3.4-fold increase in collagen binding activity and 1.9-fold increase in plasma concentration of vW ristocetin cofactor, respectively. Clinical effectiveneness of substitution therapy was good. We conclude that continuous infusion of F VIII/vW Factor concentrate (Immunate) may provide sufficient haemostasis in pts with vW disease. Increase in collagen binding activity has been shown to correspond well to substitution. Further data are necessary to prove whether collagen binding activity rather than plasma concentration of vW ristocetin cofactor could be a more relevant parameter concerning dosage administration.