Abstract

Introduction: Acquired von Willebrand Disease (AVWD) is a rare bleeding disorder occurring in patients with haematological malignancies, solid tumours, immunological and cardiovascular disorders and monoclonal gammopathy of undetermined significance (MGUS). Several pathogenetic mechanisms have been proposed to explain acquired von Willebrand factor (VWF) defect including autoantibodies. Muco-cutaneous bleeding and laboratory findings are similar to those of the congenital VWD. Several approaches have been attempted to correct haemostatic abnormalities with the aim to control bleeding diathesis or to prevent bleeding during surgery. Desmopressin, plasma-derived FVIII/VWF concentrates, intravenous high dose immunoglobulin (HDIg) are the most commonly used. The efficacy of therapy is not predictable and has to be tested before surgery or invasive procedures. In several cases more than one therapeutic option is required. Case report. The patient was a 64-years-old woman with IgGλ-MGUS. Because of persistent uterine bleeding a neoplasia was suspected. The pre-operative coagulative screening showed a prolonged aPTT with markedly reduced levels of FVIII and VWF-related activities (Table 1). VWF multimeric analysis evidenced loss of high and intermediate molecular weight multimers. Patient’s personal and familial history was negative for bleeding and VWF level was normal in other family members. Desmopressin administration (s.c.0.3 μg/kg) obtained a rapid but transient correction of plasma VWF-related parameters, with a return to baseline levels within 6 hours. HDIg intravenous infusion (1 g/kg/day for two consecutive days) led to stable normalization of VWF:RCo, VWF:Ag and FVIII for at least 7 days (Table 1). A laparoscopic hystero-annessiectomy was performed after two-day HDIg infusion: no bleeding complications were observed in the peri-operative period. Histological diagnosis was endometrial hyperplasia. During the two-months follow-up no haemorrhagic episodes were reported.

Comments: In AVWD the correction of laboratory abnormalities is crucial to prevent bleeding in patient undergoing high haemorrhagic risk surgery. The choice among therapeutic options is empirical and depends on underlying disease and clinical setting. The efficacy has to be verified. In our patient HDIg infusion obtained a sustained normalisation of VWF-related parameters and prevented bleeding during surgery and in the post-operative period.

Table 1.

Patient’s laboratory parameters before and after treatment with HDIg

VWF-related parametersReference interval
basal+1*+5*+7*
*days after HDIg infusion 
aPTT (R) 1.73 1.21 1.21 1.27 <1.19 
VWF:RCo (U/dL) <8 59 56 50 46-118 
VWF:Ag (U/dL) 11 66 91 85 43-145 
FVIII (U/dL) 14 96 85 96 51-164 
VWF-related parametersReference interval
basal+1*+5*+7*
*days after HDIg infusion 
aPTT (R) 1.73 1.21 1.21 1.27 <1.19 
VWF:RCo (U/dL) <8 59 56 50 46-118 
VWF:Ag (U/dL) 11 66 91 85 43-145 
FVIII (U/dL) 14 96 85 96 51-164 

Author notes

Disclosure: No relevant conflicts of interest to declare.