Management Strategies of Stroke and Acute Coronary Syndrome In Von Willebrand Disease and Hemophilia: Experience From a Case Series and a Swiss Survey of Frequencies.

Thrombolysis and combined antiplatelet therapy is considered contraindicated in patients (pts) with bleeding disorders such as von Willebrand disease (VWD) and hemophilia (HP) presenting with stroke or acute coronary syndrome (ACS). Conservative treatment e.g. of stroke is often unsatisfactory in pts within the time window for thrombolysis. As stroke and ACS are common disorders, they may coincide with prevalent bleeding disorders such as VWD and HP and increase in frequency due to growing life expectancy in VWD and HP. An emergency protocol for safe management is desirable.

We report on the management of 5 Caucasians with known VWD or HP suffering from stroke or ACS. In addition we screened the Swiss population of VWD and HP patients over 10y for the occurrence of stroke or ACS based on the data of the Swiss Federal Statistical Office.

Pt 1 is a 54-y-old Swiss female suffering from mild VWD 1 with a relevant bleeding history and characteristic VWF multimers (Tab 1). She presented with acute stroke with right hemiparesis (NIHSS 9) 2h after onset. CT scan excluded intracranial bleeding. Substitution of VWF/FVIII concentrate aiming at 80% of VWF activity resulted in 55% VWF ristocetin cofactor activity (RCo) and 76% VWF antigen (Ag). Concomitant thrombolysis with full-dose rtPA was performed. After 24h NIHSS improved to 6, RCo was 45%, Ag 63% and no signs of bleeding occurred. Secondary prophylaxis with aspirin was started. She fully recovered after 3 months.

Pt 2, a 68-y-old Finnish female with VWD 2A presented with a minor stroke with mild left hemiparesis and a fall (NIHSS 2) 2h after onset. CT scan was normal and she was treated with dipyridamole. Symptoms regressed to NIHSS 0 after 6h.

Pt 3 to 5 had ACS. Pt 3, a 73-y-old Swiss male with hemophilia B was successfully treated for unstable angina by percutaneous coronary intervention (PCI) with stenting at a subtotal stenosis of the RCA after substitution of FIX to 65%. Postinterventionally he was on clopidogrel for 2y and then switched to aspirin. Concomitant weekly substitution of FIX led to FIX peaks of ≂f55% and nadir of ≂f15%, was then reduced in frequency and stopped after 15 months. No bleeding complications occurred.

Pt 4, a 67-y-old Finnish female with symptomatic VWD 3 presented with a NSTEMI and was successfully treated without PCI or platelet inhibition.

Pt 5, a 70-y-old Finnish male with symptomatic VWD 2A suffered from ACS and had angiography with substitution of VWF/FVIII concentrate to 40–134% RCo and 134–252% Ag. Aortocoronary bypass surgery was planned due to 3-vessel disease. No antiplatelet therapy was started.

The analysis of the Swiss Federal Statistical Office revealed 39 cases of VWD or HP with stroke or ACS over 10y (1998-2008) in the Swiss population of 7.70 millions (2008). A lower mean age at death in pts with VWD and HP (63 y) as compared to the normal population (77y), underreporting in the early years and a potential protective effect may contribute to reduced numbers. 19 pts with VWD showed 13 events of stroke and 6 of ACS while 20 hemophiliacs had 8 events of stroke and 12 of ACS.

Our survey confirms the occurrence of stroke and ACS in pts with VWD and HP. Observed treatment strategies are very heterogeneous. Intravascular mechanical intervention such as PCI appears advantageous in pts with VWD and HP. If intravascular therapy is not timely available or not possible, we suggest substitution to ≂f80% VWF immediately followed by full-dose thrombolysis as described in pt 1. Repetitive substitution of VWF on a 12–24h basis or infusion over 48h may be adequate in severe deficiencies (Blood 2009;114:5256). A FIX level of 25% may suffice for safe PCI in hemophilia B given the clinical experience with oral anticoagulation. Generally, treatment strategies for stroke and ACS in pts with VWD and HP should be individually tailored and balanced between thrombotic and bleeding risk.

No relevant conflicts of interest to declare.