Question 8.2

a)  What is the most likely diagnosis?
Von Willebrand’s disease

b)  What would you confirm your diagnosis
•    History – easy bruising, mucosal bleeding
•    Family history
•    Plasma vWF levels
•    Factor VIII levels /activity

Discussion

There is only one situation in which one might have essentially normal APTT, but an elevated bleeding time. The APTT test would be slightly elevated because Factor 8 relies on vWF activity, and in the absence of vWF one is effectively Factor 8-deficient. The PT would be normal.

Pathophysiology

• Most common inherited bleeding disorder (autosomal dominant)
• Prevalence is about 1–2%
• Only one in every ten cases have clinically relevant disease
• Caused by the deficiency or abnormality of VWF.
• VWF is required for platelet adhesion to the subendothelium
• VWF also serves as carrier of Factor VIII, protecting it from Protein C mediated inactivation (hence in VWD Factor VIII levels are low, or effectively low).

There are three main types of VWD:

• Type 1: incomplete absence of VWF; mild symptoms (most common)
• Type 2: presence of dysfunctional VWF; mild symptoms
• Type 3: virtually complete absence of VWF; severe symptoms. 

Investigations of suspected Von Willebrand disease

History and examination

• Beyond looking for ecchymoses and acute bleeding, the examination has nothing specific to offer.
• Similarly, "history of bleeding" is very nonspecific. Many people may complain of excessive bleeding, and most would not have VWF. History is unreliable, and the use of standardised bleeding history questionnaires is recommended to compute some sort of objective "bleeding risk". People with a high bleeding risk should go on to be tested biochemically.
• Severity of bleeding usually correlates with Factor VIII level.
• Type 1 usually has epistaxis and mucosal haemorrhages, bleeding after dental work, etc
• Type 3 may have haemarthrosis and deep haematomas similar to haemophilia.

Blood biochemistry and coags

• Von Willebrand Factor level
• Factor VIII level
• Ristocetin co-factor activity (VWF:RCo)
• von Willebrand factor collagen binding (VWF:CB)

Management

• DDAVP
• Replacement therapy (concentrated VWF and Factor VIII)
• In an acutely bleeding patient, platelet transfusion and tranexamic acid are indicated.