Von Willebrand's Disease Flashcards
Von Willebrand’s Disease
Von Willebrand’s disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare
*type 3 von Willebrand’s disease (most severe form) is inherited as an autosomal recessive trait. Around 80% of patients have type 1 disease
Role of von Willebrand factor
large glycoprotein which forms massive multimers up to 1,000,000 Da in size
promotes platelet adhesion to damaged endothelium
carrier molecule for factor VIII
Types
type 1: partial reduction in vWF (80% of patients)
type 2: abnormal form of vWF
type 3: total lack of vWF (autosomal recessive)
Investigation
prolonged bleeding time
APTT may be prolonged
factor VIII levels may be moderately reduced
defective platelet aggregation with ristocetin
Management
tranexamic acid for mild bleeding
desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells
factor VIII concentrate
Von Willebrand’s Disease - Example Question
A 21-year-old girl complains of easy bruising. She has menorrhagia for which she is being investigated by the gynaecology team. She takes no regular medications. Her father had prolonged bleeding after a tooth extraction.
Blood tests show:
Hb 110 g/L MCV 74 fL WBC 4.2 x 10^9/L Platelets 135 x 10^9/L APTT 1.4 INR 1.0
What is the most likely diagnosis?
Haemophilia B Anti-thrombin III deficiency > Von Willebrand's disease Immune thrombocytopenia Haemophilia A carrier
Von-Willebrand’s disease is an autosomal dominant condition (chromosome 12) that leads to a mild-moderate bleeding tendency. The prevalence of clinically significant cases is 1 in 10,000. Factor VIII is bound to vWF, which protects it from breakdown, so deficiency of vWF can lead to low factor VIII levels and a prolonged APTT. In this case the patient also has a microcytic anaemia, which would be in keeping with iron deficiency anaemia secondary to menorrhagia. Haemophilia B (Factor IX deficiency) is X-linked so does not affect females. Haemophilia A (Factor VIII deficiency) is also X-linked. Most carriers are asymptomatic. The APTT is normal in ITP. Anti thrombin III deficiency is a pro thrombotic condition.
Von Willebrands vs Haemophilia A: Example Question
A 19-year-old man is referred to see you as he has been suffering from recurrent epistaxis and he tells you that if he accidentally injures himself the wound bleeds for a long time.
Initial blood tests are as follows:
Hb 101 g/l MCV 79 fl Platelets 298 * 109/l WBC 9.2 * 109/l Bleeding time Prolonged PT 14 seconds APTT 28 seconds LDH 290 u/l (240 - 480 u/L) Factor VIIIc low Ristocetin platelet aggregation test Impaired aggregation
What is the single most likely diagnosis?
Haemophilia A Haemophilia B Haemophilia C Idiopathic Thrombocytopenic Purpura (ITP) > von Willebrand's disease
This patient has a coagulopathy and normal platelets, which immediately excludes ITP. Factor VIIIc is low, meaning that the diagnosis must either be haemophilia A or von Willebrand’s disease. In this patient two things favour the diagnosis of von Willebrand’s over haemophilia A. Firstly, the bleeding time is prolonged and secondly, the platelet aggregation is impaired in response to ristocetin. Both of these would be normal in haemophilia.
Von Willebrands Disease
Von-Willebrand’s disease is an autosomal dominant condition (chromosome 12) that leads to a mild-moderate bleeding tendency. The prevalence of clinically significant cases is 1 in 10,000. Factor VIII is bound to vWF, which protects it from breakdown, so deficiency of vWF can lead to low factor VIII levels and a prolonged APTT.
Von Willebrands vs Haemophilia A
von Willebrands = autosomal dominant
Haemophilia A = X-linked - only boys get it
Both have reduced Factor VIIIc levels
von Willebrands = prolonged bleeding time, the platelet aggregation is impaired in response to ristocetin
Haemophilia A - BLEEDING TIME IS NORMAL
