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Chapter 12: Bleeding disorders 493

Factor VIII levels above 5% causes bleeding only fol- Aetiology/pathophysiology

lowing trauma or surgery, they may not present until vonWillebrand factor (vWF) is a glycoprotein that has
later life. two functions in haemostasis. vWF acts as a bridging
Sitesofbleeding include haemarthroses (bleeding into a molecule between allowing platelet aggregation and ad-
joint causing pain and restriction of movement), mus- hesion to damaged endothelium. vWF acts as a carrier
cle bleeds (often quadriceps, iliopsoas or forearm), in- protein for circulating factor VIII increasing the half-life
tracranial bleeding (presenting as headache, vomiting of factor VIII five-fold.
and lethargy), haematuria and mucosal bleeding. Type 1 (autosomal dominant) is the most common
type.It causes are reduction in the amount of vWF.
Type 2 (usually an autosomal dominant) causes func-

Complications
tional abnormalities of vWF. There are at least four
TherehasbeensignificantHIVandHepatitisCtransmit-
subtypes.
tedinfactor VIII concentrates during the 1980s, recom-
Type 3 (autosomal recessive) causes extremely re-
binant factor VIII is now the treatment of choice. About
duced or undetectable levels of vWF.
10% of patients develop antibodies to factor VIII:c mak-
ing them very difficult to treat.
Clinical features
Type 1 and 2 causes mild disease with bleeding following
Investigations injury, menorrhagia and epistaxis. Type 3 causes spon-
Activated partial thromboplastin time is raised, but taneous bleeding from early life.

correctable with 50% normal serum (ie not due to an
inhibitor of coagulation) other coagulation measures Investigations
are normal. Activated partial thromboplastin and prothrombin
Factor VIII:c assay is low, Factor VIII:vwf is normal. times are raised, but correctable with 50% normal

serum other coagulation measures are normal.
Factor VIII:vWF and VIII:c assays are low.
Management
Bleeding is treated by intravenous administration of

Management
factor VIII concentrates. Prophylaxis is the mainstay
Treatment of bleeding and prophylaxis in severe dis-
of treatment for those severely affected to prevent re-
ease uses intermediate purity factor VIII concentrates or
current haemarthroses and permanent joint damage.
VIII:vWF concentrates. 1-desamino-8-D-arginine vaso-
Patients who develop antibodies to factor VIII con-
pressin (DDAVP) releases factor VIII from endothelial
centrates may be successfully treated with recombi-
cells and is of value in mild to moderate disease.
nant factor VIIa.
1-desamino-8-D-arginine vasopressin (DDAVP) re-

leases factor VIII from endothelial cells. The response Haemophilia B
is proportional to the pre-treated factor VIII levels
Definition
and thus is useful in mild disease.
Aninheritedcoagulationdisorderresultingfromafactor
Carrier detection is possible and antenatal diagnosis

IX deficiency.
useschorionicvillussamplingorfetalbloodsampling.
Genetic counselling should be offered to patients and
Incidence
carriers.
1in 30,000.
Age
von Willebrand disease
Inherited
Definition
An inherited coagulation disorder resulting in platelet Sex
dysfunction and low levels of circulating factor VIII. X linked; males only affected.