1. By
Ahmed Riyadh Abdul Rahman
Al-Noor University College
Disorders of haemostasis II:
inherited disorders of
coagulation
2. Inherited disorders of coagulation
Excessive bleeding may occur as a result of an
inherited defect of one or other protein involved in
coagulation. Inherited deficiency of each of the
coagulation factors has been described.
Factor VIII deficiency (haemophilia A)
Haemophilia A is the most common inherited
coagulation disorder. The factor VIII gene is on the X
chromosome so inheritance is sex-linked with the
severe disease occurring in males (Fig.1).
3.
4. Clinical features
These range from severe spontaneous bleeding,
especially into joints (haemarthroses) and muscles, to
mild symptoms, depending on the factor VIII level.
Onset in early childhood (e.g. post-circumcision).
Increased risk of post-operative or post-traumatic
haemorrhage.
Chronic debilitating joint disease caused by repeated
bleeds.
5. Laboratory features (Table 1)
o Prolonged activated partial thromboplastin time
(APTT), normal prothrombin time (PT), normal PFA-
100 test.
o Plasma factor VIII is reduced (<1% of normal in severe
cases, 1–5% in moderate cases and 5–40% in mild
cases.
o Carriers have factor VIII levels in plasma
approximately 50% of normal.
o Von Willebrand factor (vWF) level is normal.
6. Complications of treatment
HIV and hepatitis C from impure preparations
(prior to the early 1980s), subsequent AIDS,
hepatitis and cirrhosis.
Neutralizing antibodies to factor VIII in 15% of
severe patients may require immunosuppressive
therapy, treatment with porcine factor VIII, or
plasma exchange.
7. Factor IX deficiency (haemophilia B, Christmas
disease)
Haemophilia B has similar clinical features to
haemophilia A. Also sex-linked, it is four times less
common (the gene is four times smaller) and usually
milder than haemophilia A. Diagnosis is similar to
haemophilia A.
8. Von Willebrand disease (VWD)
Von Willebrand disease is usually autosomal dominant
and results from mutations in the vWF gene.
VWF is a large multimeric protein produced by
endothelial cells.
VWF carries factor VIII in plasma and mediates
platelet adhesion to endothelium.
Clinical features
• The disease is more frequent than haemophilia A;
males and females are affected equally.
• Bleeding, typically from mucous membranes
(mouth, epistaxes, menorrhagia).
• Excess blood loss following trauma or surgery.
• Haemarthroses and muscle bleeding are rare.
9. Diagnosis
• APTT is prolonged (or might be normal), PT normal.
• Factor VIII and vWF levels are reduced.
• PFA-100 is prolonged.
• Defective platelet function, reduced aggregation with
ristocetin.
• Mild thrombocytopenia may occur.
• The disease is divided into subtypes depending on
whether there is a reduction in vWF or different
types of functional defect.
10. Other conditions
• Factor XI deficiency is less frequent than
haemophilia A (higher incidence among Ashkenazi
Jews) and is autosomal recessive. It is generally
mild, but severe spontaneous and post-surgical
bleeding may occur.
• Congenital deficiencies of factors II, V, VII, X and
XIII are rare and usually cause mild bleeding
disorders.
• Factor XII deficiency prolongs the APTT but does
not cause clinical symptoms.
• Fibrinogen deficiency occurs as a moderately severe
autosomal recessive disorder. Dysfibrinogenaemia
(presence of a functionally abnormal molecule) is
both a rare
