Most severe hereditary coagulation disorder. It is
caused by defective synthesis of plasma protein factor VIII.
Classical Hemophilia; F-VIII Deficiency.
1:5000-10,000 live male births; 30% of cases are the
result of new mutations.
X-linked recessive with expression in male
children only. Gene locus is Xq28.
Defective factor VIII gene produces low levels of
functional factor VIII. Factor VIII is required in the intrinsic coagulation
cascade and, when activated and in the presence of factor XIa, leads to
activation of factor X. Affected patients are classified as mild, moderate,
or severe. Mildly afflicted patients have factor VIII levels 6 to 30% of
normal activity and experience hemorrhage secondary to trauma or surgery, but rarely
spontaneously. Patients moderately afflicted have factor VIII levels of 1 to
5% of normal activity and experience hemorrhage secondary to trauma or surgery
with occasional spontaneous hemarthroses. Severely afflicted patients have
less than 1% of normal factor VIII activity and experience frequent
spontaneous hemorrhages from early infancy requiring replacement therapy.
Although carriers usually have 50% normal activity and experience no
bleeding difficulties, levels should be obtained, as those with less than
50% activity can experience significant hemorrhage after trauma.
Elevation of the partial thromboplastin time with normal
prothrombin time and normal bleeding time. Diagnosis is established by
dosage of factor VIII antigen and factor VIII serum factor activity.
Prenatal and carrier detection are possible with restriction fragment length
polymorphism DNA analysis but are contingent upon parental analysis.
Soft tissue hematomas, including
retroperitoneal/pharyngeal hemarthroses (75%), most often of the same
target joint, pseudotumor of bone, with rare erosion into viscera,
hematuria, intracranial hemorrhage, cord compression secondary to epidural
bleeding, nerve compression secondary to hematoma, mucous membrane
hemorrhage (epistaxis, hemoptysis), peptic ulcer disease, and excessive
Hematology and anesthesiology
consultation are highly recommended before elective surgical procedures. Schedule procedures early in the week to avoid weekend
pharmaceutical delays. Ensure supply of virally inactivated or recombinant
factor VIII concentrate, which does not have the infectious risks of
fresh-frozen plasma or cryoprecipitate. Dose calculations are based on the
following formula: 1 unit factor VIII /kg increases factor VIII activity by 2%. Half-life is 8 to 12 hours. Consider desmopressin
acetate (DDAVP 0.3 μg/kg) in mild-to-moderate disease because it
increases factor VIII levels up to threefold by an unknown mechanism.
Consider antifibrinolytic therapy (ε-aminocaproic acid [EACA]
or tranexamic acid), as these agents may be useful adjuvants for mucosal and
dental bleeding although they are contraindicated with hematuria. Raise
factor VIII to normal levels before major surgical procedures.
In conjunction with a hematologist
consultation, maintain factor VIII levels postoperatively because factor
replacement may be required for 7 to 10 days, with twice-daily factor VIII
assays. Avoid regional anesthesia and intramuscular (IM) injections.
Avoid aspirin and NSAIDs.
Hemophilia B: Hereditary coagulation disorder caused by defective
synthesis of plasma ...