Haemophilia

A 31-year-old male with known haemophilia A presents with a fracture of his left

tibia sustained while playing football. The orthopaedic surgeons propose operative

application of an external fixation frame. The patient is unable to grade the severity of

his haemophilia but has had two knee haemarthroses in the previous seven years. As

part of the preoperative preparation of this patient, which one of the following should

be administered intravenously?

a) Fresh frozen plasma

b) Cryoprecipitate

c) Recombinant factor VIII concentrate

d) Recombinant factor IX concentrate

e) Desmopressin

Answer: c

Explanation

Haemophilia A is an X-linked recessive inherited coagulation disorder resulting in a

congenital deficiency or absence of clotting factor VIII. One in 5000 males are affected,

but the extent to which factor VIII plasma concentration is reduced dictates the severity

of clinical manifestation. One in 100 000 females are symptomatic carriers with a

demonstrable mild-to-moderate bleeding tendency; however, the functional gene on

the unaffected X chromosome in females makes severe bleeding diathesis very rare.

Factor VIII is involved in the intrinsic coagulation pathway, so activated partial

thromboplastin time is prolonged. Diagnosis is made by demonstrating reduced

plasma factor VIII concentrations. Unaffected individuals will have a plasma factor

VIII concentration of 0.5 to 1.5 units/mL (termed 50 to 150% activity). Mild haemophiliacs

have 4 to 50% activity, moderate have 1 to 4%, and severe haemophiliacs have

<1% of normal factor VIII activity. Patients with greater than 10 to 15% activity tend

to be asymptomatic. Spontaneous bleeding is unlikely at levels greater than 5%.

Haemorrhagic manifestations include haemarthroses, soft tissue haematomas and

intracranial haemorrhages. Platelets, vasculature, extrinsic pathway and final common

pathway are not affected, thus bleeding time, platelet count and prothrombin time will

be normal. Significant haemarthroses indicate at least moderate disease and the

planned surgery may well involve reasonable blood loss. The preoperative objective

would be to raise plasma factor VIII concentration to 1 unit/mL (100%) with factor VIII

concentrate, before proceeding. This is a recombinant engineered product that avoids

the infective risks of blood component therapy that were previously associated with

haemophilia. Cryoprecipitate would be a second-line alternative; it is sometimes used

prior to dental procedures in moderate haemophiliacs. Desmopressin can be used to

prevent bleeding complications in mild haemophiliacs.