Chapter 82: Inherited Deficiencies of Coagulation Factors II, V, VII, X, XI, and XIII and Combined Deficiencies of Factor V and VIII and of Vitamin K–Dependent Factors

INTRODUCTION

• Inherited deficiencies of coagulation factors other than factor VIII (hemophilia A) and factor IX (hemophilia B) are rare bleeding disorders that occur in most populations.

• Patients are usually homozygotes or compound heterozygotes.

• Factor XI and factor VII deficiency are rare but occur relatively frequently compared to other factor deficiencies (apart from hemophilia A and B), whereas the other deficiencies are very rare (Table 82–1).

• The severity of the bleeding disorder usually relates to the severity of the factor deficiency.

• All may be caused by decreased synthesis of a specific coagulation factor, by synthesis of a dysfunctional form of the coagulation factor, or both.

• Inherited deficiency of a coagulation factor does not protect patients from thrombosis.

• Rare bleeding disorders are often caused by mutations unique for each kindred and scattered throughout the genes.

• The molecular diagnosis is based on the mutation search in the genes encoding the corresponding coagulation factor (Table 82–2).

PROTHROMBIN (FACTOR II) DEFICIENCY

Pathogenesis

• Hypoprothrombinemia or dysprothrombinemia may be involved.

• Both are inherited as autosomal recessive disorders.

• Both interfere with hemostasis by impairing thrombin generation.

Clinical Features

• The disorders are characterized by mucocutaneous and soft-tissue bleeding, usually in proportion to the severity of the functional prothrombin deficiency.

• Bleeding may be spontaneous if prothrombin levels are less than 1%. Hemarthroses may occur.

• Individuals with higher prothrombin levels have a variable bleeding tendency, and some may be asymptomatic.

Laboratory Features

• The activated partial thromboplastin time (aPTT) and prothrombin time (PT) are prolonged. The thrombin time (TT) is normal.

• Diagnosis is established by demonstrating reduced levels of functional prothrombin.

• Both functional and antigen assays are required to identify dysprothrombinemia. Immunoelectrophoretic studies may demonstrate some forms of dysprothrombinemia.

Differential Diagnosis

• Differential diagnosis includes inherited factor V or factor X deficiency, acquired deficiency of the ...