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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).

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TABLE 82–1 WORLDWIDE DISTRIBUTION OF RARE BLEEDING DISORDERS DERIVED FROM THE WORLD FEDERATION OF HEMOPHILIA AND THE EUROPEAN NETWORK OF RARE BLEEDING DISORDERS SURVEYS
Deficiency WFH Survey (%) EN-RBD Database (%)
Fibrinogen 9 8
Factor II 1 1
Factor V 8 10
Factor V + factor VIII 2 3
Factor VII 38 39
Factor X 7 8
Factor XI 30 24
Factor XIII 5 7

EN-RBD, European Network of the Rare Bleeding Disorders (www.rbdd.eu); WFH, World Federation of Hemophilia (www.wfh.org), report of 2017.

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TABLE 82–2 GENERAL GENETIC FEATURES OF COAGULATION FACTORS
Deficiency Gene Chromosome
Factor II F2 11p11–q12
Factor V F5 1q21–25
Factors V + VIII LMAN1 18q21.3–q22
  MCFD2 2p21–p16.3
Factor VII F7 13q34
Factor X F10 13q34–qter
Factor XI F11 4q34–35
Factor XIII F13A 6p24–p25
  F13B 1q31–q32.1

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 ...

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