Hereditary coagulation disorder caused by defective
synthesis of plasma protein factor IX.
Christmas Disease; F-IX Deficiency.
Also called Christmas disease after Steven Christmas, who was first
diagnosed with the disease at 5 years of age in 1952 (and who died of AIDS at
age 46 in 1993). Sir Jonathan Hutchinson was responsible for naming
clinical disorders after patients and has become familiar for serologic
1:40,000 males (15-20% of hemophiliacs).
X-linked. Defective coagulation factor IX.
Gene map location is Xq27.1-q27.2.
Factor IX is a vitamin K-dependent clotting
factor. It is activated by either factor XIa or factor VIIa-tissue factor
complex. Once activated, it activates factor X in the presence of calcium,
phospholipid, and factor VIIIa. Because deficiency of factor VIII or factor
IX decreases factor X activity, hemophilia B is clinically indistinguishable
from hemophilia A. Affected patients are classified as mild, moderate, or
severe. Mildly afflicted patients have factor IX levels 5 to 40% of
normal activity, moderately afflicted patients have levels 1 to 5% of
normal activity, and severely afflicted patients have less than 1% of normal
Based on assays of factor IX antigen and factor IX
activity. According to the residual factor IX activity, the disorder is
classified as severe (<1%), moderate (1 to 5%), or mild (5-20% of
normal value). Prenatal and carrier detection are possible with restriction
fragment length polymorphism DNA analysis but are contingent upon parental
analysis. Elevation of the partial thromboplastin time with normal
prothrombin time and bleeding times are found.
Early onset of symptoms: increased tendency to
bleeding becomes evident in 90% of affected patients by 1 year of age.
Clinical picture very similar to hemophilia A, namely, soft tissue
hematomas, including retroperitoneal/pharyngeal hemarthroses (75%), often
at 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
postsurgical bleeding. Hepatitis infection from previous transfusions is
Hematology and anesthesiology
consultation are highly recommended before elective surgical procedures. Schedule
surgical procedures early in the week to avoid pharmaceutical delays. Ensure
supply of virally inactivated factor IX concentrate, which does not have the
infectious risks of fresh-frozen plasma. Dose calculations are based on the
following formula: 1 unit factor IX/kg increases factor IX activity by
1%. Half-life is 18 to 24 hours. Consider antifibrinolytic therapy
[epsilon-aminocaproic acid (EACA), tranexamic acid or aprotinin]
because these agents may be useful adjuvants for dental
bleeding. Raise factor IX to normal levels before major surgical
In conjunction with a hematologist
consultation, maintain factor IX levels periand postoperatively. Avoid
regional anesthesia and intramuscular injections.
Avoid aspirin and NSAIDs.
Hemophilia A: More severe hereditary coagulation disorder but
otherwise a clinically similar syndrome caused by defective synthesis of
plasma protein factor VIII.
Hemophilia B Leyden: Variant of hemophilia B in which the mutation
affects the adjacent promoter region of the gene instead of the functional
region of the factor IX gene. The prevalence is unknown (this ...