Inherited coagulation disorder caused by a deficiency
in plasma protein factor XII (FXII) characterized by in vitro delayed blood
clotting without a clinical bleeding tendency. The condition may also be
acquired and temporary.
Factor XII Deficiency; HAF Deficiency; Hageman Trait.
Coagulation disorder first described in 1955 after routine
preoperative laboratory examination of a patient named John Hageman.
From 1955 to 2002, only a few hundred reported cases.
Incidence is greater in patients of Asian origin.
Autosomal recessive. Location of the Hageman
factor gene was difficult; it was successively assigned to chromosome 6 and
then 7, and now the gene map locus has been established as 5q33-ter.
FXII is a contact factor belonging to the
kallikrein-kinin system or plasma. Patients affected with a deficiency in
FXII do not experience abnormal bleeding because there is activation by
other contact factors. The diagnosis is usually serendipitous. Partial
thromboplastin time is elevated.
Prolonged partial thromboplastin time; considerably
decreased FXII assay. Condition usually discovered during routine laboratory
Elevated partial thromboplastin time, no clinical
bleeding in normal conditions. Occasionally, mild blood loss has been
reported, mainly following trauma or surgery. Severe liver disease may lead
to reduced production of FXII, worsening the (biologic) condition. FXII
deficiency was reported to be a risk factor for thromboembolism as a result
of inactivation of fibrinolysis. The disorder may be a risk factor for early
Evaluate the coagulation profile and
specific dosage of clotting factors. Even when partial thromboplastin time
is considerably prolonged, there is no indication for fresh-frozen plasma,
and common surgical procedures should not be contraindicated. These patients
are not prone to develop a bleeding tendency but, on the contrary, might be
at risk for thromboembolism (spontaneously and perioperatively).
Classically, there are no specific
contraindications to anesthesia. However, bleeding problems may arise in
procedures requiring use of anticoagulants (cardiac surgery), requiring
close followup of both global coagulation tests and individual dosages of
clotting factors. Despite contradictory statements in the literature, these
patients might be at increased risk for thromboembolism. Close monitoring of
coagulation status and clinical and Doppler ultrasonography evaluation for
suspected thromboembolism are highly recommended.
Administration of heparin may result
in FXII deficiency; its use should be avoided in affected patients unless
absolutely necessary (cardiac surgery, thromboembolism). Similarly, use of
all anticoagulant agents is questionable and, basically, should be avoided.
Hasegawa T, Uematsu M, Tsukube T, et al: Huge left atrial thrombus with
mitral stenosis in congenital factor XII deficiency. Ann Thorac Surg 73:286, 2002.%
Roberts HR, Hoffman M: Hemophilia and related conditions—Inherited
deficiencies of prothrombin (factor II), factor V, and factors VII to XII,
in Beutler E, Lichtman MA, Coller BS (eds): Hematology. 5th ed. New York, McGraw-Hill,
1995, p 1434.
Zeerleder S, Schloesser M, Redondo M, et al: Reevaluation of the ...