Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (401 page)

   Type II hyperlipoproteinemia

   Patients with anticardiolipins may have circulating antibodies to F XII in addition to falsely decreased F XII levels. This situation may be encountered in patients with lupus anticoagulant.

Suggested Reading

Rennee T, Schmaier AH, Nickel KF, et al. In vivo roles of factor XII.
Blood.
2012;120:4296–4303.

FACTOR XI (F XI) DEFICIENCY

Factor XI deficiency is, in most cases, an inherited autosomal recessive disorder. More than 100 mutations have been described in the F XI gene. Although F XI deficiency is rare in the population at large, it is common in Ashkenazi Jews and in some Arab groups. Bleeding is highly variable since the deficient phenotype does not follow the laboratory level of the factor with respect to bleeding. Patients with mild F XI deficiency can experience bleeding complications, and those with severe deficiencies may not bleed excessively. In general, the homozygous patients display a severe deficiency of measurable F XI, from <1% to 20%. It is not usually associated with spontaneous hemorrhage, but these individuals may bleed excessively after injury or surgery, particularly of areas with high fibrinolytic activity, such as dental surgery. Spontaneous abortions have been seen in one patient with severe F XI deficiency by the author. F XI-deficient patients seem to be protected against ischemic stroke and deep vein thrombosis. On the other hand, individuals with high F XI levels are at increased risk of venous and arterial thrombosis. Patients with F XI deficiency have a normal PT, but a variably prolonged PTT. The definitive diagnosis is made by establishing F XI levels in each suspected patient. F XI is not affected by vitamin K deficiency or oral anticoagulants.

FACTOR XIII (F XIII) DEFICIENCY

   Definition

Factor XII lends to increase stability of the fibrin clot. Factor XIII deficiency is a rare condition inherited in an autosomal recessive manner. It may lead to a bleeding diathesis of varying intensity. Typically, the affected individuals bleed from the umbilical stump during the first few days of life, postoperatively, and intracranially. It is also associated with recurrent pregnancy loss and delayed wound healing disorder.

   Congenital

   A variety of mutations lead to F XIII deficiency. Most patients deficient in F XIII lack the factor in plasma and in platelets.

   Acquired

   Liver disease, prematurity, plasmacytoma, surgery, DIC.

   Acute promyelocytic and some chronic leukemias.

   Alloantibodies may develop in severely deficient patients after therapeutic exposure to the antigen. Antibody inhibitors may develop after exposure to certain drugs such as phenytoin, isoniazid, penicillin, or valproic acid. The development of antibodies against F XIII may lead to severe bleeding.

   Laboratory Findings

   A qualitative assay investigates the clot solubility in five molar urea. A plasma clot from a patient deficient in F XIII is easily dissolved in urea, acids, and bases, whereas in a normal control, the clot remains solid. If the test is positive, mixing studies are recommended to rule out a factor XIII inhibitor. If no inhibitor is detected, the deficiency should be confirmed by a quantitative test.