Inherited coagulation disorder resulting in life-long
bleeding tendency in homozygotes with poor wound healing and easy bruising.
Congenital Factor XIII Deficiency.
Coagulation disorder first described by François Henri
Duckert, a Swiss hematologist, in 1960 (before factor XIII [FXIII], the
“forgotten coagulation factor” was considered a clotting factor). Factor
XIII was determined to be a coagulation factor in the coagulation cascade
Approximately 1:2-5,000,000 population.
Autosomal recessive, often with consanguinity.
Caused by mutations (>40) in the gene encoding the catalytic α
subunit on chromosome 6. Whereas the concentration of β subunits is
relatively normal, the α subunit is absent in plasma, platelets, and
monocytes and results in severe bleeding diathesis.
FXIII is a transglutaminase enzyme that forges
covalent bonds between adjacent strands of monomeric fibrin after thrombin
activation, thereby converting fibrin monomers into fibrin polymer.
Deficiency leads to clot instability, bleeding, and poor wound healing. This
disease has a high incidence of intracranial bleeding (>25%) and is
commonly diagnosed in the neonatal period, when bleeding is noted at the
Umbilical stump bleeding is pathognomonic. Laboratory
diagnosis requires a clot solubility test with 5M urea or 1%
monochloroacetic acid, or FXIII assay.
Umbilical stump bleeding (>90%), intracranial
bleeding (>25%), superficial bleeding/subcutaneous hematomas (>50%),
hemarthrosis (25%), normal prothrombin time, partial thromboplastin time,
and platelet count. Treatment usually entails fresh-frozen plasma 5 ml/kg at
monthly intervals as prophylaxis. Treatment with cryoprecipitate is
effective. Virally inactivated FXIII concentrates exist but are reportedly
not commercially available everywhere.
Suspect FXIII deficiency when
bleeding exists in the presence of normal coagulation parameters and
platelet count. Consult hematologist for treatment recommendations and
availability of FXIII concentrates. Treat patients emergently with
fresh-frozen plasma 5 ml/kg.
Avoid regional anesthesia. Ensure blood
bank support. Avoid IM injections.
Avoid aspirin and nonsteroidal
Acquired FXIII Deficiency: Caused by liver disease, inflammatory
bowel disease, and disseminated intravascular coagulation but has no
clinically relevant bleeding.
Other Congenital Coagulation Factor Deficiencies (Dysfibrinogenemia, Decreased Fibrinogen Levels): Differential diagnosis is
obtained following proper laboratory examinations.
Anwar R, Miloszewski KJ: Factor XIII deficiency. Br J Haematol
Gerlach R, Tolle F, Raabe A, et al: Increased risk for postoperative
hemorrhage after intracranial surgery in patients with decreased factor XIII
activity: Implications of a prospective study. Stroke 33:1618, 2002.
Pernod G, Barro C, Arnutti B, et al: Surgery in severe factor XIII
deficiency: Report of a case of epilepsy neurosurgery and review.