Abstract

Rare bleeding disorders (RBDs) include inherited deficiencies of coagulation factors, fibrinogen, factor (F)II, FV, FV + FVIII, FVII, FX, FXI, and FXIII, and vitamin K-dependent anticoagulant proteins, Protein C, and Protein S. Due to their rarity and limited epidemiological data or sufficient knowledge about epidemiology and clinical outcomes, RBDs often pose significant diagnostic and therapeutic challenges. FXIII protein plays a pivotal role in stabilizing the blood clot by facilitating the cross-linking of the fibrin polymer, thus ensuring effective hemostasis. The deficiency of FXIII coagulation factor results in normal clot formation but a lack of stability to maintain the clot, which leads to prolonged bleeding. Approximately 95% of affected individuals have a deficiency of the A subunit, while the remaining have a B subunit deficiency.

 Congenital FXIII deficiency is a rare, autosomal recessive disorder with variable bleeding manifestations. Though rare, acquired cases are also seen mostly in older patients with autoimmune disease, malignancy, and DIC. They manifest with a normal coagulation profile, demanding a high level of suspicion in a patient with a bleeding disorder for accurate diagnosis. Factors such as a strong family history of bleeding disorders, consanguineous marriage, and recurrent early miscarriages gave a strong suspicion. Patients with moderate and mild deficiency can have only mucocutaneous bleeding or may be completely asymptomatic. Severe bleeding manifestations, such as CNS or umbilical cord bleeding, or recurrent hemarthroses and hematomas are common in severe deficiency.

 Following a normal coagulation workup, clot solubility tests may be used, though their sensitivity and specificity are limited. The preferred diagnostic approach includes quantitative FXIII assays and immunological testing. The management plan includes comprehensive education to patients and their families, prophylactic precautions, lifestyle, and treatment. The mainstay of treatment is replacement of missing factors with recombinant FXIII concentrates. Due to limited availability, high cost of rFXIII concentrates, other alternative options are transfusion of cryoprecipitate, fresh frozen plasma (FFP). However, these alternatives carry risks such as infection transmission and infusion-related complications. A multidisciplinary approach should be taken to achieve an optimum outcome, patient safety, and minimize complications.

Keywords

FXIII deficiency, recombinant FXIII concentrate, clot solubility test, rare bleeding disorders