Factor XIII (fibrin stabilizing factor)

Factor XIII (fibrin stabilizing factor)

Sample for Factor XIII (fibrin stabilizing factor)

• Plasma (Citrate) is needed, and it is stable for 2 hours at 4 °C only.

Indication for Factor XIII (fibrin stabilizing factor)

• To find the deficiency of factor XIII.

Pathophysiology of fibrin stabilizing factor (XIII)

1. Factor XIII deficiency is congenital and inherited as an autosomal recessive trait with a severe coagulation defect.
   1. Clinically the homozygous deficiency has moderate to severe hemorrhagic episodes.
2. Factor XIII is present in the plasma, platelets, monocytes, and macrophagic cells.
   1.  Factor XIII has a molecular weight of 320.000 daltons and circulates with fibrinogen.
   2. It consists of two subunits α₂ – unit and β₂ – unit chains.
   3. Factor XIII is also present in the above cell precursors in the bone marrow.
   4. Factor XIII has a long half-life of 5 to 9 days.

Functions of factor XIII:

1. Factor XIII cross-linked fibrin and other proteins.
2. It stabilizes the clot. Its >5% activity requires to form a normal clot.
3. The stabilized fibrin clot in factor XIII deficiency becomes insoluble in various substances like urea.
4. This factor helps in wound repair and healing.

Factor XIII’s role in stable clot formation

Deficiency of factor XIII (Fibrin stabilizing factor):

1. Congenital deficiency:
   1. It is transmitted as an autosomal recessive trait.
   2. First, bleeding is noted in newborns.
   3. In later life, bleeding episodes are mild with severe trauma or surgery.
   4. Delayed bleeding after trauma.
   5. Poor wound healing.
   6. Inadequate scar formation.
   7. Bleeding is common after separating the umbilical cord in case of factor XIII deficiency.
2. A secondary deficiency may be seen in various conditions:
   1. Malignancies like AML.
   2. In liver diseases.
   3. Presence of circulating inhibitors.
   4. Associated with hypofibrinogenemia in obstetric complications.
   5. This type of deficiency is subclinical.

Factor XIII (Fibrin stabilizing factor) deficiency

Signs and symptoms of XIII (Fibrin stabilizing factor) deficiency:

1. There is easy bruising and soft tissue bleeding which may be due to trauma.
   1. There may be a severe bleeding tendency.
   2. The bleeding tendency may be like hemophilic patients; these patients may have hemarthrosis and deep tissue bleeding.
   3. This bleeding is characterized by the initial stoppage of bleeding followed by the recurrence of the bleeding after 36 hours or more after the initial trauma.
      1. This resulted from the fibrin clot dissolution that formed in the beginning and was not stabilized by factor XIII.
      2. Acquired partial deficiency has been reported with a few diseases like leukemia, DIC, and severe liver disease.
2. It may lead to spontaneous miscarriage in early pregnancy.
   1. There may be bleeding from the umbilical cord, which may be from 1 to 9 days of birth.
3. It may lead to CNS hemorrhage, which is quite common. This may be the first symptom.
   1. Patients with CNS hemorrhage may have headaches, vomiting, seizures, and focal neurologic defects.
4. Some of the females may have intra-abdominal bleeding during menses.
5. There will be bleeding into the joints (hemarthrosis).
6. There is poor wound healing.

Normal factor XIII (Fibrin stabilizing factor)

1. Plasma concentration = 2.5 mg/dl.

Source 1

1. The test is negative with factor XIII above the minimal hemostatic level of 0.02 to 0.05 U/mL (x1000 = 20-50 U/L).
   1. OR 2  to 5% (x0.01 = 0.02 to 0.05, fraction) of normal concentration.
   2. The clot will be stable for 24 hours with factor XIII above the hemostatic level.
   3. In the absence of factor XIII, the clot will dissolve, often within 2-3 hours or less.

Lab diagnosis of factor XIII deficiency:

1. PT, APTT, fibrinogen, bleeding time, and platelet count are normal.
   1. All these parameters may be normal in congenital deficiency.
2. The clot is soluble in 5 Molar urea solution, which will not occur in a normal person.
3. A whole blood clot is qualitatively friable.

Factor XIII screening test:

1. In factor XIII deficiency, coagulation tests are usually normal.
2. The other coagulation tests do not detect the deficiency of factor XIII.
3. The minimum level required for factor XIII is about 5%.
4. Principle of the test:
   1. Stabilization of the clot is dependent on factor XIII.
      1. The clot is soluble in 5 M urea.
   2. In the test after 24 hours, the presence of a formed clot indicates plasma factor XIII concentration greater than 1 to 2%.
   3. In the homozygous deficiency of factor XIII, the fibrin clot dissolves within one hour and indicates a deficiency of less than 1%.

Treatment of factor XIII (Fibrin stabilizing factor) deficiency:

1. The following blood substitutes can be tried.
   1. Fresh frozen plasma.
   2. Cryoprecipitate.
   3. Factor XIII concentrate.
   4. Factor XIII recombinants.