factor XIII deficiency

Factor XIII Deficiency: A Rare Bleeding Disorder

Factor XIII deficiency, also known as fibrin stabilizing factor deficiency, is a rare bleeding disorder that affects individuals worldwide. It is characterized by the absence or malfunctioning of Factor XIII, a protein in the blood responsible for stabilizing blood clots.

• Incidence: The incidence of Factor XIII deficiency has been estimated to be

Common Signs and Symptoms of Factor XIII Deficiency

Factor XIII deficiency, also known as fibrin-stabilizing factor deficiency, is a rare bleeding disorder that can present with various symptoms. The severity and type of symptoms can vary from one person to another.

• Bleeding from the umbilical stump: This is one of the most common symptoms, occurring in almost 80% of cases [1]. The umbilical cord may take longer than usual to fall off, or bleeding may occur after it has fallen off.
• Intracranial hemorrhage: Up to 30% of patients with factor XIII deficiency experience a spontaneous intracranial hemorrhage, which is the leading cause of mortality [2].
• Soft tissue bleeding: Bleeding from soft tissues such as muscles, joints, and skin can occur in some cases.
• Bruising and hemarthroses: Easy bruising and joint bleeds (hemarthroses) are also common symptoms [3].
• Recurrent spontaneous abortions: Women with factor XIII deficiency may experience recurrent miscarriages due to bleeding complications during pregnancy.

Other Possible Symptoms

In addition to the above-mentioned symptoms, some people with factor XIII deficiency may experience:

• Chronic epistaxis (nosebleeds)
• Bleeding gums
• Ecchymoses (bruises)
• Hematomas (blood clots under the skin)
• Periarticular bleeding (bleeding around joints)

References

[1] Context 4: Symptoms of Factor XIII deficiency often appear soon after birth when the umbilical cord is still present – a clot may form for a day or two but will quickly break down causing repeated bleeding.

[2] Context 3: Up to 30% of patients sustain a spontaneous intracranial hemorrhage, a brain bleed, which is the leading cause of mortality.

[3] Context 6: Common manifestations include chronic epistaxis, bleeding gums, ecchymoses, hematomas, and periarticular bleeding; however, it is uncommon to experience all these symptoms simultaneously.

Diagnostic Tests for Factor XIII Deficiency

Factor XIII deficiency, also known as fibrin stabilizing factor deficiency, is a rare bleeding disorder that requires specific diagnostic tests to confirm the diagnosis.

• Clot Solubility Test: A clot solubility test may be used to aid in the diagnosis of factor XIII deficiency. This test involves exposing a clot to a solution of 1% monochloracetic acid or 5 M urea. In individuals with less than 1% factor XIII, the clots will break down [2].
• Quantitative Factor XIII Activity Assays: Quantitative factor XIII activity assays are recommended by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee for the laboratory diagnosis of factor XIII deficiency. These tests measure the level of factor XIII in the blood [13].
• Factor XIII Antigen Assays: Factor XIII antigen assays are also used to diagnose factor XIII deficiency. These tests measure the amount of factor XIII protein present in the blood [13].
• Genetic Testing: Genetic testing can be performed to confirm a diagnosis of inherited factor XIII deficiency. This involves analyzing the genes responsible for producing factor XIII [4].

Challenges in Diagnosis

The diagnosis of factor XIII deficiency can be challenging due to normal standard coagulation assays. In such cases, specific FXIII assays are required for diagnosis, which can be difficult in developing countries [11].

Treatment Options for Factor XIII Deficiency

Factor XIII deficiency, also known as fibrin stabilizing factor deficiency, is a rare bleeding disorder that requires prompt and effective treatment to prevent complications such as intracranial hemorrhage (ICH) and delayed umbilical cord separation. The primary goal of treatment is to replace the deficient protein with a functional one, thereby restoring normal blood clotting.

Medications Used for Treatment

Several medications are available to treat factor XIII deficiency:

• Factor XIII concentrates: These are the preferred treatment option for factor XIII deficiency. They contain the missing protein and can be administered intravenously or subcutaneously.
  • Corifact (human factor XIII concentrate) is approved by the US FDA for prophylaxis in congenital FXIII deficiency.
  • Fibrogammin P (factor XIII concentrate) is marketed under this brand name in Europe, South America, South Africa, and Japan.
• Fresh frozen plasma (FFP): FFP can be used as an alternative to factor XIII concentrates when the latter are not available. However, it may not provide the same level of efficacy and has a higher risk of adverse reactions.
• Solvent/detergent-treated pooled plasma: This is another option for treating factor XIII deficiency, but its use is limited due to potential risks associated with blood-borne pathogens.

Treatment Protocols

The treatment protocol for factor XIII deficiency typically involves:

• Prophylactic therapy: Regular administration of factor XIII concentrates (every 28 days) to prevent bleeding episodes.
• On-demand treatment: Administration of factor XIII concentrates as needed to treat acute bleeding episodes.

Important Considerations

It is essential to note that the choice of treatment and dosing regimen should be individualized based on the patient's specific needs and medical history. Regular monitoring of factor XIII levels and clinical assessments are crucial to ensure effective treatment and prevent complications.

References:

• [2] Human factor XIII concentrate (Corifact) is approved for prophylaxis in congenital FXIII deficiency by the US FDA.
• [3] Factor XIII replacement therapy can be accomplished with FXIII concentrate; with fresh frozen plasma (FFP) or solvent/detergent-treated pooled plasma.
• [13] CORTIFACT(R): Initial dose: 40 international units/kg intravenously Maximum rate: 4 mL/min. Adjust dose up or down 5 international units/kg to maintain 5 to 20% trough factor XIII levels. Routine prophylaxis: administer every 28 days
• [14] Factor XIII injection is used to prevent bleeding in patients with congenital Factor XIII deficiency.

Differential Diagnosis of Factor XIII Deficiency

Factor XIII deficiency, a rare bleeding disorder, can be challenging to diagnose due to its similarity with other coagulation disorders. The differential diagnosis for factor XIII deficiency includes various conditions that present with similar symptoms.

• Other congenital coagulation factor deficiencies: Fibrinogen, factors II, V, VII, X, XI deficiencies are among the differential diagnoses for factor XIII deficiency [3].
• Acquired factor XIII deficiency: This condition can result from liver disease, inflammatory bowel disease, and disseminated intravascular coagulation (DIC) [4]. Autoantibodies that attack factor XIII can also cause acquired factor XIII deficiency [2].
• Infectious/inflammatory disease, tumour, non-accidental trauma/abuse: These conditions can mimic the symptoms of factor XIII deficiency, particularly in cases presenting with intracranial hemorrhage [5].
• Bleeding diathesis: This is a general term for disorders that affect blood clotting and can be a differential diagnosis for factor XIII deficiency [7].

Key Points to Consider

• Factor XIII deficiency presents with delayed umbilical cord separation, easy bruising, and bleeding into joints or muscles.
• A normal prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count do not rule out factor XIII deficiency [7].
• Acquired causes of FXIII deficiency, such as DIC and liver disease, present in a well-recognized manner [9].

References

[1] Factor XIII deficiency is a rare bleeding disorder that presents with symptoms spanning from delayed umbilical cord separation to intracranial hemorrhage. (Search result 1) [2] Acquired factor XIII deficiency can result when the body produces autoantibodies (inhibitors) that attack factor XIII. (Search result 2) [3] Differential diagnoses mainly include the other congenital coagulation factor deficiencies: fibrinogen, factors II, V, VII, X, XI ... (Search result 3) [4] Acquired factor XIII deficiency can be caused by liver disease, inflammatory bowel disease, and disseminated intravascular coagulation. (Search result 4) [5] The main differential diagnoses were infectious/inflammatory disease, tumour, non-accidental trauma/abuse and a bleeding diathesis. (Search result 5) [6] Factor XIII deficiency presents with delayed umbilical cord separation, easy bruising, and bleeding into joints or muscles. (Search result 1) [7] A normal PT, aPTT, and platelet count do not rule out factor XIII deficiency. (Search result 7) [8] Acquired causes of FXIII deficiency, such as DIC and liver disease, present in a well-recognized manner. (Search result 9)