Factor XI Deficiency - A Rare Inherited Blood Disorder

What Is Factor XI?

Factor XI is also known as plasma thrombin antecedent. It is one of the clotting factors, and clotting factors are the proteins produced by the liver and flowing into the bloodstream; these are specialized proteins that help in the clotting process or coagulation of the blood at the site of injury. In blood, inactive forms of clotting factors are circulating; at the time of stimulus, these factors get activated and start forming a plug to stop the bleeding. Deficiency of any of the clotting factors can lead to prolonged bleeding and clotting time. Factor XI (plasma thrombin antecedent) plays an important role in coagulation, including intrinsic and extrinsic pathways.

What Is Factor XI Deficiency?

Factor XI (plasma thrombin antecedent) deficiency is a bleeding disorder that leads to prolonged bleeding time because of the insufficient production of factor XI by the individual's body. Factor XI deficiency is a rare inherited autosomal recessive disorder, or sometimes it can also be acquired due to some underlying issues. It was first introduced in 1953 in the medical literature. The severity of the disorder depends on the degree of deficiency, though a mild deficiency can also lead to delayed clotting. Factor XI deficiency does not tend to bleed easily, but the clot formation is delayed due to the insufficient supply of clotting factors.

What Are the Causes of Deficiency of Factor XI (Plasma Thrombin Antecedent)?

Factor XI (plasma thrombin antecedent) deficiency can be caused by genetic inheritance of acquired bleeding disorder.

• An inherited deficiency of factor XI shows an autosomal recessive pattern. It is caused by the genetic mutation of the gene FII; it helps in the formation of factor XI (plasma thrombin antecedent). The variant in the FII gene leads to the deficient or dysfunctional formation of factor XI, causing the deficiency or shortage of factor XI. Factor XI is a clotting factor that plays an important role in the coagulation cascade.

• An acquired deficiency of factor XI (plasma thrombin antecedent) is caused by some underlying issues, such as liver diseases that may lead to insufficient production of factor XI (plasma thrombin antecedent) or due to some dysfunction of the immune system leading to the destruction of effective factor XI (plasma thrombin antecedent).

• Patients suffering from factor XI deficiency with some other disease are said to have Noonan syndrome.

What Are the Clinical Features of Factor XI (Plasma Thrombin Antecedent) Deficiency?

The deficiency of factor XI (plasma thrombin antecedent) leads to prolonged bleeding and clotting.

• It increases the bleeding tendency depending upon the severity of the deficiency; if the deficiency is mild, the bleeding will be less.

• It may lead to prolonged bleeding after any surgical procedure involving dental treatment (for example, tooth extraction), tonsillectomy, circumcision, and other minor or major surgical procedures.

• Internal bleeding may cause dark-colored swollen regions filled with blood called hematomas.

• Easy bruising.

• Epistaxis (nose bleeding).

• Heavy bleeding in females during the menstrual cycle or prolonged bleeding after giving birth.

• Bleeding into the joints.

• Hematuria (blood in urine) is seen in some cases.

• Gastrointestinal hemorrhage.

• Weakness.

• Anemia.

• Recurrent infections.

• Pale skin.

• Fatigue.

• Headache and confusion.

• Gum bleeding while brushing.

What Are the Investigations for the Diagnosis of Factor XI (Plasma Thrombin Antecedent) Deficiency?

The following investigations can diagnose the deficiency of factor XI (plasma thrombin antecedent):

1. Factor XI (plasma thrombin antecedent) deficiency is an inherited disorder, so it is very important to record medical and family history.

2. Physical examination helps to understand the associated signs and symptoms.

3. Bleeding and Clotting Tests - These are a type of blood test to determine the bleeding time and clotting time of the injury, which is the total time taken by the body’s mechanism to form and clot and stop the bleeding.

4. Platelet Function Test - This is done to determine the ability of platelets.

5. Prothrombin Test - This is done to evaluate blood clotting time.

6. Partial Prothrombin Test - It is a blood test done to find out the time required for clot formation.

7. Factor XI Assay - This investigation is done to get the confirmation of the deficiency of factor XI (plasma thrombin antecedent).

What Are the Treatment Modalities for Factor XI Deficiency (Plasma Thrombin Antecedent)?

Factor XI deficiency can be treated and manageable with supportive and preventive measures.

Following are some treatment modalities for deficiency of factor XI:

1. Transfusion of Fresh Frozen Plasma - Patients with a deficiency of factor XI (plasma thrombin antecedent) are advised for intravenous transfusion. Fresh frozen plasma is a substitute that is collected from the donors, and these are rich in coagulation factors.

2. Factor XI (Plasma Thrombin Antecedent) Concentrates - Transfusion of factor XI concentrates; these are blood components collected from the donors and consist of clotting factors that can lead to thrombotic events.

3. Antifibrinolytics - These are the drugs used for the treatment of factor XI (plasma thrombin antecedent) deficiency. Tranexamic acid or Aminocaproic acid can be administered to stop the bleeding.

4. Preventive measures should be taken before or during surgical procedures. It is also important to inform a healthcare provider about the deficiency so they can plan the treatment or procedure accordingly.

5. Hormonal Therapy - Factor XI deficiency may lead to menstrual bleeding in females. Admission of oral contraceptives or birth control pills can help regulate the hormonal balance of the body.

6. Inhibitors - In an individual with a deficiency of factor XI (plasma thrombin antecedent), the development of inhibitors can also be seen. Inhibitors are a kind of autoantibodies that can damage the effective factor XI in the body; therefore, to avoid the defect caused by the inhibitors, recombinant factor VIIa is a choice of drug administered to the patient.

Conclusion

Factor XI deficiency is a rare bleeding disease; it can be caused by genetic inheritance of the autosomal recessive FII gene, which initiates the production of factor XI (plasma thrombin antecedent), or it can also be acquired, which can also be treated with the supportive treatment. Therefore, living with a deficiency of factor XI is manageable; there are specific preventive measures that can be taken before any surgery or dental procedure. However, advanced treatment modalities have increased the management of the diseases, so it is always advisable to consult a specialist regarding the condition.