Fibrinogen (Factor I), Afibrinogenemia, Dysfibrogenemia

Fibrinogen (Factor I)

Sample

1. The blood is collected in a 0.2 ml ESR solution and 1.8 ml blood.
2. Or citrated plasma can be used. Stable for several months at -20 °C.
   • Citrate 4 mg/mL is used.
3. Don’t use heparin.
4. Don’t collect blood in the glass tubes.

Purpose of the test (Indications)

1. It is part of the coagulation panel.
2. This is done for prolonged bleeding.
3. This is done to investigate abnormal PT, APTT, or bleeding disorder.
4. As a follow-up of a bleeding disorder.
5. This is done to diagnose DIC.

Precautions

1. Blood transfusion in the last month may affect the test result.
2. Diet rich in omega-3 and omega-6 fatty acids will reduce the level of fibrinogen.
3. Estrogen and oral contraceptives will increase the level.
4. Anabolic steroids, androgens, phenobarbiturates, streptokinase, and valproic acid decrease the level.

Pathophysiology of Fibrinogen (Factor 1)

1. Fibrinogen is a complex glycoprotein  (Polypeptide) that, through enzyme action, is converted to fibrin.
   1. The molecular weight is 340,000 and consists of two identical subunits, each containing three dissimilar polypeptide chains (Aα, Bβ,  and γ); these are linked by a disulfide bond.
   2. Fibrinogen is plasma soluble and is converted into fibrin.
2. On electrophoresis, it is present in the β- globulin fraction.
   

   Electrophoresis showing a band of fibrinogen

3. The fibrin with platelets forms the clot.
4. Fibrinogen is essential for the clotting mechanism.
   1. Basically, this will occlude the blood vessel and stop the bleeding.
   2. Fibrin trapped the platelets aggregates at the site of vascular injury.
   3. Then fibrin converts unstable platelets plug to firm, stable hemostatic plug.
   4. Fibrin binds the thrombin and reduces its activity.
5. This is part of a common pathway in clotting.
6. Thrombin converts fibrinogen into fibrin.
   

   Synthesis of fibrinogen and its role to form a clot

7. Fibrinogen is produced by the liver and acts as an acute-phase protein.
8. Increased level of fibrinogen is a risk factor for:
   1. Coronary heart disease.
   2. Myocardial infarction.
   3. Stroke.
   4. Peripheral arterial disease.
      

      Fibrinogen synthesis

Normal Fibrinogen

Source 1

• Newborn = 125 to 300 mg/dL
• Adult = 200 to 400 mg/dL
  • To convert to SI unit x 0.01 = g/L

Source 2

• Adult = 200 to 400 mg/dl or 2 to 4 G/L
• Newborn = 125 to 300 mg/dl.
• Critical value is = < 100 mg/dl (may cause spontaneous bleeding).

Increased fibrinogen level is seen in:

1. Inflammation and infections ( Rheumatoid arthritis, pneumonia, tuberculosis).
2. Acute myocardial infarction.
3. Coronary heart disease.
4. Nephrotic syndrome.
5. Cancer, Multiple Myeloma, and Hodgkin’s disease.
6. Pregnancy and Eclampsia.
7. Cigarette smoking.
8. In the case of stroke.
9. In cigarette smoking.
10. In pregnancy.
11. Trauma.

Decreased Fibrinogen level is seen in;

1. Liver diseases like hepatitis and cirrhosis.
2. DIC (secondary fibrinolysis).
3. Cancers.
4. Dysfibrinogenemia
5. Primary fibrinolysis.
6. Malnutrition.
7. Blood transfusion:  if a large volume is given, it may dilute the fibrinogen level.
8. Fibrinolysins.
9. Advanced carcinomas.

Afibrinogenemia:

1. This is rare and usually inherited as an autosomal recessive trait.
   1. If the parents do not show the disease, they can still have affected children.
   2. When 2 carriers of autosomal recessive positive parents have children, each child has a:
      1. 25% chances to be affected.
      2. 50% chances to be an unaffected carrier.
      3. 25% chances to be unaffected and not a carrier.
2. There is a severe lake of fibrinogen, and blood will not clot.
3. Signs and symptoms:
   1. In the case of afibrinogenemia, if the fibrinogen level is <0.1 g/L, it will have bleeding abnormality from mild to severe.
   2. This disease is present from birth.
   3. The first symptom is bleeding from the umbilical cord, which will not stop and is difficult to stop.
   4. There may be gastrointestinal bleeding.
   5. There may be nose bleeding (epistaxis) or bleeding from the oral mucosa.
   6. There may be bleeding episodes, bruises, and poor wound healing.
   7. Females may have excessive menstruation.
   8. There may be spontaneous abortion.
   9. There may be CNS hemorrhage.
   10. Evidence of bleeding in the joints.
4. Diagnosis: Following tests are advised:
   1. Prothrombin time (PT)>
   2. Activated partial thromboplastin time (APTT).
   3. Fibrinogen level in the blood.
   4. Reptilase time.
   5. Thrombin time.
5. Prolonged bleeding tests time and fibrinogen level <0.1 g/L, indicating afibrinogenemia.

Dysfibrinogenemia:

1. There is abnormal fibrinogen due to a structural abnormality which results in an abnormal function.
2. This may be:
   1. Congenital or Inherited: There is an increased risk of bleeding, thrombosis, or both in the same patient or family.
      1. Some of the patients are asymptomatic.
      2. The prognosis is good. The event of thrombosis and bleeding is mild.
   2. Acquired:  Where the fibrinogen is dysfunctional due to autoimmune diseases or liver diseases, plasma cell dyscrasia, or cancers.
      1. There is more bleeding than thrombosis.
      2. The prognosis is worse because of liver disease.
3. This leads to relatively mild hemorrhage in the case of congenital cause.
4. Few of these may have a tendency for thrombosis in case of acquired cause.
5. Diagnosis:
   1. Prothrombin time (PT) is prolonged.
   2. Activated partial thromboplastin (APTT) is also prolonged.
   3. Thrombin time (TT) is the most sensitive test for dysfibrinogenemia in the case of bleeding tendency and may not be prolonged in the case with a tendency for thrombosis.
   4. Reptilase time is prolonged.

• Critical value is <60 mg/dL.

Value for the layman:

• This is advised when there is a history of bleeding or bruises.
• If the patient has epistaxis.

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