Fibrinogen (Factor I), Afibrinogenemia, Dysfibrogenemia

Sample
- The blood is collected in a 0.2 ml ESR solution and 1.8 ml blood.
- Or citrated plasma can be used. Stable for several months at -20 °C.
- Citrate 4 mg/mL is used.
- Don’t use heparin.
- Don’t collect blood in the glass tubes.
Purpose of the test (Indications)
- It is part of the coagulation panel.
- This is done for the prolonged bleeding.
- This is done to investigate abnormal PT, APTT or bleeding disorder.
- As follow up of a bleeding disorder.
- This is done to diagnose DIC.
Precaution
- Blood transfusion in the last month may affect the test result.
- Diet rich in omega-3 and omega-6 fatty acids will reduce the level of fibrinogen.
- Estrogen and oral contraceptives will increase the level.
- Anabolic steroids, androgens, phenobarbiturates, streptokinase and valproic acid decrease the level.
Pathophysiology
- Fibrinogen is a complex glycoprotein (Polypeptide) that, through enzyme action is converted to fibrin.
- 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.
- Fibrinogen is plasma soluble and is converted into fibrin.
- On electrophoresis, it is present in the β- globulin fraction.
- The fibrin with platelets forms the clot.
- Fibrinogen is essential for the clotting mechanism.
- Basically, this will occlude the blood vessel and stop the bleeding.
- Fibrin trapped the platelets aggregates at the site of vascular injury.
- Then fibrin converts unstable platelets plug to firm stable hemostatic plug.
- Fibrin binds the thrombin and reduces its activity.
- This is part of a common pathway in clotting.
- Thrombin converts fibrinogen into fibrin.
- Fibrinogen is produced by the liver and acts as an acute-phase protein.
- Increased level of fibrinogen is a risk factor for:
- Coronary heart disease.
- Myocardial infarction.
- stroke.
- Peripheral arterial disease.
Normal
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:
- Inflammation and infections ( Rheumatoid arthritis, pneumonia, tuberculosis).
- Acute myocardial infarction.
- Coronary heart disease.
- Nephrotic syndrome.
- Cancer, Multiple Myeloma, and Hodgkin’s disease.
- Pregnancy and Eclampsia.
- Cigarette smoking.
- In the case of stroke.
- In cigarette smoking.
- In pregnancy.
- Trauma.
Decreased Fibrinogen level is seen in;
- Liver diseases like hepatitis and cirrhosis.
- DIC (secondary fibrinolysis).
- Cancers.
- Dysfibrinogenemia
- Primary fibrinolysis.
- Malnutrition.
- Blood transfusion, if large volume given that may dilute the fibrinogen level.
- Fibrinolysins.
- Advanced carcinomas.
Afibrinogenemia:
- This is rare and usually inherited as an autosomal recessive trait.
- If the parents do not show the disease but still they can have affected children.
- When 2 carriers of autosomal recessive positive parents have children, each child has a:
- 25% chances to be affected.
- 50% chances to be an unaffected carrier.
- 25% chances to be unaffected and not a carrier.
- There is a severe lake of fibrinogen and blood will not clot.
- Signs and symptoms:
- In the case of afibrinogenemia, if the fibrinogen level is <0.1 g/L, it will have bleeding abnormality from mild to severe.
- This disease is present from birth.
- The first symptom is bleeding from the umbilical cord which will not stop and difficult to stop.
- There may be gastrointestinal bleeding.
- There may be nose bleeding (epistaxis) or bleeding from the oral mucosa.
- There may be bleeding episodes, bruises, and poor healing of the wound.
- Females may have excessive menstruation.
- There may be spontaneous abortion.
- There may be CNS hemorrhage.
- Evidence of bleeding in the joints.
- Diagnosis: Following tests are advised:
- Prothrombin time (PT)>
- Activated partial thromboplastin time (APTT).
- Fibrinogen level in the blood.
- Reptilase time.
- Thrombin time.
- Prolonged bleeding tests time and fibrinogen level <0.1 g/L, indicating afibrinogenemia.
Dysfibrinogenemia:
- There is abnormal fibrinogen due to a structural abnormality and result in an abnormal function.
- This may be:
- Congenital or Inherited, there is an increased risk of bleeding or thrombosis or both in the same patient or family.
- Some of the patients are asymptomatic.
- The prognosis is good. The event of thrombosis and bleeding is mild.
- Acquired where the fibrinogen is dysfunctional due to autoimmune diseases or liver diseases, plasma cell dyscrasia, or cancers.
- There is more bleeding than thrombosis.
- The prognosis is worse because of liver disease.
- Congenital or Inherited, there is an increased risk of bleeding or thrombosis or both in the same patient or family.
- This leads to relatively mild hemorrhage in the case of congenital cause.
- Few of these may have a tendency for thrombosis in case of acquired cause.
- Diagnosis:
- Prothrombin time (PT) is prolonged.
- Activated partial thromboplastin (APTT) is also prolonged.
- 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.
- 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.