Fibrinogen (Factor 1)

What Sample for Fibrinogen (Factor 1) is needed?

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.

What are the Indications for Fibrinogen (Factor 1)?

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 disorders.
4. As a follow-up of a bleeding disorder.
5. This is done to diagnose DIC.

What are the precautions for Fibrinogen (Factor 1)?

1. Blood transfusion in the last month may affect the test result.
2. A 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.

What is the structure of Fibrinogen (Factor 1)?

1. Fibrinogen is a complex glycoprotein  (Polypeptide) produced in the liver that, through enzyme action, is converted to fibrin.
2. The molecular weight is 340,000 daltons.
3. Fibrinogen consists of two identical subunits containing three dissimilar polypeptide chains:
   1. 2 = Aα
   2. 2 = Bβ
   3. 2 = γ
   4. Connected by a disulfide bond (17 pairs of disulfide bonds).
   5. It is 45 nm long, containing two outer D-domains, each connected to the central E domain by a coiled-coil segment.

4. Fibrinogen is plasma soluble and is converted into fibrin.
5. It has a half-life of three days.
6. On electrophoresis, it is present in the β- globulin fraction.

What is the role of fibrinogen (Factor 1) in the clotting mechanism?

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

Fibrinogen (Factor 1) functions?

1. The liver produces fibrinogen, and it acts as an acute-phase protein.
2. Increased level of fibrinogen is a risk factor for:
   1. Atherosclerosis.
   2. Arterial thrombosis.
      1. Coronary heart disease.
      2. Myocardial infarction.
      3. Peripheral arterial disease.
   3. Stroke.
3. Fibrinogen has a role in the immune system.
4. Fibrinogen has the main role in the blood clotting system.

What is the normal Fibrinogen level?

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.
• The critical value is = < 100 mg/dL (may cause spontaneous bleeding).

What are the conditions where there is an Increased fibrinogen (Factor 1) level?

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 a stroke.
9. In cigarette smoking.
10. In pregnancy.
11. Trauma.

What are the conditions where there is a Decreased Fibrinogen (Factor 1) level?

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.

How will you define 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% chance to be affected.
      2. 50% chance to be an unaffected carrier.
      3. 25% chance to be unaffected and not a carrier.
2. There is a severe lake of fibrinogen, and blood will not clot.
3. What are the Signs and symptoms of afibrinogenemia?
   1. In the case of afibrinogenemia, if the fibrinogen level is <0.1 g/L (<60 mg/dL), 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.

How will you diagnose afibrinogenemia?

1. The 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.
2. Prolonged bleeding time (BT) and fibrinogen level <0.1 g/L (<60 mg/dL), indicating afibrinogenemia.
3. Diagnostic values are:
   1. Plasma fibrinogen is absent.
   2. BT is increased in 1/3 of the cases.
   3. PT, APTT, and TT are abnormal.

How will you define Dysfibrinogenemia?

1. There is an abnormal fibrinogen due to a structural abnormality, which results in an abnormal function. This change is in amino acids or carbohydrate composition.
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 tend to thrombosis in case of acquired cause.
   1. >50% of the cases have no bleeding episodes.
   2. 29% to 25% of the cases have mild to moderate bleeding or thrombosis, or both.

How will you Diagnose Dysfibrogenemia?

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.
   1. TT  may not be prolonged in the case of a tendency for thrombosis.
   2. Fibrin formation is abnormally slow, with prolonged TT and reptilase time,
4. Reptilase time is prolonged.

How will you differentiate different types of fibrinogens?

Laboratory test	Hypofibrinogenemia	Afibrinogenemia	Dysfibrogenemia
Fibrinogen level	Decreased	Not detectable	Normal/Abnormal form
Fibrinogen immunoassay	Abnormal	Absent	Normal
Platelets aggregation	Normal	Abnormal	Normal
Prothrombin time (PT)	Prolonged	Prolonged	Prolonged/Normal
Bleeding time (BT)	Normal	Prolonged	Normal
APTT	Prolonged	Prolonged	Prolonged/Normal
Thrombin time (TT)	Prolonged	Prolonged	Prolonged
Reptilase time	Prolonged	Prolonged	Prolonged

• The critical value of Fibrinogen (Factor 1) = <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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