Fibrinogen (Factor 1), Acute Phase Protein

Acute-phase protein (Acute Phase Reactants)

• Acute-phase protein is raised in inflammatory conditions.
• When there is an increase in a protein called positive acute-phase protein.
  • In the case of a decrease in the acute phase protein, it is called negative phase protein.
• The acute phase proteins (positive) are proteins whose concentration increases in the plasma, and after the disease episode is over, it decreases and may become normal.

Fibrinogen (Factor 1)

Sample

• The patient blood is needed to prepare plasma.
• The sample is stable for 8 hours at room temperature.
• It can be stored for several months at -20 °C.

Indications

1. For the evaluation of bleeding disorder.
2. If there is excessive bruising.
3. In case of bleeding from the gums and nose.
4. In the case of Bleeding in the GIT and blood in the stool.
5. In the case of blood in the urine.
6. If there is a rupture of the spleen.

Precautions

1. Avoid clot formation.
2. Avoid collecting the blood from the heparinized blood vessel.
3. Avoid contamination with tissue that contains tissue thromboplastin.
4. Avoid contamination with heparin.
5. Blood transfusion in the last month may affect the result.
6. Diet rich in Omega-3 and Omega-6 fatty acids reduces the level of fibrinogen.
7. Oral contraceptives and estrogen increase the level.
8. Drugs like anabolic steroids, phenobarbital, streptokinase,  valproic acid, and asparaginase.

Pathophysiology Fibrinogen (Factor 1)

1. Fibrinogen (factor 1) is an acute-phase protein.
2. This is β-globulin and is usually absent from the serum.
3. It is a fibrillary group of glycoproteins.
4. This consists of three pairs of polypeptide chains.
   

   Electrophoresis showing a band of fibrinogen

5. It is synthesized in the liver, the major source of coagulation factors.
6. Fibrinogen may act as an acute-phase protein.
   

   Fibrinogen synthesis

1. When fibrinogen is transfused:
   1. 50% disappear in 48 hours.
   2. 75% disappear in 6 days.
   3. Half-life is 3.5 to 4 days. (Another source says 100 to 150 hours).
2. This is an essential protein for blood clot formation (30% activity for normal coagulation is required).
3. It is a complex protein with enzymatic action that is converted into fibrin.
4. In the process of clotting, all the fibrinogen in the plasma is converted to fibrin.
   1. Conversion of fibrinogen into fibrin is the final step in coagulation, and it takes place under the influence of thrombin.
   2. This is part of the common pathway in coagulation.
5. The serum is laking fibrinogen.

6. The fibrinogen has a major effect on RBC sedimentation rates by coating the cells.
   1. This allows the cells to settle (sediment) faster.
   2. So increased fibrinogen indicate raised ESR.
7. Disseminated intravascular coagulopathy (DIC): In this case, fibrinogen is decreased.
   

   Fibrinogen level in DIC

Significance of fibrinogen:

1. This is raised by inflammation or tissue injury. Fibrinogen plays an important role in the body’s acute reaction in response to trauma or various severe diseases.
2. It is a risk factor for coronary heart disease and stroke.
3. Snake venom leads to the depletion of fibrinogen.
4. Fibrinogen is decreased in the DIC.
5. Fibrinogen level increases by cigarette smoking.
6. There is an influence fo genetics.
   

   Snake venom and Fibrinogen

Normal level of Fibrinogen (Factor 1)

• Source 2
  • Newborn    =  125 to 300 mg/dL
  • Adult           =  200 to 400 mg/dL (2 to 4 g/L)
• Source 4
  • 200 to 400 mg/dL (2 to 4 g/L)
• Another source
  • 175 t o 400 mg/dL.

Critical value of Fibrinogen (Factor 1) = <100 mg/dL

An elevated level of Fibrinogen (Factor 1) is seen in:

1. Acute infections.
2. Myocardial infarction and Sudden cardiac death.
3. Patients with malignancies.
4. Inflammatory conditions like Rheumatoid arthritis and Glomerulonephritis.
5. In the case of traumatic injury.
6. Patient with a stroke.
7. In pregnancy.
8. People who are cigarettes smokers.
9. Patients with peripheral artery disease.
10. This is raised in acute and chronic inflammation.
11. Older age.
12. Diabetes mellitus.

A high level of fibrinogen is associated with increased risk of:

1. Coronary heart disease.
2. Myocardial infarction.
3. Stroke.
4. Peripheral arterial disease.

Reduced level of fibrinogen is seen in:

1. Patients with severe liver diseases.
2. Consumptive coagulopathy like DIC.
3. Malnourished patients.
4. In case of a large volume of blood transfusion.

Afibrinogenemia (Congenital):

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 affect 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:
5. 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.
6. 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 fibrinogen is dysfunctional due to autoimmune diseases, 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.

• Another source: 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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