Coagulation:- part 7 – Blood Coagulation Factors and Their descriptions
Blood Coagulation Factors
- There is a cascade of coagulation factors needed for proper coagulation.
- The following is a description of the coagulation factors.
- The following diagram shows the role of each coagulation factor.
Fibrinogen, Factor I:
- Fibrinogen is necessary for the clotting mechanism.
- Fibrinogen is a globulin protein.
- Fibrinogen is produced by the liver and is also called acute-phase proteins.
- It is raised in acute inflammation and necrosis.
- This is the precursor of Fibrin.
- Fibrinogen (factor I) converts to Fibrin.
- It is part of the common pathway.
- Fibrinogen when exposed to thrombin then it splits into fibrin and forms a polymerized clot.
- Increased level of fibrinogen is associated with:
- increased risk of coronary heart disease.
- Myocardial infarction.
- Peripheral arterial disease.
- Decreased level of the fibrinogen level is seen in:
- Liver diseases.
- DIC (disseminated intravascular coagulopathy).
- Blood transfusion in the last month will affect the result.
- A diet containing omega-3 and omega-6 fatty acids reduces the fibrinogen level.
- Estrogen and oral contraceptives also increase the fibrinogen level.
- Anabolic agents, phenobarbitol, streptokinase, and valproic acid reduce the level of fibrinogen.
- Adult = 200 to 400 mg/dL
- Newborn = 125 to 300 mg/dL
- Critical value = <100 mg/dL
Prothrombin, Factor II:
- Prothrombin is a glycoprotein with a molecular weight of 71,600 daltons, present in the blood and plasma.
- Prothrombin is a vitamin K-dependent clotting factor.
- This is produced in the liver. and needs vitamin K for its production.
- It is most abundant and has the longest half-life of the vitamin K-dependent clotting factors.
- It takes about 3 weeks before the body stores of vitamin K are exhausted.
- Prothrombin is converted to thrombin which in turn stimulates platelet aggregation and activates cofactors (factor X or prothrombinase), Factor C, and Factor XIII.
Thromboplastin, Factor III, or Tissue factor:
- Thromboplastin is generated by the extrinsic and intrinsic pathways.
- Thromboplastin is an enzyme that is released from the damaged cells, particularly from the platelets.
- This is found in the brain, lungs, and other tissues. It is also present in the platelets.
- This is a tissue factor and it will activate VII when blood is exposed to tissue fluid.
- It converts prothrombin to thrombin.
Ionized Calcium Factor IV:
- Ionized calcium is important for the clotting system.
- Ionized calcium is needed in the clotting system at the following stages:
- This active form of Calcium is needed to activate thromboplastin.
- Convert Prothrombin to Thrombin.
- Activate factor XIII to XIIIa.
- Activate factor X to Xa.
- For the formation of fibrin.
- Calcium in the blood, 50% is ionized and a very small amount is needed in the clotting mechanism.
Proaccelerin, Factor V:
- This is a globulin and is labile in the plasma.
- This is synthesized in the liver and its molecular weight is 350,000 daltons, has a short half-life, and is heat-labile.
- It is present in the α-granules of the platelets.
- This is not vitamin K-dependent
- In the presence of factor VIII, it helps the normal coagulation process.
- This will deteriorate rapidly in the oxalate plasma and is slightly slow in the citrated plasma.
- This is consumed in the clotting process and not found in the serum.
- This helps as a cofactor to transfer prothrombin to thrombin.
- Congenital deficiency of Factor V is called parahemophilia.
- Factor V deficiency leads to:
- Gingival bleeding.
- Gastrointestinal bleeding.
- CNS bleeding.
- Umbilical bleeding.
- Acquired deficiency of factor V is seen in the case of antibodies and is also associated with liver disease, carcinoma, tuberculosis, and DIC.
- Bleeding tendency is seen when this is <10% where the normal value is 50 to 150% of normal.
- PT and APTT are prolonged in factor V deficiency.
- Thrombin time is normal.
- Treatment: These patients are treated with fresh or frozen plasma.
- Cryoprecipitate does not contain an adequate amount of factor V.
Proconvertin, Factor VII:
- This is beta-globulin with a molecular weight of 50,000 daltons.
- This has a half-life of 4 to 6 hours and is produced in the liver.
- This is a vitamin K- dependent factor.
- This factor is not destroyed or consumed during the clotting process, so it is found in the serum and in the plasma.
- This factor is activated by thromboplastin.
- The division of the coagulation system into intrinsic and extrinsic pathways does not found in vivo because activated factor VIIa can activate factor IX and X.
- Thromboplastin activates factor X.
- The deficiency of factor VII is very rare.
- This may be seen in liver diseases.
- Warfarin therapy.
- Dietary vitamin K deficiency.
- These patients develop deep muscle hematoma.
- These patients may have a joint hemorrhage.
- There may be epistaxis.
- There may be menorrhagia.
- PT is prolonged.
- APTT is normal (factor VII is not measured in this test).
- This may be seen in liver diseases.
- Diagnosis of factor VII deficiency needs one stage factor assay.
- Patients with <1% activity may have severe bleeding manifestation (normal factor VII value is 65 to 140% of normal).
- Treatment needed with fresh frozen plasma.
- Vitamin K supplementation.
- Prothrombin complex concentrates.
Factor VII deficiency:
|Tests||Normal /seconds||In the deficiency of factorVII|
|Prothrombin time (PT)||10.0 to 14.0||>20 seconds|
|Activated partial thromboplastin time (APTT)||23.0 to 36.0||>36.o seconds|
|Factor VII assay||1.0 U/mL||<0.01 U/mL|
|Russell’viper venom||<25.0||18.0 seconds|
Antihemophilic factor, Factor VIII:
- This factor is produced by the liver’s sinusoidal and endothelial cells.
- This is a glycoprotein with a molecular weight of 330,000 daltons and is a very important factor.
- Its synthesis site is not clear, but ideas are that it may be liver.
- Severe liver failure does not lead to its deficiency.
- It is considered that cells present in different organs like fibroblasts, lymphocytes, macrophages, and vascular endothelial cells may be a source.
- Factor VIII is present in the plasma, and is a complex with von Willebrand’s factor and circulates in plasma.
- This is a very labile factor.
- After the blood transfusion, its 50% activity is lost in 8 to 12 hours.
- It is stable in the fresh frozen plasma.
- The process of lyophilization will preserve its activity with a very small loss of it.
- Hemophilia is characterized by the deficiency of this factor VIII.
- This factor is consumed during clotting, so not found in the serum.
- This factor has different fractions and these are divided on the basis of molecular weight.
- High molecular weight type.
- A low molecular weight type.
- In hemophilia, classical factor VIII deficiency is deficient in the low molecular weight molecule, and high molecular weight molecule is normal.
- This is a cofactor for factor IX a + calcium and phospholipids complex converts factor X into Xa.
- Factor VIII is also an acute-phase protein.
Christmas factor, Factor IX:
- This is a stable protein factor. This is a single-chain glycoprotein with a molecular weight of 60,000 daltons.
- This is synthesized in the liver and is vitamin K- dependent.
- This takes part in the intrinsic pathway.
- This is not consumed during the clotting process.
- It has a half-life of 20 hours.
- This is also not consumed by aging and is present in the serum and plasma.
- There is no significant loss of storing blood or plasma at 4 °C for 2 weeks.
- This is also called antihemophilic factor B or Christmas factor.
- This is an essential component of the intrinsic thromboplastin generation system.
- This helps factor Va + factor VIIIa lead to their amplification.
Stuart-Prower factor, Factor X:
- This is alpha globulin with a molecular weight of 58,800 daltons.
- It is composed of a light chain and a heavy chain held together by a single disulfide bond.
- It requires Vitamin K for its synthesis in the liver.
- Its half-life is roughly 40 hours.
- This is also called thrombokinase.
- This is a relatively stable factor and is not consumed in the clotting process.
- This is found in serum and plasma.
- Factor Xa is inactivated by a serine protease inhibitor.
- This factor helps to convert prothrombin to thrombin.
Plasma thromboplastin antecedent, Factor XI:
- This is beta-globulin.
- This is also called antihemophilic factor C.
- This is partially consumed during clotting.
- This is found in the serum.
- Half-life a few hours.
- This is needed in the intrinsic pathway to form the thromboplastin generation cascade.
- Factor XI and factor XII are “contact factors” for the clotting.
Hageman’s factor, Factor XII :
- This is globulin.
- This is not consumed during clotting.
- Hageman factor + glass contact converted from the inactive active form.
- This is a surface contact factor.
- This is activated by collagen.
Fibrin stabilizing factor (Fibrinase), Factor XIII:
- This factor acts in the presence of Calcium.
- This is a serum factor.
- The addition of Ca++ and serum factor (Factor XIII) give rise to coarse to fibrin clot formation.
- This stabilizes polymerized fibrin monomer in the initial stage of clot formation.
- Factor VI does not exist.
Normal values of clotting factors
|Factors||Normal value Source 1||Normal value Source 2||Normal value Source 3|
Adult 200 to 400 mg/dL
Newborn 125 to 300 mg/dL
|200 to 400 mg/dL|
|Quantitation minimum hemostatic level mg/dL||Plasma concentration mg/dL|
|Factor II (Prothrombin)||10 to 15 mg/dL||80 to 120 % of normal||10 to 15|
|Factor III (Thromboplastin)|
|Factor IV (Ionized calcium)||4.60 to 5.08 mg/dL|
|Factor V (Labile Factor)||5 to 10 mg/dL||50 to 150% of normal||0.5 to 1.0|
|Factor VI||Not existing|
|Factor VII (Stable factor)||5 to 20 mg/dL||65 to 140% of normal||0.2|
|Factor VIII (Antihemophilic factor)||30 mg/dL||55 to 145% of normal||1.0 to 2.0|
|Factor IX (Christmas factor)||30 mg/dL||60 to 140% of normal||0.3 to 0.4|
|Factor X (Stuart factor)||8 to 10 mg/dL||45 to 155% of normal||0.6 to 0.8|
|Factor XI (Plasma thromboplastin)||25 mg/dL||65 to 135% of normal||0.4|
|Factor XII (Hageman factor)||50 to 150% of normal||2.9|
|Factor XIII (Fibrin-stabilizing factor)||2.5|
|Von Willebrand factor||1.0|