Coagulation – part 1 – Blood Coagulation process, Coagulation factors, and factors deficiency
Sample
- The plasma is needed, take 5 ml of venous blood and add sodium citrate as the anticoagulant.
- Perform the assay immediately or as soon as possible.
- For factors II, V, VII, and X, place the citrated plasma on ice immediately, and the sample is stable for 2 hours.
- Freeze if it is delayed >2 hours.
Purpose of the test (Indications)
- To measure the coagulation factor concentration in the blood.
- To find the inherited or acquired bleeding disorders.
- If there is a history of bruises or excessive bleeding.
- If there are prolonged PT or PTT.
- Acquired conditions like Vit. K deficiency or liver disease.
- Maybe advised to monitor the treatment of a patient with factor deficiency.
Pathophysiology
- Definition of blood coagulation:
- Blood coagulation is the process that consists of a series of biochemical reactions, that will transform the blood coagulation factors into an insoluble gel through the conversion of soluble fibrinogen into fibrin.
- Blood coagulation factors can be divided by physical properties:
- Contact proteins:
- Hageman factor (XII).
- Plasma thromboplastin component (XI).
- Prekallikeri (PK).
- High molecular weight kininogen (HMWK).
- Prothrombin protein:
- Prothrombin (II).
- Stable factor (VII).
- Christmas factor (IX).
- Stuart-Power factor (X).
- Fibrinogen group:
- Fibrinogen (I).
- Labile factor (V).
- Antihemophilic factor (VIII).
- Fibrin stabilizing factor (XIII).
- Contact proteins:
- Deficiency of these blood coagulation factors may be due to:
- inherited genetic defects.
- Acquired.
- Drugs therapy.
- Causes of acquired factor deficiency are:
- Snake venom.
- Liver diseases.
- Uremia.
- Vit. K deficiency.
- Anticoagulant ingestion of warfarin.
- Massive blood transfusion.
- Some of the cancers.
- Disseminated intravascular coagulopathy.
- There is a balance between the factors leading to clotting and the factors causing dissolution.
- The first reaction of the body to bleeding is constriction of the blood vessels.
- This will be effective in the small blood vessel injuries but not in the large blood vessels.
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Process of blood coagulation:
- In the large blood vessel injuries, there is the activation of the clotting factors to plug the injured site.
- Primary phase initiated by the platelets aggregation.
- The secondary phase is the activation of clotting factors.
- In phase three there is factor X is activated by proteases (VIIa, IXa with XIIIa).
- V1Ia can activate 1X and X directly.
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The blood clotting pathways are:
- The intrinsic pathway where the factor XII and other proteins form a complex on the injured endothelium.
- XII
XIIa
XI to XIa complex form of VIII + XI + X
- activated X is formed.
- Then the common pathway starts.
- XII
- The intrinsic pathway where the factor XII and other proteins form a complex on the injured endothelium.
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- The extrinsic pathway where there is a complex formation between Tissue factor (factor III or thromboplastin) and factor VII.
- Activated factor VIIa forms which stimulate factor X.
- Alternately factor VIIa activates factor IX and X.
- The extrinsic pathway where there is a complex formation between Tissue factor (factor III or thromboplastin) and factor VII.
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- Common pathway Xa
Prothrombin to Thrombin in the presence of factor V, calcium, and phospholipids on the surface of platelets.
- Thrombin
Fibrinogen Fibrin is
polymerized into the stable clot.
- Thrombin also activates factor VIII to stimulate platelet aggregation and fibrin polymerization.
- Prothrombin is Vit K dependent factor.
- Thrombin
- Common pathway Xa
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- Plasmin degenerates the fibrin polymer into fragments which are taken up the phagocytic cells.
- Fibrinogen is considered an acute phase protein and increased in many diseases.
- Factor XII deficiency observed as an increased risk of Myocardial infarction and venous thrombosis.
- Fibrinogen is also considered as a coronary risk factor and stroke.
- Determine the exact factor deficiency for the replacement therapy.
Normal values of clotting factors
Factors | Normal value Source 1 | Normal value Source 2 | Normal value Source 3 |
Fibrinogen |
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 |
- Reference values are different from various sources.
Fibrinogen
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Fibrinogen level increased is seen in:
- Acute inflammatory reactions.
- Trauma.
- Coronary heart disease.
- Cigarette smoking.
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Fibrinogen decreased level is seen in:
- Liver diseases like hepatitis and cirrhosis.
- DIC ( disseminated intravascular coagulopathy ).
- Fibrinolysis.
Prothrombin
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The decreased level is seen in:
- Vit.K deficiency.
- Liver disease.
- Oral anticoagulants.
- Circulating inhibitor or lupus-like anticoagulants.
- Decreased synthesis.
Factor V deficiency:
- Liver diseases.
- Factor V inhibitor.
- Myeloproliferative disorders.
- DIC and fibrinolysis.
- Mild decrease in the newborn.
Factor VII deficiency:
- Liver diseases.
- Kwashiorkor.
- Normal newborn.
- treatment with coumarin-like drugs.
Factor VIII
- Factor VIII increased in:
- Late normal pregnancy.
- Thromboembolic conditions.
- Liver diseases.
- Post-operative patients.
- Normal newborn.
- Rebound phenomenon after sudden stoppage of coumarin-like drugs.
- Factor VIII deficiency:
- due to the presence of factor VIII inhibitors.
- DIC.
- Von Willebrand disease.
- Myeloproliferative disorders.
Factor IX deficiency:
- Liver diseases and cirrhosis.
- Nephrotic syndrome.
- Anticoagulant antibody formation.
- Normal newborn.
- Drugs like Dicoumarol.
- DIC.
- Vit K Deficiency.
Factor X deficiency:
- Vit K deficiency.
- Liver Diseases.
- Oral anticoagulants.
- DIC.
- Amyloidosis.
- Normal newborn.
Factor XI deficiency:
- Liver diseases.
- Intestinal malabsorption leading to Vit K deficiency.
- DIC.
- Newborn.
Factor XII deficiency:
- Nephrotic syndrome.
- Liver diseases.
- Chronic myelocytic leukemia.
- Normal newborn.
Factor XIII deficiency:
- Postoperative patients.
- Liver diseases.
- In persistent increased fibrinogen level.
- Acute myeloid leukemia.
- DIC.
- circulating anticoagulants.
Diseases leading to coagulation factor deficiency:
Disease | Factor deficiency |
Disseminated intravascular coagulopathy | I, V, VIII (1, 5, 8) |
Liver diseases | I, II, V, VII, IX, X, XI (1, 2, 5,7, 9. 10, 11) |
Autoimmune diseases | VIII (8) |
Congenital deficiency | I, II, V, VII, VIII, IX, X, XI, XII (1, 2, 5, 7, 8, 9, 10, 11, 12) |
Vit K deficiency | II, VII, IX, X, XI (2, 7, 9, 11) |
Heparin therapy | II (2) |
Warfarin therapy | II, VII, IX, X, XI (2, 7, 9, 10, 11) |
Fibrinolysis | I, V, VIII (1, 5, 8) |