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Coagulation:- part 1 – Blood Coagulation process, Coagulation factors, and factors deficiency

September 14, 2023HematologyLab Tests

Table of Contents

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  • Blood Coagulation process
      • Sample for Blood Coagulation
      • Purpose of the test (Indications) for Blood Coagulation
      • Definition of blood coagulation:
      • Blood coagulation factors can be divided by physical properties:
    • Blood coagulation process:
      • The blood coagulation process is divided into three phases:
      • The first stage, the primary phase:
      • The second stage, the secondary phase:
      • The third stage, in Phase Three:
    •  The blood coagulation pathways are:
      • The intrinsic pathway:
      • The extrinsic pathway:
      • Common pathway:
        • Normal values of clotting factors:
      • The deficiency of  blood coagulation factors may be due to the following:
      • Causes of acquired factor deficiency are:
    • Various blood coagulation factors:
      • Fibrinogen:
      • Fibrinogen level increase is seen in:
      • Fibrinogen decreased level is seen in:
      • Prothrombin decreased level is seen in the following:
      • Factor V deficiency:
      • Factor VII deficiency:
      • Factor VIII increased in:
      • Factor IX deficiency:
      • Factor X deficiency:
      • Factor XI deficiency:
      • Factor XII deficiency:
      • Factor XIII deficiency:
        • Diseases leading to coagulation factor deficiency:
      • Questions and answers:

Blood Coagulation process

Sample for Blood Coagulation

  1. If the plasma is needed, take 5 ml of venous blood and add sodium citrate as the anticoagulant.
  2. Perform the assay immediately or as soon as possible.
  3. For factors II, V, VII, and X,  place the citrated plasma on ice immediately, and the sample is stable for 2 hours.
    1. Freeze if it is delayed >2 hours.

Purpose of the test (Indications) for Blood Coagulation

  1. To measure the coagulation factor concentration in the blood.
  2. To find the inherited or acquired bleeding disorders.
  3. If there is a history of bruises or excessive bleeding.
  4. If there is prolonged PT or PTT.
  5. Acquired conditions like Vit. K deficiency or liver disease.
  6. Maybe it is advised to monitor the treatment of a patient with factor deficiency.

Definition of blood coagulation:

  1. 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.
  2. The body’s first reaction to bleeding is constricting the blood vessels.
    1. This will be effective in small blood vessel injuries but not in large blood vessels.

Blood coagulation factors can be divided by physical properties:

  1. Contact proteins:
    1. Hageman factor (XII).
    2. Plasma thromboplastin component (XI).
    3. Prekallikeri (PK).
    4. High molecular weight kininogen (HMWK).
  2. Prothrombin protein:
    1. Prothrombin (II).
    2. Stable factor (VII).
    3. Christmas factor (IX).
    4. Stuart-Power factor (X).
  3. Fibrinogen group:
    1. Fibrinogen (I).
    2. Labile factor (V).
    3. Antihemophilic factor (VIII).
    4. Fibrin stabilizing factor (XIII).

Blood coagulation process:

  1. The blood coagulation process involves:
    1. Series of biochemical reactions.
    2. It transforms circulating substances into an insoluble gel.
    3. This gel is by the conversion of fibrinogen to fibrin.
    4. This whole process needs blood coagulation factors, phospholipids, and calcium.
  2. The blood coagulation process consists of:
    1. Extrinsic pathway.
    2. Intrinsic pathway.
  3. In blood vessel injuries, the clotting factors are activated to plug the injured site.

The blood coagulation process is divided into three phases:

The first stage, the primary phase:

  1. It is initiated by platelet aggregation.
  2. Platelets adhere to collagen and have changes in shape.
  3. Platelets degranulate and release:
    1. Ionized Ca++.
    2. Magnesium.
    3. Serotonin.
    4. Epinephrine.
    5. Phosphate.
    6. ADP and ATP.
    7. Alpha granules release fibrinogen, platelet-derived growth factor, plasminogen activator inhibitor, albumin, β-thromboglobulin, fibrinonectin, and factor V (absorbed from plasma).
    8. The release of these chemicals leads to secondary aggregation, which is irreversible.
  4. Ultimately, platelets change shapes and adhere to each other.
Role of Platelets in coagulation

Role of Platelets in coagulation

The second stage, the secondary phase:

  1. It is the activation of clotting factors.

The third stage, in Phase Three:

  1. The factor X is activated by proteases (VIIa, IXa with XIIIa).
  2. Va can activate IX and X directly.
  3. The above reaction is responsible for thrombus formation.
  4. The adherent and aggregated platelets release factor V and expose factor 3 to accelerate the coagulation process.
  5. It will stabilize the platelets plug with a fibrin clot.
Blood coagulation process

Blood coagulation process

 The blood coagulation pathways are:

The intrinsic pathway:

  1. It is initiated by foreign substances like collagen, subendothelium, or phospholipids, which will activate factor XII, involving contact factors and factor XI.
  2. Where factor XII and other proteins form a complex on the injured endothelium.
  3. XII   XIIa    XI to  XIa and form a complex of VIII + XI + X.
  4. Activated Xa is formed.
  5. Then, the common pathway starts.
Blood coagulation process: Intrinsic pathway

Blood coagulation process: Intrinsic pathway

Intrinsic pathway

Intrinsic pathway

The extrinsic pathway:

  1. It is a complex formation between the Tissue factor (factor III or thromboplastin) and factor VII.
  2. Activated factor VIIa forms, which stimulates factor X.
  3. Alternately, factor VIIa activates factors IX and X.
Blood coagulation process: Extrinsic pathway

Blood coagulation process: Extrinsic pathway

Blood coagulation process: Extrinsic pathway

Blood coagulation process: Extrinsic pathway

Common pathway:

  1. The common pathway starts with the activation of factor X by extrinsic or intrinsic pathways or both.
  2. (Xa)  converts  Prothrombin to Thrombin (active form)  in the presence of factor V, calcium, and phospholipids on the surface of platelets.
  3. Thrombin converts Fibrinogen to Fibrin polymerized into a stable clot.
  4. Thrombin also activates factor VIII to stimulate platelet aggregation and fibrin polymerization.
  5. Prothrombin is a Vit K-dependent factor.
Common pathway

Common pathway

Blood coagulation process: Common pathway

Blood coagulation process: Common pathway

Blood coagulation process: Coagulation pathways

Blood coagulation process: Coagulation pathways

  1. Plasmin degenerates the fibrin polymer into fragments that are taken up by the phagocytic cells.
  2. Fibrinogen is considered an acute-phase protein and is increased in many diseases.

Normal values of clotting factors:

Factors Normal value Source 1 Normal value Source 2 Normal value Source 3
  • Factor 1 (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 (Tissue Thromboplastin or tissue factor)
  • 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-Prower 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
  • High-molecular-weight kininogen (HMWK)
  • 6.0 to 9.0 mg/dL
  • Prekallikrein (PK)
  • 3.0 to 5.0 mg/dL
  • Reference values are different from various sources.

The deficiency of  blood coagulation factors may be due to the following:

  1. Inherited genetic defects.
  2. Acquired.
  3. Drugs therapy.

Causes of acquired factor deficiency are:

  1. Snake venom.
  2. Liver diseases.
  3. Uremia.
  4. Vit. K deficiency.
  5. Anticoagulant ingestion of warfarin.
  6. Massive blood transfusion.
  7. Some of the cancers.
  8. Disseminated intravascular coagulopathy.
  9. There is a balance between the factors leading to clotting and the factors causing dissolution.

Various blood coagulation factors:

  1. Factor XII deficiency was observed as an increased risk of Myocardial infarction and venous thrombosis.
    1. Fibrinogen is also considered a coronary risk factor that leads to stroke.
  2. Determine the exact factor deficiency for the replacement therapy.

Fibrinogen:

Fibrinogen level increase is seen in:

  1. Acute inflammatory reactions.
  2. Trauma.
  3. Coronary heart disease.
  4. Cigarette smoking.

Fibrinogen decreased level is seen in:

  1. Liver diseases like hepatitis and cirrhosis.
  2. DIC ( disseminated intravascular coagulopathy ).
  3. Fibrinolysis.

Prothrombin decreased level is seen in the following:

  1. Vit. K deficiency.
  2. Liver disease.
  3. Oral anticoagulants.
  4. Circulating inhibitors or lupus-like anticoagulants.
  5. Decreased synthesis.

Factor V deficiency:

  1. Liver diseases.
  2. Factor V inhibitor.
  3. Myeloproliferative disorders.
  4. DIC and fibrinolysis.
  5. Mild decrease in the newborn.

Factor VII deficiency:

  1. Liver diseases.
  2. Kwashiorkor.
  3. Normal newborn.
  4. Treatment with coumarin-like drugs.

Factor VIII increased in:

  1. Late normal pregnancy.
  2. Thromboembolic conditions.
  3. Liver diseases.
  4. Postoperative patients.
  5. Normal newborn.
  6. Rebound phenomenon after sudden stoppage of coumarin-like drugs.

Factor VIII deficiency:

  1. due to the presence of factor VIII inhibitors.
  2. DIC.
  3. Von Willebrand disease.
  4. Myeloproliferative disorders.

Factor IX deficiency:

  1. Liver diseases and cirrhosis.
  2. Nephrotic syndrome.
  3. Anticoagulant antibody formation.
  4. Normal newborn.
  5. Drugs like Dicoumarol.
  6. DIC.
  7. Vit K Deficiency.

Factor X deficiency:

  1. Vit K deficiency.
  2. Liver Diseases.
  3. Oral anticoagulants.
  4. DIC.
  5. Amyloidosis.
  6. Normal newborn.

Factor XI deficiency:

  1. Liver diseases.
  2. Intestinal malabsorption leads to Vit K deficiency.
  3. DIC.
  4. Newborn.

Factor XII deficiency:

  1. Nephrotic syndrome.
  2. Liver diseases.
  3. Chronic myelocytic leukemia.
  4. Normal newborn.

Factor XIII deficiency:

  1. Postoperative patients.
  2. Liver diseases.
  3. In persistent increased fibrinogen level.
  4. Acute myeloid leukemia.
  5. DIC.
  6. Circulating anticoagulants.

Diseases leading to coagulation factor deficiency:

Disease Factors 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)

Questions and answers:

Question 1: What oral contraceptives cause factor deficiency?
Show answer
Oral contraceptives cause deficiency of factor X.
Question 2: What will be the fibrinogen level in DIC?
Show answer
Fibrinogen level in DIC will be decreased.

Possible References Used
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