Coagulation System

Coagulation System


COAGULATION SYSTEM

  • Blood coagulation process – 
  • Cascade system involves activation of various coagulation factors in sequential fashion resulting in fibrin formation.

COAGULATION/CLOTTING FACTORS:

FACTOR NO. COAGULATION FACTOR HALF-LIFE IN HRS
Factor I Fibrinogen. 100-150
Factor II Prothrombin. 60 hrs
Factor III Thromboplastin/Tissue factor. 6 hrs
Factor IV Calcium ions.
Factor V Labile Factor 24 hrs
Factor VI Earlier referred as “Accelerin”. Now dropped.
Factor VII Stable factor/Earlier referred as “Pre-Accelerin”.
Factor VIII Anti-hemophilic globulin.  8-12 hrs
Factor IX Christmas Factor. 24 hrs
Factor X Stuart-Prower Factor.  45-52 hrs
Factor XI Plasma Thromboplastin Antecedent (PTA). 48-84 hrs
Factor XII Hageman factor. 150 hrs
Factor XIII Fibrin Stabilizing Factor/Laki Lorand factor.
HMWK High Molecular Weight Kininogen. 
Pre – K Pre-Kallikrein.
Ka Kallikrein.
PPL Platelet Phospholipids.

COAGULATION PATHWAYS:

  • Divided into – 
  • Intrinsic pathway (Contact pathway).
  • Extrinsic Pathway.

1. INTRINSIC PATHWAY:

  • Largely an “In Vitro” pathway.
  • Initiation of intrinsic coagulation pathway occurs when factor XII (Hageman factor/Contact factor) is exposed to negatively charged surface. 
  • Eg: With Glass, Kaolin etc.
  • Activates factor XII → Forming factor XIIa.
  • Factor XIIa hydrolyzes Pre-kallikrein to Kallikrein.
  • In turn, activates more XII → Forming XIIa.
  • Ultimately forms activation complex with Factor X entering common pathway.

2. EXTRINSIC PATHWAY:

  • Largely an in vivo pathway.
  • Activated by Factor III/Tissue factor/Thromboplastin at site of tissue injury.
  • First step in extrinsic pathway – 
  • Activation of factor VII (Pre-accelerin) by tissue factor (factor III).
  • Tissue factor is cofactor for both factor VII & VIIa (activated factor VII).
  • TF-VIIa complex catalyzes activation of factor X.
3. COMMON PATHWAY:
  • Common step in both intrinsic & extrinsic pathway –
  • Activation of Factor X.
  • Prothrombinase complex – 
  • Converts inactive prothrombin to active thrombin
  • Includes platelet phospholipid, factor V, factor X & factor IV (Calcium ions).
  • Prothrombin converts fibrinogen to fibrin.
  • Factor XIII – Also referred as “Fibrin stabilizing factor”
  • Gets activated by thrombin.
  • Results in covalent cross-linkages formation.
  • Provides three-dimensional strength to fibrin meshwork in clot.
  • Hence, stabilization of clot ensured.

IMPORTANT POINTS ON COAGULATION PATHWAYS:

1. Factors involved in intrinsic system –

  • XIII, XII, XI, IX, VIII, X, V, IV (Ca2+), Prothrombin & fibrinogen.

2. Factors involved in extrinsic system –

  • VII, III, IV (Ca2+), X, V, Prothrombin, Fibrinogen & XIII.

3. Factor II, VII, IX, & X – Vitamin K dependent factors.

4. ln vivo coagulation is predominantly occurring via extrinsic pathway.

5. In vitro coagulation is predominantly occurring via intrinsic pathway.

6. Most clotting factors are synthesized in liver.

  • Except for a component of factor VIII.

7. Factor VIII has 2 components –

  • Factor VIIIc (coagulant factor VIII) – Synthesized in liver (main source) & kidney.
  • Von Willebrand factor (vWF) – Synthesized in endothelium (main source) & megakaryocytes.

FIBRINOLYTIC SYSTEM:

 

  • Coagulation balanced with fibrinolysis to limit hemostatic plug to injury site.
  • Injured vascular endothelium secretes plasminogen activator.
  • Converts inactive plasminogen to active plasmin.
  • Plasmin breaks down fibrin.
  • Resulting in production of fibrin degradation products.
  • Fibrinolytic system is regulated by Plasminogen Activator Inhibitors (PAI’s).
  • Secreted by endothelium.

REGULATION OF PROCESS OF CLOTTING:

  • Natural anticoagulants involved in regulation:

1. Anti-thrombin III –

  • Most important.
  • Contributes 75% of Anti-thrombin activity.
  • Binds to heparin-like molecules on endothelial surface.
  • In turn, this complex inhibits factor II (thrombin).
  • Also inhibits factor IX, X, XI & Xll.

2. α2 – Macroglobulin – 

  • Contributes most of remaining anti-thrombin activity.

3. Heparin cofactor II & α2 – Antitrypsin – 

  • Minor inhibitor of prothrombin under physiological conditions.

4. Protein “C” & “S” –

  • Are Vitamin K dependent proteins.
  • Thrombomodulin bind to thrombin.
  • This complex activates protein ‘C’.
  • Along with protein’S’ (as co-factor) →  Inactivates Factor V & VIII.

5. Tissue factor pathway – 

  • Secreted by endothelium,
  • Inactivates tissue factor VII & factor X.
Exam Question
 

COAGULATION SYSTEM

COAGULATION FACTORS/CLOTTING FACTORS:

FACTOR NO. COAGULATION FACTOR
Factor I Fibrinogen.
Factor II Prothrombin.
Factor III Thromboplastin/Tissue factor.
Factor IV Calcium ions.
Factor V Labile Factor.
Factor VI

Earlier referred as “Accelerin”. Now dropped.

Factor VII Stable factor/Earlier referred as “Pre-Accelerin”. 
Factor VIII Anti-hemophilic globulin. 
Factor IX Christmas Factor.
Factor X Stuart-Prower Factor. 
Factor XI Plasma Thromboplastin Antecedent (PTA).
Factor XII Hageman factor.
Factor XIII Fibrin Stabilizing Factor/Laki Lorand factor.
HMWK  High Molecular Weight Kininogen. 
Pre – K Pre-Kallikrein.
Ka Kallikrein.
PPL

Platelet Phospholipids.

HALF-LIFE OF CLOTTING FACTORS:

FACTOR HALF-LIFE IN HRS.
Prothrombin 60 hrs
Factor VIII/Anti-hemophilic globulin. 8-12 hrs.

COAGULATION PATHWAYS:

1. INTRINSIC PATHWAY:

  • Largely an “In Vitro” pathway.
  • Initiation of intrinsic coagulation pathway occurs when factor XII (Hageman factor/Contact factor) is exposed to negatively charged surface. 
  • Factor XIIa hydrolyzes Pre-kallikrein to Kallikrein.

2. EXTRINSIC PATHWAY:

  • Activated by Factor III/Tissue factor/Thromboplastin at site of tissue injury.
  • First step in extrinsic pathway – 
  • Activation of factor VII (Pre-accelerin) by tissue factor (factor III).
3. COMMON PATHWAY:
  • Common step in both intrinsic & extrinsic pathway –
  • Activation of Factor X.
  • Prothrombinase complex – 
  • Converts inactive prothrombin to active thrombin
  • Includes platelet phospholipid, factor V, factor X & factor IV (Calcium ions).
  • Prothrombin converts fibrinogen to fibrin.
  • Factor XIII – “Fibrin stabilizing factor”.

IMPORTANT POINTS ON COAGULATION PATHWAYS:

1. Factors involved in intrinsic system –

  • XIII, XII, XI, IX, VIII, X, V, IV (Ca2+), Prothrombin & fibrinogen.

2. Vitamin K dependent factors – 

  • Factor II, VII, IX, & X.

3. Von Willebrand factor (vWF) –

  • Mainly synthesized in endothelium.

4. Plasmin breaks down fibrin.

REGULATION OF CLOTTING PROCESS:

1. α2 – Macroglobulin – 

  • Contributes most of remaining anti-thrombin activity.

2. Heparin cofactor II – 

  • Minor inhibitor of prothrombin under physiological conditions.

3. Protein “C” & “S” –

  • Are Vitamin K dependent proteins.
  • Inactivates Factor V & VIII.
Don’t Forget to Solve all the previous Year Question asked on Coagulation System

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