Coagulation Factors: A Comprehensive Guide
Essential reference for medical professionals and students
Contact Activation (Intrinsic) Pathway
Factor XII (Hageman Factor)
Function:
- Initiates contact activation pathway
- Activates Factor XI
- Role in inflammation and complement activation
Laboratory Values:
- Half-life: 50-70 hours
- Synthesized in liver
- Vitamin K independent
Associated Conditions:
- Factor XII deficiency: Usually asymptomatic
- Prolonged aPTT but no bleeding tendency
- May have increased thrombotic risk
Factor XI (Plasma Thromboplastin Antecedent)
Function:
- Activated by Factor XIIa
- Activates Factor IX
- Contributes to thrombin generation
Laboratory Values:
- Half-life: 40-50 hours
- Synthesized in liver
- Vitamin K independent
Associated Conditions:
- Factor XI deficiency (Hemophilia C)
- More common in Ashkenazi Jews
- Variable bleeding tendency
- Treatment: Fresh Frozen Plasma or Factor XI concentrate
Factor IX (Christmas Factor)
Function:
- Forms tenase complex with Factor VIIIa
- Activates Factor X
- Essential for normal hemostasis
Laboratory Values:
- Half-life: 18-24 hours
- Synthesized in liver
- Vitamin K dependent
Associated Conditions:
- Hemophilia B (Christmas Disease)
- X-linked recessive inheritance
- Treatment options:
- Factor IX concentrate
- Recombinant Factor IX
- Extended half-life products
Factor VIII (Antihemophilic Factor A)
Function:
- Cofactor for Factor IXa
- Forms tenase complex
- Circulates bound to von Willebrand factor
Laboratory Values:
- Half-life: 8-12 hours
- Synthesized in liver and endothelium
- Vitamin K independent
Associated Conditions:
- Hemophilia A
- X-linked recessive inheritance
- Treatment options:
- Factor VIII concentrate
- Recombinant Factor VIII
- Extended half-life products
- Emicizumab (bispecific antibody)
Tissue Factor (Extrinsic) Pathway
Factor VII (Proconvertin)
Function:
- Binds to tissue factor
- Activates Factor X and Factor IX
- Initial trigger of coagulation
Laboratory Values:
- Half-life: 4-6 hours
- Synthesized in liver
- Vitamin K dependent
Associated Conditions:
- Factor VII deficiency
- Autosomal recessive inheritance
- Treatment options:
- Recombinant Factor VIIa
- Fresh Frozen Plasma
- Prothrombin Complex Concentrate
Common Pathway
Factor X (Stuart-Prower Factor)
Function:
- Forms prothrombinase complex with Factor Va
- Converts prothrombin to thrombin
- Central role in coagulation cascade
Laboratory Values:
- Half-life: 40-45 hours
- Synthesized in liver
- Vitamin K dependent
Associated Conditions:
- Factor X deficiency
- Amyloidosis
- Treatment options:
- Prothrombin Complex Concentrate
- Fresh Frozen Plasma
Factor V (Proaccelerin)
Function:
- Cofactor for Factor Xa
- Forms prothrombinase complex
- Regulated by Activated Protein C
Laboratory Values:
- Half-life: 12-15 hours
- Synthesized in liver and megakaryocytes
- Vitamin K independent
Associated Conditions:
- Factor V deficiency
- Factor V Leiden mutation (resistance to APC)
- Treatment options:
- Fresh Frozen Plasma
- Platelet transfusions
Factor II (Prothrombin)
Function:
- Converted to thrombin by Factor Xa
- Thrombin converts fibrinogen to fibrin
- Activates Factors V, VIII, XI, and XIII
Laboratory Values:
- Half-life: 60-72 hours
- Synthesized in liver
- Vitamin K dependent
Associated Conditions:
- Prothrombin deficiency
- Prothrombin G20210A mutation (thrombophilia)
- Treatment options:
- Prothrombin Complex Concentrate
- Fresh Frozen Plasma
Factor I (Fibrinogen)
Function:
- Converted to fibrin by thrombin
- Forms fibrin clot
- Supports platelet aggregation
Laboratory Values:
- Half-life: 100-120 hours
- Synthesized in liver
- Normal range: 200-400 mg/dL
Associated Conditions:
- Afibrinogenemia
- Hypofibrinogenemia
- Dysfibrinogenemia
- Treatment options:
- Fibrinogen concentrate
- Cryoprecipitate
- Fresh Frozen Plasma
Factor XIII (Fibrin Stabilizing Factor)
Function:
- Cross-links fibrin polymers
- Stabilizes fibrin clot
- Promotes wound healing
Laboratory Values:
- Half-life: 7-12 days
- Synthesized in liver and megakaryocytes
- Vitamin K independent
Associated Conditions:
- Factor XIII deficiency
- Clinical features:
- Delayed umbilical cord healing
- Intracranial hemorrhage
- Poor wound healing
- Treatment options:
- Factor XIII concentrate
- Fresh Frozen Plasma
- Cryoprecipitate
Natural Anticoagulants
Protein C and Protein S (Continued)
Function:
- Inactivates Factors Va and VIIIa
- Protein S acts as cofactor for Protein C
- Activated by thrombin-thrombomodulin complex
- Anti-inflammatory properties
Laboratory Values:
- Protein C half-life: 8-10 hours
- Protein S half-life: 42 hours
- Both vitamin K dependent
- Synthesized in liver
Associated Conditions:
- Protein C deficiency:
- Type I: Quantitative defect
- Type II: Qualitative defect
- Neonatal purpura fulminans
- Protein S deficiency:
- Increased thrombotic risk
- Pregnancy complications
- Treatment options:
- Protein C concentrate
- Fresh Frozen Plasma
- Anticoagulation
Antithrombin III (AT III)
Function:
- Primary inhibitor of thrombin
- Inhibits Factors IXa, Xa, XIa, XIIa
- Activity enhanced by heparin
- Major natural anticoagulant
Laboratory Values:
- Half-life: 48-72 hours
- Normal range: 80-120%
- Synthesized in liver
- Vitamin K independent
Associated Conditions:
- Antithrombin deficiency:
- Type I: Quantitative defect
- Type II: Qualitative defect
- Clinical manifestations:
- Venous thromboembolism
- Pregnancy complications
- Heparin resistance
- Treatment options:
- Antithrombin concentrate
- Direct oral anticoagulants
- Alternative anticoagulation strategies
Regulatory Proteins and Inhibitors
Tissue Factor Pathway Inhibitor (TFPI)
Function:
- Inhibits Factor VIIa/tissue factor complex
- Inhibits Factor Xa
- Regulates initiation of coagulation
Laboratory Values:
- Present on endothelial cells
- Released by heparin
- Multiple isoforms
Associated Conditions:
- TFPI deficiency: Rare
- Clinical significance:
- Potential thrombotic risk
- Role in cancer-associated thrombosis
Von Willebrand Factor (vWF)
Function:
- Carrier protein for Factor VIII
- Platelet adhesion to subendothelium
- Platelet-platelet interactions
- Essential for primary hemostasis
Laboratory Values:
- Half-life: 8-12 hours
- Synthesized in endothelium and megakaryocytes
- ABO blood group affects levels
Associated Conditions:
- Von Willebrand Disease types:
- Type 1: Partial quantitative deficiency
- Type 2: Qualitative defects
- Type 3: Complete deficiency
- Treatment options:
- Desmopressin (DDAVP)
- Von Willebrand factor concentrate
- Factor VIII/vWF complex concentrates
- Antifibrinolytic agents
Thrombomodulin
Function:
- Binds thrombin
- Activates Protein C
- Anticoagulant and anti-inflammatory properties
Laboratory Values:
- Expressed on endothelial cells
- Soluble form in plasma
- Levels increase with endothelial damage
Associated Conditions:
- Clinical significance:
- Sepsis
- DIC
- Inflammatory conditions
- Therapeutic applications:
- Recombinant thrombomodulin in development
- Potential treatment for DIC
