MLAB 1227: Coagulation
Keri Brophy-Martinez
Secondary Hemostasis
Part Two
Coagulation Cascade
• Consists of four interacting sets of reactions
▫ Complex formation on phospholipid membranes
▫ Intrinsic pathway activation
 Activated by trauma within vascular system where
endothelium is exposed
 Slow
 Utilizes enzymes and proteins present in the plasma
▫ Extrinsic pathway activation
 Activation occurs when TF enters the vascular system
 Fast
 Utilizes enzymes and proteins present in the plasma and
TF
▫ Common pathway
Complex formation
• Cascade occurs on cell surface membranes
• Subendothelial tissue and activated platelet
surfaces provide the phospholipid
• Clotting factors bind to phospholipid membrane
surface, which forms a complex of enzyme,
substrate and cofactor
Intrinsic/Contact Pathway
Activation
• Contact factors:
▫ Factors XII, XI, PK and HK
• Interaction of contact factors activate Factor X
• Activated in vitro, when exposed to and bound to
negatively-charged surfaces, such as glass,
kaolin, celite and ellagic acid
• Does not require Ca++
• Purpose
▫ Generation of Thromboplastic Activity
Intrinsic/Contact System: Next
steps
1. XII is activated
2. XIIa activates PK which loops
back and activates more XII
3. XIIa and HK convert XI to XIa
4. XIa and Ca++ ions covert IX to
IXa
5. IXa forms a complex with PF3
(from platelet membrane), Ca++
and VIII to activate X
Intrinsic/Contact Pathway:
Coagulation Factors
• Factor XII – Hageman Factor, Contact Factor
▫ Produced in liver
▫ Activated by negatively charged substances such as exposed
collagen. In vitro it is also activated by glass
▫ XIIa has several functions (which are aided by cofactor HMWK)
 activates XI
 converts prekallikrein (PK) to kallikrein to make more XII
 activates plasminogen in the fibrinolytic system
 Activates complement system
▫ Deficiencies of this factor causes no coagulation problems
Intrinsic/Contact Pathway:
Coagulation Factors
• Prekallikrein (PK), Fletcher Factor
▫ Produced in liver
▫ Circulates in plasma bound to HK
▫ PK is converted to kallikrein and has several functions:
 when converted to kallikrein by Factor XII it then
loops back and accelerates the activation of larger
amounts of Factor XII
 converts HK to kinins
 activates plasminogen
 activates the complement system
 acts as a chemoattractant factor to attract
macrophages
Intrinsic/Contact Pathway:
Coagulation Factors
• High molecular weight kininogen (HMWK/HK),
Fitzgerald Factor
▫ Produced in liver
▫ HMWK has several functions
 Acts as a cofactor with Factor XII to
 activate Factor XI
 convert Prekallikrein (PK) to kallikrein
 activating plasminogen
 Is converted to kinins by kallikrein which cause
 inflammatory reactions
 Pain
Intrinsic/Contact Pathway:
Coagulation Factors
• Factor XI – Plasma Thromboplastin
Antecedent (PTA), Rosenthal's
antihemophilic C factor
▫
▫
▫
▫
Produced in liver
HK is needed as a cofactor with XII for its activation
Can also be activated by thrombin
Needed for formation of plasma thromboplastin
Intrinsic/Contact Pathway:
Coagulation Factors
• Factor IX – Antihemophilic B Factor,
Plasma Thromboplastin Component
(PTC), Christmas Factor
▫ Produced in liver
▫ Vitamin K dependent
▫ Necessary to form plasma thromboplastin
Intrinsic/Contact Pathway:
Coagulation Factors
• Factor VIII – Antihemophilic A Factor
▫ MW = >1,000,000 (composed of several parts)
▫ Has two functional subunits: VIII:C and VIII:vWF (VIII:Ag and VIII:R)
▫ VIII:vWF Produced in endothelial cells and platelets; VIII:C production site
unknown
▫ Necessary for formation of plasma thromboplastin
▫ Abnormalities of Factor VIII are the most common hereditary coagulation
disorders (hemophilia A and vonWillebrands)
▫ Increased in pregnancy & inflammation
▫ Consumed during coagulation, not found in serum
▫ Heat labile: Deteriorates rapidly in stored plasma
Intrinsic/Contact Pathway
• Monitored by the Activated Partial
Thromboplastin Time (APTT)
• Detects abnormalities to factor VIII, IX, XI, XII
• Monitors heparin therapy
References
• McKenzie, Shirlyn B., and J. Lynne.
Williams. "Chapter 30." Clinical
Laboratory Hematology. Boston: Pearson,
2010. Print.