MLAB 1227: Coagulation Keri Brophy-Martinez

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MLAB 1227 CoagulationKeri Brophy-Martinez

• Secondary Hemostasis
• Part Two

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Intrinsic/Contact Pathway Coagulation Factors

• Factor VIII Antihemophilic A Factor
• MW gt1,000,000 (composed of several parts)
• Has two functional subunits VIIIC and VIIIvWF
  (VIIIAg and VIIIR)
• VIIIvWF Produced in endothelial cells and
  platelets VIIIC 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

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Intrinsic/Contact Pathway

• Monitored by the Activated Partial Thromboplastin
  Time (APTT)
• Detects abnormalities to factor VIII, IX, XI, XII
• Monitors heparin therapy

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References

• McKenzie, Shirlyn B., and J. Lynne. Williams.
  "Chapter 30." Clinical Laboratory Hematology.
  Boston Pearson, 2010. Print.