MLAB 1227: Coagulation Keri Brophy-Martinez

1
MLAB 1227 CoagulationKeri Brophy-Martinez

• Secondary Hemostasis
• Part Three

2
Extrinsic Pathway Activation

• Cell injury releases TF into vasculature
• TF provides the phospholipid component where the
  coagulation factors interact
• TF complexes with Ca and VIIa to activate X

3
Extrinsic PathwayCoagulation Factors

• Factor III Tissue Thromboplastin/Tissue Factor
  (TF)
• Manufactured in most body tissues especially
  lungs, brain, placenta, RBC membranes. Does not
  circulate unless damage occurs to tissues
• Purpose
• Attracts calcium ions to help the formation of
  procoagulant enzyme complexes.
• Converts prothrombin to thrombin

4
Extrinsic Pathway Coagulation Factors

• Factor VII Proconvertin (Stabile Factor)
• Produced in liver
• Vitamin K dependent
• Is especially sensitive to Coumadin anticoagulant
  therapy
• Purpose
• Activated by tissue thromboplastin(TF)

5
Extrinsic Pathway

• Monitored by the Protime (PT) test
• Monitors oral coagulation therapy such as
  coumadin, coumarin
• Detects abnormalities in Factor VII, exclusively,
  but can also pick up deficiencies in the common
  pathway

6
Common Pathway

• Activation of either or both pathways results in
  the conversion of factor X to Xa
• In the common pathway all prothrombin is
  converted to thrombin, which in turn is converted
  to fibrin on the phospholipid surface at the site
  of injury.

7
Common Pathway

• Thrombin enzyme not normally present in plasma.
  Three functions
• Converts fibrinogen (I) to fibrin (Ia)
• Causes potent platelet aggregation
• Aids in stabilizing fibrin clot by activating
  Factor XIII
• Activates Protein C to control the extent of
  clotting

8
Common Pathway Coagulation Factors

• Factor X Stuart Factor (Stuart-Prower)
• Produced in liver
• Vitamin K dependent
• Activated form acts with V, Ca and PF3 to form
  active thromboplastin

9
Common Pathway Coagulation Factors

• Factor V Proaccelerin (Labile Factor)
• Produced in liver
• Deteriorates rapidly in room temperature
• Purpose
• Essential in thromboplastin formation
• Increased in pregnancy inflammation
• Consumed during coagulation, not found in serum

10
Common Pathway Coagulation Factors

• Factor II Prothrombin
• Manufactured in the liver
• Vitamin K dependent
• Purpose
• Upon exposure to V, Xa, PF3 and Ca, it is
  converted to thrombin
• Stimulates platelet aggregation in presence of
  Ca

11
Common Pathway Formation of Fibrin

• Thrombin acts upon fibrinogen (Factor I) to form
  fibrin (Ia)
• Fibrin clot is stabilized by Factor XIII by
  crosslinking the fibrin polymers

12
Common PathwayCoagulation Factors

• Factor I Fibrinogen
• MW 341,000
• Normal value in plasma 200-400 mg/dl
• Manufactured in the liver
• Absent in serum
• Purpose
• Upon exposure to thrombin, forms fibrin

13
Common Pathway Coagulation Factors

• Factor XIII Fibrin Stabilizing Factor
• Produced in liver and platelets
• Necessary to form a stable clot causes a
  crosslinking of fibrin monomers

14
Misc Coagulation Factors

• Factor IV Calcium
• Obtained through diet and bone storage
• Needed in intrinsic and extrinsic pathways
• Removed by citrate
• Purpose
• Acts as a cofactor in many reactions of the
  coagulation cascade
• Needed for binding to the phospholipid surface,
  proper platelet function, XIII activation

15
Misc Coagulation Factors

• There is no Factor VI

16
Misc.

• All enzymatic reactions require a phospholipid
  surface, either supplied by the membranes of
  activated platelets (PF3) or damaged tissues
  (TF). This phospholipid requirement limits
  coagulation reactions to the site and prevents
  clotting.

17
HELP!!! How Will I Ever Get This Down.

• 1. Simplified enzymatic coagulation event
• VIII V
• XII ----XI---IX------X---------II-------IIa-------
  -I
• VII

18
Next steps

• Change the sequence to Arabic numerals
• 8 5
• 12119102T 1
• 7
• T thrombin

19
Learning the PT/PTT Pathways

• 8 5
• 12119102T 1
• 7
• T thrombin

PT
PTT
20
Vitamin K Dependant Factors

• C
• s s
• 8 5
• 12119102T 1
• 7
• Think of the central core for those requiring
  Vitamin K. Protein C and S also require Vitamin
  K.

Protein C inhibits factors 8 and 5. Indicated by
X
21
Extended Coagulation sequence

• 8 5
• 12119102T 1
• 7

13
22
Misc.
Thrombin sensitive factors Factors destroyed by
plasmin Factors found in platelets

• 8 5
• 12119102T 1
• 7

13
23
References

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