Secondary hemostasis

- Intrinsic and extrinsic coagulation

- Leading to formation of a stable fibrin clot around the platelet plug
- 3D process (takes place in surface platelet or endothelial cell pm)
- These pathways can occur in the absence of a cell surface
- 16 coagulation factors
o 8 are enzymes and 6 are cofactors
- Enzymes: serine protease – cleave peptide bonds and hace serine residue
- Inactivate enzyme are called zymogen
- Binding to phospholipid (Ca as a cofactor which makes enzyme more stable
and reactive)

Enzyme (2,7,9,10,11,12,13) (7) Cofactors (1, 3, 4, 5, 8 pre K) (6)

1. Factor II – prothrombin 1. Factor I –fibrinogen

2. Factor VII – stable factor
3. Factor IX – Christmas factor
4. Factor X – Stuart-Prower factor
5. Factor XI – plasma
thromboplastin
6. Factor XII – Hageman factor
7. Factor XIII – fibrin stabilizing
factor (FSF)
2. Factor III – tissue thromboplastin
3. Factor IV- plasma calcium
4. Factor V – Labile factor
5. Factor VIII – antihemophilic factor
6. Prekallikrein – Fletcher factor
(pre-K)

High molecular weigh kininogen (HMWK) – Fitzgerald factor

Platelet factor 3 –platelet phospholipid

1. 12 ->12a
2. 11 -> 11a
3. 9 -> 9a
4. 8 ->8a
5. 10 -> 10a
 Intrinsic pathway

- Factors that are involved: 12,11,10,9,8,5,2,1, pre K, and HMWK (11)

- This pathway is tested by APTT (activated partial thrombinplastin time)
- Intrinsic system is initiated by factor XII (Hageman factor)
- Damaged vascular will exposed negative charge subendothelial tissue
o Inactive factor 12 binds to the negative charge surface.
o The negative polarity activates factor 12 by causing the molecule to expose
serin
o 12 ->12a

XIIa reations

- There are 3 products of XIIa reactions

o 1. Prekallikrein (zymogen)
o 2. Plasminogen (zymogen)
o 3. Factor 12a

Prekallikrein

- Factor XIIa cleaves preK to produce bradykinin

- Bradykinin increase local vasodilation and membrane permeability to increase
blood flow
- Cofactor is HMWK

Plasminogen

- Factor XIIa cleaves plasminogen to an active form called plasmin that will initiate
clot dissolution reactions

Factor XIIa

- Activate factor 11 (PTA) to form 11a

CONTACT FACTOR COMPLEX = 12a, HMWK, prekallikrein

Note for factor XII

Deficiency factor 12 patients will develop: 1) PE 2) thrombotic disorder 3) develops clot

rather than BLEEDING

Factor XI (11) – plasma thromboplastin antecedent

- Factor 11 is activated by thrombin, 12a, and contact factor to become factor 11a
- Factor 11 deficiency is hemophilia C

Factor IX (9) – Christmas factor

1. Made in LIVER
2. Is vitamin K dependent
a. Vitamin K factors (5): 2,7,9,10, C and S
3. Factor 9 production is controlled by X chromosome -> factor 9 deficiency is
sex-linked
4. Factor 9 deficiency = Christmas disease = hemophilia B

What are 2 X-linked coagulopathies? (Hemophilia A (Factor 8 def.) and

hemophilia B)

5. Factor 9 bound to Ca and activated by factor 11a or 7a

Factor VIII (8) (fibrin stabilizing factor – FSF)

- Made in liver
- vWF as a carrier for factor 8
o each vWF monomer has 4 domains that bind 1) factor 8, 2) GP Ib/IX/V, 3) GP
IIb/IIIa and 4) collagen
o binding factor 8 to vWF to extend the factor’s lifespan
o factor 8 is activated to form factor VIII:c and combines with factor IXa 9a,
Ca, PF3 to form the tenase complex which activates factor X -> Xa
Note for Factor VIII

- deficiency factor 8 = hemophilia A = normal VWF

- deficiency vWF = decrease factor 8 = decrease vWF

Factor VIII and vWF

Factor VIII vWF

- activated by thrombin - activated by the release of granules
and damaged endothelial tissue
- X-linked - Autosomal dominant and recessive
- Made by liver - Made by endothelial cells and
megakaryocyte platelet

HEMOPHILIA – 8a 9b 11c