1. THROMBOSIS

2. Why don’t you bleed to death from a minor injury?
HAEMOSTASIS
Why don’t you bleed to death from a minor injury?
Successful haemostasis depends on
vessel wall
platelets
coagulation system
fibrinolytic system

3. Blood Vessels constrict to limit blood loss
arteries, veins, capillaries
mechanism not fully understood

4. Platelets adhere to damaged vessel wall adhere to each other
form a platelet plug
platelet release reaction

5. Platelet Release Reaction
ATP ADP
ADP, thromboxane A2 cause platelet aggregation
5HT, platelet factor 3 also released
PF3 important in coagulation
Platelets coalesce after aggregation

7. Coagulation
Cascade
Series of inactive components converted to active components
Prothrombin Thrombin
Fibrinogen Fibrin

8. Coagulation
1 ml of blood can generate enough thrombin to convert all the fibrinogen in the body to fibrin
Tight regulation therefore required
Balance of procoagulant and anticoagulant forces

9. Control of Coagulation
Thrombin destroys factors V and VIII
Thrombin inhibitors
anti-thrombin III*
alpha 1 anti-trypsin
alpha 2 macroglobulin
protein C and S*
* inherited deficiency may thrombosis

10. Plasminogen activators Fibrinolytic therapy widely used
Breakdown of fibrin
Plasminogen Plasmin
Plasminogen activators
Fibrinolytic therapy widely used
streptokinase
tPA

11. Endothelium Anti-thrombotic plasminogen activators prostacyclin
nitric oxide
thrombomodulin

12. Thrombosis Definition
Thrombosis is the formation of a solid mass of blood within the circulatory system
INAPPROPRIATE ACTIVATION OF THE HEMOSTATIC PROCESS IN UNINJURED VASCULATURE OR FORMATION OF THROMBUS IN THE SETTING OF RELATIVELY MINIMAL VASCULAR INJURY

13. FACTORS PREDISPOSING TO THROMBOSIS
virchows triad

14. ENDOTHELIAL INJURY Abnormalities of the vessel wall atheroma
direct injury
inflammation

15. ABNORMALITIES OF BLOOD FLOW
TURBULENCE
Endothelial injury
Local areas of stasis
Disrupt laminar flow
Moves platelets from center of flow to the vessel wall
Prevent dilution of activated clotting factors by flowing blood
Slow down the inflow of clotting factor inhibitors
Promotes endothelial cell

16. Abnormalities of blood components
HYPERCOAGUABILITY:
ANY ALTERATION OF THE COAGULATION PATHWAY THAT PREDISPOSES TO THROMBOSIS
PRIMARY (GENETIC)
FACTOR V GENE MUTATION AND PROTHROMBIN GENE MUTATIONS MOST FREQUENT
V becomes resistant to protein c inactivation
Prothrombin levels elevated
SECONDARY (ACQUIRED)
Bed rest – immobilization, post-op
obesity,
- smokers
cancer,
atrial fibrillation,
myocardial infarction,
tissue damage (surgery, burns)
post-partum

17. Appearances of thrombi- Arterial Thrombi Morphology i-
pale
granular
lines of Zahn
lower cell content

18. Arterial Thrombi Morphology
Adherent masses of blood that demonstrate areas of pale alternating with areas of red
Lines of Zahn

19. Arterial Thrombi Morphology

20. Arterial Thrombi Outcome
Similar to venous thrombi
Resolution
Organization/Incorporation/Recanalization
Embolization (arterial)
Propagation

21. Disseminated Intravascular Coagulation (DIC)
Sudden onset of fibrin thrombi in the microcirculation with consumption of coagulation factors and formation of fibrin degradation products
A potential complication of any disease state/process associated with the widespread activation of thrombin

22. Thrombi Morphology: Venous
Appearances of thrombi
Venous
soft
gelatinous
deep red
higher cell content
Usually occlusive
Red (because they form in stasis syndrome and have more associated enmeshed RBCs)
Long - forming a cast of vein with markings on them from venous valves
Red blood cells alternating with peripheral areas of fibrin

23. Venous Thrombi: Clinical

24. Venous Thrombi: Outcomes of thrombosis ( Fates): Lysis
complete dissolution of thrombus
fibrinolytic system active
bloodflow re-established
most likely when thrombi are small

25. Outcomes of thrombosis ( Fates):
Propagation
progressive spread of thrombosis
distally in arteries
proximally in veins

26. Outcomes of thrombosis
Organisation
reparative process
ingrowth of fibroblasts and capillaries (similar to granulation tissue)
lumen remains obstructed

27. Outcomes of thrombosis
Recanalisation
bloodflow re-established but usually incompletely
one or more channels formed through organising thrombus

28. Outcomes of thrombosis
Embolism
part of thrombus breaks off
travels through bloodstream
lodges at distant site

29. VENOUS THROMBI FATES

30. Effects of thrombosis Arterial Venous ischaemia congestion infarction
depends on site and collateral circulation
Venous
congestion
oedema
ischaemia
infarction

31. Coronary artery thrombosis

32. Coronary artery thrombosis