1. Due to ? The above figure in the lung is mostly due to
a. Increased capillary hydrostatic pressure
b. Tuberculosis of lung
c. Lymphatic fibrosis
d. Decreased plasma osmotic pressure
e. Acute lobar pneumonia
Due to ?

2. Thrombosis
Dr. Riham Abu-Zeid
Prof. of Pathology

3. ILOS By the end of the Lecture you will be able to:
Define thrombus
Differentiate between thrombus and clot
Explain the pathogenesis of thrombosis
Describe a thrombus
List sites of thrombosis
Explain the fate of a thrombus
Explain clinical effect/outcome of a thrombus

4. Which one is a thrombus? Test tube with a blood sample
-Intact endothelium > blood flow by inhibiting activation of platelets and coagulation factors
-Endoth cells (stim by injury or inflamm cytokines)upregulate exp of procoagulant factors and inhibit anticocoagulant factors
-Loss of endoth>expose vWF BM collagen >plt adhesion,activation and clot formation
Test tube with a blood sample
Artery seen during a surgery

5. Thrombus What? When? Where ? Why? solid mass during life within CVS
Mechanism

6. Thrombus
A solid mass formed of blood elements that develops within CVS during life
Normal hemostasis is a consequence of tightly regulated processes that maintain blood in a fluid, clot-free state in normal vessels while inducing the rapid formation of a localized hemostatic plug at the site of vascular injury.
thrombosis; The pathologic form of hemostasis in uninjured vessels( disturbed flow ) or minor injury.
the vascular wall, platelets, and the coagulation cascade
NB:Clotting: transformation of soluble fibrinogen into a fibrin network outside body-or after death

7. Mechanism of thrombus formation1
Endothelial injury 2
Platelet Adhesion >Platelet Activation>
Activation of intrinsic coagulation pathway
Concomitantly injured endothelial cells (due to injury/ dysfunction) Tissue factor >
Activation of extrinsic coagulation pathway 3
LINES of Zahn
Platelets >ridges =Pale areas
Between it Fibrin & RBCs & WBCs = red areas

8. Predisposing Factors for pathogenesis of thrombosis
Why does a thrombus happen ?
Virchow’s Triad

9. How does endothelial injury initiate thrombosis?

10. A. Endothelial injury Tissue factor > Platelet adherence
Endothelial damage
Exposure of subendoth COLLAGEN & ECM factors
Tissue factor >
activate extrinsic coagulation pathway
Depletion (Local)of
Prostacyclin?(prevents adhesion)
Plasminogen?(fibrinolytic)
Platelet adherence
The balance between endothelial anti- and prothrombotic activities determines whether thrombus formation, propagation, or dissolution occurs. At baseline, endothelial cells exhibit antiplatelet, anticoagulant, and fibrinolytic properties;
Activated endoth after injury (mech –dysfunction –turbulance) shift occurs and they acquire numerous procoagulant activities
Prostacyclin prevents platelet adhesion
Plasminogen has fibrinolytic effect
PGI2 (prostaglandin I2)>> prevents plt adhesion(anticoagulant)
tissue factor>activate extrinsic coag factor
Activation of intrinsic coagulation pathway
Fibrinogen>fibrin

11. A. Endothelial injury Endothelial inj.
-Exposure of subendothelial collagen
-Platelet adherence
Tissue factor release
Local depletion of
Prostacyclin (prevent plt adhesion )
Plasminogen (fibrinolytic)
heart :Myocardial infarction
arterial :atherosclerosis
inflammation
trauma
Endothelial inj.

12. How does alteration of blood flow
(turbulence /stasis) initiate thrombosis?
  turbulance :chaotic property اضطراب

13. B. Altered blood flow Turbulence Stasis Dilated chambers (M.S)
eg . Atherosclerotic plaques
sites of bifurcation
Stasis
Dilated chambers (M.S)
Myocardial infarction
Varicose Veins
Small vessels in polycythemia
Stasis also in small vessels in polycythemia
disturbed flow Promote Endothelial activation (through flow induced changes in endothelial gene expression
Laminar flow : plts and white blood cells are in the center separated from endothelium by slow moving plasma
pd to local thrombosis & leuc adhesion

14. B. Stasis & turbulence Retard inflow of clotting factors inhibitors
Mechanism of thrombosis due to stasis/turbulance
Retard inflow of clotting factors inhibitors
No dilution of clotting factors
Disturbed laminar flow>
Platelet adhesion
inhibitor CF CF CF
Endothelial activation
No dilution of activated clotting factors by fresh –flowing blood
Retard inflow of clotting factors inhibitors…….Permit build up of thrombi

15. B. Altered blood flow Stasis & turbulence
1-Disturb Laminar flow
Platelets come in contact with endothelium
2-Endothelial activation >local thrombosis
3-Prevent dilution of activated clotting factors
4-Retard inflow of clotting factors inhibitors
Altered flow
Stasis/turbulance

16. How does hypercoagulability cause thrombosis?

17. C.Hypercoagulability
Any alteration of the coagulation pathway that predispose to thrombosis
Genetic
Acquired (secondary)
Prolonged bed rest
Cancer
Advanced age
Fractures
Surgery
Burns
I. Overactivation of clotting factors (mutation in factor V or prothrombin gene)
II.
Deficiency of anticoagulants
Hypercoagulability is associated with oral contraceptive use and the hyperestrogenic state of pregnancy, probably related to increased hepatic synthesis of coagulation factors and reduced synthesis of antithrombin III.
In disseminated cancers, release of procoagulant tumor products predisposes to thrombosis.
The hypercoagulability seen with advancing age has been attributed to increasing platelet aggregation and reduced endothelial PGI2 release. (normally inhibits plt adhesion)
Smoking and obesity promote hypercoagulability by unknown mechanisms.
Surgery and trauma > vascular inj >procagulant release > release of clotting factors from liver

18. Conditions associated with thrombosis and their pathogenesis
Hyperestrogenic states
e.g pregnancy &OCP
Increased hepatic synthesis of coagulation factors & decrease prothrombin III (anticoagulant)
Thrombosis
Cardiac
Stasis
Trauma

19. Release of pro-coagulant tumor products
Cancer
Increased platelets aggregation and decrease PGI2 (normally inhibits adhesion)
Old age
Release of anti-phospholipid antibodies….> induce platelets aggregation
inhibit PGI2
dec. protein C (normal anticoagulant)
SLE
PGI2 release. (normally inhibits plt adhesion)
Protein C is normally an anticoagulant

20. A thrombus is formed of
Fibrin and red blood cells
Red blood cells and white blood cells
Platelets, fibrin threads ,red blood cells and white blood cells
Fibrin ,red blood cells and white blood cells

21. Describe a thrombus (Mixed )
Gross :
Intravascular
solid mass
showing pale strands (laminations) alternating with red areas
Usually vein in slow blood
Pale and red thrombi

22. Describe a thrombus Lines of Zhan Microscopic Platelets (pale)
Occlusion of the lumen by a mass adherent to the vessel wall.
shows pale areas :fused platelets and fibrin perpendicular to wall of blood vessel (lines of Zahn)
alternating with dark red areas :
entangled red blood cells
and WBCs.
Q1.In flowing blood
Q2 No
Platelets
(pale)
Fibrin ,RBCs,
Leucocytes
Dark red

23. Fate of Thrombus Dissolution if small and early
Enaymaic degradation by lysosomal enz
Dissolution is the result of fibrinolytic activation, which leads to rapid shrinkage and even total lysis of recent thrombi. With older thrombi, extensive fibrin polymerization renders the thrombus substantially more resistant to proteolysis, and lysis is ineffectual. This is clinically significant because therapeutic administration of fibrinolytic agents (e.g., t-PA in the setting of acute coronary thrombosis) is generally effective only within a few hours of thrombus formation.
Organization with persistance of on or more capillaries in the fibrosed tissue …..recanaliztion
It is result of fibrinolytic activation, which leads to rapid shrinkage and even total lysis of recent thrombi.
With older thrombi, extensive fibrin polymerization makes thrombus more resistant to proteolysis
Thus therapeutic administration of fibrinolytic agents is effective only within a few hours of thrombus formation
-arterial thrombi :retrograde
-venous thrombi: extend in the direction of blood flow toward the heart
Organization>Ingrowth of endothelial cells –smooth muscles –fibroblasts> contracts restore flow
OR organization persistance of one or more capillaries in the fibrosed thrombus
Formation of capillary channels>recanalize
; arterial thrombi tend to grow in a retrograde direction from the point of attachment, while venous thrombi extend in the direction of blood flow (thus both tend to propagate toward the heart). The propagating portion of a thrombus tends to be poorly attached and therefore prone to fragmentation, generating an embolus.
Dissolution by fibrinolysis
;recent thrombi
Calcification
(phlebolith)
Dislodgement
Enzymatic fragmentation

24. Dissolution by fibrinolysis 2. Embolization
3. Organization Propagation
5. Calcification
Organization and recanalization
Organization & incorporation into wall

25. Site Morphology Pale thrombus Red thrombus
Rapidly flowing blood (arteries )
Nearly stagnant) blood
(adj. to vascular occlusion)
Morphology
Firm pale
Red gelatinous
Mainly platelets
Few platelets +mainly RBCS,WBCS +Fibrin
Red thrombus sometimes indistinguishable from clot
Pale in artery : main process is endothelial inj.> more platelet adherence
Red thrombi in vein occur dt activity of clotting factors (stasis)
plt have secondary role sluggish circ.:allow more RBCs to be trapped
result of activation of the coagulation cascade, and platelets play a secondary role. Because these thrombi form in the sluggish venous circulation, they also tend to contain more enmeshed erythrocytes and are therefore called red, or stasis, thrombi. The veins of the lower extremities are most commonly affected (90% of venous thromboses); however, ve
Mixed:
in slowly flowing blood: veins
a red thrombus interrupted by a pale thrombus at site of anastomosis

26. Where does a thrombus occur?
Vein
Artery
Heart
Capillaries
All of the above
jbArtery or cardiac occurs at site of endoth inj while venous at stasis
Veins are most frequent due to:
1. Weak, thin wall (superficial or deep veins)
2. Low pressure & velocity

27. Sites of thrombi A.Cardiac B.Arterial C.Venous D.Capillary
Mural :on mural endocardium
Vegetation :on valve _
B.Arterial
C.Venous
D.Capillary
Phlebothrombosis
Thrombophlebitis
thrombosis in veins without inflammation
thrombosis in veins with inflammation
Mural
Cardiac and arterial more common dt endoth inj –turbulance
Venous more dt stasis
In the dilated left atrium in mitral stenosis or myocardial infarct , where they may be attached to the wall (mural thrombus )
or are free in the atrial lumen and may plug the mitral valve (ball-valve thrombus).
Thrombosis in arteries: at sites of endothelial injury, most commonly due to atheroma (Fig.7.13), turbulence (arterial bifurcation) or stasis (aneurysms).
Migratory thrombophlebitis
Vegetation

28. A. Cardiac May be free and plug the valve (ball-valve)
Dilated Left atrial mural thrombus in MS
Large mural thrombus on top of myocardial infarction
May be free and plug the valve (ball-valve)
Valvular :These may occur in various forms of endocarditis, and hypercoagulability.
Aortic Valve Thrombi=vegetation

29. B.Arterial Pale at the periphery (old organized part)
Lumen is obliterated with a laminated thrombus
Pale at the periphery (old organized part)
Dark in the center
(recent thrombus)

30. B. Arterial On endoth. injury dt. atheroma Turbulence at bifurcation
Stasis as aneurysm
Occluding thrombus in small arteries coronary–cerebral

31. Propagates towards heart
c. Venous thrombosis
Stasis occurs proximal to occlusion .
propagating thrombus
end by embolus (to the lung).
Extend in direction of blood flow, i.e: toward the heart.
1-Phlebothrombosis
Saphenous
Varicosities
Superficial
Popliteal-femoral
Bed rest-CHF-trauma –surgery
Deep
Propagates towards heart

32. Deep Venous Thrombosis
In large leg veins or a above knee veins (popliteal-femoral)
Local pain and edema
Circumvented ( compensated) by collaterals
>50% are silent ie. pass unnoticed
Embolize to lung more commonly than superficial vein thrombosis
(may be 1st symptom)
Swollen, painful, dusky red left lower limb
Assoc. with stasis & hypercoagulability states (remember)
Can occur in healthy ambulatory people without abnormality
Deep venous thrombosis (DVT)

33. After ionizing radiation
c. Venous thrombosis
2-Thrombophlebitis
Damage of vein after inflammation ….> thrombosis.
Aseptic
After ionizing radiation
Inflammation …...> thrombosis
Septic
Septic emboli
Pyaemic abscess

34. 3-Migratory Thrombophlebitis (Trousseau’s Syndrome)
C.Venous thrombosis
3-Migratory Thrombophlebitis (Trousseau’s Syndrome)
= Recurrent attacks of multiple venous thrombosis at different and changing sites:
in association with various forms of cancer especially cancer pancreas.
Due to release of procoagulant substances by the cancer cells.
Multiple thrombosis in
superficial and deep veins

35. D. Capillary
Inflammation
DIC

36. Effects of thrombosis Venous Arterial Congestion & Edema
distal to obst.
Embolize
Infarction
Pyemic abscess
Massive pulm. embolism
ischemia eg.coronary/cerebral
Infarction/gangrene
Embolize as venous
Embolize> infarction –pyemic abscess -massive embolism

37. DIC Obstetric complications Advanced Malignancy
Wide spread of fibrin thrombi
Circ. insufficiency
Consumption of platelets & coagulation proteins
Fibrinolytic mechanisms are activated
Serious bleeding
are not usually visible on gross inspection, they are readily apparent microscopically

38. Difference between thrombus and clot
During life inside CVS
Postmortem or outside body
In flowing blood
Stagnant blood
Adherent to vessel wall
Not adherent
Firm & friable
Soft and gelatinous
Pale or red(stasis) with pale strands (laminations =platelets)
Red (no pale strands)
Platelets +fibrin+RBCS+WBCS fibrin+RBCS+WBCS
Clotting: transformation of soluble fibrinogen into a fibrin network

39. Which one is a thrombus a b
b (intravascular)

40. A 55 year old male had a major surgery and has been recombinant in bed for 2 weeks. He has been complaining of pain in his thigh above popliteal fossa with slight hotness
Angiogram revealed a thrombus
Do you expect to find a it in the veins or the arteries?

41. State true or false and correct the false statement
Vegetation is a thrombus in a vein
Stasis retards inflow of clotting factor inhibitors and this contributes in thrombus formation
3. White strands in thrombus are formed of leucocytes
4. Migratory thrombophlebitis is multiple emboli in different sites F T F F

42. Thrombosis Fate of Thrombosis Effects of thrombosis
Pathogenesis
Fate of Thrombosis
Sites: cardiac , arterial venous, capillary
Effects of thrombosis
Types of thrombi :Pale /Red