2. Hemostasis and thrombosis
• Hemostasis is a precisely
orchestrated process involving
platelets, clotting factors, and
endothelium that occurs at the
site of vascular injury and
culminates in the formation of a
blood clot, which serves to
prevent or limit the extent of
bleeding
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3. Hemostasis and thrombosis
• Normal hemostasis – rapid and localized hemostatic plug formation at a
site of vascular injury.
• Thrombosis
• Pathologic opposite to hemostasis.
• Inappropriate activation of normal hemostatic process:
• Clot (thrombus) in uninjured vessel
• Thrombotic occlusion of a vessel after minor injury
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4. • Both hemostasis and thrombosis depends on 3 components:
• Endothelium
• Platelet
• Coagulation cascade
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5. Normal
hemostasis
• Sequence of events at sites of
vascular injury:
I. Arteriolar vasoconstriction
II. Primary hemostasis (platelet
plug)
III. Secondary hemostasis – fibrin
deposition
IV. Permanent plug
• Polymerized fibrin and platelet
aggregate
V. Counter regulatory response
• Restricts hemostatic plug at site of
injury
• Tissue plasminogen activator
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7. So when does the process of
coagulation becomes pathologic?
• If body is unable to mount coagulation, bleeding diathesis
• Platelets (number, functional abnormalities)
• Clotting factor deficiencies
• Hemophilia A,B and C
• Vascular abnormalities
• Vasculitis or amyloidosis
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13. Endothelial injury
• Most important factor in thrombus formation
• Exposure to the highly thrombogenic sub endothelial ECM (collagen & tissue
factors) platelet adherence & contact activation
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14. Stasis or turbulence blood flow
• Normal blood flow is laminar.
• Stasis & turbulence brings platelets to the surface and reduce PGI2, t-PA
• Stasis is major factor in venous thrombi
• Turbulence is pathogenesis mzm for arteries and cardiac thrombosis
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15. Hypercoagulability
• Any alteration of the coagulation
pathway that predisposes to
thrombosis
• Primary hypercoagulable states
• Mutations in factor V (Leiden factor)
• Mutation in prothrombin gene
• Antithrombin III deficiency
• Protein C or S deficiency
Secondary hypercoagulable states
• High risk
• Prolonged immobilization
• Myocardial infarction
• Tissue damage
• Cancers
• DIC
• Low risk factors
• Atrial fibrillation
• Cardiomyopathy
• Oral contraceptives
• Smoking
• Hyper estrogenic states E.g –pregnancy
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16. Cont’d,…
• Don’t forget these terms
• Mural thrombi
• Vegetation
• The most common site of
arterial thrombi in increasing
order of frequency
• Femoral arteries
• Cerebral arteries
• Coronary arteries
• Common site venous
thromboembolism
• Leg veins
• Vena cava
• Dural venous sinuses
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18. Clinical significance
• Thrombi are clinically significant because:
• They can cause blood vessel obstruction (arterial thrombi causing myocardial
infarction) or
• Possible sources of emboli (venous thrombi causing pulmonary embolism, deadly
complication)
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19. Venous thrombosis
(phlebothrombosis)
• Affects the lower extremity
veins~90%
• Divided in to
• superficial and
• deep venous thrombosis
• Superficial VT
• Usually occurs in saphenous venous
system
• E.g in varicosities
• Predisposes to infection after
slight trauma Varicous Ulcer
• Rarely embolizes
• Causes local edema ,pain
,tenderness(i.e symptomatic
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20. Deep Vein Thrombosis (DVT)
• May embolize, hence serious
• Occurs in deep veins of calf muscles
• May cause pain or edema
• Asymptomatic in ~50%, because of collateral bypass channels. Might be
noted after causing pulmonary embolism.
• Higher incidence in middle aged & elderly people ,due to increased
platelet aggregation & decreased PGI2 by endothelium
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21. Predisposing factors to DVT
• Trauma, surgery, prolonged bed
rest
• Reduced physical activity
• Injury to vessels
• Procoagulant release from tissues
• Reduced t-PA activity (fibrinolysis)
• Pregnancy & puerperal states
• Increase coagulation factors &
decrease synthesis of antithrombic
substances
• Myocardial infarction & heart
failure stasis in the left side
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22. • Malnutrition, debilitating conditions (cancer) marantic thrombosis
• Inflammation of veins (thrombophlebitis)
• Migratory thrombophlebitis- unknown etiology
• sometimes associated with cancer, especially pancreatic cancer Trosseau
syndrome
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23. Arterial thrombosis
• Following abnormal vessel wall & turbulence is commonest predisposing
factor
• Myocardial infarction causing dyskinetic contraction & endocardial
damage.
• May narrow or occlude the lumen of arteries such as coronary &cerebral
arteries myocardial & cerebral infarctions respectively
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25. Causes of embolism
• Thrombus (90% cases)
thromboembolic
• Unless specified embolism
thromboembolism
• Platelet aggregates
• fragment of a tumor
• Less commonly, emboli are
composed of fat droplets, bubbles
of air or nitrogen, atherosclerotic
debris
(cholesterol emboli), tumor
fragments, bits of bone marrow,
or amniotic fluid
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26. • Thromboembolism, based on the
site of origin & impaction, is
divided in to:
• Pulmonary thromboembolism (PTE)
• Systemic thromboembolism
• Crossed embolism(paradoxical
embolism)
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27. Consequences
• Systemic embolization
• Ischemic necrosis (infarction) of downstream tissues, whereas
• Embolization in the pulmonary circulation
• Hypoxia, hypotension, and right-sided heart failure
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28. Pulmonary thromboembolism
• Embolus in the pulmonary
arteries & their branches
• Derived from thrombus in the
systemic veins or right side of
the heart.
• ~95% arise from deep leg veins and
follows venous return, pass
through heart and arrest pulmonary
arteries
a. If large thrombus block
right ventricle out flow or
bifurcation of the main
pulmonary trunk (saddle
embolus) or both of its
branches sudden
circulatory arrest and death
b. It may result in cor-
pulmonale or CVA collapse if
60% of blood volume is
obstructed
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29. Very small embolus (60-80% of cases)
• Clinically silent, obstruction of medium sized arteries these embolus
may cause pulmonary hemorrhage but not infarction, because
collaterals from bronchial circulation.
• But in poor cardiorespiratory condition, medium arteries obstruction
pulmonary infarction
• Small end-arterial vessel obstruction causes infarction.
• Recurrent thromboembolism pulmonary hypertension in the long
run
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30. Systemic thromboembolism
• 80% arise from intracardiac mural thrombi
• 2/3 of intramural thrombi associated with left ventricular wall infarcts & 25%
with dilated left atria (rheumatic heart diseases)
• Remainder originate from aortic aneurysms, thrombi overlying ulcerated
atherosclerotic plaques, fragmented valvular vegetations, or the venous system
(paradoxical emboli);
• 10% to 15% of systemic emboli are of unknown origin.
• Major sites of embolization: lower extremities(75%), brain(10%),
intestines, kidneys, spleen
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32. Fat Embolism
• Fat globules in the circulation
• Commonly - fractures of long bones or,
• Rarely - soft tissue trauma and burns.
• the fat enters the circulation by rupture of the marrow vascular sinusoids
or rupture of venules.
• 90% of individuals with severe skeletal injuries
• fewer than 10% of such patients show any clinical findings.
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33. • Fat embolism syndrome
• pulmonary insufficiency,
• neurologic symptoms,
• anemia, and
• thrombocytopenia and
• fatal in about 10% of cases.
• Typically, the symptoms appear 1 to 3 days after injury,
• sudden onset of tachypnea, dyspnea, and tachycardia.
• Neurologic symptoms - irritability and restlessness, with progression to delirium
or coma.
• The pathogenesis of this syndrome involves both mechanical obstruction and
chemical injury.
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34. Air Embolism
• Gas bubbles within the circulation can obstruct vascular flow (and cause
distal ischemic injury) almost as readily as thrombotic masses.
• Air may enter the circulation during obstetric procedures or as a
consequence of chest wall injury.
• in excess of 100 mL of air is required to produce a clinical effect;
• bubbles -> physical obstructions and may coalesce to form frothy masses
sufficiently large to occlude major vessels.
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35. Amniotic Fluid Embolism
• is a grave but uncommon complication of labor and the immediate
postpartum period (1 in 50,000 deliveries).
• mortality rate in excess of 80%.
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36. • Onset –
• sudden severe dyspnea,
• cyanosis, and
• hypotensive shock,
• seizures and coma.
• If the patient survives,
• pulmonary edema ,
• DIC - release of thrombogenic substances from amniotic fluid.
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38. Infarction
• Potential consequence of thromboembolic events Ischemic necrosis
Infarction
• Infarct – is an area of ischemic necrosis caused by occlusion of either the
arterial supply or venous drainage in a particular tissue
• ~99% of all infarction result from thrombotic or embolic events
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39. • Other mechanisms (mostly arterial)
• Local spasm
• Atheroma expansion due to hemorrhage in to atheromatous plaque.
• External compression of vessels, e.g. trauma (compartment syndrome)
• Entrapment of vessels at hernial sacs etc….
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40. Development and Types of infarcts
• Development and size of infarcts
• Nature of vascular supply,
collaterals
• Rate of development of occlusion
• Susceptibility of the tissue for
hypoxia
• Oxygen content of the blood
• Duration and severity of ischemia
• Types
• The basis of their color (reflecting
the amount of hemorrhage) in to:
• hemorrhagic (red) infarcts
• Anemic (white) infarcts
• Presence or absence of microbial
infection
• Septic infarcts
• Bland infarcts
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42. Types
• Red infarcts occur in:
• Ovarian torsion-venous occlusion
• In loose tissues (lung)
• Allow blood to collect in infarct zone
• Tissue with dual circulation
• In previously congested tissues
• Areas where blood flow
reestablished(arterial occlusion &
necrosis)
• White infarcts occur in:
• Arterial occlusion - in single artery
sites
• Solid organs - heart, spleen, kidney
• Why is this so? Show off your hands
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43. Clinical examples of infarction
• Myocardial infarction(MI)
• Following occlusion of coronary
arteries by thrombus formed on
ulcerating atheroma
• Is white infarct (why?)
• Can cause sudden death,
cardiac failure etc…
• Cerebral infarcts
• May appear as pale or hemorrhagic
• Can result in increased intracranial
pressure
• Is one type of cerebrovascular
accidents or stroke
• Lung infarcts
• Are typically dark red &conical
(wedge shaped, why?)
• Can result in hemoptysis, piercing
type chest pain
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44. Disseminated Intravascular
Coagulation (DIC)
• Acute or chronic thrombohemorrhagic disorder occurring as a result of
progressive activation of coagulation pathway beyond physiologic set
point due to disease resulting in failure of all components of hemostasis
• Hence the name consumptive coagulopathy
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45. Etiology and Pathogenesis
• DIC is not a primary disease
• Pathologic activation of coagulation system
• Massive or prolonged release of soluble tissue factors &/or endothelial derived
thromboplastin in to the circulation with generalized
• Two mechanisms to cause DIC
• Release of tissue factor or thromboplastin substance
• Wide spread injury to endothelial cells
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46. • Tissue thromboplastin is derived from trauma, burns, surgery, obstetrics
procedures like placenta, dead fetus or amniotic fluid; cancers like acute
promylocytic leukemia, adenocarcinoma of the lung
• In our set up commonly from gram negative sepsis, i.e. bacterial
endotoxin
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47. • Endothelial injury result from:-
• Ab-Ag complex deposition in lupus erythematosis
• Extreme temperature
• Hypoxia, acidosis, shock
5/28/2023 hemodynamics 47
