1. Hemodynamic Disorders
Hemodynamic Disorders
 Edema
 Edema
 Hyperemia and Congestion
 Hyperemia and Congestion
 Hemorrhage
 Hemorrhage
 Hemostasis and Thrombosis
 Hemostasis and Thrombosis
 Embolism
 Embolism
 Infarction
 Infarction
 Shock
 Shock
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2. THROMBOSIS -Virchow triad
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3. Thrombosis
Thrombosis
 Clot in an inappropriate site ––uninjured blood vessel
 Clot in an inappropriate site uninjured blood vessel
 DIC (Disseminated Intravascular coagulation)- multiple fibrin
 DIC (Disseminated Intravascular coagulation)- multiple fibrin
thrombi
thrombi
 Pathogenesis = Virchow’s triad
 Pathogenesis = Virchow’s triad
 1. Endothelial injury  loss of balance between Pro & Anti
 1. Endothelial injury  loss of balance between Pro & Anti
thrombotic effects of EC towards Pro; ↑Hemodynamic stresses ((HTN,
thrombotic effects of EC towards Pro; ↑Hemodynamic stresses HTN,
Turbulent blood flow); other damaging factors (Homocystinuria,
Turbulent blood flow); other damaging factors (Homocystinuria,
↑Cholesterol, smoking)
↑Cholesterol, smoking)
 2. Blood flow alterations  Turbulence (leads to EC injury, Stasis;
 2. Blood flow alterations  Turbulence (leads to EC injury, Stasis;
Turbulence & Stasis lead to  Platelet activation, Clotting factor
Turbulence & Stasis lead to  Platelet activation, Clotting factor
activation and accumulation, ↓inflow of clotting factor inhibitors, pts.
activation and accumulation, ↓inflow of clotting factor inhibitors, pts.
with AS, Aneurysms, Sickle cell, Hyper viscosity syndromes
with AS, Aneurysms, Sickle cell, Hyper viscosity syndromes
 3. Hypercoagulabulity  can be primary (genetic) or secondary
 3. Hypercoagulabulity  can be primary (genetic) or secondary
(acquired)
(acquired)
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4.  Hypercoagulabulity
 Hypercoagulabulity
 1. Primary  suspect in aapatient <50 yr old with
 1. Primary  suspect in patient <50 yr old with
recurrent thrombi in the absence of acquired risk factors
recurrent thrombi in the absence of acquired risk factors
 A). Most common ones  Mutations (point) in
 A). Most common ones  Mutations (point) in
Factor V & Factor II ((Prothrombin) Genes; lead to
Factor V & Factor II Prothrombin) Genes; lead to
venous thrombi (DVT),
venous thrombi (DVT),
 B). Rare ones Homocystinuria ((cause ↓Anti B). Rare ones Homocystinuria cause ↓Anti-
thrombin III & Endothelial Thombomodulin  lead to
thrombin III & Endothelial Thombomodulin  lead to
Arterial & Venous thrombi, Atherosclerosis)
Arterial & Venous thrombi, Atherosclerosis)
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5.  Hypercoagulabulity
 Hypercoagulabulity
 22.Secondary  Drugs, Autoimmune diseases
 . Secondary  Drugs, Autoimmune diseases
 A). Heparin induced Thrombocytopenia  in 5% of users of un A). Heparin induced Thrombocytopenia  in 5% of users of un-
fractionated (High Molecular weight) heparin, produce anti –platelet factor
fractionated (High Molecular weight) heparin, produce anti –platelet factor
44antibodies, also cause platelet dysfunction (bleeding), replaced by low
antibodies, also cause platelet dysfunction (bleeding), replaced by low
molecular weight heparin
molecular weight heparin
 B). Anti-Phospholipid Antibody syndrome  can be Primary
 B). Anti-Phospholipid Antibody syndrome  can be Primary
(without underlying cause) or Secondary ((SLE, Drugs, infections)
(without underlying cause) or Secondary SLE, Drugs, infections)
 Cause  Anti body against Phospholipid (cardiolipin) or epitopes of
 Cause  Anti body against Phospholipid (cardiolipin) or epitopes of
Prothrombin
Prothrombin
 In vitro ––Ab inhibits clot formation but in Vivo, promotes clotting.
 In vitro Ab inhibits clot formation but in Vivo, promotes clotting.
 False positive test with syphilis antigens ((cardiolipin)
 False positive test with syphilis antigens cardiolipin)
 Mechanism  inhibit PGI2, Platelet activation, interfere with Protein
 Mechanism  inhibit PGI2, Platelet activation, interfere with Protein
C activity
C activity
 Clinical  in aaclassic case, female with recurrent miscarriages,
 Clinical  in classic case, female with recurrent miscarriages,
recurrent arterial & venous thrombi, cardiac vegetations (Libman -recurrent arterial & venous thrombi, cardiac vegetations (Libman
Sack’s), Thrombocytopenia
Sack’s), Thrombocytopenia
 Rx  Anticoagulants in early stages, Immunosuppressant in advanced
 Rx  Anticoagulants in early stages, Immunosuppressant in advanced
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6. Thrombus - Morphology
Arterial
Arterial
 Almost always arise from
 Almost always arise from
heart
heart
 Grow in retrograde
 Grow in retrograde
fashion (direction of
fashion (direction of
flow)
flow)
 Forms at site of
 Forms at site of
Endothelial injury (AS),
Endothelial injury (AS),
turbulence (aneurysms)
turbulence (aneurysms)
 Pale/ white
 Pale/ white
 Lines of Zahn
 Lines of Zahn
 Firmly adherent to vessel
 Firmly adherent to vessel
wall
wall
 From emboli  Cause
 From emboli  Cause
infarctions (lower
infarctions (lower
extremities ––75%, Brain,
extremities 75%, Brain,
Kidney, spleen)
Kidney, spleen)
Venous
Venous
• Deep veins (popleteal 
• Deep veins (popleteal 
Femoral Iliac),
Femoral Iliac),
• Antigrade (towards heart• Antigrade (towards heartdirection of flow)
direction of flow)
• At site of stasis (lower
• At site of stasis (lower
extremities)
extremities)
•
•
•
•
•
•
Red //dark
Red dark
No lines of Zahn
No lines of Zahn
Loosely attached (easily
Loosely attached (easily
embolize)
embolize)
• Emboli cause Pulmonary
• Emboli cause Pulmonary
embolism ((silent in 50%
embolism silent in 50%
of pts.)
of pts.)
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7.  ? Arterial or venous thrombus
 ? Arterial or venous thrombus
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8. Thrombus - Morphology
• Venous
• Venous
• Loosely attached
• Loosely attached
(easily embolize)
(easily embolize)
• Red/ dark
• Red/ dark
• Post mortem clot
• Post mortem clot
• Not attached
• Not attached
• Chicken fat
• Chicken fat
supernatant
supernatant
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9.  Thrombi on heart valves --Vegetations
 Thrombi on heart valves Vegetations
 1. Infective acute ((staph. aureus), sub acute ((strep.
 1. Infective acute staph. aureus), sub acute strep.
viridians), cause infective Endocarditis (IE)
viridians), cause infective Endocarditis (IE)
 2. Sterile 
 2. Sterile 
 A). Autoimmune ––pts. With SLE ––Libman sack’s
 A). Autoimmune pts. With SLE Libman sack’s
((unique with vegetations on both Atrial & Ventricular
unique with vegetations on both Atrial & Ventricular
surfaces of valve)
surfaces of valve)
 B). Others  cancers, hypercoagulable states etc.,
 B). Others  cancers, hypercoagulable states etc.,
 Thrombi – Clinical features (by occlusion or
 Thrombi – Clinical features (by occlusion or
embolization)
embolization)
 Arterial – infarctions ((also called gangrene in lower limbs),
 Arterial – infarctions also called gangrene in lower limbs),
 Venous- DVT  PE
 Venous- DVT  PE
 Thrombi – Clinical course
 Thrombi – Clinical course
 Fresh or recent propagation, embolization, resolution
 Fresh or recent propagation, embolization, resolution
 Old  organization (inflammation, Fibrosis), Re
 Old  organization (inflammation, Fibrosis), Re
-canalization
-canalization
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10. Thrombi – Clinical course
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11. Thrombus
Arterial
Venous
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12. Organization & Recanalization
H&E-stained section
Stain for elastic tissue
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