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Hemodynamic Disorders
Edema Hyperemia and Congestion Hemorrhage Hemostasis and Thrombosis Embolism Infarction Shock
Hemodynamic Disorders
Edema Hyperemia and Congestion Hemorrhage Hemostasis and Thrombosis Embolism Infarction Shock
Dr. Krishna Tadepalli, MD, www.mletips.com
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Feature Hemostasis Thrombosis
What is it? Blood clot Blood clot
Where is it? Site of vascular injury
In an uninjured vessel
Why is it? Trauma (common)
Atherosclerosis
What happens later?
Stops blood loss (deserved effect)
Produce complications (Emboli)
Dr. Krishna Tadepalli, MD, www.mletips.com
2
Hemostasis Events following vascular injury 1. transient vasoconstriction ( by neurogenic
mechanisms, Endothelin – vasoconstrictor of Endothelial cells), reduce blood loss
2. Primary Hemostasis formation of Primary haemostatic plug ( by platelet adhesion, activation & Aggregation),
3. Secondary Hemostasis Platelets + Fibrin
( from coagulation pathways- either intrinsic or extrinsic), forms secondary haemostatic plug
Hemostasis Events following vascular injury 1. transient vasoconstriction ( by neurogenic
mechanisms, Endothelin – vasoconstrictor of Endothelial cells), reduce blood loss
2. Primary Hemostasis formation of Primary haemostatic plug ( by platelet adhesion, activation & Aggregation),
3. Secondary Hemostasis Platelets + Fibrin
( from coagulation pathways- either intrinsic or extrinsic), forms secondary haemostatic plug
Dr. Krishna Tadepalli, MD, www.mletips.com
3
Hemostasis Role of Endothelium 1. Produce Pro-thrombotic ( Plasminogen
activator inhibitors – PAI, Tissue factor, vWF) and Anti-thrombotic factors ( Vasodilators – PGI2, NO; tPA, Heparin like molecules & Thombomodulin)
2. Balance of these factors determine the end result ( clot or dissolution of clot)
Hemostasis Role of Endothelium 1. Produce Pro-thrombotic ( Plasminogen
activator inhibitors – PAI, Tissue factor, vWF) and Anti-thrombotic factors ( Vasodilators – PGI2, NO; tPA, Heparin like molecules & Thombomodulin)
2. Balance of these factors determine the end result ( clot or dissolution of clot)
Dr. Krishna Tadepalli, MD, www.mletips.com
4
PAI
Dr. Krishna Tadepalli, MD, www.mletips.com
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Coagulation pathway
Role of Platelets Granules α granules( contain clotting factors &
Growth factors), Dense or δ granules ( ADP, Ca++, Neuropeptides, Epinephrine)
Response to injury bind to sub-endothelial ECM ( vWF + Gp -Ib) Adhesion
Expose Phospholipid complexes (helps in intrinsic clotting pathway) & release ADP& Ca++
Aggregate with other platelets ( with fibrin by Gp IIb-IIIa on platelet surfaces
Coagulation pathway
Role of Platelets Granules α granules( contain clotting factors &
Growth factors), Dense or δ granules ( ADP, Ca++, Neuropeptides, Epinephrine)
Response to injury bind to sub-endothelial ECM ( vWF + Gp -Ib) Adhesion
Expose Phospholipid complexes (helps in intrinsic clotting pathway) & release ADP& Ca++
Aggregate with other platelets ( with fibrin by Gp IIb-IIIa on platelet surfaces
Dr. Krishna Tadepalli, MD, www.mletips.com
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Hemostasis
Dr. Krishna Tadepalli, MD, www.mletips.com
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Aspirin in patients at risk for coronary thrombosis-It irreversibly acetylates and inactivates cyclooxygenase-1 due to its ability to block TxA2 synthesis EQ
Dr. Krishna Tadepalli, MD, www.mletips.com
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Dr. Krishna Tadepalli, MD, www.mletips.com
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Coagulation pathwayCoagulation pathway
Dr. Krishna Tadepalli, MD, www.mletips.com
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Coagulation pathway
Most important step in this pathway (either intrinsic or extrinsic) formation of
Thrombin Thrombin produces it effects through
PARS( Protease activated receptors – 7 GPCR family)
Major effects of Thrombin Fibrin formation from Fibrinogen On Platelets TxA2
On Endothelial cells NO, tPA, PGI2
act also on Lymphocytes, Neutrophils, Monocytes
Coagulation pathway
Most important step in this pathway (either intrinsic or extrinsic) formation of
Thrombin Thrombin produces it effects through
PARS( Protease activated receptors – 7 GPCR family)
Major effects of Thrombin Fibrin formation from Fibrinogen On Platelets TxA2
On Endothelial cells NO, tPA, PGI2
act also on Lymphocytes, Neutrophils, Monocytes
Dr. Krishna Tadepalli, MD, www.mletips.com
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Coagulation pathway Thrombin
Coagulation pathway Thrombin
Dr. Krishna Tadepalli, MD, www.mletips.com
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Anti - CoagulantsNatural ones
1. Antithrombins( AT-III) inactivate Thrombin; Factors IX to XII; bind to heparin like molecule on endothelium
2. Proteins – C & S produced by liver; need Vit. K for activation; inactivate Factors V, VIII
Tissue Factor Pathway Inhibitors (TFPI) inhibit factors VII, X
Anti - CoagulantsNatural ones
1. Antithrombins( AT-III) inactivate Thrombin; Factors IX to XII; bind to heparin like molecule on endothelium
2. Proteins – C & S produced by liver; need Vit. K for activation; inactivate Factors V, VIII
Tissue Factor Pathway Inhibitors (TFPI) inhibit factors VII, X
Clinical significanceHeparin act through AT-III; Monitor PTT (Intrinsic pathway), Antidote is Protamine, can produce HIT (heparin induced thrombocytopenia); can be given in pregnancy (as it can’t cross placenta); need frequent injectionsWarfarin act through inhibition of Vit K mediated carboxylation of clotting factors (II,VII, IX, X); Extrinsic pathway Monitor PT; Antidote is Vit.K1 ; contraindicated in pregnancy (teratogenic)
Clinical significanceHeparin act through AT-III; Monitor PTT (Intrinsic pathway), Antidote is Protamine, can produce HIT (heparin induced thrombocytopenia); can be given in pregnancy (as it can’t cross placenta); need frequent injectionsWarfarin act through inhibition of Vit K mediated carboxylation of clotting factors (II,VII, IX, X); Extrinsic pathway Monitor PT; Antidote is Vit.K1 ; contraindicated in pregnancy (teratogenic)
Dr. Krishna Tadepalli, MD, www.mletips.com
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Fibrinolytic pathway
Most important step in this pathway formation of Plasmin from Plasminogen Tissue Plasminogen activator (tPA) is important in this
conversion
Plasmin breaks down excess Fibrin Fibrin split products or Fibrin degradation products (FSP or FDP)
Most important component of FDP D-dimer
Fibrinolytic pathway
Most important step in this pathway formation of Plasmin from Plasminogen Tissue Plasminogen activator (tPA) is important in this
conversion
Plasmin breaks down excess Fibrin Fibrin split products or Fibrin degradation products (FSP or FDP)
Most important component of FDP D-dimer
Clinical significanceD-dimer positivity (≥200 ng) patient had clot and it is lysed by PlasminConditions where D-dimer is positive DIC, DVT, PE
Clinical significanceD-dimer positivity (≥200 ng) patient had clot and it is lysed by PlasminConditions where D-dimer is positive DIC, DVT, PE
Dr. Krishna Tadepalli, MD, www.mletips.com
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Fibrinolytic pathwayFibrinolytic pathway
Dr. Krishna Tadepalli, MD, www.mletips.com
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