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ByDR MONKEZ M YOUSIFProfessor of Internal MedicineZagazig University2012Anticoagulationpart 1 (Thrombophilia)
Objectives• Physiology of coagulation• Thrombophilia (Hypercoagulation states)• Venous thromboembolism• Anticoagulants• Ca...
Definition of thrombophiliaA disorder associated with anincreased tendency to thrombosis.
VESSEL WALLENDOTHELPLATELETSPLASMAFACTORS(procoagulation,anti-coagulation)HEMOSTASIS = the arrest of bleedingfrom an injur...
The Role of Platelets in HemostasisCollagen OtherfactorsTFThrombinActivatedplateletActivatedplateletActivatedplateletAdhes...
Coagulation CascadeXII XIIaXI XIaIXVIII VIIIaXXaIntrinsic Pathway Extrinsic PathwayEndothelial activation orexposure of su...
Fibrinolysis
Coagulation Cascade:Regulation• Antithrombin (III)– Regulates activity of all serine proteases– Inhibitory activity enhanc...
The Cell-based Model of CoagulationVIIIaIXa+ activates variousfactorsAPC/PSTFPIAntithrombin
What is a Thrombus?Intravascular mass of fibrin and blood cellsArterial thrombi (White thrombi)– High shear rates– Primari...
LDLLDLMackness MI et al. Biochem J 1993;294:829-834.EndotheliumVessel LumenMonocyteModified LDLMacrophageMCP-1AdhesionMole...
Virchow’s thrombosismodelThrombosisVessel wallinjurySlow bloodflow (Stasis)Hypercoagulability
Injury or Activation ofEndothelium• Atherosclerosis– Life style - smoking, obesity• Immune mediated– Heparin induced throm...
Abnormal Blood Flow Decreased mobility Vessel Obstruction Eccomomy class syndrome Pregnancy
Risk Factors for Venous ThrombosisAcquiredPregnancyAdvancing agePrior thrombosisImmobilizationMajor surgeryMalignancyEstro...
Site of Thrombosis vs. Coag. DefectAbnormality Arterial VenousFactor V Leiden - +Prothrombin G20210A - +Antithrombin defic...
Type I (non immune mediated) The more common form, May occur in up to 15% of patients receivingtherapeutic doses of hepa...
Type II (immune type of HIT)Pathogenesis involves the formation of antibodies(usually IgG) against the heparin-platelet fa...
J Thromb Haem 1,1471, 2003
The incidence of HIT is about 3-5% inpatients exposed to UFH, the incidence ismuch lower with the use of LMWH.In patient...
Suspicion• Fall in platelet count by 50% following heparinexposureThe clinical spectrum• Isolated HIT• HIT (T), that may...
Lab diagnosis• Functional assays---heparin induced platelet aggregation,---serotonin release assay,• Immunoassays---Ab to...
TreatmentStopping Heparin andDirect thrombin inhibitors ArgatorbanPlatelet transfusion should be avoidedOnce the plate...
Bilateral foot ischemia secondary to HIT post open heart surgery
Bilateral foot ischemia secondary to HIT post open heart surgery
Arm ischemia secondary to HIT post open heart surgery
Anticoagulation  part 1 (thrombophilia)
Anticoagulation  part 1 (thrombophilia)
Anticoagulation  part 1 (thrombophilia)
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Anticoagulation part 1 (thrombophilia)

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  • Homeostasis:The ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes
  • Transcript of "Anticoagulation part 1 (thrombophilia)"

    1. 1. ByDR MONKEZ M YOUSIFProfessor of Internal MedicineZagazig University2012Anticoagulationpart 1 (Thrombophilia)
    2. 2. Objectives• Physiology of coagulation• Thrombophilia (Hypercoagulation states)• Venous thromboembolism• Anticoagulants• Case studies
    3. 3. Definition of thrombophiliaA disorder associated with anincreased tendency to thrombosis.
    4. 4. VESSEL WALLENDOTHELPLATELETSPLASMAFACTORS(procoagulation,anti-coagulation)HEMOSTASIS = the arrest of bleedingfrom an injured vesselHemostatic abnormalities can result in procoagulation or/and anti-coagulationconditions
    5. 5. The Role of Platelets in HemostasisCollagen OtherfactorsTFThrombinActivatedplateletActivatedplateletActivatedplateletAdhesionAggregationContractionSecretionPrimaryHemostasis=ActivatedplateletActivatedplateletActivatedplateletActivatedplateletThis plug of activated platelets, localised to the site of injury, provides thephospholipid surface upon which Secondary Hemostasis takes place
    6. 6. Coagulation CascadeXII XIIaXI XIaIXVIII VIIIaXXaIntrinsic Pathway Extrinsic PathwayEndothelial activation orexposure of subendotheliumTissue FactorVIITF/VIIaKallikreinHMWKPrekallikreinIIaIICa2+PLVa VOrganizedFibrin/PlateletthrombusFibrinogenFibrinCa2+PLCa2+Cross-linkedfibrin polymerXIIIaCa2+IXa
    7. 7. Fibrinolysis
    8. 8. Coagulation Cascade:Regulation• Antithrombin (III)– Regulates activity of all serine proteases– Inhibitory activity enhanced by heparin• Protein C and Protein S– Regulate the activity of co-factors of coagulationVa/VIIIa
    9. 9. The Cell-based Model of CoagulationVIIIaIXa+ activates variousfactorsAPC/PSTFPIAntithrombin
    10. 10. What is a Thrombus?Intravascular mass of fibrin and blood cellsArterial thrombi (White thrombi)– High shear rates– Primarily platelet aggregates + fibrin strandsVenous Thrombi (Red thrombi)– Low shear rates– Primarily red cells and fibrin strands (fewplatelets)
    11. 11. LDLLDLMackness MI et al. Biochem J 1993;294:829-834.EndotheliumVessel LumenMonocyteModified LDLMacrophageMCP-1AdhesionMoleculesCytokinesPathophysiology of AtherosclerosisFoamCellHDL Promote Cholesterol EffluxIntimaHDL InhibitOxidationof LDL
    12. 12. Virchow’s thrombosismodelThrombosisVessel wallinjurySlow bloodflow (Stasis)Hypercoagulability
    13. 13. Injury or Activation ofEndothelium• Atherosclerosis– Life style - smoking, obesity• Immune mediated– Heparin induced thrombocytopenia– Antiphospholipid Antibody Syndrome (LupusInhib)• Trauma• Artificial Surface (vascular graft)• Inflammation/Infection
    14. 14. Abnormal Blood Flow Decreased mobility Vessel Obstruction Eccomomy class syndrome Pregnancy
    15. 15. Risk Factors for Venous ThrombosisAcquiredPregnancyAdvancing agePrior thrombosisImmobilizationMajor surgeryMalignancyEstrogens (OCP, HRT< SERMs)APA syndromeMyeloproliferative disorders, IBDHITProlonged air travelInheritedAntithrombinDeficiencyProtein C deficiencyProtein S deficiencyFactor V Leiden (FVL)Prothrombin G20210ADysfibrinogenemias(rare)Mixed/UnknownHomocysteineFactor VIII, IX, XIAPC resistance in theabsence of FVLFree TFPIPAI-I, PAI-II
    16. 16. Site of Thrombosis vs. Coag. DefectAbnormality Arterial VenousFactor V Leiden - +Prothrombin G20210A - +Antithrombin deficiency - +Protein C deficiency - +Protein S deficiency - +Hyperhomocysteinemia + +Lupus Anticoagulant + +
    17. 17. Type I (non immune mediated) The more common form, May occur in up to 15% of patients receivingtherapeutic doses of heparin Benign and self limiting side effect. Rarely causes severe thrombocytopenia Usually doesnt require heparin discontinuation.Heparin induced thrombocytopenia(HIT)
    18. 18. Type II (immune type of HIT)Pathogenesis involves the formation of antibodies(usually IgG) against the heparin-platelet factor 4(PF 4) complex. The HIT Abs trigger procoagulanteffect serious arterial and venousthrombosis
    19. 19. J Thromb Haem 1,1471, 2003
    20. 20. The incidence of HIT is about 3-5% inpatients exposed to UFH, the incidence ismuch lower with the use of LMWH.In patients with de novo exposure to heparin afall in the platelet count in those with HIToccurs between day 5 and 14.
    21. 21. Suspicion• Fall in platelet count by 50% following heparinexposureThe clinical spectrum• Isolated HIT• HIT (T), that may be arterial (Stroke, MI, PAD)or venous in nature.
    22. 22. Lab diagnosis• Functional assays---heparin induced platelet aggregation,---serotonin release assay,• Immunoassays---Ab to heparin-PF 4 complexes.
    23. 23. TreatmentStopping Heparin andDirect thrombin inhibitors ArgatorbanPlatelet transfusion should be avoidedOnce the platelet count is > 100.000/CC warfarin may bestarted at low dose.
    24. 24. Bilateral foot ischemia secondary to HIT post open heart surgery
    25. 25. Bilateral foot ischemia secondary to HIT post open heart surgery
    26. 26. Arm ischemia secondary to HIT post open heart surgery

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