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Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
Hemostasis Surgury 2
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Hemostasis Surgury 2

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  • 1.
  • 2. Antithrombin III
  • 3. Protein C system
    Thrombin + thrombomodulin
    Protein C
    aProtein C + protein S
    Cleaves Factor Va and VIIIa
  • 4. Thrombin + thrombomodulin
    Thrombin-activatable fibrinolysis inhibitor (TAFI)
    Removes the terminal lysine on the fibrin molecule, renders the clot more susceptible to lysis by plasmin
  • 5. Degradation of the Fibrin Clot
    Natural part of hemostasis
    Fibrin fibrils in the clot are dense, dissolution occurs at “coiled coils” to form oligomers which are digested into smaller units
    Highly regulated in terms of gene expression
    Plasmin
    Tissue plasminogen activator (t-PA)
    urokinase
    streptokinase
  • 6. Plasminogenesis
  • 7. Plasmin
    Serine protease formed from plasminogen
    Plasminogen found in plasma and extracellular space and has high affinity for fibrin
    Inactive and requires activation to plasmin by urokinase and t-PA
    Formation of plasmin is highly regulated
    Cleaves fibrin into degradation products.
    Circulating plasmin is inhibited by α2-antiplasmin.
    Forms complex with plasmin and prevents it from binding to fibrin
  • 8. Tissue Plasminogen Activator
    Serine protease released from ECs in response to injury (in response to thrombin and some vasoactive peptides)
    Chiefly responsible for conversion of plasminogen to plasmin
    Secretion highly regulated at transcriptional level
    Major binding is to fibrin clots and extracellular matrix
    Highly specific ( site of clot formation )
    Inhibited by plasminogen activator inhibitor-1 (PAI-1)
    Recombinant protein used clinically to inhibit thrombosis
  • 9. Urokinase
    Serine protease secreted as pro-urokinase
    Produced by endothelial cells, fibroblasts, and monocytes/macrophages
    Potent plasminogen activator but non-specific
    secreted as one chain: fragments in urine generated by plasmin
    Functions to degrade ECM, enabling cells to migrate
    Half life of only 7 minutes
    Inhibited by plasminogen activator-2 (PAI-2)
    synthesis tightly regulated by cytokines and inflammatory mediators
    Used clinically (e.g. Abbokinase)
  • 10. Streptokinase
    Protein isolated from certain types of streptococci bacteria
    Potent plasminogen activator
    Less selective than t-PA
    Can result in circulating plasmin
    Can produce degradation of fibrinogen as well as fibrin
    May result in formation of plasmin in excess of that inhibited by α2-antiplasmin and result in bleeding
  • 11. BECAUSE OF THE COMPLEX NATURE OF HEMOSTASIS, POTENTIAL INTERFERENCE IN THE PROCESS CAN OCCUR AT MANY LEVELS.
  • 12. HEMOSTATIC DEFECTS
    CONGENITAL
    Coagulation Factor deficiency
    Hemophilia
    von Willebrand’s disease
    Factor XI,II, V, X, XIII deficiency
    Platelet function defects
    Glanzmann’s thrombastenia
    Bernard-Soulier syndrome
    Storage pool disease
  • 13. HEMOSTATIC DEFECTS
    Major surface protein abnormality
    Glanzmann’s thrombastenia
    Glycoprotein IIb / IIIa
    Absence of platelet aggregation
    Bernard-Soulier syndrome
    Glycoprotein Ib / IX / V
    Absence of platelet adhesion
  • 14. HEMOSTATIC DEFECTS
    ACQUIRED Platelet abnormalities
    quantitative defects
    failure of production
    Bone marrow disorder
    shortened survival
    ITP / DIC
    Sequestration
    hypersplenism
  • 15. Conditions of Excess Bleeding
    Hemophilia ( inherited sex-linked rec. )
    Hemophilia A (classic)- deficiency of Factor VIII (85%)
    Hemophilia B – deficiency of Factor IX (15%)
    Spontaneous bleeding
    Joints frequently, crippling arthropathies
    Retroperitoneal hematoma
    Gastrointestinal/ genitourinary
    NORMAL PLATELET FUNCTION
  • 16. Conditions of Excess Bleeding
    von Willebrand’s disease
    Autosomal dominant
    Low level of vWF
    CARRIER FOR FACTOR VIII
    NORMAL PLATELET ADHESION
    ABNORMAL PLATELET FUNCTION
    Easy bruising and mucosal bleeding
    Menorrhagia is common
  • 17. Conditions of Excess Bleeding
    Thrombocytopenia
    Most common abnormality of hemostasis in surgical patients
    Platelets fall from normal 150-400,000 to < 100,000/µl
    Massive blood loss
    Heparin induced
    Impaired platelet function
    Vit b12 / folic acid def
    ITP
    hypersplenism
  • 18. Conditions of Excess Bleeding
    Coagulopathy of liver disease
    Vitamin K deficiency
    Required by liver for formation of prothrombin and Factors VII, IX, X and protein C
    Leads to serious bleeding tendencies
  • 19. Conditions of Clotting Dysfunction
    Thromboembolic conditions
    Can result when endothelial surface is compromised or BF is slow
    Associated with atherosclerosis, infection, or trauma
    Femoral venous thrombosis
    When BF is slow (bed ridden, prolonged sitting)
    Clot grows and large piece can break off
    Can pass through right side of heart to lodge in pulmonary arteries (pulmonary embolism)
    If large enough can be fatal
  • 20. COAGULANTS
    Thrombosis
    Inappropriate activation of hemostatic mechanism;
    Venous –associated with stasis of blood with small platelet component
    Arterial – associated with artherosclerosis with large platelet component
  • 21. COAGULANTS
    Vitamin K
    Essential for the formation of clotting factors (II, VII, IX and X)
    Given orally or thru IV (Natural Vit K requires Bile-acid while Menadiol Na Phosphate does not but takes longer to act)
    USE – bleeding 2o to oral anticoagulants, babies, Vit. K deficiencies
  • 22. COAGULANTS
    Antifibrinolytic Agent
    Tranexamic acid (Inhibit plasminogen activation),for conditions with bleeding or risk of bleeding,life-threatening bleeding following thrombolytic drug administration and hereditary angioedema.
    Aprotinin-inhibits proteolytic enzymes, used for hyperplasminemia due to fibrinolytic overdose & during cardiac surgery
  • 23. Conditions of Clotting Dysfunction
    Disseminated intravascular coagulation
    Clotting activated in widespread areas
    Often from severe trauma or shock (endotoxin)
    Plugging of vessels limits oxygen delivery
    lethal in ~85% of the cases
  • 24. ANTICOAGULATION
    AND
    BLEEDING
  • 25. Prevention of Blood Clotting
    Critical for clots to dissolve or not form when not needed
    Endothelial cell surface-
    Most important factor – integrity prevents contact activation of intrinsic clotting system by collagen
    Charged EC glycocalyx repels platelets and clotting factors
    Thrombomodulin-EC membrane protein, binds thrombin to slow clotting process. Thrombomodulin-thrombin complex activates a protein C which inactivates Factors V and VIII.
  • 26. Removal of Thrombin (blocks common pathway)
    Fibrin – absorbs 85-90% of thrombin by absorption into fibers
    Anti-thrombin III – binds remaining thrombin
    Prevention of Blood Clotting
  • 27. Vitamin K cycle (post-translational carboxylation)
    Factors VII, IX, X and prothrombin
  • 28.
  • 29. Anticoagulants for Clinical Use
    Heparin
    Coumarins
    Aspirin
    Cyclooxygenase inhibitor
    Prevents formation of thromboxane A2 and activation of platelets
    Calcium-deionizing agents
    Sodium, ammonium and potassium citrate combines with calcium in blood
    Several factors require calcium for activation
    Used in test tubes to prevent clotting
  • 30. Antithrombin III
  • 31. ANTICOAGULANT
    Heparin -binds to antithrombin III
    Combines with anti-thrombin III and increases activity 100-1000X
    Immediate effect ,half life of 60-90min
    Monitor by aPTT
  • 32. ANTICOAGULANT
    Low molecular weight heparin- 4-6 kDa
    Selective Xa inhibitor
    More favorable antithrombotic effect,less bleeding,highly predictable bioavailability
    Longer half life
  • 33. ANTICOAGULANTS
    Coumarin derivatives- warfarin,acenocoumarol,phenprocoumon
    Block coagulation factors(2,7,9,10)
    Warfarin decreases formation of Factors VII, IX and X by the liver
    Competes with vitamin K for reactive sites
    Restoration after coumarin tx- 3-5 days
    Prothrombin time
    INR- corrects the differences of the various thromboplastin activity. INR=1 no anticoagulation
  • 34. ANTICOAGULATION
    Antiplatelet Drugs
    Aspirin
    Dipyridamole
    Thienopyridine Derivatives
    Glycoprotein IIB/IIIA receptor antagonists
    Other antiplatelet drugs
  • 35. ANTICOAGULATION
    Antiplatelet Drugs
    Aspirin
    Inhibits cyclooxygenase irreversibly
    Inhibits TXA2
    Main drug – acute MI, High-risk for MI, after coronary artery Bypass, after angioplasty, unstable coronary syndromes,TIA and AF if oral anticoagulant is contraindicated
  • 36. ANTICOAGULATION
    Antiplatelet Drugs
    Dipyridamole
    Phosphodiesterase inhibitor
    Additive effect to aspirin
    Less effective than aspirin
    Headache but no excess risk of bleeding
  • 37. ANTICOAGULATION
    Antiplatelet Drugs
    Thienopyridine Derivatives
    Inhibits ADP-dependent aggregation
    Orally given, additive with aspirin
    Ticlopidine slow onset, unwanted effects-blood dyscrasias (neutropenia)
    Clopidogrel – same as Ticlopidine except for neutropenia
  • 38. ANTICOAGULATION
    Antiplatelet Drugs
    Glycoprotein IIB/IIIA Receptor Antagonists
    Abciximab – for angioplasty patient as adjunct to heparin and aspirin, reduces restenosis, Tirofiban – an oligopeptide
    Abciximab - Risk of bleeding & immunogenicity limits its use
    They inhibit diverse agonists (e.g. ADP, TXA2 etc. )
  • 39. ANTICOAGULATION
    Thrombolytic agents- plasminogen activators.
    Recombinant endogenous plasminogen activators(recombinant tPA)
    Streptokinase- exogenous source
    bleeding
  • 40. ANTICOAGULATION
    Fibrinolytic Drugs
    Streptokinase
    Protein extracted from cultures of streptococci
    Activates plasminogen, given IV
    Additive with aspirin
    Action blocked by antistreptococcal antibodies
    Allow 1 year before it can be used again
  • 41. ANTICOAGULATION
    Fibrinolytic Drugs
    Alteplase, Duteplase and Reteplase
    Recombinant tPA (plasminogen activator)
    ‘Clot-selective’ – fibrin bound plasminogen
    Not antigenic-substitute for patients w/ ab for streptokinase
    Reteplase –longer half-life, bolus admn.simple
  • 42. Tests of hemostasis
    Primary deficiency/ defect in one component
    Pharmacologic therapy
    Anticoagulant/ antiplatelet
    Comorbid condition
    Thrombocytopenia
    Sepsis/ hepatic disease
  • 43. Tests of hemostasis
    Careful review of patient’s clinical history
    most important/ initial approach
    Drug use
    Basic laboratory tests
    Platelet count
    Prothrombin time ( PT ) or INR
    Activated partial thromboplastin time ( aPTT )
    Bleeding time ( BT ) and clotting time ( CT )
  • 44. Evaluation of surgical patient
    Patients history
    Questions to ask
    Prolonged bleeding or swelling after biting the lip or tongue
    Bruises without apparent injury
    Prolonged bleeding after dental extraction
    Excessive menstrual bleeding
    Bleeding problems associated with major and minor operations
    Medical problems receiving a physician’s attention within the past 5 years
    Medications including aspirin or remedies for headache taken within the past 10 days
    Relative with a bleeding problem
  • 45. Four levels of concern
    Level I Hx(-); Sx (m) no test
    Level II Hx(-); Sx (M) platelet ct
    PTT
    Level III Hx (suggestive) PT, PTT, BT, CT, pltelet ct
    Level IV Hx(+) Hematologic consultation
  • 46. Platelet dysfunction
    Normal 150,000 to 400,000 /ul
    Clinical signs of thrombocytopenia
    < 100,000 / ul
    Increased bleeding complications in major surgical procedures
    < 50,00 / ul
    Increased bleeding complications in minor surgical procedures
    < 20,000 / ul
    SPONTANEOUS HEMORRHAGE
  • 47. Platelet dysfunction
    Bleeding time ( BT )
    Evaluate platelet , vWD and vascular dysfunction
    Several methods
    Ivy test = 7mins
    Clotting time ( CT )
    … + Aspirin use
  • 48. Clotting dysfunction
    PT reagent contains
    thromboplastin and calcium + plasma = clot
    PT measures
    Factors I, II, V, X and VII
    Factor VII extrinsic pathway
    Abnormal coagulation due to Vit K deficiency
    warfarin / coumadin therapy
  • 49. Clotting dysfunction
    Variations in thromboplastin activity from different sources
    PT value is adjusted = INR
    ISI ( international sensitivity index )
    Value for each batch of thromboplastin
    Optimal reagent has as ISI of 1.3 to 1.5
    INR = ( PTpatient / PTnormal )ISI
    INR- corrects the differences of the various thromboplastin activity. INR = 1.0 is NORMAL
  • 50. Clotting dysfunction
    aPTT reagent contains
    Phospholipid substitutes, activator and calcium + plasma = clot
    aPTT measures
    Factors I, II and V of the common pathway
    Factors VIII, IX, X and XII
    intrinsic pathway
    Heparin therapy
  • 51. HEMOSTASIS
    RENE PSA MENDOZA, MD, MHSA
    Associate Professor, Department of Surgery
    FEU-NRMF Institute of Medicine

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