Slide 1CoagulationThrombiCoagulation activators and inhibitorsDisruption of clotting cascade OR thinning bloodHeparinHeparin continuedHeparinHeparin-limitationsLMWHLMWHDirect Thrombin inhibitorsWarfarin (Coumadin)CoumadinCoumadinDabigatran (Pradaxa®)Pradaxa continuedAnti-plateletAspirinClopidogrel (Plavix)GP IIb/IIIaThrombolyticsThrombolyticsAMIAMI continuedHemophiliaAnemia (Low RBC count)Drugs that treat AnemiaHematopoietic agentsNSG 325Module 5Hematology, anti-coagulants, anemiaHemostasis-stop the bleeding!Injury to vessel causes:◦Formation of platelet plug (Platelet aggregation)◦Reinforcement of platelet plug with fibrin◦Clot is removed by plasmin (enzyme that digest fibrin)CoagulationArterial thrombus: heart attack (MI), stroke (CVA)◦Treatment: thrombolytic/ manually move (PTCA)Venous thrombus: immobility, sitting on plane (DVT) blood pools and clots, PE◦Treatment: HeparinThrombiCoagulation activators and inhibitorsAnti-coagulants◦Disrupts clotting cascade at various pointsHeparin, LMWH, Warfarin Anti-platelets◦Inhibits platelet aggregationAspirin, Clopidogrel (Plavix), IIb/IIIa inhibitorsThrombolytics◦Lysis of fibrin, dissolution of clotDisruption of clotting cascade ORthinning bloodDecreases fibrin formation by promoting anti-thrombinChemically: Highly polar DOES NOT CROSS MEMBRANES EASILY! Routes: SQ or IVHalf life: 90 minutesIV course: bolus and then continuous infusionUSE: PE, CVA, MI, DIC, cardiac surgery, dialysis, prevent post-op DVTHeparinAdverse effects: Hemorrhage (10% of patients)Antidote- protamine sulfate (inactivates heparin)Heparin induces thrombocytopenia (HIT)- immune mediated response to heparin reduced platelets, paradoxical increase in thrombi formationHeparin continuedMonitor therapyaPTTnormal= 40 secondstarget=60-80 secondsplatelet countMeasured in unitsIV form is weight basedHeparinNarrow range of anti-coagulation without bleedingWeight-based dosingHighly variable dose response- require frequent lab draws (Q6H)Medication errorsCHEAP and EFFECTIVE and REVERSABLEHeparin-limitationsLow molecular weight heparinEnoxoparin (Lovenox)SQLonger ½ life means it can be dosed Q 12 H or QDAppropriate for patients to give themselves dose at homeDoesn’t require aPTT monitoringTreat MI, prevent DVT, tx DVT, PELMWHAE-bleeding, thrombocytopeniaWeight basedCost more than heparin, but easy to give at home no lab cost…May cost less in long runLMWHBivalirudin (Angiomax)Lepirudin (Refuldan)Argatraban (Acova)IV infusionsExpensiveCan be used instead of heparin for people with HITDirect Thrombin inhibitorsBlocks synthesis of factors VII, IX, X, and prothombin (these are factors that are dependent of vitamin K). Used for long term prophylaxis of thrombosis◦DVT◦Heart valves◦Afib◦TIA’s◦MI’sWarfarin (Coumadin)Monitor Prothrombin time (PT) and INR (International normalized ratio)Delayed onset of action, ½ life ~ 2 days◦Days for peak effect, days for return to normalResponse if variableMultiple drug reactionsCoumadinSE: BleedingContraindicated in pregnancyBound with proteinSpecial interacting drugs: Heparin, aspirin, acetaminophen, phenobarb, “azole” antifungals….list is longMonitor every 2 weeks- when stable can switch to monthlyVitamin K for overdose (reversal agent)Dietary teaching: avoid fluctuations in vitamin K intake. Highest content in green leafy vegetables. MVI, canola oil, mayonnaiseCoumadinDirect thrombin inhibitorApproved 2010- 5 advantages over coumadin◦No need to monitor labs◦Few drug-food interactions◦Lower risk of bleeding◦Same dose regardless of age, weightDabigatran (Pradaxa®)Used to treat:◦Afib◦DVT (not approved in US)Rapid onset Take twice a daySE: bleeding, GI upsetNO ANTIDOTEPradaxa continuedSuppress platelet aggregation (bulk of arterial thrombosis)Ischemic CVATIAStable anginaUSACoronary stentsAMIPrevious MIPrevention of MIAnti-plateletDose < 325 mg/dayInhibits cyclosoxygenase, blocks synthesis of TXAEffects last 7-10 daysCheap! $3.00/monthAE- GIB, hemorrhagic strokeAspirinBlocks ADP receptorsUse secondary prevention of MI, CVA, prevent stent stenosisAE: bleeding, abdominal pain, dyspepsia, diarrhea, rash. TTP low incidence in first 2 weeks of taking. Interaction with PPI’s Some people can’t metabolizeExpensive brand name $200/monthGeneric $15/monthClopidogrel (Plavix)tirofiban (Aggrastat); eptifibatide (Integrilin); abciximab (ReoPro)Most effective anti-platelet; usually given with low-dose heparinUse: short-term to prevent ischemic events during ACS or during PCIDecrease risk of re-occlusion Reversible blockade; IV only; expensiveSE: major bleeding especially at PCI access siteGP IIb/IIIastreptokinase, alteplase (tPA), tenecteplase, reteplase, urokinaseDissolve existing thrombi, not prevent themUsed to treat acute MI, massive PE, ischemic stroke, DVT, but now you go to the cath lab and get a stent put in. Now its used for a thrombolytic stroke (have to present to ER w/i 3 hrs of symptom onset and have CT scan to make sure they are not bleeding)Plasmin digests fibrin; All of these agents convert plasminogen to plasminSE: bleeding, intracranial is the greatest concernMore effective if the drug is started early after sx onsetThrombolyticsOnly used in acute situations$$$$streptokinase carries risk of allergic reaction, the only one that does, repeat courses may be ineffectiveTable 52-10 p. 656 lists absolute and relative contraindicationsThrombolyticsAngina-imbalance between oxygen supply and demand in heartWithout oxygen heart muscle will die (necrosis)Treatments include:◦M-morphine-vasodilitation, pain control, decrease preload and afterload◦O- oxygen◦N-nitroglycerin-reduce preload, decrease O2 demand, increase collateral supply◦A- prevent platelet aggregationAMIReperfusion- thrombolytic- break down clotPrimary Cardiac Intervention (PCI)◦Angioplasty or stentHeparin- decrease building of clotBBACEAMI continuedType A-deficient in clotting factor VIIIType B-deficient in clotting factor IXNormal platelet aggregation, fibrin production is abnormalFactors can be given to reduce stop bleedingFactors can cause allergic reactionsHemophiliaDecreased production of