Anticoagulation & Blood Disorders

Vitamin K Antagonist Vitamin K required for activation of 2, 7, 9, 10 Factor Xa Inhibitor AT inactivates thrombin (IIa) and Xa UFH, LMWH, and fondaparinux binds to AT Thrombin Inhibition Directly blocks thrombin (DTI) Decreased amount of fibrin available Warfarin (Jantoven , Coumadin) Dosing: ? 10 mg for 2 days then adjust Goal INR 2-3: for most pts Metabolism: CYP2C9 (S) and CYP3A4 (R) A miodarone: reduce warfarin by 30-50% A void tamoxifene Bleeding risk ? : NSAID, SSRI, SNRI, antiplatelets Acute DVT/PE W arfarin + parenteral anticoagulation M inimum 5 days U ntil INR ? 2 for at least 24 hours Reversal: oral vitamin K preferred M ajor bleeding: IV vitamin K + PCC INR>10 w/o bleeding: PO vitamin K 2.5-5 mg Perioperative Management H old 5 days before major surgery B ridge w/LWMH or UFH for high risk and stop 24 hrs before surgery Resume 12-24 hrs after if hemostasis Unfractioned Heparin (UFH) Dosing: 5,000 U Q8-12hrs = VTE PPX Goal aPTT = 1.5 - 2.5 times control Goal anti-Xa = 0.3 – 0.7 U/mL *Check Q6H until therapeutic then Q24H 1 mg protamine 100 units of heparin Low Molecular Weight Heparin (LMWH) Dosing 30mg Q12 or 40mg QD = VTE PPX 1mg/kg Q12 or 1.5mg/kg QD = VTE/UA/NSTEMI 0.75mg/kg Q12 = STEMI ? 75 years old 30 mg bolus + 1 mg/kg then 1mg/kg Q12 = STEMI < 75 years old BW: neuraxial anesthesia, spinal puncture at risk of hematoma and paralysis Peak anti-Xa level 4hrs after dose 1mg protamine 1mg enoxaparin 0.5mg protamine 1mg enoxaparin given > 8hrs ago ------------------------------------------------------------------------Factor Xa Inhibitors (PO and Injectables) apixaban (Eliquis) Dosing 5mg BID = stroke PPX 2.5mg BID ? 80years, ? 60kg, or SCr ? 1.5 10mg BID x 7 days, 5mg BID = DVT/PE Tx 2.5mg BID = DVT PPX after surgery Can be crushed, mix in water/D5W/apple juice rivaroxaban (Xarelto) Dosing 15mg BID x 21days, 20mg QD = DVT/PE Tx 2.5mg BID + aspirin = CVD risk ? in CAD/PAD If ? 15mg, take with food edoxaban ( Savaysa ) Dosing 60mg QD = DVT/PE Tx, Stroke PPX in nonvalvular AF (start 5-10 days after parenteral anticoagulation) CrCl >95, do not use, ? efficacy fondaparinux ( Arixtra ) Dosing 2.5mg = VTE PPX CI: < 50kg, CrCl < 30 ------------------------------------------------------------------------Direct Thrombin Inhibitor D abigatran (Pradaxa) Dosing 150mg BID = DVT/PE Tx, Storke PPX in nonvalvular AF (start 5-10 days after parenteral anticoagulation) I n the original container. D o not break, open, or chew capsule argatroban & bivalirudin ( Angiomax ) use for HIT and high HIT risk pts ANEMIA Check MCV80-100CKD, hemolysis,blood lossmalignanciesBM failureLow HGB/HCTS/Sx Anemia>100vitamin B12,folate< 80iron ------------------------------------------------------------------------Iron Deficiency Anemia Dx and Tx L ow = Hgb, MVC, reticulocytes, iron, TSAT, ferritin High = TIBC Goal: ? Hgb in 1-2 weeks continue tx 3-6mos or until normal Oral Iron ferrous sulfate – common (325mg tab) ferrous sulfate dried – Slow Fe, Slow Iron Antidote = deferoxamine ( Desferal ) ? Fe absorption: PPI, H2RA, antacids ?other absorption: levothyroxine, quinolone, INSTIs, bisphosphonates, tetracyclines IV Iron all stable in NS, except feraheme (NS or D5W) all carry risk for HSR ferric gluconate ( Ferrlecit ) if hemodialysis ------------------------------------------------------------------------Macrocytic Anemia Dx and Tx Low = Hgb, reticulocyte, folate/vitamin B12 High = MCV cyanocobalamin/vitamin B12 Nascobal : 500mcg in one nostril weekly PO/SL: 1,000-2,000mcg QD IM/Deep SC: 100-1,000mcg QD/weekly/monthly folic acid/folate/vitamin B9 0.4-1mg QD Normocytic Anemia anemia of CKD EPO: hormone produced by kidney, stimulates bone marrow to produce RBC ESA: help maintain Hgb, ineffective if iron stores low HD pts: IV iron 1 st line Non-HD pts: PO iron supplement epoetin alfa (Epogen, Procrit) Dosing 50-100 U/kg 3x/ wk = CKD 150 U/kg 3x/ wk or 40,000 U weekly = Chemo Start when Hgb < 10 Stop when Hgb > 11 darbepoetin (Aranesp) Dosing 0.45mcg/kg weekly or monthly = CKD 2.25mg/kg weekly or 500 mcg Q3wk = Chemo **Not indicated when anticipated outcome is a cure for cancer **EPO ?overall survival and ?tumor growth ------------------------------------------------------------------------Drug Induced Hemolytic Anemia Immune-Mediated drug binds to RBC antibody develops attack RBC Positive Direct Coombs Test: detects Abs G6PD Deficiency G6PD enzyme : protects RBC from oxidative stress IV Ironsiron sucrose (Venofer)ferumoxytol (Feraheme)iron dextran (Infed, Desferrum)ferric gluconate (Ferrlecit)ferric carboxymaltose (Injectafer)ferric derisomaltose (Monoferric)ferric pyrophosphate citrate (Triferic) SICKLE CELL DISEASE Complications Vascular Occlusion VOC/Acute pain crisis lower back, hip, legs, abdomen, chest Acute Chest Syndrome Acute stroke avoid estrogen containing drugs Chronic pain, Bone death, Pulmonary HTN, Renal Infection Risk functional asplenia: fibrotic, shrinking S. pneumoniae, H. influenzae, N. meningitidis ------------------------------------------------------------------------- Non-Drug Tx Blood Transfusion for stroke, anemia, acute chest syndrome Goal Hgb = < 10 When iron overloads , chelation therapy is needed Bone marrow transplantation = ONLY CURE ------------------------------------------------------------------------Drug Tx Immunization & Abx Hib, Pneumococcal, Meningiococcal PPX PO PCN positive at birth: BID until 5 years of age spleen removal: indefinitely hydroxyurea: stimulate HgbF production Use if : ? 3 pain crises in a year severe acute chest syndrome chronic anemia disability Contraception required female – 6 months male – 12 months folic acid supplement recommended L-glutamine ( Endari ): reduce acute complications ADR: GI complications voxelotor ( Oxbryta ): inhibit HgbS polymerization crizanlizumab ( Adakveo ): ? VOC frequency Iron Chelation Therapy deferasirox ( Exjade , Jadenu ) deferiprone ( Ferriprox )