Hematologic Pharmacology Jennifer Kean MSN, RN, CCRN

Parenteral anticoagulants Heparin Low molecular weight heparins Enoxaparin (Lovenox) Dalteparin Activated factor Xa inhibitor Fondaparinux

Purpose Expected pharmacological action: Heparin prevents clotting by activating antithrombin, thereby indirectly inactivating both thrombin and factor Xa This inhibits fibrin formation Enoxaparin primarily inactivates factor Xa and is much less able to inactivate thrombin Fondaparinux inactivates factor Xa, thus decreasing thrombin production

Therapeutic uses Heparin Low-molecular weight heparins Treats disorders needing prompt anticoagulation (evolving stroke, pulmonary embolism, massive DVT) As an adjunct for patients having open heart surgery or hemodialysis, or as adjunct therapy for myocardial infarction Low dose for prophylaxis against post-op DVT Low-molecular weight heparins Prevent DVT in post-op patients Treat acute DVT or PE along with warfarin

Complications Hemorrhage due to overdose: nursing actions Monitor vital signs Withhold heparin and administer protamine sulfate Monitor PTT every 4-6 hours Observe for bleeding, tarry stools, bruising, petechiae, tachycardia Low platelet count (heparin-induced thrombocytopenia) Monitor platelet count periodically Toxicity/overdose: give protamine sulfate (the antidote) Neurologic damage due too hematoma formation from spinal or epidural anesthesia

Contraindications/precautions Thrombocytopenia and unexplained bleeding Surgery of the eye, brain and spinal cord Lumbar puncture Patients who have hemophilia, increased capillary permeability (CHF), dissecting aneurysm, hepatic or kidney disease Interactions: Aspirin, NSAIDs, can increase risk for bleeding Avoid concurrent use whenever possible Take precautionary measures to avoid injury

Nursing administration Document baseline vital signs, CBC, platelet count, H&H Read the label carefully- heparin comes n different concentrations Monitor aPTT Administer sub-q injections in the abdomen, deep into the tissue, at a 90- degree angle and at least 2 inches away from the umbilicus Do not aspirate and rotate injection sites Instruct client to report unusual bleeding: gums, tarry stools, bruising, etc. and to use an electric razor Instruct client to avoid use of OTC NSAIDs (ibuprofen and naproxen; acetaminophen is ok)

Nursing evaluation Indications of effectiveness include the following: Heparin: aPTT of 60-80 seconds (2-3x the baseline) Heparin, enoxaparin, and fondaparinux: no development or no further development of venous thrombi or emboli

Oral anticoagulants: warfarin (Coumadin) Expected action: oral anticoagulants antagonize vitamin K, thereby preventing the synthesis of 4 coagulation factors(VII, IX, X, prothrombin) Therapeutic uses: Prevent DVT and PE Prevent thrombus formation in patients with afib or prosthetic heart valves Prevent recurrent MI, TIA, PE, and DVT Complications: Hemorrhage: monitor vital signs, PT/INR; for overdose, administer vitamin K REMEMBER: for heparin, monitor PTT and for warfarin, monitor PT/INR

Contraindications/precautions Pregnancy: warfarin is pregnancy risk category X due to high risk of fetal hemorrhage Breastfeeding, thrombocytopenia, and unusual bleeding Surgery of the eye, brain, spinal cord or lumbar puncture Vitamin K deficiencies, liver disorders, and alcoholism Hemophilia, dissecting aneurysm, peptic ulcer disease, severe hypotension

Interactions Concurrent use of: aspirin, clopidogrel, dipyridamole, ticlopidine, abciximab, glucocorticoids, sulfonamides, acetaminophen, cimetidine, and parenteral cephalosporins- all increase risk of bleeding Discourage concurrent use if possible Monitor PT/INR Check OTC med use Concurrent use of: phenobarbital, carbamezipine, rifampin, phenytoin, oral contraceptives, and vitamin K- decrease effectiveness of warfarin Excessive intake of foods high in vitamin K (dark green leafy vegetables)- decrease effectiveness of warfarin

Nursing administration Give orally at the same time each day Document baseline vital signs, PT/INR, CBC, platelets, and H&H It can take 1 week or more to reach therapeutic levels; the patient may still have to take heparin with warfarin until the PT/INR reaches 2-3x the baseline Instruct client to avoid alcohol and OTC meds If client needs surgery, warfarin must be discontinued several days prior to

Direct thrombin inhibitors: dabigatran, argatroban These meds work by inhibiting thrombin, thus preventing a thrombus from forming Therapeutic uses: Dabigatran prevents stroke or embolism in patients with afib Argatroban prevents or treats thrombosis in patients who cannot take heparin due to allergy or heparin-induced thrombocytopenia (HIT)

Complications and Contraindications Unusual or unexplained bleeding: GI, GU, intracranial GI discomfort, nausea, vomiting, ulcer formation: take with food Back pain, nausea, hypotension and headache CONTRAINDICATIONS: Pregnancy or breastfeeding Active bleeding or allergy Liver or kidney impairment

Interactions Rifampin decreases levels of drug in body Other thrombolytics and anticoagulants can increase the risk for bleeding Nursing administration: Swallow capsule whole, do not crush (dabigatran) Argatroban is given IV via continuous infusion Periodically check PTT and PT/INR

Direct inhibitors of factor Xa: rivaroxaban and apixaban Provide anticoagulation by directly inhibiting factor Xa Treats afib and prevents DVT?PE in patients having joint replacement surgery; also prevents stroke and embolism in patients with nonvalvular afib No antidote is available for severe bleeding Monitor Hgb and Hct, report unusual bruising or bleeding Document baseline LFTs Contraindications/precautions: pregnancy, allergy, other anticoagulants, liver or kidney impairment Interactions: erythromycin, diltiazem, verapamil, amiodarone: increase riak for bleeding; rifampin, carbamezapine, phenytoin:decrease therapeutic levels

Antiplatelets Aspirin, abciximab, clopidogrel, ticlodopine, prasugrel, ticagrelor Purpose: prevent platelets from clumping together by inhibiting enzymes and factors that usually lead to arterial clotting and inhibit platelet aggregation; these meds alter bleeding time Therapeutic uses: prevention of acute MI and also reinfarction, prevent ischemic strokes and TIAs, acute coronary syndrome, intermittent claudication and thromboembolism following surgery Administration: oral and IV

Complications GI effects: nausea, vomiting, dyspepsia- take with food Hemorrhagic stroke Gastric bleeding, thrombocytopenia Tinnitus, hearing loss Hypotension and bradycardia Diarrhea Headache, dizziness

Contraindications/precautions/interactions Pregnancy/breastfeeding Bleeding disorders and thrombocytopenia Peptic ulcer disease, liver or kidney disease Concurrent use of other antiplatelets or anticoagulants Corticosteroids can decrease the effects of aspirin Caffeine can increase aspirin absorption Proton pump inhibitors decrease effectiveness

Thrombolytic medications: alteplase (TPA), reteplase Expected action: these meds dissolve clots that have already formed Used to treat acute MI, massive PE, ischemic stroke; given IV only Complications: serious risk of bleeding-internal and superficial Limit venipuncture and injections Apply pressure dressings to recent wounds Monitor for changes in vital signs and LOC Monitor PTT, PT/INR, H&H Contraindications: pregnancy, prior intractranial hemorrhage, active internal bleeding, surgery within 2 months, pericarditis or endocarditis, brain tumors, liver or kidney disorders

Interactions and nursing administration Concurrent use of other meds that cause bleeding Outcomes are much better if these meds are administered within 2-4 hours of onset of symptoms Should only be given where the patient can be closely monitored (ICU) Document baseline labs Limit injections and venipunctures Administer proton pump inhibitors to prevent/reduce GI bleeding

Growth factors Therapeutic uses: Replacement of neutrophils and platelets after chemotherapy Hastening of bone marrow function after bone marrow transplant Increase red blood cell production in patients with chronic kidney disease Erythropoetin (Epogen): increases RBC production Filgastrim (Neupogen): increases WBC production Interleukin-11: increases platelet production

Erythropoetin Used for anemia due to chronic kidney disease or chemotherapy Complications: cardiac events from increased RBCs Monitor H&H levels and blood pressure Seizures from a too-rapid rise in blood cell counts DVT Headache, body aches Contraindications: uncontrolled hypertension, pregnancy, some cancers Nursing administration: check BP often, do not mix with other meds in the syringe (always given IV), give three times per week, monitor H&H and labs

Filgastrim Therapeutic uses: increase neutrophil count after chemotherapy, decrease risk of infection, build up stem cells before transplant Complications: bone pain- give acetaminophen, leukocytosis-monitor CBC 3x/week, splenomegaly and risk of splenic rupture Contraindications: pregnancy/breastfeeding, weight < 45 kg (99 lbs), cancer of the bone marrow, sickle cell anemia, respiratory disease Nursing administration: do not agitate the vial of medication, monitor CBC, teach pt. sub-q administration for home care

Interleukin-11 Uses: to increase the production of platelets, decrease thrombocytopenia and the need for platelet transfusions Complications: peripheral edema, dyspnea on exertion- monitor I&O,, tachycardia, afib- monitor HR and EKG, transient blurring of vision- withhold med and notify provider, allergic rxn and anaphylaxis Contraindications: cancer of the bone marrow, heart failure of pleural effusion, cardiac dysrhythmias Nursing administration: document baseline CBC and platelet count, administer once daily sub-q