1. Hematologic Pharmacology
Jennifer Kean MSN, RN, CCRN

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

3. 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

4. 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

5. 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

6. 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

7. 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)

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

9. 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

10. 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

11. 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

12. 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

13. 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)

14. 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

15. 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

16. 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

17. 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

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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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