NUR 3031-002 Basic Concepts of Pharm: Drugs Affecting Coagulation

Physiology and Pathyphysiology of Coagulation: Hemostasis Stage 1

Formation of platelet plug

- Platelet aggregation

Physiology and Pathyphysiology of Coagulation: Hemostasis Stage 2 Coagulation

Intrinsic Coagulation Pathway

Extrinsic Coagulation Pathway

- Keeping hemostasis under control

- Physiologic removal of clots

Physiology and Pathyphysiology of Coagulation: Thrombosis

Arterial Thrombosis

Venous Thrombosis

Indications for Anticoagulant Therapy:

DVT

Atherosclerosis

Stroke

Acute Coronary Syndrome: Unstable angina, MI

PVD

Oncologic Process

Genetic Predisposition

Coagulation Cascade

Series of events leading to blood clot formation.

- All meds work together and meet at 10A to block coagulation cascade

Important Laboratory Values NTN

- Complete Blood Count (hemoglobin and hematocrit)

- Prothrombin Time (PT) - warfarin drug

- Activated Partial Thromboplastin Time (aPTT) - heparin drug

- International Normalized Ratio (INR)

- Blood Type & Screen

- Blood Type & Crossmatch

Lab Values: Prothrombin Time PT

11-13 Seconds Normally

On warfarin: 1.5-2 times normal

Lab: International Normalized Ratio (INR)

Normal INR: 1

Warfarin Therapy: 2-3

Mechanical Mitral Valve: 2.5-3.5

Lab Values: Hemoglobin

13-19 Normal Hemoglobin

Lab Values: Hematocrit

30-50 Normal Hematocrit

Lab Values: Activated Partial Thromboplastin Time (aPTT)

25-35 Seconds w/o Heparin

Iv Heparin Therapy: 1.5-2 times normal (60-80 seconds)

Pharmacotherapeutics: Anticoagulants

Interrupt Clotting Cascade:

- Heparin

- Enoxaparin (Lovenox)

- Warfarin (Coumadin)

Anticoagulants: MOA

Prevent blood clots from forming or extending by interrupting the clotting cascade

- Thin the blood

- DO NOT break down existing clots

Anticoagulants: Pharmacokinetics

Anticoagulants Delivered:

IV, SubQ, or PO

Pharmacotherapeutics: Thrombolytics

Lyse (dissolve) existing clots

• Recombinant Alteplase (Activase, tPA)

• Tenecteplase (TNKase)

Pharmacotherapeutics: Antiplatelet Agents

Antiplatelets interfere with platelet membrane function and platelet aggregation

• Clopidogrel Bisulfate (Plavix)

• Aspirin

Warfarin (Coumadin) MOA

- Blocks Vitamin K

- Prevents activation of prothrombin and other factors

Warfarin (Coumadin) Monitoring:

Warfarin is monitored by INR:

Target INR: 2-3

-- if on a mechanical mitral valve: 2.5-3.5)

Warfarin (Coumadin) Dosage

Target depends on indication; dose is individualized by INR results

- Blood given everyday to determine warfarin dose

Warfarin (Coumadin) Contraindications

Warfarin in contraindicated in PREGNANCY

- Fetal Warfarin Syndrome

Warfarin (Coumadin) Toxicity Antidote

Antidote for Warfarin:

- VITAMIN K (Phytonadione)

- 4F-PCC (KCentra) for life-threatening bleeding

Both Given TOGETHER

Warfarin (Coumadin) Pharmacodynamics:

Highly Protein Bound

Inactivated by CYP2C9

Warfarin (Coumadin) Pharmacodynamics: Onset

- Initial dose response seen in 8-12 hours

- Several days for peak effects

- Half-life 1.5-2 days

Warfarin (Coumadin): Adverse Effects

Hemorrhage

LOTS of drug interactions: look for s/s of bleeding everywhere

Heparin:

Unfractionated heparin binds with antithrombin

and helps it inactivate thrombin and factor Xa (10a)

- Low molecular weight or other heparins only

inactivate Factor Xa.

Heparin MOA

Prevents the conversion of prothrombin to thrombin, fibrinogen to fibrin

Heparin Monitoring:

Continuous IV therapy monitored by activated

partial thromboplastin time (aPTT)

• Therapeutic aPTT levels are 1 - 1/2 and 2 times the control level

• Normal aPPT is 40 seconds

Therapeutic effects of Heparin aPPT is 60-80

seconds

Heparin Plasma Level:

When on heparin, plasma levels can be highly variable, therefore requires intensive monitoring

Heparin Half Life:

Short Half-Life (1.5 Hours)

Metabolism and Excretion:

Hepatic metabolism

Renal Excretion

Heparin Antidote

Antidote for Heparin toxicity is PROTAMINE SULFATE

Heparin Adverse Effects:

Adverse Effects of Heparin:

Hemorrhage

• Spinal/epidural hematoma

• Heparin Induced Thrombocytopenia (HIT)

• Precipitous drop in platelet level

• Autoimmune response

• Antibodies work against heparin- platelet-protein complexes

• Hypersensitivity Reactions

• Chills, fever, urticaria

Heparin Adverse Effects: Heparin Induced Thrombocytopenia (HIT)

Autoimmune response to heparin that depletes platelets.

• CREATING CLOTS

Normal Platelets: 150,000-450,000

HIT Platelets: 45,000-50,000

Heparin Dosage:

Dosed in UNITS:

- IV Heparin is HIGH ALERT

-- 2 nurses check off initial doses and dose changes

- Use a volumetric pump device, check drug compatibility

Heparin Low Dose Therapy:

Subcutaneous Heparin

Proper needle gauge & length

• Do not massage/avoid umbilicus

• Does not require monitoring

• Q12H or Q8H dosing interval

Enoxaparin (Lovenox)

Low Molecular Weight Heparin: LMWH (Bonding to Xa)

- Increased bioavailability and longer half life

- Predictable Dose Response

Enoxaparin (Lovenox) Administration:

Enoxaparin (Lovenox) Administration:

• Administered subcutaneously

• Proper needle gauge & length

• DO NOT EXPEL AIR BUBBLE

• Do not massage/Avoid umbilicus

• Daily or Q12H dosing interval

Direct Thrombin Inhibiitors

Dabigatran (PO)

Argatroban (IV)

Direct Thrombin Inhibiitors MOA

Direct Thrombin Inhibitors: Binds with thrombin in the blood and directly inhibits it

Direct Thrombin Inhibiitors: Adverse Effects

Adverse Effects of Direct Thrombin Inhibitors:

- BLEEDING

Direct Thrombin Inhibiitors: Therapeutic Use (Dabigatran)

Atrial fibrillation, DVT/PE treatment &

prophylaxis

Direct Thrombin Inhibiitors: Therapeutic Use (Argatroban)

Treats HIT

Direct Thrombin Inhibiitors: Dabigatran vs Warfarin

Dabigatran: fewer drug interactions than warfarin

Direct Thrombin Inhibiitors: Antidote

• Idarucizumab (Praxbind) (for dabigatran only)

Facotor Xa Inhibitor NTN:

Rivaroxaban (Xarelto)

Apixaban (Eliquis)

Facotor Xa Inhibitor: MOA

Binds with factor Xa and inhibits production of thrombin

Facotor Xa Inhibitor: Therapeutic Uses

• Prevention of DVT and PE following total hip replacement (THR) or knee replacement (TKR) surgery

• Prevention of stroke in patients with atrial fibrillation

• Treatment of DVT and PE

Facotor Xa Inhibitor: Adverse Effects

Adverse effects of Factor Xa Inhibitors:

• Bleeding

• Use with caution in patients with renal impairment and hepatic impairment

• Avoid in pregnancy (LMWH preferred)

Facotor Xa Inhibitor: Drug Interactions

Fewer drug interactions than warfarin

• No routine monitoring

Facotor Xa Inhibitor: Antidote

4F-PCC (Kcentra).

Andexanet alfa (Andexxa) withdrawn from US market Dec 2025

Antiplatlet Agents:

Clopidogrel Bisulfate (Plavix)

Aspirin

Adenosine Diphosphate Receptor Antagonists: Clopidogrel Bisulfate (Plavix)

Prodrug - undergoes metabolism to its active form

• Irreversible antiplatelet effects

• Platelet function and bleeding times return

to normal 7-10 days after the last dose

Clopidogrel Bisulfate (Plavix): Therapeutic Uses

Prevent blockage of coronary artery stents

• Prevention of thrombotic events (ischemic

stroke, MI, and vascular death) in patients

with ACS

• In patients with ACS combine with aspirin

Clopidogrel Bisulfate (Plavix): Adverse Effects

• Bleeding

• Thrombotic Thrombocytopenic Purpura

(TTP)

Clopidogrel Bisulfate (Plavix) Adverse Effects Thrombocytopenic Purpura

(TTP)

Similar to HIT: Low Platelets

Clopidogrel Bisulfate (Plavix) Drug Interactions

• Proton Pump Inhibitors (PPIs)

• Used to decrease the risk of GI bleeding in high-risk patients

• PPIs inhibit P450 and may decrease

metabolism of clopidogrel

Thrombolytics (Fibrinolytics) Medications

Recombinant alteplase (Activase, tPA)

Tenecteplase (TNKase): single IV bolus; FDA-approved for stroke 2025

Thrombolytics (Fibrinolytics) Medications MOA

Catalyzes the conversion of plasminogen into plasmin

• Plasmin digests the fibrin meshwork of clots

Thrombolytics (Fibrinolytics) Medications Therapeutic Uses

• MI

• Ischemic stroke

• Massive pulmonary embolism

• Occluded central venous catheter (Cathflo)

Thrombolytics (Fibrinolytics) Medications Adverse Effects

Very HIGH risk of bleeding

• Monitor for bleeding

• All sites

• Major bleeding: stop infusion; Aminocaproic Acid (Amicar)

Thrombolytics (Fibrinolytics) Medications Antidote

Aminocaproic Acid (Amicar)

- Stop infusion and give ASAP

Hemostatic Agents:

(Amicar) aminocaproic acid

Hemostatic Agents: (Amicar) aminocaproic acid MOA

A systemic hemostatic drug that stops blood loss by enhancing coagulation.

- Administer with an IV Pump

- Place pt on a cardiac monitor to detect dysrhythmias

Hemostatic Agents: (Amicar) aminocaproic acid Adverse Effects

Adverse Effects of aminocaproic acid (Amicar):

Nausea

Anorexia

Nursing Responsibilities:

• Obtain patient history for contraindications to therapy

Monitor for:

• Vital sign changes

• Signs of bleeding

• Blood work abnormalities (hematocrit, hemoglobin, platelets, PT, aPTT , INR)

• Arrhythmias

• Respiratory difficulties

Key Points of Nursing Assessment:

- Nursing History & Physical

- Is the agent used appropriate for the goal of therapy?

- Significant laboratory values

- Assessment

- Adverse Effects

- Patient Teaching

A patient is receiving an intravenous infusion of heparin to treat a

pulmonary embolism. What laboratory value will the nurse monitor to

evaluate treatment with this medication?

A. Activated partial thromboplastin time (aPTT)

B. Prothrombin time (PT)

C. Platelet count

D. Hemoglobin and hematocrit

A. Activated partial thromboplastin

Rationale: PT is on heparin. When on heparin, always evaluate heparin dosage with aPTT

Which patient does the nurse identify as most likely needing an increased dose of

warfarin [Coumadin] to have the same anticoagulant effect?

A. Patient taking acetaminophen [Tylenol] for back pain

B. Patient taking cimetidine [Tagamet] to prevent gastric ulcers

C. Patient taking oral contraceptives to prevent pregnancy

D. Patient taking prednisone [Deltasone] for rheumatoid arthritis

C. Patient taking oral contraceptives to prevent pregnancy

Rationale: Estrogen-containing oral contraceptives increase the production of clotting factors (including factors VII, X, and fibrinogen). More clotting factors means a stronger tendency to clot, which opposes warfarin’s effect. The patient therefore needs a higher warfarin dose to reach the same anticoagulant effect (same INR).

What is the antidote for heparin?

A. Ferrous sulfate

B. Atropine sulfate

C. Protamine sulfate

D. Magnesium sulfate

C. Protamine sulfate

During administration of alteplase [Activase], the patient's IV site starts

to ooze blood around the catheter. Which action by the nurse is most

appropriate?

A. Discontinue the infusion of alteplase.

B. Assess the patient's vital signs.

C. Apply direct pressure over the puncture site.

D. Administer aminocaproic acid [Amicar].

c. Apply direct pressure over the puncture site.

Rationale: Oozing and leaking of blood around the catheter is normal when receiving a thrombolytics.

• Only if major, uncontrollable leakage of blood: stop infusion and administer Amicar