Coagulation Modifiers FULL

Antiplatelets drugs

• NSAIDs (aspirin)

• Adenosine diphosphate (ADP) receptor antagonists

• Glycoprotein IIb/IIa receptor antagonists

• Phosphodiesterase-3 enzyme inhibitors

Prodrug of antiplatelet NSAIDs

Aspirin (asa)

MOA of aspirin

• Inhibits prostaglandin synthesis that cause platelet aggregation

• Inhibition lasts for lifespan of platelet (7-10 days)

Why are other NSAIDs not used as antiplatelets drugs?

NSAIDs other than aspirin have some antiplatelet effects but it subsides when drugs eliminated; effects do not last long

Lifespan of platelet

7-10 days

Aspirin’s & ADPRAs duration of effect

7-10 days; same as platelet lifespan

• Long term prevention of MI and CVA

• Prevent clotting in patients with prosthetic valves

• Immediate treatment with suspected or actual acute MI, TIA, CVA (~85% of strokes are thrombotic)

Aspirin indication

Drug used to prevent clot formation in patients with prosthetic valves

Aspirin & warfarin

Adverse effects of this drug

• Uncommon with small dose

• Increased risk for bleeding, stomach ulcers, tinnitus

• Has no antidote

  • If severe bleeding, transfusion may be required

SE of aspirin

Treating salicylism

Blood transfusion, gastric lavage, activated charcoal, hemodialysis, HCO3- infusion

Drug contraindicated if patient has

• Ulcers

• Active bleeding

• Pregnancy

• Children under 16 years of age (Reye’s syndrome)

Aspirin contraindications 

DNU for children under 16 years of age due to risk of developing Reye’s syndrome

Aspirin

S&S of salicylism

• CV: increased HR

• CNS: tinnitus, hearing loss, dizziness, HA, confusion

• GI: NVD

• Metabolic: sweating, thirst, hyperventilation, metabolic acidosis

Prodrug of ADP receptor antagonist

Clopidogrel (Plavix)

Name the ADP receptor antagonists

Clopidogrel, prasugrel, ticagrelor

MOA of ADP receptor antagonists

• Irreversibly block ADP receptor on platelets, preventing them from activating

• Prevents platelet aggregation; inhibition lasts for platelet lifespan (7-10 days)

Drug used for

• Prophylaxis treatment for MI, stroke, vascular death with atherosclerosis 

• Prevent clotting around post coronary stent placement

• Afib (for patients unable to tolerate vitamin K antagonist e.g. warfarin)

Clopidogrel (ADP receptor antagonists) indication

Drug given to patient after they’ve had a coronary stent placed

Clopidogrel (ADP receptor antagonist

Drug used to treat Afib if patient is unable to tolerate vitamin K antagonist such as warfarin

Clopidogrel (ADP receptor antagonist)

These drugs has these adverse effects:

• Increased risk of bleeding

• Pruritis (itchiness), rash, purpura, and diarrhea

SE of Clopidogrel (ADP receptor antagonists)

Drugs not recommended for patients with genetic variations of CYP2C19 function

• Therapeutic effect neutralized; patients with this disorder are “poor metabolizers” (~2-14%) remain at risk for MI, CVA, and death

• Genomic testing not routinely recommended

BBW of ADP receptor antagonists (grels)

Nursing implications of ADP receptor antagonists 

• Dual antiplatelet therapy (ADP + ASA) shown to be beneficial post PCI (stent placement)

  • Recommended for at least 12 months

  • 18 months if tolerated

Patient education for antiplatelets

• Regular supervision & periodic blood tests required

  • Test hemoglobin ( < 7) & platelet count ( < 150,000/50,000)

• Inform providers (including dentists) of using drug before any invasive diagnostic testing or treatments (hold antiplatelet meds 5-7 days prior

• Take ASA with food or after meals along with 8 oz of water to decrease stomach irritation

  • Don’t crush or chew coated tablets

Patients taking antiplatelets with a hemoglobin less than seven

Send your patient to heaven

Dangerous blood values for patients taking antiplatelets

• Hgb < 7 (deadly)

• Plt < 150,000 (use w/ caution)

• Plt < 50,000 (deadly)

Platelets less than 150

This is iffy; use antiplatelets with caution

Platelets less than 50

This is risky; do not administer antiplatelets (deadly)

Normal platelet count

130,000-400,000 uL

You can crush and chew enteric-coated aspirin tablets. True or false?

False

Aspirin should be taken with meals + 8 oz of water to reduce stomach irritation. True or false?

True

Anticoagulants types

• Heparins

• Vitamin K antagonists (warfarin)

• Direct-acting oral anticoagulants (DOACs)

  • Direct thrombin inhibitors

  • Factor Xa inhibitors

Prodrug of Heparins

Heparin 

MOA of Heparin

• Combines with antithrombin III to inactivate clotting factors (9-12: IX, X, XI, and XII)

  • Inhibit conversion of prothrombin to thrombin

• Prevents thrombus formation (prevent clot from getting bigger or forming new clots)

• Inhibits additional coagulation

Heparin/warfarin can break down existing clots. True or false?

False

Pharmacokinetics of heparin

• Unable to be absorbed by GI tract

• Administered IV or subQ

  • IV acts immediately

  • SubQ acts within 20-30 mins

GI tract does not absorb this drug

Heparin

Heparin is used only for short-term therapy. True or false?

True

Why is heparin used only for short-term anticoagulant therapy?

Because it’s fast-acting and has a short half-life

Drug that can be used to treat

• Prophylaxis to prevent DVT/PE

• Patients post-op/on bedrest > 5 days

• Treat MI

• Acute thromboembolic disorders (DVT, PE, thrombophlebitis) 

• DIC

Heparin indication

Acute thromboembolic disorders are treated by

DVT, thrombophlebitis, PE; heparin

Drugs that treats DIC

Heparin

Life threatening condition where person is clotting and bleeding at the same time. Widespread clotting depletes blood of coagulation factors, which then leads to widespread bleeding.

• Treated by heparin 

Disseminated intravascular coagulation (DIC)

How does heparin treat DIC?

Heparin prevents blood coagulation long enough for clotting factors to be replenished.

Adverse effects of these drugs include

• Hemorrhage/bleeding

• Local irritation at injection site (erythema/mild pain)

• HIT (thrombocytopenia)

SE of heparin

Potential life-threatening complication caused by rare immune-mediated response (~1-3% of population). Platelets are destroyed by the spleen, decreasing platelet count. Is caused by heparin; treat with DTI (argatroban)

• Immune-mediated response can activate some platelets, causing clot formation and micro-emboli

• Individuals with platelet activation develop cyanotic/purple fingers/toes (due to microembolism)

Heparin-induced thrombocytopenia (HIT)

Drug is contraindicated in:

• HTN (severe; high risk for bleeding/vascular damage)

• Active bleeding (GI ulcers, intracranial bleeding)

• Recent surgery of the eye, spinal cord, or brain

• Dissecting aortic aneurysm

• Severe kidney or liver disease (renal & hepatic)

Heparin contraindications

Nursing implications of heparin

• Narrow therapeutic window and highly subjective individual response → monitor aPTT values

  • Therapeutic range is aPTT = 45-70 seconds (1.5-2.5x the control/baseline)

• Lab draws

  • Continuous = anytime

  • Intermittent = 1 hour before next scheduled dose

  • Not necessary for low dose or LMWHs

• Double check dosage with another nurse

• High aPTT → stop heparin and administer protamine sulfate

2 major limitations of heparin

• Narrow therapeutic window (margin)

• Highly variable individual-dose response

Must monitor labs (aPTT)

Therapeutic range of heparin (aPTT)

aPTT 45-70 seconds (1.5x-2.5x control/baseline)

When can you draw labs for a person on continuous infusion of heparin?

Any time

When to draw labs for patient under intermittent administration of heparin?

1 hour before next scheduled dose

Low dose heparins or LMWHs do not need lab draws. True or false?

True

At some facilities, administration of this drug requires double-checking with another nurse

Heparin

High aPTT indicates

Active bleeding

If patient on heparin has high aPTT, what should the nurse do?

Stop/hold heparin; notify provider; consider administering antidote protamine sulfate

Antidote for heparin overdose (toxicity)

Protamine sulfate

LMWH

Low-molecular-weight-heparin

Prodrug of LMWH

Enoxaparin (Lovenox)

Common suffix for LMWHs

-parin 

MOA of LMWH

• Synthetic heparins with small molecular structures

• Specific to active factor X

Advantages of LMWH

• More predictable response

• No lab draws

• No need to monitor blood coagulation

  • Simplifies outpatient therapy and safety

Anticoagulant drug ideal for outpatient therapy

LMWHs

Pharmacokinetics of LMWH

• SubQ = slightly delayed onset of action

• Longer duration of action = difficult to rapidly stop therapy

Nursing implications of LMWH

• Educate patients on how to self-administer LMWH medication

• No lab draws

• Antidote is protamine sulfate

Why is heparin used for more acute conditions rather than LMWH?

LMWH has longer duration and delayed onset of action; heparin can be adjusted/stopped quickly if needed

Antidote for heparin and LMWH overdose

Protamine sulfate

Prodrug of vitamin K antagonists

Warfarin (Coumadin)

MOA of warfarin (vitamin K antagonist)

• Acts in the liver to prevent synthesis of vitamin K-dependent clotting factors (factors II, VII, IX, and X)

• Competitive antagonist to hepatic use of vitamin K

Vitamin K dependent clotting factors

Factors II, VII, IX, and X

Pharmacokinetics of vitamin K antagonists

• Anticoagulant effects do not occur until 3-5 days

• May be given with heparin

  • Transition from IV/SubQ heparin to oral warfarin

  • Given together for 2-3 days

Warfarin can safely be given with heparin. True or false?

True

Long-term prevention or management of venous thrombotic disorders

• DVT, PE, Afib, clotting around prosthetic valves

Warfarin (vitamin K antagonist) indication

Drugs used treat patients with prosthetic valves

Aspirin & warfarin

Nursing implications of Vitamin K antagonists

• Monitor labs

  • Narrow therapeutic window

  • Highly variable dose response

  • Daily evaluation of PT (18 sec) & INR (2-3) until a stable/therapeutic dose is reached

• Med administration:

  • Institutions will have different protocols for therapeutic ranges

  • Hold dose if INR is > 3 and notify provider

• Interacts with medications & vitamin K food

• Antidote for overdose (high INR) is phytonadione (vitamin K) or Kcentra (prothrombin complex concentrate)

  • Administered if INR > 5 and S&S of bleeding present

  • Phytonadione works slowly ~6 hours

  • Use Kcentra for acute/urgent cases

Therapeutic warfarin PT levels =

18 seconds

Therapeutic warfarin INR =

2-3

How often is INR checked in warfarin anticoagulant therapy?

Every 2-4 weeks 

INR 3.0-4.5

Excessive warfarin dose; high bleeding risk and slower clotting time

INR will go up if you eat

• Coumadin (warfarin)

• Alcohol

• Aspirin

INR will go down if you eat

• Vit K vegies

• CoQ10

• Green tea

Normal INR

0.8-1.2

What should the nurse do if patient on warfarin anticoagulant therapy has INR > 3?

Hold dose and notify provider

Higher INR = _____ blood while lower INR = ______

Thinner; thicker

Low INR can lead to

Higher stroke risk from clot; faster clotting time

Medications that interact with Warfarin

ASA, NSAIDs, certain antibiotics, clopidogrel, several antidepressants

Foods high in vitamin K

Green leafy vegetables

• Parsley

• Watercress

• Green onions

• Leaf lettuce

• Basil

• Broccoli

• Pomegranates

• Kiwi

• Spinach

• Cucumbers

• Prunes

• Walnuts

• Cabbage

• Cauliflower

• Avocados

Patient warfarin education about vitamin K foods

• Encourage consistent intake or in moderation; do not drastically change diet

• Do not change intake of foods that are high in vitamin K

Antidotes for warfarin

Phytonadione (Vitamin K); Kcentra (PCC)

You can use phytonadione (vitamin K) to treat acute warfarin overdose. True or false?

False

Used to treat/reverse urgent major or life-threatening hemorrhage caused by warfarin overdose

Prothrombin complex concentrate [PCC human] (Kcentra)

Phytonadiaone (vitamin K)

Antidote for warfarin; works slowly (~6 hours) for effect

DOACs

Direct-acting oral anticoagulants

AKA non-vitamin K oral anticoagulants or new/novel oral anticoagulants (NOACs)

DOACs

2 classes of DOACs

• Direct thrombin inhibitors (DTIs)

• Factor Xa inhibitors

Advantages of DOACs

• Less variability/subjectivity in drug effect

• Require no lab monitoring

• May become first choice for oral anticoagulants

Prodrug of DTIs (DOAC)

Dabigatran etexilate (Pradaxa)

MOA of dabigatran etexilate (DTI/DOAC)

• Directly and reversibly inhibits thrombin (key enzyme in coagulation cascade)

• Indirectly inhibits thrombin induced platelet aggregation

Drug that is used for:

• Treatment and prevention of DVT and PE

• Stroke prevention in nonvalvular Afib

Dabigatran (DTI/DOAC) indication

Antidote for DTI (dabigatran)

Idarucizumab (Praxbind)

DNU for patients with prosthetics valve

Dabigatran (DTIs) & -xabans (Xa inhibitors) contraindications