(7): 34: Anticoagulant drugs II: non-coumarins and 35: Fibrinolytic drugs

Anticoagulant drugs II: non-coumarins

Types of anticoagulants

1. Indirect anticoagulants

   1. Heparins

      1. MOA

      2. Drugs/Reversal

      3. Caution

      4. Adverse effect

2. Direct anticoagulants

   1. Direct Factor Xa Inhibitors

      1. MOA

      2. Drugs/Reversal

      3. Caution

      4. Advantage

      5. Fun Facts

         1. Uses

         2. Interaction

   2. Direct Thrombin (IIa) Inhibitors

      1. Drugs

Heparins

MOA

All enhance antithrombin III (ATIII) → inhibit clotting factors.

Heparins

Drug

Drug	MOA	Monitoring
UFH	Inhibits IIa + Xa	aPTT goal = 1.5–2.5× baseline.
LMWH	Mainly inhibits Xa	Usually none
Fondaparinux (Arixtra)	Inhibits Xa only	Usually none

• UFH: Long chain; IV/SC; immediate anticoagulation.

• LMWH: Short chain; SC; more predictable.

• Fondaparinux: Synthetic; SC;

• LMWH/fondaparinux → monitoring may be needed in renal dysfunction, obesity, pregnancy.

Heparin

Caution

• Never administer heparin IM → hematoma.

• Avoid heparin with active bleeding or a history of HIT.

Heparin Reversal

Protamine

• UFH → Full reversal.

• LMWH → Partial reversal.

• MOA: Protamine (+) binds heparin (−) → neutralizes anticoagulant effect.

Heparin

Adverse Effect

• Heparin-Induced Thrombocytopenia (HIT)

• Other heparin adverse effects:

  • bleeding

  • long-term use → osteoporosis, alopecia, hypersensitivity.

Heparin-Induced Thrombocytopenia (HIT)

1. What is it? ↓ Platelets BUT ↑ thrombosis (clot formation).

2. How it happens? Heparin + platelet factor 4 → immune reaction.

3. Treatment - Alternative anticoagulant → Argatroban.

Direct Factor Xa Inhibitors

• MOA: Directly inhibit factor Xa → block coagulation.

• Drugs: Rivaroxaban (Xarelto) + Apixaban (Eliquis)

• Reversal → Andexanet alfa (Andexxa).

• Caution - Dose adjustments may be needed with renal dysfunction or low body weight.

• Advantages:

  • Oral

  • rapid onset

  • no routine INR

  • predictable, fixed dosing

• Fun Facts

  • Uses: AF stroke prevention, DVT/PE, postoperative clot prevention.

  • Interactions: CYP3A4 + P-glycoprotein.

Direct Factor Xa Inhibitors

drugs

Rivaroxaban	Apixaban
Once daily in professor's comparison	Twice daily
Higher GI bleeding risk	Lower GI bleeding risk

Direct Thrombin (IIa) Inhibitors

Drug	MUST KNOW
Argatroban (Acova)	IV used for HIT/hepatic clearance monitor aPTT
Dabigatran (Pradaxa)	Oral prodrug/rapid onset use → AF stroke prevention and VTE treatment/prevention. no routine INR

• Both inhibit thrombin directly, without ATIII.

• Dabigatran

  • ⭐ Dabigatran reversal → Idarucizumab (Praxbind).

Warfarin Comparison to DIRECT anticoagulants!

Warfarin (Coumadin)

• Inhibits vitamin K recycling → decreases clotting factor production.

• Delayed onset, requires INR monitoring.

• Many food and drug interactions.

Direct Xa/IIa inhibitors

• faster, more predictable effects.

Clinical Scenarios

1. UFH - Acute DVT/PE needing immediate anticoagulation

2. LMWH - Pregnancy

3. Argatroban - HIT

4. UFH / Argatroban - Severe renal dysfunction

5. Oral direct anticoagulants - Long-term AF stroke prevention

Fibrinolytic Drug

Fibrinolytic Drugs - topics

• Mechanism

• Meds

• Cautions

• Adverse Effects

• Clinical Uses

Anticoagulants =

Prevent clot formation/extension.

Fibrinolysis

Mechanism

Fibrinolytics = DISSOLVE an existing clot.

Fibrinolytic Drugs

Drug	MUST KNOW
Streptokinase	Bacterial protein → allergy risk older/cheaper
Alteplase	Recombinant tPA shorter half-life
Tenecteplase	More fibrin-specific longer half-life → single IV bolus

• All administered IV.

Fibrinolytic

Clinical Uses

Used for serious clot-related vessel obstruction:

• Acute ischemic stroke

• STEMI (heart attack)

• Pulmonary embolism

• Severe DVT / other life-threatening obstructions.

⭐ STEMI:

• PCI preferred when promptly available.

• If PCI unavailable/delayed → fibrinolytic therapy may be used during transfer.

• TIME IS MUSCLE → treatment delays increase heart damage.

Fibrinolytic

Adverse Effects

• Streptokinase → allergic reactions.

• Bleeding → most important.

  • Intracranial hemorrhage → bleeding inside skull.

• Reperfusion injury → Blood returns → damaged vessel may BLEED.

Fibrinolytic

Contraindications

Absolute — Do NOT use	Relative — Weigh risks
History of intracranial hemorrhage	Anticoagulation with high INR
Certain recent ischemic strokes	Recent major surgery
Serious recent trauma	Pregnancy
Suspected aortic dissection	Peptic ulcer

Fibrinolytics increase the risk of severe bleeding.

Antifibrinolytic / Reversal

Tranexamic acid

🧠 TRANEXAMIC = Tells clot to STAY.

Tranexamic acid

• MOA: Blocks plasminogen/plasmin binding → prevents fibrin breakdown.

  • Effect:

    • Stabilizes clot → helps control bleeding.

    • to counter excessive fibrinolysis.

• Cauton: Professor mentioned avoiding in DIC and genitourinary bleeding.

• Risk: Increased thrombosis.

MEMORIZE: DRUG → REVERSAL

Anticoagulant / Drug class	Reversal
UFH	Protamine — full
LMWH	Protamine — partial
Rivaroxaban / Apixaban	Andexanet alfa
Dabigatran	Idarucizumab
Fibrinolytics	Tranexamic acid