STEPTRACKERPHARMACOLOGY + HEMATOLOGY | HEMATOLOGY | HIGH-YIELD REVIEW

Antiplatelets & Thrombolytics

Arterial clots are platelet-rich, so they need antiplatelet drugs; established clots can be dissolved by plasminogen activators — at the cost of bleeding.

FOCUS ON

Aspirin: irreversibly acetylates COX-1 → ↓ TXA₂ for the platelet's life (7–10 days); ↑ bleeding time, PT/aPTT normal. P2Y12 (ADP) blockers: clopidogrel (prodrug, CYP2C19), prasugrel (avoid with prior stroke, > 75 y), ticagrelor (reversible, dyspnea); clopidogrel/ticlopidine → TTP; ticlopidine → neutropenia. GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban): block fibrinogen bridging; PCI; thrombocytopenia. PDE3 inhibitors: cilostazol (claudication), dipyridamole (with aspirin for stroke; ↑ adenosine — stress test). PAR-1: vorapaxar. Thrombolytics: alteplase, tenecteplase, reteplase (fibrin-selective tPA), streptokinase — convert plasminogen to plasmin; for STEMI (no PCI), ischemic stroke (< 4.5 h), massive PE. Contraindications: prior hemorrhagic stroke, recent surgery/bleeding, severe uncontrolled HTN, intracranial tumor. Reverse with aminocaproic acid or tranexamic acid (antifibrinolytics), cryoprecipitate.

DRUG

MECHANISM

USE

ADVERSE · NOTES

Aspirin

Irreversible COX-1 (and COX-2) acetylation → ↓ TXA₂

ACS, secondary prevention of MI/stroke, after stents, Kawasaki, preeclampsia prevention

GI bleeding, ulcers, asthma exacerbation (AERD), Reye syndrome, tinnitus

Clopidogrel

Irreversible P2Y12 block (prodrug, CYP2C19)

ACS, stents (with aspirin), stroke, PAD

Bleeding, TTP; poor metabolizers; omeprazole ↓ activation

Prasugrel

Irreversible P2Y12, more potent

ACS with PCI

Contraindicated with prior stroke/TIA

Ticagrelor

Reversible P2Y12; not a prodrug

ACS

Dyspnea (adenosine effect), bleeding

Ticlopidine

Irreversible P2Y12

Rarely used

Neutropenia, TTP

Abciximab · eptifibatide · tirofiban

Block GP IIb/IIIa → no fibrinogen cross-linking

High-risk PCI, ACS

Bleeding, thrombocytopenia

Dipyridamole

PDE3 inhibition + ↓ adenosine uptake

Stroke prevention (with aspirin), pharmacologic stress test

Headache, coronary steal

Cilostazol

PDE3 inhibition → ↑ cAMP

Intermittent claudication

Contraindicated in HF

Vorapaxar

PAR-1 (thrombin receptor) antagonist

Post-MI, PAD

Contraindicated after stroke

Alteplase · tenecteplase · reteplase

Recombinant tPA → plasminogen → plasmin (fibrin-bound)

Ischemic stroke (≤ 4.5 h), STEMI without timely PCI, massive PE

Hemorrhage (intracranial); ↑ PT, aPTT, ↓ fibrinogen

Streptokinase

Bacterial protein, activates plasminogen (not fibrin-selective)

Low-resource STEMI

Antigenic → allergy, can't reuse

Aminocaproic acid · tranexamic acid

Lysine analogs block plasminogen binding to fibrin

Thrombolytic overdose, trauma, postpartum and dental bleeding, hemophilia

Thrombosis

Mechanism — platelet activation targets

AdhesionvWF–GP Ib

→

ActivationADP (P2Y12), TXA₂, thrombin (PAR-1)

→

GP IIb/IIIa opensFibrinogen bridges → aggregation

Aspirin stops TXA₂, clopidogrel stops ADP signaling, abciximab stops the final common step.

Labs in antithrombotic therapy

DRUG

aPTT

BLEEDING TIME

Aspirin

—

↑

Heparin

—

↑

—

Warfarin

↑

— / ↑

—

Alteplase

↑

—

How it's tested

COMMON CONFUSIONAspirin's antiplatelet effect lasts the platelet's lifespan because platelets lack nuclei and can't make new COX; NSAIDs like ibuprofen block COX reversibly.

THE TRAPIbuprofen taken before aspirin occupies COX-1 and blocks aspirin's irreversible acetylation — give aspirin first.

YOUR APPROACHArterial (platelet) clot → antiplatelet; venous (fibrin) clot → anticoagulant; occlusive acute clot within window → thrombolytic.

If you see… think…

Fever, MAHA, thrombocytopenia, confusion on an antiplatelet → TTP (clopidogrel, ticlopidine)

Shortness of breath on an ACS antiplatelet → ticagrelor

Stent thrombosis, Asian ancestry, on clopidogrel → CYP2C19 poor metabolizer

P2Y12 blocker contraindicated after stroke → prasugrel

Final common pathway of aggregation → GP IIb/IIIa

Ischemic stroke within 4.5 hours → alteplase

Bleeding after thrombolysis → aminocaproic acid, cryoprecipitate

Nasal polyps, asthma, aspirin sensitivity → AERD (leukotriene shunt)

Child with viral illness given aspirin, hepatic failure → Reye syndrome

Claudication drug → cilostazol