Arterial clots (coronary, cerebral, peripheral arteries) are rich in platelets, so they are prevented mainly with antiplatelet drugs. Thrombolytics (fibrinolytics) go one step further: they dissolve a clot that has already formed by activating the body's own fibrin-dissolving system.

Antiplatelet drugs

Clopidogrel and prasugrel are prodrugs; clopidogrel needs the liver enzyme CYP2C19 for activation.

Thrombolytics — alteplase, tenecteplase, reteplase: tissue plasminogen activators convert plasminogen to plasmin, which breaks fibrin and dissolves the clot. They dissolve all fibrin clots, including protective ones — hence the high bleeding risk.

Antifibrinolytics — tranexamic acid, aminocaproic acid: block plasminogen activation and are used to treat bleeding, including thrombolytic-related bleeding.

Dual antiplatelet therapy (DAPT) = aspirin + a P2Y12 inhibitor. After ACS the default is 12 months if bleeding risk is low; the cardiologist may shorten it. For minor noncardioembolic stroke (NIHSS ≤ 5) or high-risk TIA, aspirin + clopidogrel started within 72 hours is used for 21 days, then a single agent.

Thrombolytic time windows

• STEMI: fibrinolysis when primary PCI cannot be done in time; door-to-needle ≤ 30 minutes, generally within 12 hours of symptom onset
• Acute ischemic stroke: within 4.5 hours of last known well for eligible clients (selected clients up to 9 hours based on advanced imaging per the 2026 AHA/ASA guideline)
• Massive (high-risk) PE with persistent hypotension

Antiplatelets

• Bleeding (GI, intracranial, access sites), bruising, nosebleeds
• Aspirin: GI irritation, peptic ulcer and GI bleeding, salicylism (tinnitus, hearing loss, dizziness) at high doses, bronchospasm in aspirin-exacerbated respiratory disease, Reye syndrome in children and teenagers with viral illness
• Clopidogrel: bleeding, rash, rare thrombotic thrombocytopenic purpura (TTP)
• Ticagrelor: dyspnea (usually mild), bradyarrhythmias, raised uric acid
• GP IIb/IIIa inhibitors: thrombocytopenia (sometimes profound, within hours), bleeding
• Cilostazol: headache, diarrhea, palpitations

Thrombolytics

• Bleeding — intracranial hemorrhage is the most feared (sudden headache, nausea, vomiting, decreasing level of consciousness, new neurologic deficit, acute hypertension)
• Internal bleeding (GI, retroperitoneal), bleeding at puncture sites and gums
• Orolingual angioedema (alteplase), especially with ACE inhibitors
• Reperfusion dysrhythmias after MI (e.g., accelerated idioventricular rhythm — often a sign of successful reperfusion)
• Hypotension, allergic reactions

Antiplatelets

• Active pathologic bleeding; history of intracranial hemorrhage (relative for aspirin)
• Prasugrel: prior stroke or TIA (boxed warning); weight < 60 kg (lower dose)
• Ticagrelor: history of intracranial hemorrhage, severe liver impairment; aspirin doses above 100 mg/day reduce its effectiveness (boxed warning)
• Aspirin: children and teenagers with viral illness (Reye syndrome), aspirin/NSAID allergy, bleeding disorders, active peptic ulcer. Pregnancy: NSAIDs and full-dose aspirin are avoided from 20 weeks; low-dose aspirin for preeclampsia prevention is an exception prescribed by the obstetric provider
• Cilostazol: heart failure

Absolute contraindications to thrombolytics (key examples)

• Any prior intracranial hemorrhage; known intracranial tumor or vascular malformation
• Ischemic stroke within 3 months (except acute stroke within the treatment window), significant head trauma or intracranial/spinal surgery within 3 months
• Active internal bleeding; suspected aortic dissection
• Acute stroke specifics: blood pressure that cannot be lowered below 185/110 mmHg, platelets < 100,000/µL (100 × 10⁹/L), INR > 1.7, therapeutic anticoagulation per protocol, blood glucose < 50 mg/dL (2.8 mmol/L) as a mimic (correct it first)

Interactions

• Any combination of antiplatelets, anticoagulants, thrombolytics, NSAIDs, SSRIs/SNRIs, and herbal products (ginkgo, garlic, high-dose fish oil) increases bleeding.
• Ibuprofen blocks aspirin's antiplatelet effect — take immediate-release aspirin at least 30 minutes before, or 8 hours after, ibuprofen.
• Omeprazole and esomeprazole reduce clopidogrel activation — pantoprazole is preferred when a PPI is needed. A PPI is recommended for clients on DAPT with high GI bleeding risk.
• Strong CYP3A4 inhibitors and inducers alter ticagrelor levels — avoid.
• Surgery: stop clopidogrel and ticagrelor about 5 days, prasugrel about 7 days before elective surgery only with cardiology approval — stopping DAPT soon after a stent risks stent thrombosis.

Antiplatelets

1. Assess for bleeding and GI symptoms; monitor hemoglobin and platelets (platelets 2–4 hours after starting a GP IIb/IIIa inhibitor, then daily).
2. Give aspirin with food or milk to reduce GI upset (enteric-coated for chronic use; chewed non-enteric-coated in suspected MI).
3. Hold pressure on arterial access sites; check for hematoma and distal pulses after PCI.
4. Verify that DAPT is not interrupted during hospital stays or procedures without a cardiology decision.

Thrombolytics (priority order)

1. Before: confirm eligibility checklist and time of symptom onset/last known well; for stroke, noncontrast CT to exclude hemorrhage; glucose; weight for dosing; two large-bore IV lines; insert catheters, nasogastric tubes, and arterial punctures before, not after, when possible.
2. Blood pressure (stroke): keep < 185/110 mmHg before and < 180/105 mmHg for 24 hours after treatment.
3. Neurologic checks and vital signs: every 15 minutes during infusion and for 2 hours, every 30 minutes for 6 hours, then hourly until 24 hours.
4. Stop the infusion and notify the provider immediately for severe headache, acute hypertension, nausea and vomiting, or worsening neurologic status (suspect intracranial hemorrhage); prepare for emergency CT.
5. No antiplatelets or anticoagulants for 24 hours after stroke thrombolysis unless ordered; follow-up imaging before starting them.
6. Watch the tongue and lips for angioedema; avoid unnecessary punctures and IM injections; apply prolonged pressure to venipuncture sites.
7. STEMI: monitor ECG for resolution of ST elevation, relief of chest pain, and reperfusion dysrhythmias.
8. Catheter clearance (alteplase 2 mg): instill per protocol, dwell, then aspirate and discard before flushing.

• Aspirin and P2Y12 inhibitors after a stent: never stop on your own, even before dental work — the stent can clot and cause a heart attack; the cardiologist decides
• Report black stools, blood in urine, vomiting blood, severe bruising, nosebleeds that will not stop, or sudden severe headache
• Avoid NSAIDs (ibuprofen, naproxen) unless approved; use acetaminophen/paracetamol for pain
• Tell dentists and surgeons about antiplatelet therapy
• Aspirin: take with food; report ringing in the ears; do not give aspirin to children or teenagers with fever or viral illness
• Ticagrelor: take twice daily; mild shortness of breath is common — report if severe or persistent; do not take more than 100 mg of aspirin daily
• Clopidogrel: avoid omeprazole and esomeprazole unless the prescriber approves
• After thrombolysis: bleeding precautions, report headache or neurologic change, and follow the secondary prevention plan (antiplatelet, statin, BP control)
• Stroke and heart attack warning signs — call emergency services immediately, because thrombolytics work only within hours

• Aspirin (salicylate) overdose: tinnitus, nausea, vomiting, hyperthermia, respiratory alkalosis early, then mixed anion-gap metabolic acidosis, confusion, seizures, noncardiogenic pulmonary edema. Treatment: activated charcoal if early, IV sodium bicarbonate to alkalinize the urine, dextrose (CNS hypoglycemia), potassium replacement, hemodialysis for severe toxicity. Avoid sedation that depresses breathing.
• Antiplatelet-related major bleeding: no specific reversal agent; stop the drug, local measures, platelet transfusion may be considered for life-threatening or intracranial bleeding (less effective with ticagrelor while the drug is still circulating); desmopressin in selected cases.
• Thrombolytic bleeding: stop the infusion; obtain CBC, PT/INR, aPTT, fibrinogen, type and crossmatch; give cryoprecipitate (fibrinogen) and an antifibrinolytic (tranexamic acid or aminocaproic acid) per protocol; platelets as indicated; neurosurgical consultation for intracranial hemorrhage.
• Angioedema: stop alteplase, maintain the airway; antihistamine, corticosteroid, and epinephrine per protocol; icatibant or C1-esterase inhibitor may be considered.

• Antiplatelets prevent arterial clots; anticoagulants prevent venous clots and cardioembolism; thrombolytics dissolve clots
• Aspirin irreversibly blocks COX-1 → effect lasts 7–10 days; chewed 162–325 mg in suspected MI
• No aspirin in children/teens with viral illness (Reye syndrome)
• Clopidogrel: prodrug via CYP2C19; avoid omeprazole/esomeprazole
• Prasugrel contraindicated after stroke/TIA; ticagrelor → dyspnea, aspirin ≤ 100 mg
• Never stop DAPT early after a stent (stent thrombosis)
• Cilostazol → contraindicated in HF
• Stroke thrombolysis within 4.5 hours; BP < 185/110 before, < 180/105 for 24 h after
• Tenecteplase stroke dose 0.25 mg/kg (max 25 mg); alteplase 0.9 mg/kg (max 90 mg)
• STEMI fibrinolysis: door-to-needle ≤ 30 minutes
• Headache or neurologic decline during thrombolysis → stop infusion, CT; treat bleeding with cryoprecipitate and tranexamic acid
• Salicylate overdose → urine alkalinization with sodium bicarbonate, dialysis if severe