4.1 Thrombolytics, Anticoagulants, and Antiplatelets

Intravenous reperfusion drugs and antithrombotic agents generate high-stakes pharmacology items. Wrong milligrams, a missed hemorrhage screen, or a dual-antiplatelet course meant for a carotid stent applied to a CHANCE-style minor stroke are typical traps. This independent OpenExamPrep section covers alteplase, tenecteplase, antiplatelets including short dual therapy, unfractionated and low-molecular-weight heparins, warfarin, and direct oral anticoagulants (DOACs). Specific reversal after hemorrhage is the next section. Mechanical thrombectomy windows live in the acute ischemic stroke chapter. You still need the drug doses here, because items isolate pharmacology from imaging selection.

Why these drugs matter on this exam

A 100 kg patient does not receive 90 mg of tenecteplase. Aspirin given before CT can convert an unrecognized intracerebral hemorrhage (ICH) into a bleed you cannot reverse with idarucizumab. Full-dose heparin is not standard treatment for garden-variety arterial ischemic stroke. After a large hemispheric infarct, starting apixaban the same night the National Institutes of Health Stroke Scale (NIHSS) peaks is a hemorrhagic-transformation setup. Know the numbers, the clocks, and which trial applies to which anatomy.

Alteplase

Alteplase (recombinant tissue plasminogen activator, tPA) converts plasminogen to plasmin. For eligible adults with acute ischemic stroke, the established intravenous dose is 0.9 mg/kg, maximum 90 mg. Give 10% as a bolus over about 1 minute; infuse the remaining 90% over 60 minutes. For a 70 kg adult that is 63 mg total (6.3 mg bolus, 56.7 mg infusion). For a 110 kg adult the calculated 99 mg is capped at 90 mg (9 mg bolus, 81 mg infusion). The usual clock is 0–4.5 hours from last known well when eligibility criteria are met. Pretreatment blood pressure should be at or below 185/110 mm Hg; after treatment keep blood pressure below 180/105 mm Hg. Confirm no hemorrhage on noncontrast CT (or equivalent) before dosing. After intravenous thrombolysis, hold antiplatelets and anticoagulants for about 24 hours until a follow-up scan excludes hemorrhage, unless a specific procedure (for example, carotid stenting) forces an individualized exception.

Alteplase is not a benign enzyme. Symptomatic intracranial hemorrhage, orolingual angioedema (especially in patients taking ACE inhibitors), and systemic bleeding are the feared complications. Stop the infusion if the patient acutely declines, obtain immediate CT, and treat blood pressure and coagulopathy as ICH. Do not finish the bag through a new dilated pupil.

Tenecteplase

Tenecteplase is a genetically modified tPA with greater fibrin specificity and a longer half-life, which allows a single intravenous bolus. The Alteplase Compared to Tenecteplase (AcT) 2022 trial and subsequent randomized evidence supported 0.25 mg/kg, maximum 25 mg, as a practical alternative to alteplase. An 80 kg patient receives 20 mg as one bolus; a 120 kg patient receives the 25 mg cap, not 30 mg. The 2026 AHA/ASA early-management guideline recommends tenecteplase 0.25 mg/kg (max 25 mg) or alteplase 0.9 mg/kg (max 90 mg) for eligible adults within 4.5 hours (Class 1). Tenecteplase 0.4 mg/kg is not recommended (no benefit). Bolus logistics matter in a thrombectomy-bound patient: you can give tenecteplase and move, rather than running a 60-minute alteplase pump during transfer.

Do not mix the two products’ dose tables. Tenecteplase 0.25 mg/kg is not “a little less alteplase.” Alteplase 0.9 mg/kg is not given as a single push. If a center’s protocol still uses only alteplase, that is a formulary fact, not a reason to invent a 0.4 mg/kg tenecteplase rescue when the pump is empty.

Antiplatelets after ICH is excluded

Once imaging has excluded hemorrhage (or after the 24-hour post-lytic scan), aspirin is the default early antiplatelet for most arterial ischemic stroke. A common load is 162–325 mg, then daily low-dose aspirin. Give it after the scan, not on the ambulance stretcher because the NIHSS was 4.

Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is for a defined population: minor noncardioembolic ischemic stroke (CHANCE/POINT used NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), started within 24 hours in patients who did not receive intravenous alteplase in the original trials. CHANCE used a clopidogrel 300 mg load and 21 days of DAPT. POINT used a 600 mg clopidogrel load and 90 days of DAPT and showed more major hemorrhage. Pooled analysis found that ischemic benefit clustered in the first 21 days, which is why many protocols use about 21 days of DAPT and then monotherapy. THALES tested aspirin plus ticagrelor for 30 days in NIHSS ≤5; know that ticagrelor DAPT exists, but do not treat it as identical to CHANCE clopidogrel dosing.

Carotid artery stenting (CAS), intracranial stenting, and some endovascular constructs are a different indication. Stent thrombosis can close a recently opened vessel, so DAPT is typically continued 30–90 days (protocol-dependent; intracranial stents often toward 90 days), not stopped at day 21 because you memorized CHANCE. Conversely, giving 90 days of DAPT to every NIHSS 2 lacunar stroke because “dual is stronger” copies POINT’s bleeding without copying POINT’s enrollment. Prasugrel is generally avoided in patients with prior TIA or stroke because of hemorrhage risk in TRITON-TIMI 38.

Heparin, enoxaparin, warfarin, and DOACs

Unfractionated heparin (UFH) and enoxaparin appear in three different roles that items love to conflate. (1) Venous thromboembolism (VTE) prophylaxis after stroke or ICH, often low-dose LMWH once hemorrhage is stable. (2) Therapeutic anticoagulation for venous thrombosis, some dissections, mechanical valves perioperatively, or as a bridge. (3) Not a routine lytic substitute for typical large-artery or lacunar arterial stroke—the International Stroke Trial and TOAST-era evidence did not make full-dose heparin a first-line reperfusion drug. A heparin infusion because the CTA “might show a clot” is not evidence-based reperfusion.

Warfarin remains relevant for mechanical valves, some antiphospholipid syndromes, and severe kidney disease that limits DOACs. Typical atrial-fibrillation INR target is 2–3; many mechanical mitral valves sit near 2.5–3.5. Onset takes days; bridging decisions are indication-specific. Reversal is 4-factor prothrombin complex concentrate plus vitamin K, detailed in section 4.2.

DOACs used for nonvalvular atrial fibrillation and venous thromboembolism include apixaban, rivaroxaban, dabigatran, and edoxaban. Rough adult AF doses you should recognize: apixaban 5 mg twice daily (2.5 mg twice daily if at least two of: age ≥80 years, body weight ≤60 kg, serum creatinine ≥1.5 mg/dL); rivaroxaban 20 mg daily with food (15 mg daily when creatinine clearance is reduced into the labeled window); dabigatran 150 mg twice daily (75 mg twice daily in selected U.S. renal-impairment labeling); edoxaban 60 mg daily (30 mg daily in reduced clearance; avoid when creatinine clearance is very high per label because of ischemic-stroke signal). These are starting maps, not a license to ignore hospital renal protocols. Dabigatran is a direct thrombin inhibitor; the other three are factor Xa inhibitors—that distinction drives which reversal agent you reach for.

Delayed anticoagulation after large infarcts

Cardioembolic stroke creates a two-clock problem: the next embolus versus hemorrhagic transformation of infarcted brain. Risk rises with infarct volume, thrombolysis or thrombectomy, uncontrolled blood pressure, dual antithrombotics, and already-visible petechial or parenchymal hemorrhage.

A traditional European teaching device is the 1–3–6–12-day rule (TIA / mild / moderate / severe). ELAN (2023) randomized earlier DOAC start (within 48 hours for minor or moderate infarcts; day 6–7 for major infarcts) versus later starts (days 3–4, 6–7, and 12–14). Early treatment was not associated with a burst of symptomatic ICH, and the composite of ischemic and hemorrhagic events was not worse. The exam-relevant residue is not “start apixaban in the scanner.” It is: small and moderate infarcts can often start a DOAC within 1–2 days if imaging is clean; large infarcts still wait on the order of a week in the early ELAN arm, and longer if there is parenchymal hematoma (especially PH2). Aspirin may temporize arterial risk while you wait. Mechanical VTE prophylaxis continues. Restart after ICH is a separate, later decision (often weeks), covered conceptually in 4.2.

Agent, dose, and reversal pointer table

Reversal mechanics, ANNEXA-I numbers, and PATCH belong in section 4.2. This table is the dosing map you carry into those items.

Exam traps

Giving tenecteplase 0.9 mg/kg or alteplase as a single 90 mg push. Using tenecteplase 0.4 mg/kg because “more fibrin specificity needs more milligrams.” Loading aspirin before the CT. Copying 21-day CHANCE DAPT onto a carotid stent, or 90-day POINT DAPT onto every TIA. Ordering a heparin drip as primary treatment of lacunar stroke. Starting a DOAC the evening of a malignant MCA infarct because ELAN said “early.” Forgetting that dabigatran is not an FXa inhibitor. Mixing AF DOAC doses with post-stent DAPT.

Worked numbers worth rehearsing: 90 kg alteplase = 81 mg (8.1 mg bolus, 72.9 mg over 60 minutes). 100 kg alteplase = 90 mg cap (9 + 81). 100 kg tenecteplase = 25 mg cap, not 25% of 90. Blood pressure 190/112 mm Hg is a treat-then-lyse problem, not a reason to skip the lytic forever if you can bring pressure down promptly in eligible patients.