Study guide
4.1 Thrombolytics, Anticoagulants, and Antiplatelets
ABIM Neurocritical Care Subspecialty Certification Exam
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1 Introduction & Exam Overview
1.1 Current Exam Facts 1.2 Eligibility, Practice Pathway, and the IM Training Route 1.3 Format, Scoring, Pearson VUE, and Score Reports 1.4 How to Use This Independent Study Guide
2 ICU Neurologic Exam, Cerebral Physiology, and CSF
2.1 Neurological Examination in the ICU 2.2 Cerebral Physiology, ICP, CBF, and Autoregulation 2.3 CSF Physiology
3 Core Neuropharmacology
3.1 Osmotic Agents 3.2 Anti-Seizure Drugs 3.3 Anesthetics, Sedatives, Analgesia, and Paralytics 3.4 Antihypertensives, Vasopressors, and Inotropes
4 Reperfusion Drugs, Airway, and Ventilation
4.1 Thrombolytics, Anticoagulants, and Antiplatelets 4.2 Reversal of Anticoagulation After Acute Hemorrhage 4.3 Airway Management and Tracheostomy 4.4 Mechanical Ventilation
5 Hemodynamics and Shock
5.1 Hemodynamic Monitoring 5.2 IABP, Temporary VADs, LVAD, and ECMO 5.3 Diagnosis and Management of Shock
6 Nutrition, Temperature, and ICU Prophylaxis
6.1 Nutrition (01.J) 6.2 Temperature Control (01.K) 6.3 ICU Prophylaxis, Delirium, and Early Mobility (01.L)
7 General Trauma
7.1 Emergency Evaluation of Polytrauma, Chest, and Abdominal Trauma 7.2 Long-Bone Fractures and Fat Embolism 7.3 Burns, Electrical Injury, and Hanging/Strangulation
8 Pulmonary Critical Care
8.1 Pulmonary Physiology and ARDS (01.N.1–2) 8.2 PE, Pneumonia, and Pulmonary Edema (01.N.3, 7–8) 8.3 COPD, Asthma, PAH, and Bronchoscopy Basics (01.N.4–6, 9)
9 Cardiovascular Critical Care
9.1 Cardiovascular Physiology, Stress Cardiomyopathy, ACS, and Valves 9.2 Arrhythmias and Pacing 9.3 Acute Aortic Dissection and Cardiac Ultrasound
10 Renal and Infectious Disease
10.1 AKI, RRT, and Renal Drug Dosing 10.2 Acid-Base and Electrolyte Disorders 10.3 Severe Sepsis, Septic Shock, and Infective Endocarditis 10.4 Antimicrobial Use and Infection in the Immunosuppressed
11 Endocrine and Salt-Water Disorders
11.1 Pituitary Apoplexy, DI, and Panhypopituitarism (01.R.1–4) 11.2 SIADH and Cerebral Salt Wasting (01.R.5–6) 11.3 Thyrotoxicosis, Myxedema, Adrenal Crisis, and Dysglycemia (01.R.7–9)
12 Gastrointestinal Critical Care
12.1 GI Physiology, Acute Abdomen, Bleed, Ileus, and Perforation (01.S.1–5) 12.2 Mesenteric Ischemia and Abdominal Compartment Syndrome (01.S.6–7) 12.3 Fulminant Liver Failure, Cirrhosis Decompensation, and Hepatic Dosing (01.S.8–10)
13 Hematologic Disorders
13.1 Anemia, Transfusion, Thrombocytopenia, Coagulopathy, and DIC (01.T.1–4) 13.2 VTE in the Neuro ICU (01.T.5) 13.3 Chemo/Immune, SCT, CAR-T, Sickle Cell, and TMA (01.T.6–10)
14 Neuroimaging
14.1 CT of Brain and Spine 14.2 MRI and CT/MR Perfusion 14.3 Noninvasive Angiography and Catheter Angiography
15 EEG, EMG, and CSF Analysis
15.1 EEG, Standard and Processed (02.B) 15.2 Basic EMG Interpretation (02.G) 15.3 CSF Analysis (02.H)
16 ICP, TCD, and Multimodality Monitoring
16.1 ICP Monitoring (02.C) 16.2 Transcranial Doppler (02.D) 16.3 Brain-Tissue Oxygen and Multimodality Monitoring (02.E–F)
17 Brain Death and Bedside Procedures
17.1 Brain Death Prerequisites and Clinical Exam (02.I) 17.2 Apnea Testing and Ancillary Studies (02.I) 17.3 Vascular Access, Thoracic Echo, and Lung Ultrasound (02.J–L)
18 Coma, Anoxia, and Intracranial Hypertension
18.1 Coma and Other States of Altered Consciousness (03.A) 18.2 Global Anoxia-Ischemia and Post-Resuscitation Encephalopathy (03.A.1) 18.3 Toxidromes, ICU Delirium, and Hypertensive Encephalopathy (03.A.2–4) 18.4 Intracranial Hypertension as a Disease State (03.B)
19 Acute Ischemic Stroke
19.1 IV Reperfusion Therapy (03.C.3) 19.2 Mechanical Thrombectomy Windows and Imaging Selection (03.C.3) 19.3 Malignant Hemispheric Infarction and Basilar Artery Occlusion (03.C.1–2)
20 Intraparenchymal Hemorrhage
20.1 Intracerebral Hematoma (03.D.1) 20.2 Cerebellar Hematoma (03.D.2) 20.3 Intraventricular Hemorrhage (03.D.3)
21 SAH, CVST, and Spinal Cord Infarction
21.1 Aneurysmal Subarachnoid Hemorrhage (03.E.1) 21.2 Non-Aneurysmal SAH (03.E.2) 21.3 Cerebral Venous Sinus Thrombosis (03.F) 21.4 Spinal Cord Infarction (03.G)
22 Vascular Anomalies and Traumatic Brain Injury
22.1 Unruptured Aneurysm, Cavernoma, AVM, and Dural AVF (03.H) 22.2 Diffuse Axonal Injury and Cerebral Contusions (03.I.1–2) 22.3 Epidural Hematoma, Subdural Hematoma, and Penetrating Injury (03.I.3–4, 7) 22.4 Arterial Dissection and Carotid-Cavernous Fistula (03.I.5–6)
23 Spine, Hydrocephalus, and CNS Infection
23.1 Spinal Cord Injury, Central Cord, and Neurogenic Shock (03.J) 23.2 Unstable Spine Fractures (03.K) 23.3 Hydrocephalus and CSF Diversion (03.L) 23.4 Acute CNS Infections (03.M)
24 Seizures and Neuromuscular Emergencies
24.1 Status Epilepticus and Seizures (03.N) 24.2 Guillain-Barré Syndrome (03.O.1) 24.3 Myasthenic Crisis (03.O.2) 24.4 Motor Neuron Disease, Acute Myopathies, Rhabdomyolysis, and CINM (03.O.3–6)
25 Inflammatory Disease, Neuro-Oncology, and Special Populations
25.1 Fulminant Demyelinating Diseases (03.P) 25.2 Autoimmune Encephalitis and Acute Autonomic Hyperactivity (03.Q–R) 25.3 Neuro-Oncology and Treatment Complications (03.S) 25.4 Pregnancy/Post-Partum, Post-Transplant, and Pediatric Patients (03.T–U)
26 Neurosurgical and Perioperative Complications
26.1 Postoperative Seizures, Hemorrhage, Ischemia, and Hyperperfusion (04.A, C, D, H) 26.2 Infection, CSF Leak, and Pneumocephalus (04.B, E, F) 26.3 Complications of EVD and Lumbar Drain (04.G, I)
27 Ethics, Prognostication, and Organ Donation
27.1 Communication, Decision-Makers, Advance Directives, and DNR (05.A, B, G) 27.2 Uncertainties of Prognostication and the Self-Fulfilling Prophecy (05.C) 27.3 Palliative Care, Withdrawal, Withholding, and Futility (05.D–F) 27.4 Donation After Cardiac Death and Care of the Organ Donor (05.H–I)
4.1 Thrombolytics, Anticoagulants, and Antiplatelets
Key Takeaways Explain This Topic AI
Alteplase for eligible ischemic stroke is 0.9 mg/kg IV (maximum 90 mg): 10% over about 1 minute, remainder over 60 minutes; pretreatment BP ≤185/110 mm Hg and post-treatment BP <180/105 mm Hg.
Tenecteplase 0.25 mg/kg as a single IV bolus (maximum 25 mg) is an accepted alternative after AcT 2022 and later AHA/ASA updates; tenecteplase 0.4 mg/kg is not recommended.
After hemorrhage is excluded, aspirin 162–325 mg is standard; short DAPT (aspirin plus clopidogrel, benefit concentrated in 21 days in CHANCE/POINT) is for minor noncardioembolic stroke or high-risk TIA, not a substitute for longer DAPT after carotid or intracranial stenting.
Full-dose heparin is not routine treatment of typical arterial ischemic stroke; warfarin and DOACs (apixaban, rivaroxaban, dabigatran, edoxaban) treat cardioembolism and other indicated states, with infarct-size-based delay after large infarcts.
Last updated: September 2026
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 ExamFinch 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.
Agent Typical adult neuro use Key dose facts Reversal pointer
Alteplase IV stroke thrombolysis 0.9 mg/kg IV, max 90 mg; 10% bolus, rest over 60 min Stop infusion; treat as ICH; no specific antidote
Tenecteplase IV stroke thrombolysis 0.25 mg/kg IV once, max 25 mg; do not use 0.4 mg/kg Same as alteplase if hemorrhage occurs
Aspirin After ICH excluded; post-lytic after 24-h scan Load 162–325 mg DDAVP ± platelets only in selected settings (see 4.2; not PATCH-style routine)
Clopidogrel + aspirin Minor stroke / high-risk TIA Load 300–600 mg clopidogrel; DAPT often ~21 days Same antiplatelet caveats
DAPT after stent/CAS Stent thrombosis prevention Often 30–90 days, protocol-specific Do not stop at day 21 solely because of CHANCE
- UFH VTE prophylaxis or selected therapeutic use Prophylaxis vs infusion aPTT/anti-Xa Protamine
- Enoxaparin VTE prophylaxis or therapeutic LMWH Renal adjustment; not a stroke lytic Protamine (incomplete)
- Warfarin Valves, selected AF/VTE INR target by indication 4F-PCC + vitamin K 10 mg IV
- Dabigatran AF/VTE (direct thrombin inhibitor) 150 mg BID typical AF dose Idarucizumab 5 g
Apixaban / rivaroxaban / edoxaban AF/VTE (FXa inhibitors) See labeled renal/age/weight rules Andexanet alfa; 4F-PCC off-label alternative
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.