Intravenous alteplase (recombinant tissue plasminogen activator, tPA) remains a cornerstone of reperfusion therapy for selected adults with acute ischemic stroke (AIS). Because fibrinolysis carries a finite risk of symptomatic intracranial hemorrhage and systemic bleeding, treatment pathways rely on exclusion criteria that function as practical contraindications in routine practice. These criteria integrate neuroimaging, vital signs, laboratory values, antithrombotic exposure, and recent procedural history. They are not a single static checklist frozen in time: eligibility also depends on time from symptom onset (or last known well), stroke severity, institutional protocol, concurrent endovascular candidacy, and product labeling. This article explains the clinical reasoning behind the major exclusion themes reflected on the calculator page, how they interlock, and what the interactive tool does and does not replace at the point of care.

Why “contraindications” are framed as exclusions

In stroke care, the language of exclusions is used because many decisions are risk–benefit judgments under time pressure rather than binary rules in every scenario. Absolute contraindications in a strict pharmacologic sense (for example, situations where drug labeling forbids administration regardless of context) overlap heavily—but not perfectly—with guideline exclusion lists. Emergency and stroke teams therefore treat certain findings as hard stops in default pathways: intracranial hemorrhage on imaging, uncontrolled severe hypertension despite treatment, and coagulopathy thresholds are common examples. Other items are better understood as relative cautions where experienced clinicians may still proceed in selected cases after explicit documentation of reasoning, often in consultation with neurology and pharmacy.

The CalcMD calculator separates items into two bands—typical exclusions and relative cautions—to mirror how teams verbally triage cases. It is a memory and teaching aid, not an eligibility engine. It does not ingest imaging files, laboratory feeds, or automated blood pressure trends; the user must confirm each domain independently.

Neuroimaging and intracranial catastrophes

Noncontrast computed tomography (CT) of the head remains the most widely used initial gate for thrombolysis candidacy in many centers. The presence of intracranial hemorrhage—parenchymal, subdural, epidural, or substantial subarachnoid blood—generally excludes IV alteplase because fibrinolysis can worsen bleeding mass effect and neurological injury. Even when clinical suspicion points toward ischemia, the imaging rule is blunt: acute blood on CT (or MRI sequences interpreted as hemorrhage) removes the patient from the standard IV thrombolysis track unless a separate research or specialized pathway applies.

Subarachnoid hemorrhage (SAH) deserves distinct emphasis. Thunderclap headache, meningismus, or CT patterns concerning for SAH prompt a different diagnostic and management trajectory. IV tPA for AIS is not given when SAH is demonstrated or strongly suspected in a way that makes SAH the working neurovascular emergency, because aneurysmal or non-aneurysmal SAH carries hemorrhagic risk that thrombolysis would amplify.

Beyond hemorrhage, certain structural intracranial vascular lesions—for example, known high-risk aneurysms or arteriovenous malformations—are typically treated as exclusions when the perceived bleeding risk from the lesion is prohibitive under protocol. Similarly, some intracranial neoplasms are associated with fragility of regional vessels or mass effect; many pathways default to exclusion when malignant or high–bleeding-risk lesions are known, pending specialist input.

Established infarction and tissue at risk

CT hypodensity in a multilobar pattern involving a large fraction of a cerebral hemisphere is interpreted as evidence of substantial established infarction. Large ischemic burden correlates with higher rates of hemorrhagic transformation after reperfusion therapy. Classic teaching thresholds cite hypodensity beyond roughly one-third of the middle cerebral artery territory (or multilobar involvement) as a treatment exclusion in many guideline tables. Modern imaging with MRI and advanced perfusion imaging refines decision-making in extended-window and wake-up stroke paradigms, but the noncontrast CT “large hypodensity” rule remains a foundational screening concept in community and academic settings alike.

Hemostasis, platelets, and anticoagulation

Thrombolysis assumes a hemostatic environment that can tolerate plasmin generation. Platelet counts below conventional thresholds (commonly fewer than 100,000 per microliter in standard lists) exclude IV tPA because primary hemostasis is already impaired. Inherited or acquired bleeding diatheses—including severe liver dysfunction with coagulopathy, disseminated intravascular coagulation, or other disorders—are treated similarly.

Anticoagulant exposure is stratified by drug class and timing. Patients on warfarin with an elevated INR above typical cutoffs (often greater than 1.7 in classic AIS exclusion tables) are excluded because vitamin K antagonism plus fibrinolysis compounds intracranial bleeding risk. Unfractionated heparin use within a recent window with a prolonged activated partial thromboplastin time also features in standard exclusions. Direct oral anticoagulants (DOACs)—direct thrombin inhibitors and oral factor Xa inhibitors—require attention to time since last dose and, where available, drug-specific laboratory assays or reversal strategies; institutional algorithms differ, and many pathways require normal or acceptable assay results before thrombolysis. The calculator collapses these nuances into a single checkbox prompt precisely because the correct answer is protocol- and lab-dependent; the bedside team must apply local criteria rather than a website toggle.

Recent ischemic stroke, trauma, and surgery

A prior ischemic stroke within the preceding three months (distinct from the presenting event) appears on many exclusion lists due to concerns about blood–brain barrier vulnerability and hemorrhagic transformation in recently injured tissue. Significant closed head or facial trauma in the same interval raises worry for occult intracranial injury that may not be fully appreciated on an initial scan. Intracranial or intraspinal surgery within three months is likewise a common exclusion because surgical beds and dural planes may bleed with fibrinolysis.

Separately, major surgery or serious systemic trauma on the order of two weeks is often classified among relative cautions: the patient may have ongoing surgical bleeding risk, large hematoma reservoirs, or hemodynamic instability that complicates blood pressure management during and after tPA. These scenarios frequently trigger multidisciplinary discussion even when imaging of the brain is reassuring.

Arterial access and noncompressible puncture sites

Recent arterial puncture at a noncompressible site—classically within seven days—raises the possibility of a retroperitoneal or deep hematoma that could expand with fibrinolysis. Femoral catheterization for angiography or intra-aortic balloon support is a prototypical example. While many patients with remote radial access do not trigger the same concern, protocols emphasize location and compressibility of the access site rather than the mere fact of arterial line placement.

Blood pressure, perfusion, and treatment safety

Elevated blood pressure at presentation is common in AIS due to stress response, chronic hypertension, or attempted autoregulation. Persistent severe hypertension increases the risk of hemorrhagic conversion and systemic bleeding during thrombolysis. Standard pathway language therefore includes systolic blood pressure at or above 185 mmHg or diastolic at or above 110 mmHg that remains refractory to repeated antihypertensive therapy as an exclusion in many tables. The nuance is operational: teams often attempt controlled lowering with serial checks; “refractory” implies that despite reasonable acute management, targets are not safely achieved within the time window available for treatment decisions.

Metabolic mimics: hypoglycemia

Hypoglycemia can produce focal neurological deficits that mimic stroke. Administering thrombolysis in that setting risks harm without benefit. Point-of-care glucose is therefore mandatory. Serum glucose below approximately 50 mg/dL (2.7 mmol/L) is treated as an exclusion until corrected and the deficit is reassessed; if symptoms resolve with glucose normalization, the episode may have been metabolic rather than ischemic.

Relative cautions and the spectrum of clinical judgment

Several items do not always function as automatic hard stops but still shape informed consent and documentation. Minor or rapidly improving symptoms challenge the equipoise of thrombolysis: some patients improve spontaneously, yet others with subtle deficits may still harbor disabling penumbra. Seizure at onset with residual deficit creates ambiguity between Todd paralysis and persistent ischemic injury; careful examination, imaging, and sometimes observation enter the calculus.

Recent gastrointestinal or genitourinary hemorrhage (often within about three weeks in teaching lists) flags mucosal bleeding diathesis that could reactivate under fibrinolysis. Recent myocardial infarction within three months appears in some relative-caution tables because of systemic bleeding risk, concomitant antithrombotic therapy, and hemodynamic vulnerability. In each case, teams weigh NIH stroke scale severity, age, comorbidity, imaging, blood pressure control, and patient goals.

How the CalcMD checklist relates to real pathways

The on-page tool invites clinicians and learners to tick items that apply, then generates a structured summary of selected exclusions and cautions. If any typical exclusion is selected, the interface states that IV alteplase would usually not proceed under conventional criteria pending specialist review—this mirrors the default stance of many hospital order sets. If no exclusions are selected, the tool explicitly states that eligibility is still unproven: onset time, advanced imaging criteria, institutional extensions, blood pressure trajectories, and medication reconciliation remain obligatory steps.

Trainees can use the checklist to rehearse handoffs: imaging result, glucose, platelet count and coagulation studies, anticoagulant timing, blood pressure trend, puncture history, and infarct size on CT. Attending physicians may use it as a second-pass safety scan after primary assessment, reducing omission errors under cognitive load.

Scope limits and safe use

This educational resource does not implement extended-window thrombolysis rules, perfusion-based selection, wake-up stroke MRI algorithms, tenecteplase labeling differences, pediatric stroke pathways, pregnancy-specific guidance, or mechanical thrombectomy triage. It cannot interpret digital images or laboratory interfaces. Any patient-level decision must follow current institutional protocols, FDA prescribing information, and specialty society statements as interpreted by the responsible licensed clinicians.