Thrombolysis with rt-PA (Actilyse) is approved for the treatment of acute ischemic stroke since 1996. However, only 10-15% people receive this very effective treatment. One of the factors for low rates of thrombolysis is a large number of relative contraindications. This talk discusses, how we can include several of the patients with relative contraindications for thrombolytic treatment.

1. RELATIVE CONTRAINDICATIONS
FOR THROMBOLYSIS-Are they
real contraindications?
DR SUDHIR KUMAR MD DM
CONSULTANT NEUROLOGIST
APOLLO HOSPITALS, HYDERABAD

2. THROMBOLYSIS IN AIS
• Thrombolysis in acute ischemic stroke with tissue
plasminogen activator has been approved for two
decades,
• Still, only 10-15% of eligible patients are able to
receive this treatment,
• There are several factors responsible for low
thrombolysis rates,
• Relative contraindications account for a good
proportion of “denial of thrombolysis”.

3. ABSOLUTE CONTRAINDICATIONS (1)
• Presence of intracerebral hemorrhage on brain scan,
• Systolic BP>185 mmHg, or Diastolic BP>110 mmHg,
despite treatment with antihypertensive medications,
• Serious head trauma or stroke within the previous three
months,
• Platelet count<1,00,000
• Current use of anticoagulant, with INR>1.7
• Patients on therapeutic dose of LMWH, within the
previous 24 hours.

4. ABSOLUTE CONTRAINDICATIONS (2)
• Patients on direct thrombin inhibitors (dabigatran)
• Patients on factor Xa inhibitors (apixaban,
rivaroxaban)
• Involvement of more than one-third of hemisphere
on CT/MRI scan

5. RELATIVE CONTRAINDICATIONS
• Advanced age
• Mild or improving stroke symptoms
• Severe stroke and coma,
• Recent major surgery,
• Arterial puncture of noncompressible vessel,
• Recent genitourinary or gastrointestinal hemorrhage,
• Seizure at onset,
• Recent MI,
• CNS structural lesions,
• Dementia

6. ADVANCED AGE
• Advanced age is not a contraindication as per AHA
guidelines,
• However, alteplase drug insert lists that rt-PA risks
may be increased in people above 75,
• IST-3 and SITS-international stroke thrombolysis
registry have shown that rt-PA is safe in people
above 80; and functional outcome is better in those
thrombolysed
• In summary, evidence does not support excluding
patients older than 80 from receiving rt-PA.

7. THROMBOLYSIS BEYOND 4.5 HOURS
• IV thrombolysis is not recommended beyond 4.5
hours stroke onset,
• However, several small and large studies have
shown benefit in selected cases,
• MR perfusion/CT perfusion may be done to select
cases with salvageable brain tissue and IV rt-PA
may be administered in them.

8. MILD OR IMPROVING STROKE
SYMPTOMS (1)
• FDA label does not recommend using rt-PA for minor
stroke symptoms,
• 20-30% of patients with minor or improving stroke
symptoms when thrombolysis is being considered
can have substantial disability at 3 months
• NIHSS 0-4 is considered as mild stroke, however,
one can have major disability within this score too-
severe monoparesis, gait imbalance, aphasia, visual
deficits.

9. MILD OR IMPROVING STROKE
SYMPTOMS (2)
• Patients with mild neurological symptoms may have
proximal vessel occlusion, and they have higher risk
of deterioration and disability later,
• Patients with early improvement may also have
higher chances of neurological decline later,
• AHA guidelines: Thrombolysis may be considered in
patients with mild stroke deficits or those with rapidly
improving symptoms (Class IIb, level of evidence C)

10. SEVERE STROKE AND
COMA(1)
• FDA package insert: Higher risk of ICH in patients with
severe stroke (NIHSS>20 or 25)
• IV thrombolysis is beneficial in patients with severe
stroke, and these patients may derive maximum benefit
• NINDS: Improved outcomes in patients with NIHSS>20
• IST-3: Greater benefits with IV rt-PA in patients with
NIHSS>25
• VISTA: Greater odds of better functional outcome in
those with NIHSS>22

11. SEVERE STROKE AND COMA(2)
• Coma was excluded in NINDS trial, so as to exclude
stroke mimickers,
• However, coma can be a presentation of basilar
artery thrombosis, where thrombolysis is useful,
• Current AHA guidelines do not mention severe
stroke (or coma) as a relative contraindication for IV
thrombolysis within 3 hours; however, cautions
against treating patients with NIHSS>25 after 3
hours.

12. HYPOGLYCEMIA OR HYPERGLYCEMIA
• Hypoglycemia (<50) or hyperglycemia (>400) are
relative contraindications,
• Hypoglycemia can cause focal neurological deficits
(stroke mimic) and can also cause MRI changes,
• IV rt-PA may be administered after lack of
improvement with IV dextrose,
• Blood sugars may be brought down with insulin, and
rt-PA administered once RBS<400 mg%

13. RECENT MAJOR SURGERY
• Drug insert lists recent surgery as a warning, not an
absolute contraindication,
• AHA guidelines also lists this as a relative
contraindication, but it is not listed as a contraindication
in European Stroke Initiative Recommendations,
• Potential risk of bleeding at operative site; and risks of
systemic hemorrhage
• IV rt-PA can be given in selected cases; however; if
bleeding risk is high, endovascular therapy may be
preferred.

14. ARTERIAL PUNCTURE OF A
NONCOMPRESSIBLE VESSEL
• Arterial puncture within 7 days is listed as a warning
in drug package insert, and a relative
contraindication in AHA guidelines,
• Generally, this group of patients are critically ill, with
jugular or subclavian catheters, with poor functional
status; therefore, less likely to benefit from
thrombolysis,
• There is no data to oppose or support this.

15. RECENT GI OR GU BLEED
• 2013 AHA guidelines state recent GI/GU bleeding
within 21 days as a relative contraindication to IV rt-
PA (active bleeding is an absolute contraindication)
• 21 days has been arbitrarily chosen and is over-
cautious.
• In selected cases, IV rt-PA may be considered.
• If bleeding risks are higher, intra-arterial
thrombolysis may be preferred.

16. SEIZURE AT ONSET
• Seizure at onset with post-ictal neurological deficits is
considered a relative contraindication as per AHA guidelines
• Purpose is to exclude Todd’s paresis (a stroke mimic)
• However, seizures can occur in “real” strokes too,
• Moreover, thrombolysis in a stroke mimic is safe and risk of
symptomatic ICH is low,
• Only 2 patients out of 300 thrombolysed patients with seizure
at onset had ICH,
• As per a recent survey, 91% of stroke neurologists would
administer rt-PA in a patient with seizure at onset.

17. RECENT MYOCARDIAL
INFARCTION
• Recent MI during 3 months prior to stroke is a
relative contraindication as per AHA guidelines, but it
is not a contraindication as per European guidelines
or according to the drug label.
• Possible risks include myocardial wall rupture,
hemorrhagic conversion of post-MI pericarditis and
systemic embolization of ventricular thrombi.
• Myocardial fibrosis and scarring are complete by 7th
week; and hence, it has been suggested to reduce
the relative contraindication period to 7 weeks (from
current 3 months)

18. CNS STRUCTURAL
LESIONS
• Presence of intracranial neoplasm, AVM or
aneurysm is a contraindication as per AHA
guidelines and drug label,
• Few case reports reported “successful” thrombolysis
with rt-PA; especially if tumor was small and extra-
axial
• Published data also supports safety of thrombolysis
in patients with small, incidental, unruptured
intracranial aneurysm.

19. DEMENTIA
• Dementia was not listed as a contraindication in most
thrombolysis trials, and is not a contraindication as per
recent guidelines too,
• Still, presence of dementia leads to under-utilization of
thrombolysis
• This could be because of fear of increased bleeding, or
lesser expectation of good functional outcome,
• Published data shows that the risk of ICH is not
increased due to dementia.
• IV rt-PA can be given in carefully selected cases.

20. COMMENTS/QUERIES
Whatsapp: 9866193953
Email: drsudhirkumar@yahoo.com