We are presenting our personal experience regarding thrombolytic therepy in ac ischaemic stroke patients at jaiswal hospital and neuro institute ,kota,Rajasthan,INDIA

1. THROMBOLYSIS IN ACUTE
ISCHEMIC STROKE
Experience at our stroke unit in
2011-2012
DR Sanjay Jaiswal, D.MDR Sanjay Jaiswal, D.M
Member World Stroke OrganizationMember World Stroke Organization
Senior Consultant Neurologist &Senior Consultant Neurologist &
Stroke NeurophysicianStroke Neurophysician
Jaiswal Hospital and Neuro Institute, KOTAJaiswal Hospital and Neuro Institute, KOTA

2. OutlinesOutlines
 The burden of disease & Stroke FactsThe burden of disease & Stroke Facts
 PathophysiologyPathophysiology
 Stroke mimicsStroke mimics
 Pre thrombolysis work up.Pre thrombolysis work up.
 Safety and efficacy of IVSafety and efficacy of IV t PA .t PA .
 Inclusion and Exclusion criteria's.Inclusion and Exclusion criteria's.
 How Tpa is administered.How Tpa is administered.
 Time frame (Door to needle time)Time frame (Door to needle time)
 Our stroke teamOur stroke team

3. THE BURDEN OF STROKE
 Anually more than 15 million people world wideAnually more than 15 million people world wide
suffer a stroke, 5.5 million die and 5 million are leftsuffer a stroke, 5.5 million die and 5 million are left
with permanent disability.with permanent disability.
 Stroke is 2nd most common cause of death.Stroke is 2nd most common cause of death.
 In India 1.5million people suffer from Acute StrokeIn India 1.5million people suffer from Acute Stroke
every year.every year.
 1880 people die every day in India due to1880 people die every day in India due to
strokestroke

4.  World wide some one dies of stroke every 6World wide some one dies of stroke every 6
seconds.seconds.
 Every two second some one some where inEvery two second some one some where in
world suffers from stroke.world suffers from stroke.
 Stroke kills more people each year than AIDS,Stroke kills more people each year than AIDS,
TB, and Malaria put together.TB, and Malaria put together.
 Incidence of stroke is increasing in India andIncidence of stroke is increasing in India and
other developing countriesother developing countries

5. Stroke Facts
 80 % of strokes are Ischemic .80 % of strokes are Ischemic .
 Only 15 % of stroke patients reach inOnly 15 % of stroke patients reach in
hospital within 3 hrs.hospital within 3 hrs.
 1-5% are thrombolysed1-5% are thrombolysed

6. Reasons for lack of thrombolysis
1. Patient’s inability to recognize stroke symptoms.
 40% of stroke patients can’t name a single symptom40% of stroke patients can’t name a single symptom
of stroke.of stroke.
 85% of patients believe that their symptoms are not85% of patients believe that their symptoms are not
serious enough to seek urgent treatment.serious enough to seek urgent treatment.
2. Physician’s lack of experience with stroke
thrombolysis and therefore reluctance to “risk”
treatment
3. Lack of organized delivery of care in most of the
medical centers throughout the country.

7. Nandigram et al 2003
 Observed lack of knowledge regarding strokeObserved lack of knowledge regarding stroke
thrombolysis among medical professionals inthrombolysis among medical professionals in
india.india.
 Significant majority of the GPs were not awareSignificant majority of the GPs were not aware
of the beneficial effects of thrombolysis.of the beneficial effects of thrombolysis.

10. CASE 1CASE 1
 76 Yr old Retired Head Master, relative of a doctor.76 Yr old Retired Head Master, relative of a doctor.
 No H/O HTN, DM,CADNo H/O HTN, DM,CAD
 Presented with H/O Acute onset Rt hemiparesis withPresented with H/O Acute onset Rt hemiparesis with
difficulty in walking independently at 6.30 PM ,wasdifficulty in walking independently at 6.30 PM ,was
brought on wheel chair.brought on wheel chair.
 Reached to our hospital at 7.50 PM.Reached to our hospital at 7.50 PM.
 CT head –No e/o hemorrhage ,haematological investCT head –No e/o hemorrhage ,haematological invest
done. Clinical work up completed. by 9.00 PM.done. Clinical work up completed. by 9.00 PM.

12.  Consent received at 10 .00 PM ( 1 hour wasted byConsent received at 10 .00 PM ( 1 hour wasted by
relatives in giving consent )relatives in giving consent )
 Thrombolysis started at 10.00 PMThrombolysis started at 10.00 PM
 Motor power started improving during thrombolysis.Motor power started improving during thrombolysis.
 In 24 hrs pt was able to walk with little support.In 24 hrs pt was able to walk with little support.
 Discharged on 6 day with mild Neurodeficit.Discharged on 6 day with mild Neurodeficit.
 A doctor who is relative of the patient playedA doctor who is relative of the patient played
important role in explaining beneficial effects ofimportant role in explaining beneficial effects of
thrombolysisthrombolysis

13. CASE 2
 76 Yr old male F/O a Doctor had stroke.76 Yr old male F/O a Doctor had stroke.
 At 8.30 AM had left sided weakness with slurred speech and confusedAt 8.30 AM had left sided weakness with slurred speech and confused
state ,not able to walk.state ,not able to walk.
 Brought into hospital at 9.30 AM.Brought into hospital at 9.30 AM.
 Pt wheeled straight into CT scan.Pt wheeled straight into CT scan.
 Pt shifted to stroke unit, IV Line started and blood withdrawn.Pt shifted to stroke unit, IV Line started and blood withdrawn.
 k/c HT, CAD, H/O Angioplasty 15 yrs ago, on anti HT +k/c HT, CAD, H/O Angioplasty 15 yrs ago, on anti HT +
ASAASA.(missed ASA for 2 days).(missed ASA for 2 days)

15.  Lt UL– Lifting against gravity but weak grip.Lt UL– Lifting against gravity but weak grip.
 Lt LL –2- /5, not able to walk independentlyLt LL –2- /5, not able to walk independently
 Poor comprehension with dysarthriaPoor comprehension with dysarthria
 CT--. No hemorrhage seenCT--. No hemorrhage seen
 BP---140/80BP---140/80
 RBS– 118 MG%, CBC, PT , APTT- Normal.RBS– 118 MG%, CBC, PT , APTT- Normal.
 Option of thrombolysis given to his son.Option of thrombolysis given to his son.
 Consent for tPA taken.Consent for tPA taken.

16.  IV tPA started at 11.30 am. (stroke to needle time 3 hrs)IV tPA started at 11.30 am. (stroke to needle time 3 hrs)
 By the time infusion was finished , pt became alert and hisBy the time infusion was finished , pt became alert and his
motor power improved significantly.motor power improved significantly.
 By evening (6 hrs post thrombolysis) pt. was walkingBy evening (6 hrs post thrombolysis) pt. was walking
independently and and had normal speech.independently and and had normal speech.
 Discharged on 3Discharged on 3rdrd
day with no neurodeficit, WITHday with no neurodeficit, WITH
COMPLETE RECOVERY.COMPLETE RECOVERY.

19. CASE 3CASE 3
 68 Yr old male,68 Yr old male,
 k/c HT, CAD, h/o CABG 10 yrs ago, on anti HT + ASA.k/c HT, CAD, h/o CABG 10 yrs ago, on anti HT + ASA.
 At 9.30 PM had right sided weakness with slurred speech .At 9.30 PM had right sided weakness with slurred speech .
 Rt L/L Power 1-2 /5, Rt UL 3/5, dysarthria+Rt L/L Power 1-2 /5, Rt UL 3/5, dysarthria+
 Brought into hospital at 11.00 PM.Brought into hospital at 11.00 PM.
 Pt shifted to stroke unit, IV Line started and blood withdrawn.Pt shifted to stroke unit, IV Line started and blood withdrawn.
 CT scan head showed no e/o haemorrhage.CT scan head showed no e/o haemorrhage.
 Consent for tPA takenConsent for tPA taken

20.  IV- tPA started at 12.30 AM. (stroke to needle
time 3 hrs.
 During the infusion pt started moving Rt leg.
and his grip had improved significantly.
 By next morning (6 hrs post thrombolysis) pt
was walking independantly and with no
dysarthria.
 Patient discharged without any neurodeficit.

21. PathophysiologyPathophysiology
2 Million Neurones are lost every minute
in the period in which stroke is untreated

22. PathophysiologyPathophysiology
 ischemic penumbraischemic penumbra is the area of the brainis the area of the brain
surrounding the infarcted core,and is preservedsurrounding the infarcted core,and is preserved
by a tenacious supply of blood from collateralby a tenacious supply of blood from collateral
vessels.vessels.
 This area can be rescued if the occludedThis area can be rescued if the occluded
vessel can be reopened up to 3-8 hours fromvessel can be reopened up to 3-8 hours from
symptom onsetsymptom onset

23. Cerebral infarct <3hrsCerebral infarct <3hrs
Onset
Infarct
Ischaemic
penumbra

24. Cerebral infarct 6hrsCerebral infarct 6hrs
Infarct
Ischaemic
penumbra

25. Cerebral infarct 24hrsCerebral infarct 24hrs
Infarct
Ischaemic
penumbra

26. Penumbrae of Ischemic
Stroke  Penumbrae is the target of
any reperfusion therapy
 The fate of brain tissue
depends on
 Time
 Cerebral blood flow
 Occluded arterial flow
 Collateral blood flow
 Time is brain-We have to
act fast to rescue the
Penumbrae

27. Stroke MimicsStroke Mimics
 SyncopeSyncope
 Partial epileptic seizurePartial epileptic seizure
with Todd’s paresiswith Todd’s paresis
 Migraine attack (aura)Migraine attack (aura)
 HypoglycaemiaHypoglycaemia
 HysteriaHysteria
 IntoxicationIntoxication
 HypertensiveHypertensive
encephalopathyencephalopathy
 SubarachnoidSubarachnoid
haemorrhagehaemorrhage
 NeuroinfectionNeuroinfection
 NeoplasmNeoplasm
 Chr SDHChr SDH
 Multiple sclerosisMultiple sclerosis
 Peripheral vertigoPeripheral vertigo

28. Hyperacute Stroke: Modern
Approach of Tt
 Aim: Revascularization of penumbraAim: Revascularization of penumbra 
Break down Clot!Break down Clot!
 Methods: IV, IA, MechanicalMethods: IV, IA, Mechanical
ThrombolysisThrombolysis
 Most practical, with proven efficacy atMost practical, with proven efficacy at
place like KOTA : IV thrombolysis withplace like KOTA : IV thrombolysis with
TPA.TPA.

29. Time is BrainTime is Brain

30. Pre thrombolysis work upPre thrombolysis work up
 Should be individualizedShould be individualized
 All Pts must have emergently :All Pts must have emergently :
1.1. NCCT BRAINNCCT BRAIN
2.2. ECGECG
3.3. CBC,Plat count, B groupCBC,Plat count, B group
4.4. B GlucoseB Glucose
5.5. Coagulation-PT with INR,APTTCoagulation-PT with INR,APTT
6.6. Other metabolic tests-RFT, LFT, etcOther metabolic tests-RFT, LFT, etc

31. NCCT BRAIN
 Initial imaging modality in hyper ac stroke
 Widely available, quick, easy to perform
 Accurately identifies ICH,SAH
EARLY SIGNS OF CEREBRAL ISCHAEMIA
 Hyper dense MCA artery sign
 Hyper dense dot sign
 Hypo density of insular ribbon
 Hypoensity of basal ganglia
 loss of grey white matter differentiation in cortical ribbon
 sulcal effacement
EARLY SIGNS ARE ASSOCIATED WITH POORER OUTCOMES

32. Left and middle: Hyperdense left MCA sign (yellow arrow), hypoattenuated left basal
ganglia (red arrow), and cortical swelling (blue arrows) in the same patient. Right:
Dot sign (yellow arrow) in the left sylvian fissure.
Early CT signs in acute MCAEarly CT signs in acute MCA
strokestroke

33. NIHSS SCORENIHSS SCORE
 NIHSS SCORING CAN BE PERFORMEDNIHSS SCORING CAN BE PERFORMED
IN 7 MINUTES .IN 7 MINUTES .
 ESSENTIAL TO BE CALCULATEDESSENTIAL TO BE CALCULATED
PREDICTOR OF STROKE OUTCOME ANDPREDICTOR OF STROKE OUTCOME AND
USED AS A EXCLUSION CRITERIAUSED AS A EXCLUSION CRITERIA ..

36. Inclusion CriteriaInclusion Criteria
 Clinical signs and symptoms consistent withClinical signs and symptoms consistent with
stroke.stroke.
 Patient last seen normal within 4.5 hrs.Patient last seen normal within 4.5 hrs.
 Measurable neurological deficit.Measurable neurological deficit.

37. Exclusion Criteria
 Any hemorrhage on neuroimaging.Any hemorrhage on neuroimaging.
 Symptoms s/o SAH.Symptoms s/o SAH.
 Seizure at stroke onset with post ictal neurol deficit.Seizure at stroke onset with post ictal neurol deficit.
 Hypodensity greater than 1/3 cerebral hemisphere onHypodensity greater than 1/3 cerebral hemisphere on
CT.CT.
 SBP>185 & DBP>110SBP>185 & DBP>110
 RBS <50 or > 400 mg%RBS <50 or > 400 mg%
 Stroke with major neurol deficits-NIHS >22.Stroke with major neurol deficits-NIHS >22.
 Minor/isolated/spontaneously clearing neurol signs.Minor/isolated/spontaneously clearing neurol signs.

38. Exclusion Criteria
 Platelet count <1 lac/mm3Platelet count <1 lac/mm3
 INR>1.7INR>1.7
 Elevated APTT.Elevated APTT.
 Past h/o ICHPast h/o ICH
 Arterial puncture at non compressible site in 7 days.Arterial puncture at non compressible site in 7 days.
 Major surgery in past 14 days.Major surgery in past 14 days.
 GI bleed or hematuria in past 21 days.GI bleed or hematuria in past 21 days.
 Ischemic stroke, Myocardial infarction or serious headIschemic stroke, Myocardial infarction or serious head
trauma in last 3 months.trauma in last 3 months.
 Evidence of active bleeding or ac trauma (fracture onEvidence of active bleeding or ac trauma (fracture on
exam).exam).

39. Stroke Thrombolysis at 3-4.5 Hrs
additional Exclusion Criterias
 Age >80 yearsAge >80 years
 On oral anticoagulants regardless of INROn oral anticoagulants regardless of INR
 NIHSS of >25 (Severe stroke)NIHSS of >25 (Severe stroke)
 History of both stroke and diabetes.History of both stroke and diabetes.

40. I.VI.V t PAt PA :: Safety and efficacySafety and efficacy
Evidence for tPA < 3Evidence for tPA < 3
HoursHours

41. NINDS t PA stroke trial(1995)
 NEJM 95:333,1581-87NEJM 95:333,1581-87
 624 patients randomized624 patients randomized
 3 hour window3 hour window
At three months 30% more likelyAt three months 30% more likely
to have minimal or no disabilityto have minimal or no disability
 6.4% risk of hemorrhage6.4% risk of hemorrhage

42. NINDS tPA Stroke Trial
0
10
20
30
0
10
20
30
tPA tPAPlacebo Placebo
31
20 9
8
20
1
NIHSS Excellent
Recovery (%)
Total Death
Rate (%)
Hemorrhage
p < .05
New England Journal, 1995

43. NINDS TPA Stroke Trial
Global outcome statistic: OR=1.7, 50% v. 38%= 12% benefit
Excellent outcome at 3 months on all scales
52%
38%
43%
26%
45%
31%
34%
21%
0%
10%
20%
30%
40%
50%
60%
Barthel
Index
Rankin
Scale
Glasgow
Outcome
NIHSS
score
TPA
Placebo
N Engl J Med 1995;333:1581-7

44. Time is brain( EARLIER THE BETTER) benefit from rt-
PA declines with increasing delay from onset to
treatment time
Benefit
Harm
3 hours 6 hours
Upper and lower 95% confidence limits
Line of no effect
IST-3 protocol

45. For every 100 patients treated withFor every 100 patients treated with t PAt PA ,,
32 benefit, 3 harmed32 benefit, 3 harmed
Saver JL et al , Stroke 2007; 38:2279-2283
better outcome by 1 or more grades on the mRS

47. Stroke Thrombolysis:
Thrombolytic therapy must be given byThrombolytic therapy must be given by
an experienced physicianan experienced physician after theafter the
imaging of the brain is assessed byimaging of the brain is assessed by
physicians experienced in reading thephysicians experienced in reading the
imaging studyimaging study22
1: Hacke W et al.: Lancet (2004) 363:768-74
2: Wahlgren N et al.: Lancet (2007) 369:275-82

48. Stroke Thrombolysis:Stroke Thrombolysis:
Evidence forEvidence for t PAt PA at 3 – 4.5at 3 – 4.5
hrshrs

52. Time is Brain :Time is Brain : NINDS Recommended Stroke EvaluationNINDS Recommended Stroke Evaluation
Targets for Potential Thrombolytic CandidatesTargets for Potential Thrombolytic Candidates
Target time framesTarget time frames
Door to doctorDoor to doctor 10 minutes10 minutes
Door to CT completionDoor to CT completion 25 minutes25 minutes
Door to CT readingDoor to CT reading 45 minutes45 minutes
Door to drug treatmentDoor to drug treatment 60 minutes60 minutes

53. How to administer IV t PA
 Infuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 % ofInfuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 % of
the dose given as bolus over 1 mnt.the dose given as bolus over 1 mnt.
 Admit pt in neuro ICU or stroke unit.Admit pt in neuro ICU or stroke unit.
 Perform neurological assessment every 15 mnts duringPerform neurological assessment every 15 mnts during
the infusion and every 30 mnts thereafter for next 6 hoursthe infusion and every 30 mnts thereafter for next 6 hours
then hourly until 24 hours after treatment.then hourly until 24 hours after treatment.
 If pt develop severe headache,ac HTN, nausea,orIf pt develop severe headache,ac HTN, nausea,or
vomitting discontinue infusion and obtain emergency CTvomitting discontinue infusion and obtain emergency CT
scan.scan.
 AngioedemaAngioedema

55. Risk of hemorrhagic
transformation
 MarkedMarked
hyperglycemia orhyperglycemia or
DMDM
 CT >1/3CT >1/3 cerebralcerebral
hemispherehemisphere
 Increasing strokeIncreasing stroke
severityseverity
 Low platelet countsLow platelet counts
 Higher NIHSS scoreHigher NIHSS score
 Longer time toLonger time to
recanalizationrecanalization
~ Stroke. 2002~ Stroke. 2002

56. If intracranial hemorrhage present:
 Obtain fibrinogen results.Obtain fibrinogen results.
 Prepare for administration of 6 to 8 units of cryoprecipitatePrepare for administration of 6 to 8 units of cryoprecipitate
containing factor VIII.containing factor VIII.
 Prepare for administration of 6 to 8 units of platelets.Prepare for administration of 6 to 8 units of platelets.
 Consider alerting and consulting a hematologist orConsider alerting and consulting a hematologist or
neurosurgeon.neurosurgeon.
 Consider decision regarding further medical and/or surgicalConsider decision regarding further medical and/or surgical
therapy.therapy.
 Consider second CT to assess progression of intracranialConsider second CT to assess progression of intracranial
hemorrhage.hemorrhage.
 A plan for access to emergent neurosurgical consultation isA plan for access to emergent neurosurgical consultation is
highly recommended.highly recommended.

59. Acute Ischemic Stroke Protocol
ER arrival
Triage nurse confirm stroke onset time < 4.5 hours
ER Resident performs
Rapid evaluation (5 minutes)
1.exact time of onset
2.important history
3.quick neurological evaluation
STAT CT and blood work
Neurology Resident receives
ER stroke page and
proceeds to ER
brief history & physical exam
Page Stroke consultant
Head CT findings, laboratory data, NIH stroke scale
Confirm the criteria fulfilling thrombolytic therapy for ischemic stroke
Family’s agreement for thrombolytic therapy
Stroke onset < 4.5 hours
IV-tPA treatment
Patient is admitted to Stroke ICU for intensive monitoring/care
Stroke onset 4.5-8 hours
IA t therapy /device
Call Neuroradiologists
IA thrombolysis/device

60.  11STST
Case tPA given in 3.30 hrs.Case tPA given in 3.30 hrs.
 22ndnd
Case tPA given in 3 hrs.Case tPA given in 3 hrs.
 33rdrd
Case tPA given in 3 hrsCase tPA given in 3 hrs
 All made excellent recovery.All made excellent recovery.
 Earlier protocol ---Earlier protocol ---
window period -- 3hrs.window period -- 3hrs.
 Latest ECASS 3 trial---Latest ECASS 3 trial---
window period extended upto 4.5 hrs.window period extended upto 4.5 hrs.

61. OUR STROKE TEAM
 NeurologistNeurologist
 NeurosurgeonNeurosurgeon
 IntensivistIntensivist
 NeuroradiologistNeuroradiologist
 NeuropathologistNeuropathologist
 NeurophysiotherepistNeurophysiotherepist
 RMOS,Techs,Trained staffRMOS,Techs,Trained staff

62. TAKE HOME MESSAGE
 IV r TPA IS RECOMMENDEDIV r TPA IS RECOMMENDED
THEREPY FOR SELECTED PATIENTSTHEREPY FOR SELECTED PATIENTS
WHO REACH HOSPITAL WITHIN 4.5WHO REACH HOSPITAL WITHIN 4.5
HOURS OF STROKE ONSET.HOURS OF STROKE ONSET.
 Thrombolysis is possible in kota.Thrombolysis is possible in kota.
 Need to rush from bed to bedside.Need to rush from bed to bedside.

63. TAKE HOME MESSAGETAKE HOME MESSAGE
 At 3 months 30% more likely to have minimalAt 3 months 30% more likely to have minimal
or no disability following thrombolysis.or no disability following thrombolysis.
 There should be no protocol violation otherThere should be no protocol violation other
wise more complications.wise more complications.
 We have to increase awareness among patients,We have to increase awareness among patients,
general public and doctors regarding beneficialgeneral public and doctors regarding beneficial
effects of stroke thrombolysis.effects of stroke thrombolysis.

64. World Stroke day- 29 octoberWorld Stroke day- 29 october
WSO Slogan- entitled ‘Because I care..WSO Slogan- entitled ‘Because I care..
Because I care…
I want you to know the facts about stroke
I want you to learn how to prevent the assault of stroke
I will break the myths surrounding stroke, e.g., “stroke only happens later in
life”
I want you to have access to the best possible
treatment
I will ensure that you receive quality treatment, care
and support
I will be with you every step of the way towards your full
recovery

65. THANK YOUTHANK YOU