Thrombolysis – What can I do when it goes wrong?

Complications – recognition & management

Dr L Sekaran

Consultant Stroke Physician

Clinical Lead, Beds, Herts & Milton Keynes Stroke Network

14-03-2013

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1930 – discovery of antibiotics1950 – double helix of DNA1970 – an extremely aggressive cancer of melanoma

Events above contributed to the development of thrombolytic agent

CLOT BUSTERS!! - DISCOVERY OFTHROMBOLYTIC THERAPY FOR HEART

ATTACK& STROKE

Alteplase / recombinant tissue plasminogen activator, rtPAUseful Facts

Selective localised fibrinolysis – fibrin dependant activation TPA within the clot. – minimal systemic effects

Fibrinogen – levels decrease 60% at 4 hours, reverts to 80% at 24 hrs

Plasminogen –levels decrease 70% at 4 hrs, reverts to 80% at 24 hrs

Alpha antiplasmin – levels decerease 35% at 4 hrs and reverts to 80% at 24 hours

Clearence of rtPA – 50% in 5 minutes, 80% in 10 mts, completely in 40 mts

Antibody to rtPA - <0.5% patients transiently, NO sustained formation of antibodies

rtPA readministartion in stroke – no data available

Thrombolysis - A lot can go wrongIntracranial bleeding – infarct, normal parenchyma

Brain oedema

ERIS – early recurrent Ischemic strokes

Oro-lingual facial angio-neurotic oedema

Anaphylaxis

Fat / Cholesterol embolism

Systemic bleeding – GI, urological, ENT etc

Reperfusion arrhythmias

Symptomatic ICH

Studies Placebo rtPA P-value

NINDS 3.5% 7.9% 0.006

ECASS II 0.2% 2.4% 0.008

ECASS III 2.2% 5.3% 0.023

SITS-MOST 0.2% 1.9% 0.022

IST-3 1.0% 7.0% 0.0001

ECASS III definition – Symptomatic cerebral haemorrhage was defined as any blood in the brain or intracranially associated with a clinical deterioration of ≥ 4 points of the NIHSS for which the haemorrhage has been identified as the dominating cause of the neurologic deterioration. ECASS II definition – Any intracranial bleed and 4 points or more worsening on the NIHSS score from baseline or the lowest value in the first 7 days, or any haemorrhage leading to death. NINDS definition – A haemorrhage was considered symptomatic if it was not seen on a previous CT scan and there had subsequently been either a suspicion of haemorrhage or any decline in neurologic status. To detect intracranial haemorrhage, CT scans were required at 24 hours and 7 to 10 days after the onset of stroke and when clinical finding suggested haemorrhage. SITS-MOST definition – Local or remote parenchymal haematoma type 2 on the 22- to 36-hour post-treatment imaging scan, combined with a neurologic deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 hours, or leading to death.

Intracranial bleeding – infarct, normal parenchyma

Actilyse info leaflet from Boehringer-Ingelheim ltd ,NSW, Australia 25/10/2012, IST-3 Lancet 2012;

Category Definition

HI 1 Small petechiae along margins of infarct

HI 2 More confluent petechiae within infarct area but without space-occupying effect

PH 1 haematoma(s) < 30% of infarct area with some mild space-occupying effect

PH 2 Haematoma(s)> 30% of infarct area with significant space-occupying effect

PHr 1 Small or medium-sized clots located remote from actual infarct; mild space-occupying effect could be present

PHr 2 Large confluent dense blood clots in area remote from actual infarct; significant space-occupying effect may be present

Intracranial bleeding – infarct, normal parenchyma

J Vasc Interv Radiol 2013; 24:151–163

Intracranial bleeding – infarct, normal parenchyma

Predictors of risk of haemorrhage Hypertension

Chronic atrial fibrillation

Increasing age Increased blood glucose

High NIHSS score

Overweight Early ischaemic change on CT scan

Profound cerebral blood volume reduction Large perfusion/diffusion abnormalities (diffusion volume ≥100ml) Early blood-brain barrier disruption on FLAIR imaging sequences Leukoaraiosis of the deep white matter

Intracranial bleeding – infarct, normal parenchyma

Management;

Stop the infusion – repeat CT, fibrinogen levels, bleeding profile

Platelet infusion,

FFP, Cryoprecipitate 1 unit / 10 kg ( replace fibrinogen )

Antifibrinolytic agent – trenexamic acid 5 gm bolus IV over 15-30 mts

PH 1 HT1 HT2 PH2

PH2

63 yr M pre and post TX scans with Lt side weakness 04-02-2013 & 05-02-2013

PHr 1

Brain Oedema

Brain oedema after Thrombolysis;

Forced Reperfusion injury of already damaged tissue

Less common than after conventional treatment

More severe

Cerebrovasc Dis 1998;8:166–171

Brain Oedema

Management;

Discuss with Neurosurgery

HemicraniectomyAge - 60, time <48 hrs, infarct volume 50% MCA territory, reasonable life expectancy, NIHSS >15

Dexamethasone IV

Hypertonic solutions – IV Mannitol, IV 3% Normal saline

Post -Thrombolysis Brain oedema

During admission:

Day 2: noted to be drowsy, responding but keeping eyes shut

Day 3: intermittently seems alert and drowsy

Day 4: ‘very sleepy’

Day 5: GCS noted to be 10/15 by NS, 14/15 on Drs r/v. Rpt CT r/q

Later in day 5: GCS 12/15 Discussed with RF hospital and transferred

During RF admission:

Day 5: transferred

Day 6: right decompressive craniectomy, taken to ITU post-op

Day 7: extubated, GCS 11/15

Day 8: on ward, continuing dense left hemiplegia

Day 14: transferred back to L&D, GCS 13-14/15

An early Assessment of a TIA case

An early Assessment of a TIA case

Early Recurrent Ischemic Stroke

Rare – 0.6%

IST-3 – 1%

Due to emboli from cardiac / aortic

Usually within the first few hours

Further deterioration after thrombolysis

Neuro-observations / Neurocritical care

Circulation. 2006;114:237-241 IST-3, Lancet ;May 23, 2012DOI:10.1016/S0140-6736(12)60768-5

08-01-2013 14.29 hrs weakness of all 4 limbs and GCS was E-1, M-1, V-1

Intubated & ventilated

09-01-2013 11.49 MRI Brain scans

Oro-lingual angio-neurotic edema

Rare 0.02% after Tx in MI1-5% after Tx in Stroke

Histamine, bradykinin mediated

More common in those who are already on ACEI, less so on ARBs/hereditary complement deficiencies.

Increases C3a, C4a, C5a, C2Increases Bradykinin

Unilateral angioedema - Insular cortex in sympathetic and parasymp. Regulation – autonomic dysregulation leading to angioedema on the hemiparetic side CMAJ,2000;162(9);1281-1284

Oro-lingual angio edema

Management;

Stop infusion

Stop ACEI / ARBs

IV hydrocortisone 100-200 mg

IV diphenhydramine 50 mg

IV Ranitidine 50 mg

Other;RashUrticariaLaryngeal edema

- Respond to above treatment

JNNP,2010;81;1079

AnaphylaxisRare

Anti alteplase antibodies

Transient

Not seen sustained levels

Management;

As for angioedema

Early anaesthetic evaluation, intubation, tracheostomy

Adrenaline avoided unless really required

Fat / Cholesterol embolism

Uncommon after thrombolysisMay be not recognised

Petechial rashSoB, hypoxiaTachycardiaLivedo reticularis

J Emer Trauma shock; 2009; 2(1);29-33

MRI – imaging modality, T2WI

Management;Supportive measuresHigh flow O2IV AlbuminVentilation if needed

Systemic Bleeding

Pre Tx CT Post Tx CT, bleeding PR Caecal Ca

Reperfusion Arrhythmias

Atrial fibrillation

Ventricular arrhythmias

Bradycardia / Heart Blocks

Majority can be managed in Hyperacute Stroke Units

Alteplase – rtPA – useful facts

Intracranial bleeding – infarct / normal parenchyma – devastating in some cases

Brain oedema – fatal in some cases

ERIS – early recurrent Ischemic strokes – rare 0.6 -1.0%

Oro-lingual facial angio-neurotic oedema – 1-5%

Anaphylaxis – uncommon but be prepared

Fat / Cholesterol embolism – unrecognised in this setting

Systemic bleeding – GI, urological, ENT etc

Reperfusion arrhythmias