Posts Tagged ‘thrombolysis in stroke’

Thrombolytic therapy  is the specific  therapy  for Ischemic stroke ,  when administered in less than 3 hours ( Now 6 h ?)  and has proven to  save lives and brain .The only issue is , we need a 100% exclusion of hemorrhagic  stroke by a CT/MRI. The mechanism of action of thrombolytic agent is simple .It lyses cerebral thrombosis and makes way for sustained reperfusion and arrest or even  reverse  the  ischemic damage to  neurones .

And now ,   let us see ,  how we perceive the same therapy in a patient  with a  history of  recent ischemic stroke  with an  acute STEMI .

The issue is two fold.

  • He needs urgent myocardial salvage in the form of thrombolysis or PCI .
  • The thrombolysis or PCI should not worsen the  cerebral infarct.

According to  most standard literature thrombolytic therapy is an absolute contraindication in a patient with STEMI and recent history of ischemic stroke (<3 months )

The  term absolute means ‘it is medical  crime” to give TPA or Streptokinase.

How  is it possible when the same drug  is  projected a savior in acute ischemic   neurological  emergencies  and  be dangerous when administered  few months later in an evolved ischemic stroke ?

The major  reasoning  against thrombolysis in recent stroke is  the  potential concern for  converting an  indolent ischemic  infarct into hemorrhagic  infarct in  a  patient who may start  bleeding  into brain.

This is  highly conjectural  , as  a previous history of  ischemic   stroke in no way increases the bleeding risk .Conversion of ischemic to hemorrhagic   infarct tend to  occur  in the very early  hours  of acute stroke (not weeks later) .This could be part of calcium induced  reperfusion injury .

Unanswered questions

The issue become further  complicated with our  skewed  thinking pattern.

If thrombolysis  is contraindicated  in STEMI , does  it any way imply a automatic indication for  primary PCI ?

It seems so , for most of us !

How safe is PCI in a patient  with a previous  history of ischemic stroke ?

  • An emergency PCI in a patient  who is expected to have   widespread  cerebral  carotid , and peripheral vascular  disease  is fraught with added hazard.
  • Aortic arch manipulation  and aortic  valve  atherosclerotic  changes  might  increase a risk  of another stroke.
  • The drug we administer  during PCI  are  not innocuous ones  . Aspirin ,  Heparin, clopidogrel (sometimes  even 2b 3a!) will  keep the  risk  of converting the ischemic infarct into  hemorrhagic infarct remain  at  dangerous  levels . This ridicules  the  very  logic  of   PCI being preferred over thrombolysis in such situations .
  • So it is not an  easy decision to do  primary  PCI in an elderly  patient  with STEMI and a recent CVA. It is only a mirage of  medical  intellectualism  and  the blind following  of unscrutinized  scientific  literature   that   determine  many of the decision  making  in cardiology .

The argument here is ,  in a patient  with evolved ,  uncomplicated ischemic  stroke thrombolysis can safely be administered  irrespective of the age of stroke.  .This is contrary to the published literature.Let us not make unethical practice against scientific literature  but let us also understand   it is unethical  not to realise  many of the so-called scientific  evidence  are  merely speculative.I  request  the  neurologists  and cardiologists give their   input on  the issue

As far as  I have searched  the superiority or inferiority  of thrombolysis   vs PCI in  recent  ischemic CVA has never been compared one to one. The fact may be ,  such a study is never possible in the future .But  it seems PCI has won the   trial  without  a trial .

Unanswered  questions

How  many deaths have happened due to worsening of stroke after thrombolysis ?

How safe is a  combination of aspirin, heparin and clopidogrel in a patient with recent stroke ?

How shall we decide about thrombolysis  in these situations  of STEMI and recent CVA) depending upon the

  • Age of  CVA
  • Location of cerebral infarct
  • Size of the infarct
  • Residual neurological deficit

It may be prudent to redefine  the indication for thrombolysis and PCI in a patient  with history of recent or remote stroke.

  • It is logical to assess the potential   risk of   converting the ischemic cerebral infarct   into hemorrhagic infarct.
  • It is expected only large infarct in vital locations need to be feared upon for this complication
  • All small healed cerebral infarct need not be worried about reactivation.

How to asses the healing of cerebral  infarct?

The healing  and gliosis  is highly dependent  on individual response to inflammation. Some heal  within weeks. Neo vascularisation within the necrtoic area may get hyperpermiable .These are very speculative concerns. In all probability   the risk of converting an ischemic necrosis into hemorrhagic  necrosis  is less than a  percentage .The 3 months time for  fixed for infarct healing  is an arbitrary one

How good is MRI to predict a healed infarct from nonhealed infarct ?

As of now,  we have no good tools to identify the  safe infarcts that can withstand intensive  anticoagulation or even thrombolysis .If the imaging techniques improve we may able to predict complete gliosis and the vascularisation  of cerebral scars.

Post blog query

How to manage an elderly man with STEMI in a patient with recent ischemic stroke ?

A.Take him to cath lab and do primary PCI
B.Thrombolyse with TPA or Streptokinase
C.Just observe and  manage  with Heparin*

Answer : Any of the above can be correct answer .

If  we  still think  the answer is only   “A”  great reforms need to be done in  medical science  . . .

*Another important option for STEMI and recent stroke (Perceived  as inferior form of management of STEMI !)

An important option is ,  neither thrombolysis nor PCI just simple heparin for STEMI in these high risk individuals .This simple treatment has saved many lives .

See A Related video  from you tube : Forgotten hero  in cardiology

Final message

In this world of gross approximation  and perceived fears ,  it may be reasonable to  shift  the  indication of   thrombolysis for STEMI( with h/o recent stroke ) from absolute to relative contraindication.

Many of the  junior  physicians  in the learning curve may take it as granted  in the management of STEMI  “If thrombolysis is contraindicated  , then primary PCI must be indicated ” This again  is absolutely not true  !


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Thrombus formation  and subsequent lysis  either spontaneous or pharmacological is the key events in acute vascular emergencies .We know both STEMI and acute strokes can get aborted  naturally.

The thrombus which initially forms , triggers a natural lytic mechanism and this fights vigorously against the clotting process , and tries to get rid  of the intravascular clot.

The early  minutes are vital. (Like the T 20 cricket )  the win or loss is decided in the first few overs . The mantra is unrelented attack of the ball . . .ie thrombus !  In some patients  the clot  can never grow big to fill the lumen.These are lucky few .The mechanisms are common in both cerebral and coronary circulation. Here is were comes the role of antiplatelet agesnt .An aspirin or clopidogrel administered within minutes can prevent the genesis of  central core of the thrombus .(This is the  secret of aspirin scoring over stretokinase in STEMI in ISIS2 study done three deaceds ago !)

It should be realised,  our understanding about spontaneous lysis is very little considering explosive growth of other aspects of cardiology. It is mediated by circulating  TPA and antithrombin 3  .  Remember  every humans have it in their  blood .But how much ? How to augment it ‘s power at times of thrombotic crises ?

What could be the clinical correlates of spontaneous thrombolysis ?

  1. In brain classically it is TIA .
  2. In heart do we have TIA equivalents ?  .Yes it transient rest angina

Link to video on TIA of the heart

Read this article to get a glimpse of  natural cerebral thrombolysis  and shall we   extrapolate it to coronary spontaneous thrombolysis  .Why not ?

Arch Neurol — Nonocclusion and Spontaneous Recanalization Rates in Acute Ischemic Stroke: A Review of Cerebral Angiography Studies, December 2002, Kassem-Moussa and Graffagnino 59 (12): 1870

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