I had a patient who bled in a different site other than the infarct within 6 hours post thrombolysis. What is the time window for bleeding post thrombolysis and what are the sites of bleeding both in the brain and elsewhere?
Very interesting topic, as a matter of fact the time window for bleeding is very different depending on the etiology and also the size of the infarction. Some of the tools developed for this condition (like the DRAGON score) intended to assess also the time for the bleeding appearance, and the data offers us a 12h period, but specially the first 4 hours are the more critical for this condition. In the NINDS trial 22 patients developed clinically significant hemorrhages, 20 (6,4%) in the tPA group and 2 (0,6%) in the placebo-treated group. 4 symptomatic ICH ocurred outside the vascular distribution of the ischemic zone. From the 10 fatal ICHs, 8 had symptoms within the first 12 hours, and all had onset of symptoms within the first 24 hours. Also there were descriptions of bleeding at 36h and beyond (not usual)
ECASS I and II and IST3 are also good examples of this type of observations (most of the studies have shown that symptomatic ICH, OR 3,4; 95%CI 2,81-4,33). A good article from this topic could be found in Stroke 2007;38:2279-2283 and J Neurol Neurosurg Psychiatry 2008;79:1093-99
Now regarding your question about bleedings in different zones from the ischemic core, there is not a lot of data from bleedings sites far from the vascular distribution of the infarction, but from the medication preclinical studies subarachnoid hemorrhage is one of the seen far from the ischemic core and more rare (case reports) in posterior circulation, then respiratory tract (epistaxis and haemoptysis), gastrointestinal (melaena, gingival bleeding and haematemesis), urogenital and very rare haemopericardium.
Is a very interesting discussion, and I hope that you could find helpful some of the information.
Thanks for the prompt response. I had a patient who underwent decompressive hemicraniectomy on the third day post thrombolysis. repeat ct done before surgey showed only big MCA infarct with mass effect. The patient developed hypoxia and respiratory distress while on ventilator after 5 hours post surgery and succumbed. What could be the probable cause of death?
Provided there were no problems at surgery such as venous sinus injury and air embolus, did you consider neurogenic pulmonary edema. Particularly if the patient received significant intravenous fluids during the hemicraniectomy, this may have pushed them over the edge. Heart failure is also an option since many strokes present as a indication of end stage heart failure.
Last week we operated a 52 year old woman who developed with hemorrhagic transformation 8 hours after thrombolysis for ischaemic stroke. After obtaining coagulation profile and preparing packed cell she underwent craniotomy for evacuation of 40cc ICH. Her lab results were within normal range and fortunately the operation was carried out successfully with less that 300cc bleeding
Thanks. In all probability, my patient developed neurogenic pulmonary edema and succumbed to it. He had no evidence of heart failure. there was noo evidence of h'gic transformation on the table
Regarding Thrombolysis and atypic conditions, I would like to share an interesting case from my hospital in Costa Rica, and hear opinions and suggestions from all your experience.
This is a 71-years-old lady, the only remarkable past medical condition is Hypertension (35 years, very good control with Enalapril 20 mg/d). There are no other comorbidities.
The patient goes to the Emergency Room with a history of 5 hours of abdominal pain in the lower right quadrant area, vomits, without fever and no diarrhea. McBurney sign (+), but no franc peritonitis on physical examination
While she was waiting in the department for the abdominal ultrasound and labs, she starts with a sudden onset of dysarthria, right hemiparesis and global aphasia (NIHSS 20 points), concomitant BP 90/74, 83 bpm, Glucose: 118 mg/dl and sinus rythm on EKG and cardiac telemetry.
The CT scan at 30 minutes has 10 points in ASPECTS scale, immediately US documents no free liquid on the abdominal zones.
We start iv rtpA with previous family and surgeons consent at 2h from the onset of the clinical deficit. Two hours after rtpA the NIHSS scale was on 14 and 8 hours later NIHSS = 2 points.
The patient still had the abdominal pain, so another abdominal US and radiologist found a very edematous appendix, and free liquid in Morrison space. So they said it is necessary to take the patient to the surgery room
By that time Hemogram had normal red blood cells count, 12000 leucocytes, and normal platelet count. Coagulation times were normal and the rest of labs were normal. Serum fibrinogen after thrombolysis was 401 md/dl (normal), so they made 12h after iv rtPa a laparotomy with the diagnosis of Grade IV appendicitis. No bleeding complications were achieved and it was not necessary to use frozen plasma or cryoprecipitate.
Post-surgical condition was really good with IV ertapenem (the peritoneal sample was positive for a multiresistant E. coli) and she still has a NIHSS of 1 (positive for a very slight sensitive aphasia).
The control CT test shows an ischemic core in the Temporo-Parietal left zone (ASPECTS 7 points).
What are your thoughts about emergency surgery after IV thrombolysis in Stroke?
Thank you for this very interesting case.Rt-PA has a very short half-life (which is only a few minutes), which is the reason why we have to give via continous infusion over 1 hour. The general rule not to do any invasive procedure or not to give any anithrombotic drugs within the first 24 hours comes from the big RCTs on rt-PA for ensuring patients safety, esp. in case of post thrombolysis changes in the coagulation system or silent cerebral hemorrhagic transformation.
I remember also a patient who be thrombolysed with an cute left MCA infarction who developed about 6 hours after rtPA an acute myocardial infarction with a very high troponin. He had occlusion oft the right coronary artery. We gave him heparin, aspirin and clodipogral and the cardiologists did an acute PCTA 7 hours after rtPA. Concering the MCA infarction he did pretty well.
Thank you so much for your reply. Indeed, we emphasized this pharmacological condition with the surgeons when they asked us our opinion to take the patient to surgery room. Some case reports and experts recommend to be sure that serum fibrinogen should be upper than 150 mg/dl, but pharmacokinetics of this drug is enough to let us work if a surgery is needed, and the condition of the patient allows that.
Indeed ICH post-thrombolysis remote from the infarct is intriguing. I would suggest the following (by no means complete) differential to consider for workup:
Fragmented embolus with multiple infarcts - however if the ICH was in an entirely different territory / contralateral, this is not likely
Recent head trauma
Cerebral amyloid angiopathy
Hypertensive microangiopathy
Metastasis / primary tumor / AVM / DAVF at the site of the ICH
Endocarditis
Cerebral vasculitis
If it is of any help, please find enclosed my own very recent paper on the topic of remote ICH in stroke thrombolysis, published in Stroke, online on May 1 this year.
Regarding the timing of ICH following thrombolysis - a bleed after 6 hours is not surprising, they nearly always occur within 36 hours from treatment, please see the ICH analysis of the NINDS trial: National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Intracerebral hemorrhage after intravenous t-PA for ischemic stroke. Stroke. 1997;28:2109–2118, and of course the excellent paper by Daniel Strbian et al: Patient outcomes from symptomatic intracerebral hemorrhage after stroke thrombolysis. Neurology. 2011;77:341–348. Worth considering is that unbound tPA indeed has a 4-6 minute half-life in plasma, whereas it is considerably longer when bound to thrombus (unfortunately I do not have a reference ready for this, would be grateful for any good recommendation).