Gurmeen Kaur, MBBS
Yaghi S, Willey JZ, Cucchiara B, Goldstein JN, Gonzales NR, Khatri P, et al. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2017
The American Heart Association/American Stroke Association recently published a consensus statement on treatment guidelines for management of symptomatic intracranial hemorrhage (sICH), chaired by Dr. Yaghi. After extensive review of the existing literature, the consensus committee devised this guideline based on the current available evidence.
Different authors and trials have used varying definitions of what is classified as symptomatic ICH. Based on the definitions, there was a 2.5-5-fold variation in the rates of ICH noted. The incidence of sICH after alteplase in the modern era at the standard dose of 0.9 mg/kg administered over 1 hour with a 10% bolus varies from 2% to 7% in clinical trials and prospective stroke registries.
To standardize and make the various trials comparable, the group suggested that stroke centers should classify the appearance of hemorrhagic transformation according to radiographic criteria as described in ECASS II (hemorrhagic infarction [HI] type 1, HI-2, parenchymal hematoma [PH] type 1, PH-2, or remote ICH), assess the degree of neurological worsening by National Institutes of Health Stroke Scale (NIHSS) point change, and provide an attribution of causality for the worsening. The natural history of patients with sICH, particularly the PH-2 radiological subtype, is very poor, approaching 50% mortality and significant morbidity with survival.
Over years, more than 7 scores have been devised and tested to be predictive models of who is likely to have an sICH after tPA administration. Several risk factors included in these risk scores are older age, greater stroke severity, higher baseline glucose, hypertension, congestive heart failure, renal impairment, diabetes mellitus, ischemic heart disease, atrial fibrillation, baseline antiplatelet use, leukoaraiosis, and visible acute infarction on brain imaging, which were all associated with increased risk of sICH. The group concludes that while these risk scores can be helpful for guiding patients’ and their families’ expectations and perhaps to inform the intensity of medical monitoring required for individual patients after alteplase administration, they should never be used to select patients for thrombolysis based on the current evidence.
Most of the bleeds happen within 36 h after the alteplase infusion, with only half of the events being diagnosed by 5–10 h after alteplase infusion. The authors have suggested increasing the duration of the monitoring every 30 minutes from 8 hours (as currently practiced) to the first 12 hours to capture more of the early signs of neurological deterioration attributed to post thrombolytic bleeds.
Use of reversal agents after bleeding secondary to tPA has been a controversial topic. While there is no evidence of reversing patients with asymptomatic hemorrhages, the reversal of patients with asymptomatic parenchymal hemorrhage within 24 hours may be considered, particularly in the setting of an ongoing coagulopathy.
Recommendations include use of cryoprecipitate as soon as possible after detection of sICH with empirically transfusing with 10 U cryoprecipitate and anticipate giving more cryoprecipitate as needed to achieve a fibrinogen level of ≥150 mg/dL. Platelet transfusion is not routinely recommended except in those with thrombocytopenia (platelet count <100 000/μL).
Use of 4-factor PCC/ prothrombin complex concentrate is recommended in patients on warfarin treatment before getting tPA (those with a sub therapeutic INR who qualified for IV thrombolysis). PCC is the preferred modality, but if unavailable, fresh frozen plasma may be used. Adjunctive therapy with vitamin K should also only be reserved for this subgroup that was on warfarin before receiving alteplase. Antifibrinolytics have limited data but should be considered in patients with sICH, particularly in patients who decline blood products. Given lack of safety data, use of activated factor VIIa is not recommended.
Blood pressure goals in post thrombectomy patients has been a matter of debate across several studies. In patients with incomplete recanalization, higher blood pressure targets may be necessary to maintain adequate blood flow to the ischemic bed and to reduce the risk of infarct growth. On the other hand, in patients with full recanalization, stricter blood pressure control measures may be reasonable. Neurosurgical intervention has been suggested in patients with sICH for whom surgery may improve outcome despite the underlying ischemic stroke.
These consensus guidelines provide an excellent model for management of post tPA hemorrhage and coagulopathy despite the lack of evidence from large RCTs. This statement also clearly defines areas of lacking evidence and future studies should aim to address those lacunae.