I have reviewed and linked to a total of four resources on the diagnosis and treatment of intracerebral hemorrhage. This post, like many of the posts in this blog, is simply my study notes on a topic (my peripheral brain).
This post is simply a link to Dr. George Walker’s post of March 8, 2019, TICH2 from The Bottom Line which evaluates the Tranexamic Acid for hyperacute primary IntraCerebral Haemorrhage [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Sprigg, N et al. The Lancet 2018; doi: 10.1016/S0140-6736(18)31033-X.
The above article has been cited 12 PubMed Central articles.
Here are excerpts from Dr. Walker’s post:
- In adults with acute, spontaneous intra-cerebral haemorrhage (ICH) does the administration of tranexamic acid (TXA) compared to a placebo improve functional status at 90 days?
- Spontaneous ICH has a high mortality and morbidity. Haematoma expansion has been independently associated with death and poor outcome. Expansion occurs more frequently in the first three hours, however it has been shown to occur later than this.
- Multiple modalities to try to improve outcome have been studied. Early surgery (STICH-II) and intensive blood pressure lowering (INTERACT) were not shown to reduce risk of death or severe disability. Recombinant Factor VII is the most widely studied haemostatic therapy, however a Cochrane Review showed no significant reduction in death or disability.
- The use of TXA had not previously been widely studied. One small Malaysian study of 30 patients looking at TXA use in spontaneous ICH found significant haematoma expansion in the control group, and a meta-analysis of 2 RCTs showed a significant reduction in ICH progression in traumatic brain injuries.
- 124 hospital sites in 12 countries
- March 203 – September 2017
- Adult patients with intra-cerebral haemorrhage were eligible if admitted to participating hospital within 8 hours of stroke onset (or time last seen well)
- Tranexamic Acid
- 1g IV TXA in 100ml 0.9% NaCl infused over 10 minutes
- Followed by another 1g in 250ml 0.9% NaCl infused over 8 hours
- Normal saline used in place of TXA above, otherwise identical intervention
Management common to both groups
- Participants received blood pressure lowering treatment, neurosurgery and VTE prophylaxis as part of standard care.
- TXA does not affect functional status at day 90, although some potential benefits were noted with regards to reduction in haematoma expansion, early death and numbers of serious adverse events
The Bottom Line
- The signal of benefit from tranexamic acid administration seen in this trial has not been proven by conventional statistical significance thresholds
- Given some non-significant trends in certain subgroups and low rates of serious events, further work looking at certain subgroups should be considered to identify patients that may benefit
- The complementary CRASH-3 trial, investigating tranexamic acid administration in traumatic head injuries, will expand the evidence base in this area when published
- Given the good safety profile and potential small benefit, it is reasonable to administer tranexamic acid early in patients with intracerebral haemorrhage.
- [article] Tranexamic acid for hyperacute primary IntraCerebralHaemorrhage (TICH-2): an international randomised,placebo-controlled, phase 3 superiority trial
- [further reading] CT Angiographic Spot Sign by Radiopaedia
- [further reading] CRASH-3 Trial
- [further reading] Gayet-Ageron et al. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient level data from 40 138 bleeding patients by Gayet-Ageron et al.
- [further reading] Haemostatic therapies for acute spontaneous intracerebral haemorrhage. Cochrane Database of Systematic Reviews
(1) Recent advances in spontaneous intracerebral hemorrhage [PubMed Abstract] [Full Text HTML] [Full Text PDF]. F1000Res. 2019 Mar 18;8. pii: F1000 Faculty Rev-302.
(2) Ep 104 Emergency Management of Intracerebral Hemorrhage – The Golden Hour [Link Is To The Podcast And Show Notes]. Helman, A, Weingart, S, Himmel, W, Simard, R, Brindley, P. Emergency Management of Intracerebral Hemorrhage – The Golden Hour. Emergency Medicine Cases. December, 2017.
The above is an outstanding resource. It is worth listening to the 1:30 minute podcast and reviewing the show notes many times.
(3) Haemostatic treatment for intracerebral haemorrhage [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Lancet. 2018 May 26;391(10135):2081-2082.