European Stroke Organisation Conference
May 16–18, 2018

Andrea Morotti, MD

The results of the Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2) randomized controlled trial were presented at the 4th congress of the European Stroke Organisation in Gothenuburg, Sweden. Subjects with primary, spontaneous intracerebral hemorrhage (ICH) presenting within 8 h from symptom onset/last time seen well were randomized to treatment with intravenous tranexamic acid (1 g bolus followed by 1 g over an 8 h infusion) versus placebo. 1 The main outcomes of interest were hematoma expansion (defined as absolute hemorrhage growth>6mL or relative hemorrhage growth>33% from baseline volume) and the proportion of patients with death or severe disability at 3 months from the index event.

A total of 2325 met the eligibility criteria and were included in the study (mean age 68.9 years, 56% males). The mean difference in absolute hematoma growth was -1.37 mL in favor of tranexamic acid administration (p=0.04), and the proportion of patients with hematoma expansion was significantly lower in subjects in the treatment group compared with placebo (25% vs. 29%, adjusted odds ratio 0.80, 95% CI 0.66-0.98, p=0.03). However, this reduction in the extent of bleeding in the treatment group did not translate into improved outcome (ordinal shift analysis for modified rankin scale at 3 months, odds ratio 0.88, 95% CI 0.76 – 1.03, p=0.11). All the safety measures did not differ between the two treatment groups. In particular, tranexamic acid administration was not associated with an increased risk of venous or arterial thromeboembolic events.

One of the possible explanations for these disappointing results is the magnitude of hematoma growth reduction. It seems reasonable to expect that such a minimal reduction in the extent of bleeding (1.4 mL) does not impact functional outcome. Another possibility is that the presence of very broad inclusion criteria led to a heterogeneous study population. The benefits of tranexamic acid in patients at high risk of ICH expansion may have been masked by the inclusion of several patients with low probability of hematoma growth and, therefore, minimal chances to benefit from hemostatic therapy. Finally, time is brain also, and especially in ICH care. Hematoma expansion is a very early event in the natural history of ICH, with its highest frequency in the first 3 hours after symptom onset.2,3 The majority of subjects in the trial were randomized after 3 hours, when ICH expansion has probably already occurred in several patients.

In conclusion, this large trial demonstrated that tranexamic acid in acute ICH is safe and associated with a minimal reduction in the extent of bleeding, without a significant impact on ICH outcome. Secondary analyses are very much awaited. In particular, imaging predictors of ICH expansion such as the CT angiography spot sign4 or non-contrast CT markers5 may identify a subgroup of patients at high risk of  active bleeding, and, therefore, more likely to benefit from hemostatic treatment with tranexamic acid.


  1. Sprigg N, Flaherty K, Appleton JP, et al. Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial. Lancet 2018; [ahead of print].
  2. Brouwers HB, Greenberg SM. Hematoma expansion following acute intracerebral hemorrhage. Cerebrovasc Dis 2013;35(3):195–201.
  3. Dowlatshahi D, Brouwers HB, Demchuk AM, et al. Predicting Intracerebral Hemorrhage Growth With the Spot Sign: The Effect of Onset-to-Scan Time. Stroke 2016;47(3):695–700.
  4. Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, et al. Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): A prospective observational study. Lancet Neurol 2012;11(4):307–14.
  5. Boulouis G, Morotti A, Charidimou A, Dowlatshahi D, Goldstein JN. Noncontrast Computed Tomography Markers of Intracerebral Hemorrhage Expansion. Stroke 2017;48(4):1120–5.