Role of prothrombin complex concentrate (PCC) in acute intracerebral hemorrhage with positive CTA spot sign: an institutional experience at a regional and state designated stroke center

Following exclusions, eight patients with CTA spot sign who had been treated with PCC and four who had not been given PCC were identified. The scans were then reviewed by two radiologists blinded to the clinical picture who assessed haematoma expansion. The mean change in haematoma volume for the control group was an increase of 46%, while those treated with PCC saw a 13% mean volume decrease.

Intracerebral haemorrhage (ICH) may lead to irreversible brain damage and reduced long-term functional outcomes. The spot sign on CTA (CT Angiogram) describes foci of contrast enhancement within an acute parenchymal haematoma, and has been demonstrated to have a positive predictive value of 61% for haematoma expansion. The spot sign can provide information to suggest microvascular disruption and help to identify high-risk cases requiring further intervention. Acute ICH carries a high mortality and morbidity risk, with haematoma volume, location and expansion known to affect clinical outcomes. Significant expansion occurs from 6–12 hours, so a rapidly acting treatment is required. There is currently no definitive non-invasive therapeutic option available for acute ICH – fresh frozen plasma and recombinant factor VII have demonstrated reduced haematoma expansion, but no effect on mortality or functional outcome. Several factors may suggest PCC is suitable for this role; it has a small volume relative to alternative therapeutic options, can be administered rapidly, has a rapid mode of action, and can be given as a single dose due to its long half-life.

The authors retrospectively reviewed patients who had been treated between November 2013 and December 2015. They selected patients with a positive CTA spot sign who had not required surgery and had not died. Of the 85 patients identified, 23 had been treated with PCC, of whom eight had survived without further intervention. Of the remaining 62 in the control group, four had survived without surgical intervention. The CTA images were reviewed independently by two radiologists to confirm the presence of the spot sign; the subsequent scans (taken between 5 and 24 hours) were reviewed – haematoma volumes and expansion were estimated by the ABC/2 formula. The radiologists were blinded to the treatment used. The primary outcome was percentage change in intracerebral haematoma volume.

Results demonstrated the mean haematoma volume in the control group had increased by 46% (SD 37%). In the treatment group, mean haematoma volume had reduced by 13% (SD 30%) (p = 0.012). In the PCC group, 5 of 8 patients experienced a volume reduction, in the control group 3 of 4 had an increase in haematoma volume.

In their discussion, the authors remark that containment of haematoma expansion is crucial in preventing secondary volume expansion. There is little hard evidence to support medical management, and even though raised blood pressure is linked to expansion, close control does not improve mortality outcomes. The relevance of the CTA spot sign has been demonstrated in trials which have treated a positive CTA spot with surgical evacuation, and shown a corresponding mortality benefit. This study suggests that supplying extra clotting factors even in the absence of coagulopathy may reduce haematoma expansion in those with a CTA spot sign.

There are several limitations to this study:

• Sample size is very small
• A surrogate outcome is used, with no demonstrable mortality or functional benefit
• Measurement of haematoma size is subject to operator variability
• The retrospective nature of the study leaves it susceptible to selection bias
• There was no timing schedule for repeat of CT head, leaving significant room for variability.

This study raises an important clinical question and leaves significant scope for expansion. However, on its own it cannot be extrapolated into wider practice.