Patch: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial
BMC Neurology
Patch: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial
Koen de Gans 0
Rob J de Haan 2
Charles B Majoie 1
Maria M Koopman 6
Anneke Brand 4 5
Marcel G Dijkgraaf 3
Marinus Vermeulen 0
Yvo B Roos 0 2
the PATCH Investigators
0 Department of Neurology, Academic Medical Centre , H2-222, PO-box 22660 1100 DD Amsterdam , The Netherlands
1 Department of Radiology, Academic Medical Centre , PO-box 22660 1100 DD Amsterdam , The Netherlands
2 Clinical Research Unit, Academic Medical Centre , PO-box 22660 1100 DD Amsterdam , The Netherlands
3 Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre , PO-box 22660 1100 DD Amsterdam , The Netherlands
4 Department of Immune-Haematology and Transfusion Medicine, Leiden University Medical Centre , Leiden , The Netherlands
5 Sanquin Blood Bank, South West Region, Department of Research and Development , Leiden , The Netherlands
6 Sanquin Blood Bank , North West Region, PO-box 9137, 1006 AC Amsterdam , The Netherlands
Background: Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. Methods/Design: The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. Discussion: To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease. Trial registration: The Netherlands National Trial Register (NTR1303)
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Background
In studies on outcome prediction after intracerebral
haemorrhage (ICH), increasing haematoma volume is a
consistent, independent predictor of poor outcome [1,2].
A study with follow-up head CT-scans in the acute
phase showed a 33% increase of haematoma volume
during the first 24 hours in at least 38% of patients [3].
This haematoma growth mostly occurs in the first six
hours after onset [4,5]. Unsurprisingly, patients suffering
from haematoma growth have worse outcome than
those without haematoma growth [6]. At our institution
we investigated the in hospital mortality after
spontaneous ICH. We retrospectively reviewed the charts of all
ICH patients who were admitted over a three year
period and divided them in three groups. Patients using
antiplatelet therapy (APT) had a 40% in hospital
mortality (15/38 patients). In patients using oral anticoagulants
the mortality rate was 28% during stay in the hospital
(11/39) and patients without any antithrombotic
medication had a 23% mortality (27/118). This poor outcome
for APT patients was unexpected. We first considered
this high mortality rate to be an epiphenomenon since
the APT patients were older and had more previous
cardiovascular events. However, other groups had reported
similar results and identified APT use as an independent
risk factor for poor outcome [7-12].
A possible explanation for poor outcome in patients
on APT is haematoma growth. A population-based
study in 208 ICH patients showed that the baseline
haematoma volume was comparable between patients who
used APT and those who did not [11]. In contrast,
patients using oral anticoagulants had a significantly
larger haematoma on admission. Although APT use had
no influence on haematoma volume on admission, there
was more haematoma growth in patients on APT as
compared to patients not using any antithrombotic
medication. Another study also found that haematoma
growth occurs more often in patients using APT [9].
We concluded that antiplatelet agents do not cause a
more severe initial haemorrhage, but the hampered
platelet function does more often lead to increasing
haemorrhage in the first few hours after haemorrhage
onset - i.e. haematoma growth.
It seems likely that a treatment strategy which stops
this increase of haematoma volume will improve
outcome in ICH patients. Such an intervention should be
initiated as rapidly as possible to maximise its benefit. It
is hypothesised that the best and fastest treatment
option to counteract the effect of APT is platelet
tra (...truncated)