Fatal intracranial haemorrhage associated with the administration of low-molecular-weight-heparin in a child

Abstract

Strokes due to cardioembolism are in general severe and prone to early recurrence. Current recommendations for children with cardioembolic stroke include treatment for 5 to 7 days with low-molecular-weight-heparin (LMWH) [7]. We present a case of fatal intracranial haemorrhage associated with LMWH therapy in a child. A 14-month-old boy with Down syndrome had an acute stroke. The CT scan showed a non-haemorrhagic infarct of the entire right middle cerebral artery territory without signs of septic emboli or aneurysms. Echocardiography revealed a thrombus in the left atrium. Clotting evaluation showed, except for a mild thrombocytopenia of 90·10/l, no abnormalities (APTT 41 s, INR 1.21). Anticoagulation therapy was started with subcutaneous nadroparine (110 IE/kg) twice daily [8]. In addition, antibiotics for a later confirmed endocarditis, were started. After 2 days, the intracardiac thrombus was no longer detectable whereas the nadroparine was continued. In addition, his platelet count normalised. Six days later he had a cardiac arrest for which he was successfully resuscitated. A CT scan showed a massive intraventricular and subarachnoidal haemorrhage not related to the earlier ischaemic infarction. Clotting evaluation immediately after the incident revealed a platelet count of 234·10/l, an APTT of 60 s, and an INR of 1.68. Eventually, treatment was discontinued because he met brain death criteria. Other causes for the intracranial haemorrhage like effect of other medication were unlikely and there was also no history of invasive procedures or trauma during hospitalisation. In addition, impaired haemostasis was not found. Reported major bleeding complications during LMWH therapy for thromboembolic events in paediatric patients are approximately 5% [1, 5,6]. In a single-institution cohort study of 146 courses of therapeutic LMWH (enoxaparin) for various types of thrombotic diseases, two deaths were directly related to the safety and efficacy of enoxaparin [1]. In the REVIVE trial LMWH (reviparin-sodium), one death was reported in the LMWH group which was not related to the therapy [6]. In general, LMWH therapy is considered to be safe; however, recently significant and potentially fatal haemorrhagic complications have been reported in adults comparable with this case report [4]. An important issue is to carefully (re)evaluate when to start LMWH therapy in children with cardioembolic stroke. The aim of secondary prophylaxis is to balance the risk of recurrent embolism and haemorrhagic transformation of an infarction [2,7]. Studies in adults clearly show that there is no support for routine immediate anticoagulation of acute (cardioembolic) stroke. Anticoagulants do not decrease death or dependency, change progression, or prevent early recurrence in acute stroke due to cardioembolism [2]. Recommendations for antithrombotic therapy in cardioembolic stroke in paediatric patients do not correspond with this [7]. Treatment recommendations are based on grade 2C evidence, obtained in small case series or case reports [3]. Unfortunately, there have been no randomised clinical trials for primary prevention, short-term treatment, or secondary prevention of ischaemic stroke in infants and children. A properly designed clinical trial is therefore urgently required to address these issues and to determine the true incidence of major bleeding and to identify potential risk factors. M. van Heerde AE F. B. Plotz (&) Department of Paediatric Intensive Care, VU University Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands E-mail: fb.plotz@vumc.nl Tel.: +31-20-4442413 Fax: +31-20-4443045