Enoxaparin induced intracerebral haemorrhage after deep brain stimulation surgery

Editor, Critically ill neurological patients are prone to deep vein thrombosis (DVT), as they remain bedridden for prolonged periods. Thromboprophylaxis is of paramount importance for prevention of this complication. Use of low molecular weight heparin (enoxaparin) has been recommended for prevention of deep venous thrombosis. The risk of haemorrhage with enoxaparin into the operation site in neurosurgical patients can be more dangerous than with other surgeries. Enoxaparin, a low molecular weight heparin, acts by inhibiting coagulation factors such as Xa and IIa and by activating the antithrombin III. Factor Xa catalyzes the conversion of prothrombin to thrombin. Inhibition of this process by enoxaparin results in decreased thrombin and prevention of fibrin clot formation. Intracerebral bleeding has been previously reported as a perioperative complication following deep brain stimulation (DBS) surgery [1]. We report a case of anticoagulant (enoxaparin) induced intracerebral haemorrhage in an elderly patient who underwent surgery for DBS in the postoperative period. A search in literature did not reveal any similar result. A 75-year-old male was admitted with history of tremulousness of right upper limb and both lower limbs associated with sluggishness of movements, decreased volume and slurring of speech for 3 years. Over a period of 6 months, symptoms progressed to such an extent that he had a fall while walking and fractured his acetabulum. Examination revealed hypertonia, bradykinesia, rigidity and postural instability. A diagnosis of Parkinson's disease was made. He was prescribed syndopa (levodopa 100 mg + carbidopa 10 mg). After initial response, drugs had to be increased because of waning effects. There was no improvement in symptoms inspite of addition of ropinirole, entacapone and selegiline. Hence, DBS was planned. He had a past history of hypertension and coronary artery disease for which a coronary artery bypass graft surgery had been done 10 years back. There was also history of retinal detachment and subdural hematoma 12 years back. The DBS procedure was carried out in two stages. In the first stage, the microelectrodes were placed in the subthalamic nucleus bilaterally under monitored anaesthesia care. This was followed by placement of stimulator with battery in the anterior chest wall under general anaesthesia and mechanical ventilation. The trachea was extubated at the end of the procedure and patient shifted to neurosurgical ICU. On the fifth postoperative day, enoxaparin (40 mg) was administered for prophylaxis of DVT. Within a few hours of receiving the first dose of enoxaparin, the patient became unresponsive. The trachea was reintubated and the patient taken for computed tomography (CT) scan. Intracerebral haemotoma in the left basal ganglion and left fronto-parietal region with midline shift and perilesional oedema was seen on the CT scan (Fig. 1). Prothrombin time (24 s control 12 s−1) and activated partial thromboplastin time (33 s control 30 s−1) were prolonged with a normal platelet count. Enoxaparin was discontinued, and six units of fresh frozen plasma were transfused. Mechanical ventilation was continued. Patient's coagulation status returned to normal within the next 4 days, and there was an improvement in the neurological status. As the haematoma had resolved and was not expanding, the surgeons decided against its evacuation. However, soon the patient developed ventilator-associated pneumonia and sepsis due to methicillin-resistant Staphylococcus aureus to which he succumbed on the twenty-fifth day of his ICU stay.Fig. 1DBS is being increasingly practiced in elderly patients for tremor-dominant disorders, Parkinson's disease and dystonias. Although DBS is supposed to be as effective in elderly patients as in younger ones, systematic studies on the complication rate, the effectiveness and, therefore, the risk–benefit ratio of DBS in elderly patients are still lacking. Elderly population has a higher incidence of coexisting medical disorders. DBS should be considered in patients with early stages of disease, as the incidence of general complications increases with age, whereas natural life expectancy decreases. DBS is a minimally invasive neurosurgical procedure with reported perioperative surgical complications such as haemorrhage, seizure, confusion [2], venous air embolism [3] and tension pneumocephalus [4]. In the postoperative period pneumonia, skin infections [5] and transient psychoses are frequent complications. Our patient developed an intracranial haematoma, possibly due to prophylactic anticoagulation. His neurological condition worsened when a low molecular weight heparin was given 5 days after the original surgery. There were no apparent aggravating factors such as clotting derangements or sepsis. Although the aim was to prevent DVT, this case illustrates the possible hazard of enoxaparin administration. Though there are no specific guidelines on the use of enoxaparin in traumatic brain injury, some studies do not support routine prophylaxis [6], whereas others recommend safe use of enoxaparin for DVT prophylaxis within 24 h after hospital admission or after craniotomy [7]. In elective neurosurgical patients, it has been seen that there is an increase in the postoperative intracranial haemorrhage when enoxaparin was initiated preoperatively in patients with brain tumours [8]. In contrast, the frequency of the intracranial bleeds in the placebo and enoxaparin group was similar when started 24 h after surgery. Agnelli et al. [9] suggest that compression stockings, together with enoxaparin (40 mg once daily, within 24 h after surgery), is the method of choice for prophylaxis against venous thromboembolism in the majority of patients undergoing elective neurosurgical procedures. We too suggest that, until better evidence emerges, one should favour mechanical measures (antiembolism stockings, intermittent calf compression and physiotherapy) rather than pharmacological ones for the prevention of DVT in elderly patients with Parkinson's disease undergoing such procedures.