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Treatment with prothrombin complex concentrate to enable emergency lumbar puncture in patients receiving vitamin K antagonists

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Last updated:12th Mar 2020
Published:12th Feb 2020
Neurological emergencies often necessitate an urgent lumbar puncture to establish or exclude a diagnosis; however, therapeutic levels of anticoagulation are a contraindication to this procedure. This was a retrospective chart review study to establish the safety and efficacy of anticoagulant reversal using prothrombin complex concentrates (PCC) in these patients. Although small in scale, reversal of vitamin K antagonists (VKAs) appeared effective and safe, both in terms of laboratory markers and bleeding events.

Due to potential significant adverse events as a result of bleeding following a lumbar puncture, the procedure is contraindicated in patients on anticoagulants, whose INR is within the targeted range. There are several reversal methods, all with potential drawbacks. The authors of this paper sought to specifically look at using PCC for anticoagulant reversal and to determine whether it was safe in this context.

The study was carried out at a University hospital in Germany, within a busy neurological emergency department. The study period was between December 2004 and June 2014, and all patients over this time period were logged in a database. Patients who were treated with PCC to enable urgent lumbar puncture for suspected CNS infection or subarachnoid haemorrhage (SAH) were identified, and had their medical records and any imaging and laboratory results reviewed. Any identified bleeding, thromboembolic or allergy-related events were reviewed by three physicians who classified these as ‘related’, ‘probably related’, ‘possibly related’, ‘unlikely related’, or ‘not related’ to either the PCC infusion, or the lumbar puncture. Different products of 4-factor PCC were used, as were different doses; this varied depending on the clinical picture and initial INR results.

The authors established 37 cases where PCC was administered to enable lumbar puncture. The most common indication for anticoagulation was atrial fibrillation (n=30), while mechanical heart valves (n=3), previous pulmonary embolism (n=2), cardiomyopathy (n=1) and deep vein thrombosis (n=1) were also represented in this patient group. The indication for lumbar puncture was suspected CNS infection in 35 patients; the other two were suspected SAH in the absence of CT findings.

Median INR at admission was 2.2 (interquartile range [IQR] 1.8–2.9); following administration of PCC this fell to 1.3 (IQR 1.2–1.4). The median time between initiation of PCC infusion and lumbar puncture was 135 minutes. No spinal haemorrhage or allergic reactions were observed, while in one patient a clinically irrelevant subdural haematoma and small bilateral embolic strokes were detected on MRI. A myocardial infarction was diagnosed in another patient 10 hours after infusion. Encephalitis or meningitis were confirmed in 7 of 35 patients, while no evidence of SAH was established in the other two cases.

There are several limitations to the study, which are acknowledged by the authors; the retrospective design, absence of a control group, lack of established protocols for PCC dosing and the limited number of cases all hamper the ability to draw any specific conclusions. With these in mind, the study did demonstrate that PCC can be used as a rapid and safe method of reversing anticoagulants in this group of patients, with no clinically relevant bleeding side-effects established. Of the thromboembolic events, the ischaemic stroke was classified as ‘unlikely’ to be related to the PCC, as it was picked up 15 days after the procedure, with imaging appearing to demonstrate that it was recent. The myocardial infarction alone was classified as ‘possibly’ related to the PCC.