Medical treatment for spontaneous anticoagulation-related intracerebral hemorrhage in the Netherlands

They found that prothrombin complex concentrates were used in all vitamin-K antagonist (VKA) reversal, and the majority of non-vitamin K anti-coagulant (NOAC) reversal. None of the centres initiated anticoagulation in the CT room, most waited for lab results prior to reversal and it was thought by most of the responders that initiation of anticoagulation reversal was slower than stroke thrombolysis. The authors identified several recommendations to optimise reversal timing.

Spontaneous ICH has an estimated incidence of 25 per 10,000 person years, and 40% of affected patients will die within the first month, while the survivors have a high morbidity. There is a significant association with anticoagulation, as 15–20% of patients who experience an ICH are on anticoagulation at that point. Spontaneous anticoagulation-related ICH tends towards larger haematomas and higher rates of haematoma expansion – both these factors are linked with a higher mortality rate. Evidence does suggest that rapid reversal of anticoagulation works to counter the mortality increase. The optimal reversal protocol for the newer wave of anticoagulants has yet to be clearly established. On this basis, the authors decided to explore the current status of practice in the Netherlands.

The authors analysed several national and international guidelines to identify areas where there was likely to be a variation in practice – based on their findings, they constructed a questionnaire comprising 15 multiple choice questions. Stroke neurologists across the country were sent the questionnaire, with the ultimate goal of determining their opinions regarding the importance, mode and logistics of anticoagulation reversal in their respective departments.

There was a good response rate of 76.5% (65/85). Their findings were that the preferred reversal strategy for all anticoagulants was PCC; this was almost unanimous for VKAs, while much more variation existed for NOACs. Other frequently used treatments included fresh frozen plasma, activated eptacog alfa, activated PCC and plasmapheresis – although there were some respondents who would use other therapies based on local protocols. Around half of the clinicians (50.8%) said they would wait for clotting results prior to initiating treatment, and nearly half (44.3%) would contact a haemostasis specialist if the patient was using a NOAC. In general, the survey suggested that most respondents thought that the time to initiating anticoagulation reversal was slower than the time to thrombolysis with tissue plasminogen activators (such as alteplase) in acute ischaemic stroke. It was noted that PCC is available in most emergency departments (95.1%), although its administration was typically done after CT scan in the department, rather than in the CT room – where thrombolysis would usually be performed.

In their discussion, the authors note that most of the surveyed neurologists adhere to international guidelines. The limitations acknowledged were that the targeted clinicians were engaged in stroke policy – and so may have not been representative of wider practice. They also carried out the study prior to the more specific NOAC reversal agents (idarucizumab, and andexanet alfa – the latter of which is still in trials) becoming available in the Netherlands. Regarding their important finding – that anticoagulation reversal takes longer to be initiated than thrombolysis – they broke down several possible areas of delay:

• Treatment initiation was not lined up and ready to be given in the CT room – as with thrombolysis.
• Treatment was given as a bolus by fewer than one third of neurologists surveyed.
• Around half of neurologists wait for clotting results prior to giving anticoagulation reversal treatment.
• In cases where the anticoagulant was a NOAC, haematologists were frequently contacted prior to giving treatment.
• Absence of a protocol may have delayed treatment.

This study provides an interesting picture of current practice as it applies in the Netherlands, and importantly identifies key areas where speed of treatment can be optimised for patients with anticoagulation-associated ICH.