The location of an intracranial haemorrhage (ICH), the mechanism of bleed and anticoagulant class are just three of the factors influencing the timing of resumption of oral anticoagulants (OAC) following OAC-associated ICH.
A suggested decision-making approach for restarting OAC, published in the Journal of Thrombosis and Haemostasis [link here], includes a flexible time frame from as early as 1-2 weeks to 6-8 weeks post-ICH dependent on multiple considerations.
“In the majority of patients, the composite risk of both thromboembolism and rebleeding is likely minimised somewhere between 4 and 6 weeks after ICH, in line with the recommendations of the ESC and AHA/ASA guidelines,” the review article said.
The Australian coauthors, haematologists Dr Brian Grainger, Associate Professor James McFadyen and Professor Huyen Tran, said OAC should be resumed in the vast majority of post-ICH patients.
They said that five systematic reviews have confirmed that resuming OAC was associated with reduced thromboembolic events (RR 0.31-0.56) and all-cause mortality (RR 0.27-0.6).
“By comparison, the risk of ICH recurrence appears to be at equipoise, …” they said.
However the evidence on the optimal time to resume OAC was inconsistent and ultimately required weighing individual benefit and risk.
The suggested decision making framework highlights the fact that ICH occurring in a lobar location warrants later restarting of OAC as it is known to be at higher recurrence risk than deep haemorrhage.
“This is because lobar bleeds are frequently associated with cerebral amyloid angiopathy (CAA), a cerebrovascular disorder characterised by β-amyloid deposition, micro-haemorrhages, and vascular fragility,” they said.
A spontaneous bleed also warranted later resumption of OAC compared to ICH secondary to trauma.
DOACs vs warfarin
Regarding OAC class, the review said some consensus guidelines such as CHEST guidelines for antithrombotic therapy for AF [link here] recommended DOACs over warfarin except for specific patient groups including those with mechanical heart valves and high-risk antiphospholipid syndrome.
“On this basis, switching patients who were previously taking warfarin to a DOAC post-ICH should be considered,” the review said.
“It is possible that the resumption of or switch to a DOACs can safely occur at an earlier time than warfarin in most patients, however the absence of dedicated studies examining this issue precludes more specific guidance.”
The review said risk factors for thromboembolism which would encourage earlier restart of OACs included mechanical prosthetic heart valves, malignancy, AF with CHA2DS2-VASc ≥5, recent stroke or TIA, recent VTE, high-risk thrombophilia and use of reversal agents.
Risk factors for bleeding which would encourage later resumption of OACs included advanced age ≥75 years, uncontrolled hypertension (sBP> 180 mmHg), heavy alcohol use, labile or supratherapeutic INR (≥3.0) and platelet count <50 x 109/L.
Concomitant antiplatelet or NSAID use, chronic kidney disease and apolipoprotein E ε2 and ε4 polymorphisms were also factors which would suggest later restart of OAC.
The coauthors said the novel factor XI and XII inhibitors may inhibit pathologic thrombosis whilst preserving normal haemostasis.
They therefore had the potential to offer a safer alternative in the future however their bleeding safety data was still immature.
Left atrial appendage occlusion (LAAO) was also an alternative to anticoagulants in patients with AF however the evidence was mixed on the use of inferior vena cava (IVC) filters.
With both devices, the potential benefits had to be weighed against the risk of complications including pericardial tamponade, vascular injury and device erosion or embolisation with LAAO and migration, fracture, and filter thrombosis with the IVC filters.
“Multi-disciplinary collaboration between neurologists, cardiologists, neurosurgeons, haematologists and pharmacists is needed to make individualised management decisions tailored to each patient’s particular risk profile,” they concluded.