Prothrombin Complex Concentrates for Intracranial Hemorrhage on Factor Xa Inhibitors
Bibliographic record
Abstract
Prothrombin Complex Concentrates for Intracranial Hemorrhage on Factor Xa InhibitorsArticle, see p 1681 O ne of the most important advantages of the direct oral anticoagulants (DO-ACs) over warfarin is their lower risk of intracranial hemorrhage (ICH).In 4 major oral anticoagulation trials in patients with atrial fibrillation (AF), DOACs reduced the risk of ICH by ≈50% compared with warfarin, 1 including in patients at highest risk of bleeding (elderly, renally impaired, and those taking concomitant antiplatelet therapy), as well as at sites that achieved the best prothrombin-time international normalized ratio (PT-INR) control. 2 Nonetheless, ICH still occurs; for every 1000 patients with AF treated with a DOAC for 1 year, between 2 to 5 will experience ICH.[3][4][5][6][7] ICH in patients who are receiving anticoagulation results in death or permanent disability in ≈75% of cases.8 Further reducing the risk of ICH as well as the risk of its complications remains a key priority for clinical practice.In patients who experience ICH while anticoagulated with warfarin, guidelines recommend immediate reversal of anticoagulation using a prothrombin complex concentrate (PCC) that contains the vitamin K-dependent coagulation factors, II, VII, IX, and X. 9,10 In support of this recommendation, the INCH trial (International Normalized Ratio Normalization in Patients with Coumarin-Related Intracranial Hemorrhages) demonstrated that rapid warfarin reversal using a 4-factor PCC significantly reduced hematoma expansion compared with fresh frozen plasma.11 The DOACs now also have specific reversal agents: idarucizumab 12 for the factor IIa (thrombin) inhibitor dabigatran, and andexanet alfa 13 for the factor Xa inhibitors apixaban and rivaroxaban.Andexanet alfa is approved in the United States and Europe but is expensive and not available in many other countries.If a specific reversal agent is not available, guidelines recommend administration of a PCC or an activated PCC for patients treated with DOACs who develop life-threatening bleeding.9,10 Unlike idarucizumab and andexanet alfa, PCCs do not reverse the anticoagulant effect of DOACs but promote thrombin generation and thereby enhance hemostasis.It is unknown whether PCCs are effective and safe for the treatment of patients who develop ICH while taking a DOAC.In this issue of Circulation, Panos and colleagues 14 present outcomes of 663 patients admitted to 1 of 26 stroke centers in the United States who received a PCC or activated PCC for treatment of ICH during apixaban or rivaroxaban therapy.Patients were eligible for inclusion if they underwent brain scan both at baseline and within 24 hours of treatment with a PCC or activated PCC.The majority (n=521 [78.6%]) were being anticoagulated for AF, the median Glasgow Coma Scale score at presentation was 14, and the median time to administration of a PCC was 2.6 hours after presentation.Hemostasis was defined as excellent if there was a 0% to 20% increase in hematoma size at follow-up imaging compared with baseline, and good if the increase was 20.1% to 35%.In the efficacy analysis,
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.014 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.003 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.025 | 0.014 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".