Efficacy and safety of Prothrombin Complex Concentrates Weight-Based Dosing for Reversal of Warfarin Anticoagulation
Bibliographic record
Abstract
Abstract Background: Prothrombin complex concentrates (PCCs) are widely used for correcting elevated international normalized ratio (INR) levels in patients anticoagulated with warfarin requiring an urgent reversal. However, the optimal dosing regimen has yet to be defined. In 2008, the Canadian National Advisory Committee (NAC) on blood product utilization recommended a single dose of 1000 IU for all adults over 18 years of age, irrespective of INR levels, and suggested further consultation with a Hematologist if extremes in weight or INR were observed. A revision in 2011, suggested dosing based on the INR elevation as an option and in 2014 the recommendation was updated to include a possible algorithm including both INR and weight. Currently there is insufficient evidence to suggest that one approach is more efficacious than another. Our institution has been using a novel weight-based dosing protocol for PCCs since 2009, which dispenses to a maximum of 3000 IU for adults weighing over 100kg. Herein, we sought to determine the efficacy of our weight-based dosing nomogram. Methods: We conducted a retrospective cohort study of all consecutive adult patients (age > 18 years) who received PCCs using our weight based dosing regimen between April 30, 2009 and December 31, 2010. All patients were anticoagulated with warfarin. Clinical and laboratory information was obtained through chart review. The weight based regimen consisted of 1000 IU for weight less than 40kg, 1500IU for 41 to 60kg, 2000 IU for 61 to 80kg, 2500 IU for 81 to 100kg, and 3000 IU for > 100kg. Doses of PCCs were based on the concentration of factor IX. PCCs utilized at this centre were Octaplex and Beriplex. The primary outcome was reversal of warfarin anticoagulation, as defined by an INR of 1.5 or less to achieve a clinical response within 6 hours. Statistical analysis was done using descriptive statistics and chi squared analysis. Results: A total of 227 charts were included in the study from April 30, 2009 to December 31, 2010. The median age was 74 years old (range 40-95), the median weight was 76kg (range 44-200), and 56% of patients were male. Medical indications for warfarin anticoagulation included atrial fibrillation (68%), DVT (32%) and stroke (21%). The most common indication for PCCs was active bleeding (44%: 13% intracranial, 12% gastrointestinal, 4% trauma, 15% other), reversal for a procedure (22%) and reversal for surgery (30%). Prior to receiving PCCs, 29% of patients were taking Aspirin and 4% were taking Clopidogrel. The percentages of patients treated with each dose were: 1000IU (1.3%), 1500IU (17.6%), 2000IU (41.0%), 2500IU (24.2%), 3000IU (15.9%). A second dose of PCC was given to 0.4% of patients. FFP was given to 7% of patients prior to PCCs administration and 14% of patients post PCCs administration. 63% of patients received vitamin K. Seventy-nine percent of patients achieved an INR of 1.5 or less within 6 hours of PCC administration. There was a statistically significant difference in response based on pre-PCC INRs (see table 1). The median baseline INR was 2.9 (range 1.5- >10) and decreased to a median of 1.3 (range 1.0-3.7) post-PCCs administration. Planned procedures were completed in 93% of 60 patients, and planned surgeries were completed in 94% of 70 patients within 24 hours of receiving PCCs. Four patients (2%) developed a deep vein thrombosis within 30 days of receiving PCCs. Conclusion: Our study demonstrates that weight based dosing is effective in reversal of anticoagulation in patients on warfarin. Laboratory response rates are similar to other studies (Wozniak et al). Although the majority of patients in our study (99%) received doses over 1000IU; rates of thrombosis are low. Future studies comparing different strategies are needed. Table 1 INR rangePre-PCC Proportion with Post-PCC INR of 1.5 or less (%) P-value 1.5-3 110/122 (90%) 3.1-4.5 33/43 (77%) 0.037* >4.5 35/62 (56%) <0.001** *1.5-3 vs 3.1-4.5 **1.5-3 vs >4.5 Disclosures Lazo-Langner: Pfizer Bayer LEO Pharma: Honoraria. Chin-Yee:Alexion Pharmaceuticals: Research Funding.
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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 | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".