PCC – Hosp Pharm. 2013 Dec; 48(11): 951–957.
Use of PCC – 2014? PCC Dosing – year?
Comparison of 4-Factor Prothrombin Complex Concentrate With Frozen Plasma for Management of Hemorrhage During and After Cardiac Surgery A Randomized Pilot Trial. JAMA Netw Open. 2021;4(4):e213936.
A European consensus statement on the use of four-factor prothrombin complex concentrate for cardiac and non-cardiac surgical patients. Anaesthesia, 76: 381-392. https://doi.org/10.1111/anae.15181
- In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg-1. This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available.
- In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg-1) should be considered.
- A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy.
Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. The Lancet, Volume 385, Issue 9982, 2015, Pages 2077-2087,ISSN 0140-6736,https://doi.org/10.1016/S0140-6736(14)61685-8.
- In summary:
- For the endpoint of rapid INR reduction, the results from our trial are consistent with previously published (mainly observational) data and demonstrate that 4F-PCC is non-inferior and superior to plasma for rapid INR reduction in patients on VKA therapy.
- Furthermore, we noted that 4F-PCC could be given more rapidly than plasma, which is in agreement with previously published (retrospectively collected) data.24
- For the endpoint of clinical efficacy, we found no other adequately powered trial examining reversal of VKA therapy in patients needing urgent surgical procedures, and this trial therefore offers new insights into their treatment. We noted that 4F-PCC was superior to plasma for haemostatic efficacy.
- Although our study was not powered to assess safety, we did not detect any between-treatment differences for the occurrence of thromboembolic events or deaths, a finding in agreement with the existing scientific literature.11, 17, 25, 26 Additionally, although these data guide clinicians on how best to achieve urgent VKA reversal, the scientific literature concerning which patients should be urgently reversed before surgical or invasive interventions continues to evolve; for example, findings from a recent trial showed the safety of pacemaker placement without interruption of anticoagulation.29
Efficacy and safety of a four-factor prothrombin complex concentrate (4F-PCC) in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation, 128 (2013), pp. 1234-1243.
Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest, 133 (2008), pp. 160S-198S
- Among the key recommendations in this article are the following:
- For dosing of VKAs, we recommend the initiation of oral anticoagulation therapy, with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 1B); we suggest against pharmacogenetic-based dosing until randomized data indicate that it is beneficial (Grade 2C); and in elderly and other patient subgroups who are debilitated or malnourished, we recommend a starting dose of ≤ 5 mg (Grade 1C). The article also includes several specific recommendations for the management of patients with nontherapeutic INRs, with INRs above the therapeutic range, and with bleeding whether the INR is therapeutic or elevated.
- For the use of vitamin K to reverse a mildly elevated INR, we recommend oral rather than subcutaneous administration (Grade 1A).
- For patients with life-threatening bleeding or intracranial hemorrhage, we recommend the use of prothrombin complex concentrates or recombinant factor VIIa to immediately reverse the INR (Grade 1C).
- For most patients who have a lupus inhibitor, we recommend a therapeutic target INR of 2.5 (range, 2.0 to 3.0) [Grade 1A].
- We recommend that physicians who manage oral anticoagulation therapy do so in a systematic and coordinated fashion, incorporating patient education, systematic INR testing, tracking, follow-up, and good patient communication of results and dose adjustments [Grade 1B].
- In patients who are suitably selected and trained, patient self-testing or patient self-management of dosing are effective alternative treatment models that result in improved quality of anticoagulation management, with greater time in the therapeutic range and fewer adverse events. Patient self-monitoring or self-management, however, is a choice made by patients and physicians that depends on many factors. We suggest that such therapeutic management be implemented where suitable (Grade 2B).
Guideline-concordant administration of prothrombin complex concentrate and vitamin K is associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment (EPAHK study). Critical Care volume 18, Article number: R81 (2014).
- In patients on VKA therapy presenting with severe hemorrhage, international guidelines recommend, as soon as the diagnosis is confirmed, the administration of PCC (≥20 UI/kg) and vitamin K (≥5 mg) to normalize coagulation (post-reversal INR ≤1.5).
- A guideline-concordant administration dose of PCC and vitamin K administrated in the first eight hours was associated with a two-fold decrease in seven-day mortality overall and with a three-fold decrease in the ICH subgroup
- The guideline-concordant reversal was performed in 38% of the patients within eight hours after admission
- Whereas pre-reversal INR is not absolutely necessary, post-reversal INR is essential to evaluate treatment efficacy
- The post-reversal INR target must be performed systematically and immediately after PCC administration