Dear Editor,
Prothrombin factor concentrate (PCC; Octaplex®), a combination of human coagulation factors II, VII, IX and X, protein C and protein S, is a potent reversal agent for vitamin K antagonists. Along with Vitamin K, it is used in emergency management of bleeding associated with warfarin and direct oral anticoagulants (DOACs).1 Despite widespread use, there is a lack of consensus about optimal dosing,2 with current guidelines specifying large ranges for dosing or, in the case of DOACs, no dosing recommendations at all.3 Lack of clarity complicates development of clear local protocols, making accurate and timely administration more difficult, as highlighted by a serious adverse incident in which delayed administration led to a poor clinical outcome.4
This service evaluation aimed to assess current use of PCC in Belfast Health and Social Care Trust (BHSCT), to identify areas for improvement and improve alignment between local guidance and practice on-the-ground.
Two current BHSCT guidelines on management of bleeding while receiving anticoagulants provided audit standards. We sought records of all patients who received PCC within BHSCT between January and June 2016. We designed, piloted and adapted a pro-forma which was then used by Haemovigilance Specialist Nurses. Data were collated in Microsoft Excel and analysed using descriptive statistics to summarise patients’ baseline characteristics, PCC dosing, coagulation assay results and clinical outcomes.
Records were available for 62 of 98 eligible patients. Twenty-nine were female (47%). Ages ranged from 34-95 years, with a mean of 71 years. At time of PCC administration, 44 patients were receiving warfarin (71%), 8 apixaban (13%) and 6 rivaroxaban (10%). One patient was not receiving any anticoagulant (2%); information was unavailable for 3 patients (5%). Average dose of PCC was 1739 IU (range 714-4000 IU). Only 34/62 (55%) patients received doses involving use of whole (500IU) vials. Weight was recorded for 49 patients (79%) but prior to administration in only 18 cases (29%). 18/62 (29%) of weights were estimated rather than measured. Administration of PCC was associated with an average reduction in International Normalised Ratio (INR) of 2.13. The average INR after administration was 1.36. Twelve patients (28%) were deceased by 60 days after administration. Table 1 summarises other key findings.
Table 1.
Key findings
| Audit standard | Finding |
|---|---|
| Patients on warfarin should receive 15 IU/kg PCC if INR<4, 30IU/kg if INR>4 | Baseline INR <4: average dose 16.4 IU/kg (24 patients) Baseline INR >4: average dose 29.5IU/kg (9 patients) |
| Patients on DOACs should receive 40IU/kg PCC | Average dose in patients on apixaban or rivoroxiban (8 patients) 35.6 IU/kg |
| Patients on warfarin should receive 5mg IV Vitamin K in addition to PCC | Number of patients who received Vitamin K - 38 Dose of Vitamin K administered: 1mg - 1/38 (3%) 5mg - 31/38 (82%) 10mg - 6/38 (16%) No vitamin K administered - 10/48 |
| Patients on warfarin presenting with head injury should receive PCC prior to neuroimaging | Prior to neuroimaging - 1/14 (7%) After neuroimaging - 13/14 (93%) |
Most PCC dosing adhered to guidance, although many patients were not weighed prior to administration. Other areas of shortfall were identified, however. In patients with suspected intracranial bleeding, PCC was frequently administered after, rather than prior to, neuroimaging. Vitamin K was often inappropriately omitted during reversal of warfarin. We also found that it was common practice to use incomplete vials of PCC. While not precluded by current guidance, this practice could lead to PCC, at a cost of up to £21,560 per year, being discarded that could potentially improve clinical response if administered. Targeted quality improvement work is now needed to ensure that patients are weighed appropriately, PCC is given prior to neuroimaging in patients with head injury, and vitamin K is co-administered when reversing warfarin. Guidance should be updated to recommend that PCC doses involve use of complete vials. These interventions have the potential to maximise the efficacy and cost-effectiveness of PCC in the treatment of life-threatening haemorrhage.
Acknowledgements
We would like to thank the Haemovigilance Specialist Nurses for collecting the data used in this audit.
Funding
NI Haemophilia Centre supported the cost of data collection
UMJ is an open access publication of the Ulster Medical Society (http://www.ums.ac.uk).
REFERENCES
- 1.Rhoney DH, Chester KW, Darsey DA. Optimal dosage and administration practices for Vitamin K antagonist reversal with 4-Factor Prothrombin Complex Concentrate. Clin Appl Thromb. 2020;26:1–13. doi: 10.1177/1076029620947474. [DOI] [Google Scholar]
- 2.Khorsand N, Kooistra HA, Van Hest RM, Veeger NJ, Meijer K. A systematic review of prothrombin complex concentrate dosing strategies to reverse vitamin K antagonist therapy. Thromb Res. 2015;135(1):9–19. doi: 10.1016/j.thromres.2014.11.019. [DOI] [PubMed] [Google Scholar]
- 3.Makris M, Veen JJ, Tait CR, Mumford AD, Laffan M. British Committee for Standards in Haematology. Guideline on the management of bleeding in patients on antithrombotic agents. Br J Haematol. 2013;160(1):35–46. doi: 10.1111/bjh.12107. [DOI] [PubMed] [Google Scholar]
- 4.Belfast Health and Social Care Trust. Safety and quality learning letter: LL/SAI/2014/025 (AS): Head Injury in patients on Warfarin-treat as a medical emergency. Belfast: BHSCT; 2014. [Google Scholar]