Monitoring coagulation factors during surgery. A systematic review
Farmacia Hospitalaria : Organo Oficial De Expresion Cientifica De La Sociedad Espanola De Farmacia Hospitalaria. 2021;45(7):94-101
OBJECTIVE The management of surgeries in patients with hemophilia is complex and requires adequate clotting factor adjustment to avoid bleeding complications and excessive factor consumption. The aim of this systematic review is to analyze the pharmacokinetic studies published on surgery in hemophilic patients, the methodologies used, the main pharmacokinetic covariates applied, and the recommendations made by clinical guidelines. METHOD A structured search was performed in Pubmed, the Cochrane Library, and the Database of Abstracts of Reviews of Effects using the search terms hemophilia (or haemophilia), surgery and pharmacokinetics (or PK). No date or language limits were established. Results: The search yielded 186 results, from which 34 articles were selected. Many of these analyzed the use of continuous infusions with the aim of achieving stable factor VIII or IX levels and reducing overall factor consumption. However, continuous infusions have fallen into disuse. For decades, clinical guidelines have recommended the performance of comprehensive pharmacokinetic studies prior to surgery (9-11 samples). The clearance rate obtained is used to adjust the presurgical factor dose (or the infusion rate in case of continuous perfusion). Another approach is the use of population pharmacokinetic models, which allow adjustments to be made based on a more limited number of samples. However, the validity of these presurgical pharmacokinetic estimates ceases as soon as the surgical procedure is initiated, making it necessary to adjust the dose based on periodic peak and trough levels. In addition, depending on the type of surgery, clinical guidelines recommend maintaining factor VIII and IX levels above specific thresholds for certain periods of time, which makes it essential to use pharmacokinetics during the pre- and post-surgical process. In recent years, specific factor VIII and factor IX pharmacokinetic population models have been developed for surgery. The main covariates of these population pharmacokinetic models are age, blood type, and type of surgery for factor VIII; and age and body weight for factor IX. CONCLUSIONS Pharmacokinetic estimation could allow individual and standardized intraoperative dose adjustments to be conducted in patients with hemophilia. The development of specific population pharmacokinetic models for surgery, including those based on extended half- life factors, will allow an optimization of current treatments, potentially reducing factor consumption and hospital stays.