Monitoring coagulation factors during surgery. A systematic review.

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.