Current dosing practices for perioperative factor VIII concentrate treatment in mild haemophilia A patients result in FVIII levels above target

Abstract

Background In patients with haemophilia A (HA) perioperative dosing of factor VIII (FVIII) concentrate is based on body weight, historical FVIII level, in vivo recovery and FVIII level target values. In moderate and severe HA patients, this dosing regimen frequently leads to perioperative FVIII levels below and above target. This has not yet been evaluated in mild HA patients. Objectives To evaluate perioperative FVIII concentrate treatment in mild HA patients and to assess the frequency of FVIII levels below or above target. Patients/Methods This retrospective single‐centre study collected data from medical files of mild HA patients undergoing surgery and treated with FVIII concentrate. FVIII levels were compared to their target ranges and predictive factors for levels outside the target ranges were determined by logistic regression. Results Fifty surgeries performed in 34 patients were evaluated. Median age was 47 years and median historical FVIII level was 0.14 IU/mL. Preoperative peak FVIII level was above or below the target range in 80% and 6.7% of surgeries, respectively. Postoperatively, the percentages above and below target trough ranges were 55.8% and 12.8%. Patients with blood group 0 had the highest risk on the preoperative peak FVIII level being above target. In addition, patients who had a preoperative baseline FVIII level of >0.10 IU/mL higher than their historical FVIII level had a higher preoperative peak FVIII level than patients without this increase. Conclusions Dosing above FVIII target ranges with FVIII concentrates occurs frequently during perioperative treatment of mild HA patients. These results underline the necessity for better patient‐tailored treatment.

Pharmacodynamic monitoring of factor VIII replacement therapy in hemophilia A: Combining thrombin and plasmin generation

“…Our goal is to use our PD data to develop a uniform model to individualize FVIII replacement therapy based on PK/PD data for a range of FVIII products. A concomitant advantage of PD analysis is that factors influencing the hemostatic balance, such as operative stress and inflammation, are also taken into account, and thereby possibly reduce FVIII product need 41,42 . A prospective study to determine safety (ie, bleeding) and efficacy of such a regime would be highly fascinating.…”

Peri‐operative desmopressin combined with pharmacokinetic‐guided factor VIII concentrate in non‐severe haemophilia A patients

“…In a previous retrospective study in nonsevere haemophilia A patients treated with FVIII concentrate we have shown that only 12% of peri‐operative measurements of FVIII:C levels were within the physician's target range 13 . In the DAVID study, combination treatment resulted in a higher proportion of FVIII:C levels (31.5%) in the targeted range.…”

“…Continuous variables between three or more groups were compared by using a Friedman test. In order to assess the efficacy for the DAVID study of combination treatment in comparison to historical data 13 (proportion of 0.31 based on postoperative FVIII:C levels) with a power of 90% and alpha of 0.05, 25 procedures were needed. Noninferiority of the accuracy of the predicted peak range between both Little DAVID study arms was assessed by studying the difference of the deviation per arm as defined and explained in Supplementary 2.…”

“…11,12 Recent studies have shown that FVIII concentrate dosing based on body weight leads to postoperative FVIII:C trough levels above and below target ranges in a large proportion of patients. 13,14 This is clinically relevant as levels below targeted peak or trough level increase bleeding risk and levels above targeted peak levels might increase the risk of thrombosis. [15][16][17] Consequently, population pharmacokinetic (PK) models of both FVIII concentrate and desmopressin treatment have been developed to optimize dosing.…”

Case report: successful perioperative management of patients with haemophilia A using an extended half-life factor VIII (Efmoroctocog alfa) during neurosurgical procedures

“…3 According to a retrospective analysis of 50 surgeries in patients with HA, pre- and post-surgery FVIII levels were below the target range in 6.7% and 12.8% of patients, respectively. 7 In this study conventional FVIII products were administered. The use of rFVIIIFc in our patients resulted in stable activity levels above 80% during in hospital treatment.…”