Dosing Factor in Pediatric and Adult Hemophilia Patients Using Ideal Body Weight Versus actual Body Weight

Background:

Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) are X-linked inherited bleeding disorders which cause recurrent bleeding into the joints leading to significant morbidity. The cornerstone of management is treatment of bleeding with infusions of factor concentrate.(Barnes et al 2013) Adoption of prophylactic treatment with regular factor infusions has dramatically improved life expectancy and quality of life in patients with hemophilia. (Manco-Johnson et al 2007)

Dosing of factor replacement therapy is currently based on actual body weight (AW). However, given the obesity epidemic in the United States and the high cost of factor replacement, should patients be dosed based on AW or is there a role for dosing factor based on ideal body weight (IBW). Nearly half of the patients in a demographic study of the United States hemophilia population were considered either overweight or obese based on their body mass index (BMI). (Curtis et al 2015) The average cost of patients receiving prophylaxis over a three-month period ranged from $50,000 to $150,000. Estimation of dosing based on IBW could cut these expenses by almost 50 percent, an annual savings of approximately $136,000.(Graham et al 2014)

Methods:

We began a retrospective review of patient recovery studies of factor VIII and factor IX at our center to determine the effect of factor dosing based on AW versus that based on IBW. Hemophilia patients with and without inhibitors and a minimum height of 60 inches were included in this analysis. Information collected included: height, weight, dose of factor infused and the 1 hour recovery. IBW was calculated using the formula of: 50kg + (2.3kg (Actual height in inches - 60 inches)) and BMI was calculated by: (weight in kg)/(height in meter)².

Recovery was calculated by comparing the incremental increase in the pre-infusion factor activity and the 1 hour post infusion activity. Data were analyzed to determine DOSE DISCREPANCY, which is the difference between the factor dose given based on AW and calculated factor dose based on IBW and FACTOR DISCREPANCY, which is the difference between rise in factor activity based on AW and predicted rise in factor activity based on IBW. Statistical evaluation using a student's t-test and regression analysis was applied to determine if there were any differences between Dose Discrepancy and Factor Discrepancy.

Results:

We examined our database of patients with bleeding disorders (n=314). Of these, only patients who were 60 inches or taller with hemophilia were included (n=40) so that IBW could be accurately calculated. This included 38 males and 2 females, age range of 13 to 70 years, and BMIs ranging between 16.9 and 42.1. Patients were then stratified by BMI comparing BMIs below 25 (normal, n =23) versus greater than 25 (overweight or obese, n=17).

Patients with a BMI below 25 had a high correlation between the Factor Discrepancy or Dose Discrepancy. Pearson correlation coefficient of 0.789 (p<0.05). However, in patients with BMIs above 25 there was no correlation between Dose Discrepancy and Factor Discrepancy. Pearson correlation coefficient of 0.240 (p=0.322). (see figure)

ANOVAb Analysis

Non Obese Population Obese Population

Conclusions:

These data suggest that IBW is an effective way to dose patients who are at a normal BMI of 25 or less but in patients who are overweight or obese (BMI >25) IBW does not provide a reliable method to predict post-infusion factor activities. The number of patients in our study with a BMI >25 was small and the range in BMI was quite large with BMIs up to 42.1. Studies of more patients who are overweight and obese will need to be studied and differences between overweight, obese and morbidly obese will need to be evaluated. Further, prospective studies are needed to determine factor dosing regimens for hemophilia patients who have a BMI over 25.

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