Evidence-Based Minireview: For overweight or obese persons with hemophilia A, should factor VIII dosing be based on ideal or actual body weight?

Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m2), obese (30–39.9 kg/m2), and morbidly obese (⩾ 40 kg/m2). In this single-center, retrospective cohort study, patients were included if they ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours. Weight-based UFH doses were calculated using actual body weight. A total of 423 patients met the inclusion criteria, with 230 (54.4%), 146 (34.5%), and 47 (11.1%) patients in the non-obese, obese, and morbidly obese cohorts, respectively. Median times to therapeutic aPTT were 16.4, 16.6, and 17.1 hours in each cohort. Within 24 hours, the cumulative incidence rates for therapeutic aPTT were 70.7% for the non-obese group, 69.9% for the obese group, and 61.7% for the morbidly obese group (obese vs non-obese: HR = 1.02, 95% CI: 0.82–1.26, p = 0.88; morbidly obese vs non-obese: HR = 0.87, 95% CI: 0.62–1.21, p = 0.41). There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98). Based on our study, heparin dosing based on actual body weight without a dose cap is safe and effective.

Download Full-text

Ideal Body Weight May Be A Better Comparative Variable than Actual Body Weight for Donor-Recipient Matching in Orthotopic Heart Transplantation

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2018.01.1132 ◽

2018 ◽

Vol 37 (4) ◽

pp. S437

Author(s):

B. Hoemann ◽

M. Cevasco ◽

H. Takayama ◽

J. Han ◽

P. Kurlansky ◽

...

Keyword(s):

Body Weight ◽

Heart Transplantation ◽

Actual Body ◽

Ideal Body Weight ◽

Orthotopic Heart Transplantation ◽

Actual Body Weight ◽

Ideal Body

Download Full-text

The growth of lambs before and after birth in relation to the level of nutrition

The Journal of Agricultural Science ◽

10.1017/s0021859600006079 ◽

1948 ◽

Vol 38 (3) ◽

pp. 243-302 ◽

Cited By ~ 108

Author(s):

L. R. Wallace

Keyword(s):

Body Weight ◽

Actual Body ◽

Growth Curves ◽

Live Weight ◽

Constant Level ◽

Gravid Uterus ◽

Standard Diet ◽

Actual Body Weight ◽

Weight Growth ◽

Before And After

SUMMARYIn the investigation described, we have observed a t monthly intervals throughout gestation the changes taking place in a series of similar ewes, in lamb to the same ram, and each receiving the same standard diet.In following the live-weight growth curves of the ewes it was found that on a constant level of feeding the weight gains became greater during each succeeding month of pregnancy, and at corresponding stages were larger for ditocous than for monotocous ewes. This was found to be due to the fact that, although on our diet the ewes did gain slightly in actual body weight, the main increases in live weight resulted from the growth of the gravid uterus itself, and this increases in weight far more rapidly in the later stages of gestation, and is also heavier where twins are carried.

Download Full-text

Dosing and Pharmacokinetics of Polymyxin B in Patients with Renal Insufficiency

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01337-16 ◽

2016 ◽

Vol 61 (1) ◽

Cited By ~ 26

Author(s):

Visanu Thamlikitkul ◽

Yanina Dubrovskaya ◽

Pooja Manchandani ◽

Thundon Ngamprasertchai ◽

Adhiratha Boonyasiri ◽

...

Keyword(s):

Renal Function ◽

Body Weight ◽

Steady State ◽

Renal Insufficiency ◽

Actual Body ◽

Normal Renal Function ◽

Polymyxin B ◽

Poor Correlation ◽

Actual Body Weight ◽

Significant Difference

ABSTRACT Polymyxin B remains the last-line treatment option for multidrug-resistant Gram-negative bacterial infections. Current U.S. Food and Drug Administration-approved prescribing information recommends that polymyxin B dosing should be adjusted according to the patient's renal function, despite studies that have shown poor correlation between creatinine and polymyxin B clearance. The objective of the present study was to determine whether steady-state polymyxin B exposures in patients with normal renal function were different from those in patients with renal insufficiency. Nineteen adult patients who received intravenous polymyxin B (1.5 to 2.5 mg/kg [actual body weight] daily) were included. To measure polymyxin B concentrations, serial blood samples were obtained from each patient after receiving polymyxin B for at least 48 h. The primary outcome was polymyxin B exposure at steady state, as reflected by the area under the concentration-time curve (AUC) over 24 h. Five patients had normal renal function (estimated creatinine clearance [CLCR] ≥ 80 ml/min) at baseline, whereas 14 had renal insufficiency (CLCR < 80 ml/min). The mean AUC of polymyxin B ± the standard deviation in the normal renal function cohort was 63.5 ± 16.6 mg·h/liter compared to 56.0 ± 17.5 mg·h/liter in the renal insufficiency cohort (P = 0.42). Adjusting the AUC for the daily dose (in mg/kg of actual body weight) did not result in a significant difference (28.6 ± 7.0 mg·h/liter versus 29.7 ± 11.2 mg·h/liter, P = 0.80). Polymyxin B exposures in patients with normal and impaired renal function after receiving standard dosing of polymyxin B were comparable. Polymyxin B dosing adjustment in patients with renal insufficiency should be reexamined.

Download Full-text

Impact of Increased Body Weight on Acute Toxicity and Outcome of Autologous Stem Cell Transplantation for Non-Hodgkin’s Lymphoma: A Southwest Oncology Group Analysis.

Blood ◽

10.1182/blood.v104.11.352.352 ◽

2004 ◽

Vol 104 (11) ◽

pp. 352-352 ◽

Cited By ~ 3

Author(s):

Patrick Stiff ◽

Joseph Unger ◽

Stephen Forman ◽

Michael LeBlanc ◽

Thomas Miller ◽

...

Keyword(s):

Body Weight ◽

Stem Cell ◽

Actual Body ◽

Death Rate ◽

Skin Toxicity ◽

High Dose ◽

Cell Transplant ◽

Actual Body Weight ◽

Grade 5 ◽

Grade 3

Abstract Little is known about the optimal dosing of chemotherapy agents in patients significantly above their ideal body weight (IBW) who undergo high dose therapy with an autologous or allogeneic hematopoietic stem cell transplant. While dose attenuation is often advocated for overweight patients and appears to reduce acute toxicities, its effect on progression-free and overall survival (PFS/OS) is unknown. Due to a high relapse rate after autografts for relapsed/refractory NHL, SWOG has long investigated the use of augmented preparative regimens that utilize high-dose etoposide based on actual body weight (ABW) of 60 mg/kg, along with 12 Gy of TBI and cyclophosphamide (100 mg/kg) which is dosed on unadjusted IBW. We determined acute toxicities and PFS/OS using this approach in a recently completed study (S9438) of 358 patients undergoing autografts for relapsed/refractory NHL, comparing all grade 5 toxicities, grade 3–4 skin toxicities (known to be associated with high dose etoposide) and all other grade 4 toxicities in patients in this study based on % above IBW. The Devine formula for IBW with an adjustment for patients <5 feet was used. Patients at or below their IBW were dosed using their actual body weight. All patients received the preparative regimen as stated followed by autologous peripheral blood stem cells. Overall there were 31 patients with grade 5 toxicities. This group was a mean 42% above their IBW vs 24% for those surviving transplant (p=.001). Increasing % above IBW predicted grade 5 toxicity (p=.002). Even those at or 10% above their IBW had a higher toxic death rate (10.1 vs 3.6%; p=.04). While increasing weight above IBW did not predict for grade 4 lung, liver, cardiac toxicities or infections (p=.12), it did predict for grade 3/4 skin toxicities (p< .001). Skin toxicity, most commonly hand/foot syndrome was seen at rates up to 27.3% vs 7.3% for those ≥ 50 vs < 50% over IBW (p < .001). However, even those just ≥ 10% over IBW had nearly a 4 fold higher risk of skin toxicity (13.4 vs 3.6%; p=.005). While survival by % over IBW is confounded by comorbidities in overweight patients, we found no evidence of a different 2-year PFS or OS for overweight patients, even those ≥ 50% above IBW (PFS=42 vs 45%, p = .28; OS=52 vs 62%, p = .38). These multicenter trial data do establish a correlation of the ABW dosing of etoposide with significant skin toxicity. Without an apparent later PFS/OS benefit to the use of unadjusted etoposide dosing for overweight patients but higher acute skin toxicity and a higher early death rate, etoposide will be dosed using adjusted IBW [ IBW + .4 (ABW − IBW)] in subsequent studies of this regimen.

Download Full-text

Implications of Body Weight Calculations for Autologous Peripheral Blood Stem Cell Transplantation.

Blood ◽

10.1182/blood.v108.11.5445.5445 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5445-5445

Author(s):

Lijo Simpson ◽

Robert C. Wolfe ◽

Dennis A. Gastineau ◽

William J. Hogan ◽

Shaji Kumar

Keyword(s):

Body Weight ◽

Stem Cell ◽

Actual Body ◽

Stem Cell Transplant ◽

Ideal Body Weight ◽

The Body ◽

Cell Transplant ◽

Actual Body Weight ◽

Cell Dose ◽

Ideal Body

Abstract Background: Obesity is a prevalent health problem and significant heterogeneity is seen in the body weight and BMI among adult patients undergoing autologous stem cell transplantation (SCT). At least two critical steps of the SCT are influenced by the body weight. Stem cell collection targets are usually determined based on the actual body weight and conditioning chemotherapy doses are usually determined based on corrected ideal body weight. One could hypothesize that since the stem cells home to bone marrow, the ideal body weight (IBW) being based on the height may be a better indicator of the stem cell numbers required rather than the actual body weight (ABW). Since chemotherapy doses are calculated based on corrected ideal body weight, and the volume of distribution is higher in obese patients, these patients may have decreased drug exposure and hence a higher risk of progression. Methods: We retrospectively evaluated the engraftment kinetics and response outcome of 306 SCTs done at our institution between March 1998 and October 2001. These included patients who had undergone SCT for multiple myeloma (46%), NHL (34%), HD (6%) and AL amyloidosis (14%). Body weight, height, stem cell dose and engraftment data was obtained from medical records. The stem cell dose received was calculated based on their ABW as well as IBW and correlated with the time to white cell and platelet engraftment. We also evaluated the effect of BMI on the progression free survival after the stem cell transplant using various cut offs. Results: The mean (range) for the ABW, IBW and BMI were 46.6 kg to 189 Kg; 45.5 kg to 94 kg; and 17.5 to 55.8 respectively. Using logistic regression, we estimated the ability of CD34 cell dose by actual and ideal body weight to predict the likelihood of platelet engraftment (50,000) by day 21 post transplant. The coefficients using both the doses were very similar (.391 for ideal and 0.361 for actual). Using Receiver operating characteristic analysis (ROC analysis); we determined the stem cell dose cutoff that best predicted for failure to engraft neutrophils by 21 days post transplantation, median CD34 dose by ABW of 3.6 million/Kg and by IBW of 4.2 million/Kg. Similarly, for failure to engraft platelets by day 30 the cutoffs were 2.89 million/Kg by actual weight and 3.77 million/kg by ideal weight. Among the individuals with actual body weight more than 25% of ideal body weight (n=122, 40%), we calculated the optimal total CD34 dose required and compared to the actual dose infused using both the cutoff sets (286 million vs. 446 million, P < 0.001 using ANC cutoff and 251 million vs. 446 million using the platelet cutoff, P < 0.001). We then examined the effect of BMI on progression free and overall survival from transplant. The progression free and overall survival post transplant was similar for patients with BMI over 30 kg/m2 compared to those below this cutoff. There was no difference when patients with myeloma or lymphoma were studied separately. Conclusion: This study, as in previous studies, confirms that stem cell dose determined on the basis of ideal body weight is comparable to that by actual body weight in terms of engraftment kinetics. In patients significantly above the ideal body weight, it is reasonable to use a target based on ideal body weight which will allow for collection of less numbers of CD34 cells, thus conserving resources. Among patient undergoing stem cell transplant, the practice of using corrected ideal body weight does not appear to compromise the outcome of stem cell transplant.

Download Full-text