Modelling haemoglobin incremental loss on chronic red blood cell transfusions

Abstract

Background and Objectives: Understanding the impact of red blood cell (RBC) lifespan, initial RBC removal, and transfusion intervals on patient haemoglobin (Hb) levels and total iron exposure is not accessible for chronic transfusion scenarios. This article introduces the first model to help clinicians optimize chronic transfusion intervals to minimize transfusion frequency.Materials and Methods: Hb levels and iron exposure from multiple transfusions were calculated from Weibull residual lifespan distributions, the fraction effete RBC removed within 24-h (X e ) and the nominal Hb increment. Two-unit transfusions of RBCs initiated at patient [Hb] = 7 g/dl were modelled for different RBC lifespans and transfusion intervals from 18 to 90 days, and X e from 0.1 to 0.5. Results:Increased X e requires shorter transfusion intervals to achieve steady-state[Hb] of 9 g/dl as follows: 30 days between transfusions at X e = 0.5, 36 days at X e = 0.4, 42 days at X e = 0.3, 48 days at X e = 0.2 and 54 days at X e = 0.1. The same transfusion interval/X e pairs result in a steady-state [Hb] = 8 g/dl when the RBC lifespan was halved. By reducing transfused RBC increment loss from 30% to 10%, annual transfusions were decreased by 22% with iron addition decreased by 24%.Acute dosing of iron occurs at the higher values of X e on the day after a transfusion event.Conclusion: Systematic trends in fractional Hb incremental loss X e have been modelled and have a significant and calculatable impact on transfusion intervals and associated introduction of iron.

Modeling hemoglobin levels of patients chronically transfused with red blood cells

“…The fully derived equation for performing a time dependent Hb calculation for a single transfusion is: 4 where is the Hb concentration (g/dL) at time t from a single transfusion event, and the ideal Hb incr is described above. X e is the fraction of effete RBCs removed from circulation within 24 h post‐transfusion, is the Weibull RBC lifespan distribution function, and Hb endo is the net Hb contribution from patient‐produced RBCs and their subsequent rate of elimination.…”

“…A baseline X e of 0.28 was calculated based on the literature value of a mean MDS patient volume and Hb mass‐adjusted 24 h‐Hb incr of 0.717 g/dL per unit RBC divided by the assumed ideal Hb incr of 1 g/dL per unit 10 . In the first publication introducing the HMB model, 4 Hb endo was implied to be 7 g/dL due to its designation in every calculation as the initial patient Hb baseline and threshold trigger for the patient's very first RBC transfusion. The patient data modeled in this analysis comes from ongoing, established chronic transfusion therapies, so the endogenous Hb level is not set at an arbitrary value but calculated using Equation 4.…”

“…The purpose of this paper is to evaluate a previously introduced model based on an overall Hb mass-balance (HMB) calculation from chronic RBC transfusions (HMB model). 4 The data from three separate, recently published studies were fit by the HMB model to demonstrate clinical relevance, provide new insights, identify model limitations, and direct next steps for model improvements.…”

“…Thus, there is a need to develop models for multiple transfusions, that account for initial 24 h post‐transfusion Hb losses, RBC lifespan, transfusion interval, and can quantify the most significant component processes that contribute to overall Hb mass balance in clinically relevant, chronically transfused patient populations. The purpose of this paper is to evaluate a previously introduced model based on an overall Hb mass‐balance (HMB) calculation from chronic RBC transfusions (HMB model) 4 . The data from three separate, recently published studies were fit by the HMB model to demonstrate clinical relevance, provide new insights, identify model limitations, and direct next steps for model improvements.…”