Menstrual blood loss is an independent determinant of hemoglobin and ferritin levels in premenopausal blood donors

Abstract

Introduction: To prevent blood donors from developing iron deficiency (ferritin <15 μg/L) and subsequent anemia (hemoglobin <120 g/L), blood services rely on information about known risk factors, including the donor's sex and age. For example, while Finnish women are able to donate whole blood with a minimum donation interval of 91 days, women in the 18 to 25-year-old age group are recommended to donate no more than once per year. Menstrual blood loss is not accounted for in blood donation interval recommendations, despite being a known risk factor of iron deficiency. We aim to investigate to what extent menstrual bleeding is associated with ferritin and hemoglobin levels in female blood donors, and quantify the association of other menstruation-related variables not currently accounted for by blood services (i.e., use of hormonal contraception, heavy menstrual bleeding) with iron deficiency or anemia.

Material and methods: The study population consisted of 473 premenopausal and 491 postmenopausal Dutch whole blood donors. Exclusion criteria were current pregnancy, BMI ≥50, ferritin ≥200, pictorial blood assessment chart (PBAC) ≥400, and age <18 or ≥70 years. Menstrual blood loss was quantified using a PBAC, a semiquantitative method to evaluate the number of used menstrual products and the degree of staining. We identified predictors of log(ferritin)/hemoglobin and iron deficiency/anemia using Bayesian linear and logistic regression models and quantified the average percentage of variance in log(ferritin) and hemoglobin explained by the covariates.

Results: Menstrual blood loss accounted for most of the explained variance in hemoglobin (8%) and second only to the number of days since last donation for ferritin (8%). Heavy menstrual bleeding (PBAC ≥150, OR = 3.56 [1.45-8.85], prevalence 13%) was associated with anemia, and use of levonorgestrel-releasing intrauterine device was negatively associated with iron deficiency (OR = 0.06 [0.01-0.44]). After statistical control for menstrual blood loss, age was not associated with iron status.

Conclusions: Menstrual blood loss and blood donation were the most important determinants of iron status in premenopausal women. Thus, results suggest that accounting for menstrual blood loss in donation interval guidelines may benefit blood donors.

Keywords: anemia; blood donor health; ferritin; heavy menstrual bleeding; hemoglobin; iron deficiency; menstruation; pictorial blood assessment chart.

FIGURE 1

Association of PBAC score to Hb and ferritin in premenopausal users and non‐users of hormonal contraception. Marginal histograms to the right show the number of hormonal contraception users and mean Hb/ferritin for the different types of use. The upper marginal histogram similarly describes hormonal contraception use and mean PBAC score among users and non‐users. The blue vertical line represents the cutoff for HMB. Anemia and ID cutoffs are represented by the red horizontal lines in the Hb and ferritin scatter plots, respectively. A simple linear regression line of Hb/ferritin explained by PBAC score is represented by the solid blue line. HMB, heavy menstrual bleeding; IUD, levonorgestrel‐releasing intrauterine device; PBAC, pictorial blood assessment chart.

FIGURE 2

Multivariate Bayesian linear regression coefficients for ferritin (A) and Hb (B). Black horizontal bars represent 95% credible intervals of estimates of standardized coefficients and the circles show the distribution medians. A 95% credible interval has a 95% probability to contain the actual coefficient, given the data. Filled circles highlight variables whose effect distributions do not contain 0 with at least 95% probability. As age was divided by 5 and PBAC score by 50, a unit increase corresponds to 5 kg and 50 points, respectively.

FIGURE 3

Relative importance analysis (RIA) of a linear model of ferritin (A) and Hb (B). RIA estimates the average percentage of variance in the outcome variable explained by each covariate. A positive value represents a positive correlation, and a negative value represents a negative correlation. The bootstrapped 95% CIs are characterized by the black lines.

FIGURE 4

Associations of menstruation‐related variables and donor characteristics on ID (A) and anemia (B). Models are Bayesian logistic regression models. Black horizontal bars represent 95% credible intervals of estimates of standardized coefficients and the circles show the distribution medians. A 95% credible interval has a 95% probability to contain the actual coefficient, given the data. Filled circles highlight variables whose effect distributions do not contain 1 with at least 95% probability. A unit increase is equivalent to a doubling of the number of days since last blood donation. A unit increase in age corresponds to 5 years.