The prevalence and impact of iron deficiency and iron deficiency anemia in patients with mild-to-moderate bleeding disorders and bleeding disorder of unknown cause

Introduction Iron deficiency (ID) and iron-deficiency anemia (IDA) are common complications in patients with bleeding disorders. However, their prevalence and impact on the bleeding phenotype in patients with mild to moderate bleeding disorders (MBD) and especially bleeding disorder of unknown cause (BDUC) has not yet been conclusively investigated.

Method Patients from the Vienna Bleeding Biobank, a single-center prospective cohort study on patients with MBD were investigated and compared with healthy controls (HC). ID was defined as ferritin<30μg/L and/or transferrin-saturation≤15% without the presence of anemia [1]. ID combined with anemia, defined as hemoglobin<12g/dL for women and<13g/dL for men, was classified as IDA.

Results Characteristics of 646 MBD patients, including 432 patients with BDUC (66.9%), and 202 HC are reported in [Fig. 1]. Women made up the majority of both patients (83.5%) and HC (70%). MBD patients had significantly lower hemoglobin levels and prothrombin time than HC, as well as a longer aPTT, while ferritin and transferrin-saturation did not differ significantly.

Fig. 1 cohort characteristics and prevalence of ID and IDA. Bold p-values indicated significant differences; Abbreviations: BDUC – bleeding disorder of unknown cause. PFD – platelet function disorder. VWD – von Willbebrand-disease. CFD – coagulation factor deficiency. BMI – body mass index. MCV – mean corpuscular hemoglobin. MCH – mean corpuscular volume. aPTT – activated partial thromboplastin time. IQR – interquartile range. SEM=standard error of mean. IDA – iron deficiency anemia.

Overall, ID was more common in MBD patients than HC with 224 cases in patients (34.7%) and 57 cases in HC (28.2%), nevertheless not reaching statistical significance ([Fig. 1]). According to MBD diagnosis, ID was more frequent in patients with VWD (30/63, 47.6%, p=0.004) and BDUC (157/432, 36.3%, p=0.044) compared to HC, whereas ID occurred in a similar or even lower frequency in PFD (24.3%) and CFD (16.7%). There was no difference in the occurrence of IDA in all MBD patients or according to diagnoses compared to HC ([Fig. 1]).

In MBD patients, female sex and diagnosis of VWD correlated positively, while age and diagnosis of PFD correlated negatively with ID in univariate binary logistic regression analysis ([Fig. 2]). In multivariable analysis female sex, age, and VWD diagnosis prevailed as significant risk factors for ID, and BMI was also significantly associated with ID in MBD. Bleeding scores were not associated with ID in MBD patients in either uni- or multivariable binary logistic regression.

Fig. 2 Uni- and multivariable logistic regression models of risk factors for iron deficiency; Bold ORs are statistically significant. Abbreviations: OR – odds ratio. CI – confidence interval. BDUC – bleeding disorder of unknown cause. PFD – platelet function disorder. VWD –von Willbebrand-disease. CFD – coagulation factor deficiency. BMI – body mass index.

Conclusion Patients with MBD, especially with VWD and BDUC, show an increased risk for iron-deficiency but not IDA. Younger age, female sex and VWD diagnosis were identified as risk factors for ID. While a low iron storage does not seem to lead to more severe bleeding phenotypes, ID itself can present with significant comorbidities, both physical and mental, which the established questionnaires do not screen for [2].

 

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Conflict of Interest

The Vienna Bleeding Biobank is financed by CSL Behring with an unrestricted grant.

• References

• 1 Ning S, Zeller M.P.. Management of iron deficiency. Hematology Am Soc Hematol Educ Program 2019; 2019 (01) 315-322 2019000034
• 2 Percy L, Mansour D, Fraser I.. Iron deficiency and iron deficiency anaemia in women. Best Pract Res Clin Obstet Gynaecol 2017; 40: 55-67

Publication History

Article published online:
26 February 2024