Platelet reactivity and platelet count in women with iron deficiency treated with intravenous iron

Abstract

Background Iron deficiency anemia (IDA) and heavy menstrual bleeding are prevalent, interrelated issues impacting over 300 million premenopausal women worldwide. IDA is generally associated with increased platelet counts; however, the effects of IDA and its correction on platelet function in premenopausal women remain unknown. Objectives We sought to determine how IDA and intravenous iron affect platelet count and platelet function in premenopausal women. Methods Hematologic indices were assessed in a multicenter, retrospective cohort of 231 women repleted with intravenous iron. Pre‐ and postinfusion blood samples were then obtained from a prospective cohort of 13 women to analyze the effect of intravenous iron on hematologic parameters as well as platelet function with flow cytometry and platelet aggregation assays under physiologic shear. Results Following iron replacement, anemia improved, and mean platelet counts decreased by 26.5 and 16.0 K/mm3 in the retrospective and prospective cohorts, respectively. Replacement reduced baseline platelet surface P‐selectin levels while enhancing platelet secretory responses to agonists, including collagen‐related peptide and ADP. Platelet adhesion and aggregation on collagen under physiologic shear also significantly increased following repletion. Conclusion We find that intravenous iron improves anemia while restoring platelet counts and platelet secretory responses in premenopausal women with iron deficiency. Our results suggest that iron deficiency as well as iron replacement can have a range of effects on platelet production and function. Consequently, platelet reactivity profiles should be further examined in women and other groups with IDA where replacement offers a promising means to improve anemia as well as quality of life.

Estimated Intake of Potassium, Phosphorus and Zinc with the Daily Diet Negatively Correlates with ADP-Dependent Whole Blood Platelet Aggregation in Older Subjects

“…Iron has been rarely associated with the function of mature platelets, and there is a striking scarcity of literature on any relationships between iron and blood platelet reactivity [60][61][62]. However, on the other hand, iron is known to play an important role in megakaryocyte differentiation in the bone marrow [60].…”

Cow's Milk Anemia in Childhood Manifesting as Severe Cerebral Venous Sinus Thrombosis

“…18 A study in premenopausal women showed the opposite effect, with lower platelet reactivity and adhesion under flow while iron deficient compared with the iron replete state. 19 Iron deficiency causes defects in the red cell membrane and decreased red cell deformability, which leads to abberant shear stress and vascular damage, which could also be an important contributor to thrombosis risk. 20 Patients in our study also had hypoalbuminemia at presentation, which could be due to protein loss in the gastrointestinal tract because of subclinical enterocolitis associated with cow's milk.…”

“…18 A study in premenopausal women showed the opposite effect, with lower platelet reactivity and adhesion under flow while iron deficient compared with the iron replete state. 19 Iron deficiency causes defects in the red cell membrane and decreased red cell deformability, which leads to abberant shear stress and vascular damage, which could also be an important contributor to thrombosis risk. 20…”

Role of single-dose intravenous iron therapy for the treatment of anaemia after orthopaedic trauma: protocol for a pilot randomised controlled trial

“…Preliminary findings demonstrated (1) intravenous iron repletion decreases platelet count in iron deficiency, (2) iron repletion significantly increases platelet integrin activation and alpha-granule secretion in response to adenosine di-phosphate (ADP) and collagen-related peptide and (3) platelet adhesion to type-1 collagen is enhanced after IVIT. 22 This suggests that iron is vital for optimal platelet function and haemostasis. We seek to understand that the alterations IVIT has on similar platelet profiles in injured patients, which has not previously been studied.…”

“…Recent work by our multidisciplinary team has identified several clinically relevant physiologic changes of platelets in iron-deficient premenopausal women which are reversed with IVIT. Preliminary findings demonstrated (1) intravenous iron repletion decreases platelet count in iron deficiency, (2) iron repletion significantly increases platelet integrin activation and alpha-granule secretion in response to adenosine di-phosphate (ADP) and collagen-related peptide and (3) platelet adhesion to type-1 collagen is enhanced after IVIT 22. This suggests that iron is vital for optimal platelet function and haemostasis.…”