Intravenous iron treatment reduces coagulability in patients with iron deficiency anaemia: a longitudinal study

Abstract

Summary Although many case reports and observational studies have reported a correlation between iron deficiency anaemia (IDA) and thrombotic events, the mechanism for this is poorly understood. To evaluate this, we examined the change in coagulability in patients receiving treatment for IDA. Adult patients with IDA were recruited for this study and treated with intravenous iron. The change in coagulability was assessed by thrombin generation using the calibrated automated thrombogram method. The change in factor VIII (FVIII) activity was later examined as a possible link. Forty‐eight participants received intravenous iron and were included in this study. After treatment with intravenous iron, endogenous thrombin potential and peak height decreased in IDA patients by a mean of 122·4 nmol/l/min (95% confidence interval [CI]: 17·9–227, P = 0·023) and 51·9 (95% CI: 26·6–77·2, P < 0·001) respectively. Time to peak (peak time) increased by a mean of 23·6 s (95% CI: 5·4–41·9, P = 0·012). FVIII activity was reduced by a mean of 9·6% (95% CI: 2·54–16·7, P = 0·009). In conclusion, treating IDA reduces the blood's coagulability, as evidenced by the change in thrombin generation and FVIII activity levels. No correlation was found between the degree of iron deficiency correction and thrombogram parameters.

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

“…For instance, in a large retrospective cohort study including 36 327 patients with IDA, thrombocytosis (defined in their study as a platelet count >450 × 10 9 /L) was present in 32.6% of these cases, 29 and rates of thrombotic events were high and appeared to be associated with thrombocytosis. Other recent studies have also noted an upregulation of coagulation factor enzyme activities in IDA that can resolve following iron replacement therapy 30 . These and other similar findings suggest that IDA promotes thrombocytosis as well as thrombosis in some contexts, despite a general loss of platelet hemostatic function.…”

“…Other recent studies have also noted an upregulation of coagulation factor enzyme activities in IDA that can resolve following iron replacement therapy. 30 These and other similar findings suggest that IDA promotes thrombocytosis as well as thrombosis in some contexts, despite a general loss of platelet hemostatic function. In this study, we find that platelet reactivity increases following iron repletion; however, it is not clear if platelet reactivity is low in IDA or enhanced beyond normal levels following iron repletion.…”

Risk stratification and management of women with cardiomyopathy/heart failure planning pregnancy or presenting during/after pregnancy: a position statement from the Heart Failure Association of the European Society of Cardiology Study Group on Peripartum Cardiomyopathy

“…[31][32][33] Depleted iron compromises erythropoiesis, but also triggers thrombosis, coagulopathy and thromboembolic events, compromises energy metabolism in foetal and maternal tissues, impairing the functioning of myocardium and other types of muscles. [31][32][33][34][35] The effects of oral and intravenous iron supplementation in this particular patient population are under investigation.…”

Iron deficiency-induced thrombocytosis increases thrombotic tendency in rats

“…Similar results were found in children, where IDA increased clot firmness on rotational thromboelastometry 32 . Another study using a thrombin generation assay also found a decrease in coagulability in response to iron replacement therapy 33 . This was likely due to an increase in the contribution of platelets to clot formation, which can also be seen in the increased platelet area on thrombus immunohistochemistry.…”