From the Guidelines
Iron deficiency causes thrombocytosis through altered thrombopoiesis regulation, and addressing the underlying iron deficiency is crucial to normalize platelet counts. The exact mechanisms are multifaceted, involving the disruption of normal feedback mechanisms that control platelet production due to the lack of sufficient iron 1. When the body is iron deficient, it reduces the production of thrombopoietin inhibitors, leading to increased thrombopoietin activity and enhanced platelet production in the bone marrow.
Some key points to consider in the relationship between iron deficiency and thrombocytosis include:
- Iron deficiency may cause elevated levels of erythropoietin, which can cross-stimulate megakaryocyte production, further contributing to increased platelet counts.
- The hypoxic state resulting from anemia may trigger compensatory mechanisms that increase platelet counts as a response to the perceived lack of oxygen delivery to tissues.
- Iron plays a role in regulating inflammatory cytokines; its deficiency can alter cytokine profiles, particularly interleukin-6, which stimulates thrombopoiesis 1.
Given the potential for underlying gastrointestinal pathologies, such as malignancies, to cause iron deficiency anaemia, as highlighted in the British Society of Gastroenterology guidelines 1, it is essential to investigate the cause of iron deficiency thoroughly. Treatment of iron deficiency anaemia, as recommended, involves iron replacement therapy (IRT) using oral or intravenous routes 1. As iron stores are replenished, platelet counts typically normalize within weeks to months, confirming the causal relationship between iron deficiency and reactive thrombocytosis.
From the Research
Mechanisms of Iron Deficiency-Induced Thrombocytosis
- Iron deficiency is often associated with reactive thrombocytosis, which can lead to an increased thromboembolic risk in both arterial and venous systems 2.
- One mechanism thought to mediate iron deficiency-induced thrombocytosis is increased erythropoietin production 3.
- Erythropoietic stimulating agents (ESA) have long been known to increase platelet number and frequently lead to functional or absolute iron deficiency, which may be the mechanism whereby ESA increase the platelet count 3.
Clinical Consequences of Iron Deficiency-Induced Thrombocytosis
- Elevated platelet counts, especially in the setting of iron deficiency, can lead to an increased thromboembolic risk in both arterial and venous systems 2.
- Thrombocytosis is common in iron deficiency and resolves following iron repletion 3.
- The rate of thrombosis was calculated to be 7.8% in patients with IDA and 15.8% in patients with IDA and thrombocytosis, indicating a 2-fold thrombosis risk in patients with IDA and thrombocytosis compared with patients with IDA alone 4.
Treatment and Prevention of Iron Deficiency-Induced Thrombocytosis
- Iron replacement therapy can become an effective preventive strategy in a variety of clinical settings 2.
- Co-administration of iron should prevent or diminish ESA-driven thrombocytosis 3.
- Data from the DRIVE trial in hemodialysis patients suggest that IV iron administration can decrease platelet counts in patients receiving ESA 3.