What causes elevated mean platelet volume (MPV) in a patient with iron deficiency anemia?

Elevated MPV: Causes and Clinical Significance

Direct Answer

Elevated mean platelet volume (MPV) in iron deficiency anemia is paradoxically common and reflects compensatory bone marrow production of larger, younger platelets in response to increased platelet turnover or reactive thrombocytosis. 1

Primary Causes of Elevated MPV

In Iron Deficiency Anemia Specifically

• Iron deficiency itself directly causes elevated MPV, with research demonstrating that 15 patients with high MPV and normal platelet counts included 12 with heterozygous thalassemia and 3 with iron deficiency 1
• When iron deficiency presents with thrombocytosis (platelet count >450 × 10⁹/L), MPV is typically elevated, representing younger, larger platelets released from the bone marrow 1
• The mechanism involves decreased iron saturation stimulating megakaryopoiesis, with platelet counts inversely correlating with iron saturation levels (p<0.001) 2
• Iron may have an inhibitory effect on platelet production, so when iron stores are depleted, this inhibition is removed, leading to increased platelet production with larger cell size 2

General Causes of Elevated MPV

Hyperdestructive/consumptive conditions:

• All 11 patients with high MPV and low platelet count had hyperdestructive causes (immune thrombocytopenia, disseminated intravascular coagulation, etc.) 1
• Larger platelets indicate increased bone marrow production to compensate for peripheral destruction 1

Myeloproliferative disorders:

• Seven patients with high MPV and high platelet count had causes including myeloproliferative disorders, inflammation, iron deficiency, and splenectomy 1
• High MPV appears correlated with myeloproliferative disease or thalassemia 1

Cardiovascular risk states:

• MPV is increased in obesity, diabetes mellitus, metabolic syndrome, acute myocardial infarction, and stroke 3
• Growth factors and cytokines elicit production of larger, more reactive platelets in conditions causing endothelial dysfunction 3
• Large platelets are more reactive, with elevated MPV associated with shortened bleeding time and increased thromboxane B2 levels 3

Clinical Interpretation Algorithm

When you encounter elevated MPV, follow this diagnostic approach:

1. Check the platelet count simultaneously 1:

   • High MPV + Low platelets → Hyperdestructive process (ITP, DIC, hypersplenism)
   • High MPV + Normal platelets → Iron deficiency, thalassemia trait, or early myeloproliferative disorder
   • High MPV + High platelets → Myeloproliferative disorder, reactive thrombocytosis from inflammation/infection, iron deficiency, or post-splenectomy

2. Assess iron status with ferritin and transferrin saturation 4:

   • Ferritin <30 μg/L (or <100 μg/L with inflammation) confirms iron deficiency
   • Transferrin saturation <16-20% supports iron deficiency
   • Iron saturation is the most important factor affecting platelet parameters in iron deficiency 2

3. Evaluate for thalassemia if appropriate 1:

   • Twelve of 15 patients with high MPV and normal platelet count had heterozygous thalassemia 1
   • Check MCV, MCH, and consider hemoglobin electrophoresis in appropriate ethnic backgrounds

4. Consider myeloproliferative workup if indicated 1:

   • JAK2 mutation testing
   • Bone marrow biopsy if clinical suspicion high

Important Caveats and Pitfalls

Do not assume normal platelet function with elevated MPV in iron deficiency:

• Collagen-induced platelet aggregation is actually decreased in iron deficiency anemia despite elevated MPV 5
• ADP-induced aggregation is also decreased by whole blood impedance methods 5
• The increased platelet numbers may compensate for decreased individual platelet function 5

Do not rely on thrombopoietic cytokines to explain thrombocytosis:

• Thrombopoietin, interleukin-6, interleukin-11, and leukemia inhibitory factor levels do not change significantly in iron deficiency with thrombocytosis 6
• Only erythropoietin (EPO) levels correlate with platelet counts, suggesting possible cross-reactivity at the megakaryocyte level 6

Recognize inappropriately low MPV as a distinct finding:

• Low MPV with any platelet count indicates sepsis, splenomegaly, aplastic anemia, chronic renal failure, or myelosuppressive drug therapy 1
• This represents impaired megakaryocytopoiesis rather than reactive changes 1

Prognostic Significance

MPV has cardiovascular prognostic value beyond hematologic assessment:

• MPV is predictive of stroke, acute myocardial infarction, and restenosis after coronary angioplasty 3
• MPV has prognostic significance in patients with established stroke and myocardial infarction 3
• When assessing complete blood count, MPV should not be undervalued, as its increase should prompt cardiovascular risk assessment 3