Splenic Conditions Causing Iron Deficiency and Intermittent Pain
The primary splenic condition that causes both iron deficiency and intermittent pain is hereditary spherocytosis (HS), particularly in non-splenectomized patients who develop relative iron deficiency from chronic hemolysis and expanded erythropoiesis, with pain episodes occurring from splenic infarction or acute splenic sequestration.
Primary Splenic Condition: Hereditary Spherocytosis
Iron Deficiency Mechanism in HS
- Non-splenectomized HS patients develop relative iron deficiency due to expansion of erythropoiesis caused by chronic anemia, with elevated zinc protoporphyrin (ZnPP) levels inversely correlating with hemoglobin concentration, MCV, MCHC, and transferrin saturation 1.
- The iron deficiency in HS is functional rather than absolute—iron stores may be adequate, but iron availability for erythropoiesis is insufficient due to the increased demand from chronic hemolysis 1.
- Splenectomized HS patients typically do not have iron deficiency and actually show higher serum iron, transferrin saturation, and ferritin levels than normal controls 1.
Pain Mechanisms in HS
- Splenic infarction is a recognized complication of HS that presents with severe left upper quadrant pain, particularly when triggered by acute infections like Epstein-Barr virus (infectious mononucleosis) 2, 3.
- The mechanism of splenic infarction in HS involves insufficient blood flow to oxygenate the entire spleen during acute splenic enlargement, without evidence of thrombosis or arterial occlusion 2.
- Acute splenic sequestration can occur in HS, causing sudden splenic enlargement with pain, worsening anemia, and pallor 4.
Sickle Cell Disease with Splenic Involvement
Iron Deficiency in SCD
- Iron deficiency can occur in sickle cell disease but is NOT improved with iron supplementation unless biochemically proven, as medicinal iron carries risk of lifetime iron overload from repeated transfusions 4.
- Pica is common in SCD but is not related to iron status 4.
Pain Mechanisms in SCD
- Acute splenic sequestration crisis presents with sudden splenic enlargement, severe anemia, and left upper quadrant pain, representing a life-threatening complication requiring urgent evaluation 4.
- Chronic splenomegaly may develop and require splenectomy 4.
- Transient aplastic crisis from parvovirus B19 infection causes exacerbation of baseline anemia with substantially decreased reticulocyte count 4.
Diagnostic Approach
Confirming Iron Deficiency
- In the absence of inflammation, serum ferritin <30 μg/L is diagnostic of iron deficiency, while transferrin saturation <16% supports the diagnosis 5, 6.
- With chronic inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 5, 6, 7.
- In HS specifically, elevated red cell ZnPP concentrations indicate relative iron deficiency even when standard iron studies appear normal 1.
Evaluating Splenic Pain
- Left upper quadrant pain requires imaging with ultrasound or CT scan to identify splenic infarction, which appears as wedge-shaped hypodense areas 2, 3, 8.
- Splenic infarction typically presents with left upper quadrant pain, fever, and may show leukocytosis (49%), anemia (53%), or thrombocytosis (7%) 8.
- Liver-spleen scans are diagnostic in 90% of splenic infarction cases, while CT identifies the infarct in 75% 8.
Critical Clinical Pitfalls
Avoid Inappropriate Iron Supplementation
- Do not give iron supplementation in sickle cell disease unless iron deficiency is biochemically proven, as this increases risk of iron overload 4.
- In HS, address the underlying hemolysis rather than simply supplementing iron, as the deficiency is relative and functional 1.
Recognize Infection Triggers
- Acute infectious mononucleosis (EBV) is a known trigger for splenic infarction in HS patients, requiring heightened vigilance for this complication during viral illnesses 2, 3.
- Parvovirus B19 infection causes transient aplastic crisis in SCD with worsening anemia and requires isolation from at-risk individuals 4.