Evaluating and Correcting Iron Deficit in Atypical Hemolytic Uremic Syndrome (HUS)
Authors: Reynolds Samuel B , Tse William 
Published: October 2019

Introduction:

Atypical hemolytic uremic syndrome (HUS), in the absence of Shiga toxin producing E. coli, is most often complement mediated and is associated with microangiopathic hemolytic anemia (MAHA). And while this association is well understood, it is less common to encounter concurrent pre-existing iron deficiency anemia. In such patients, apart from correcting anemia with supportive blood transfusions, the calculation and correction of iron deficit is a valuable but underutilized management strategy, and is highlighted in the presented case.

Example case:

A 33 year-old Hispanic female with no significant past medical history other than iron deficiency anemia with a baseline hemoglobin of 5.4 g/dL presented to the hospital for abnormal renal function seen on outside laboratory studies. She was found on admission to have a creatinine of 15.47, BUN of 94 (baselines unknown), LDH of 451, haptoglobin of 44, hemoglobin of 6.9 (MCV 87) and platelets of 107 x 10³/µL. Vital signs were stable. Peripheral smear revealed approximately 1 schistocyte/hpf. She complained of a recent but resolving upper respiratory infection and a 10 day history of new-onset blurry vision; she self-identified as a Jehovah's Witness. The patient was tentatively diagnosed with atypical HUS in light of MAHA, Cr >1.5, platelets>30 with only occasional schistocytes and no antecedent diarrheal illness. To definitely rule out pre-existing intrinsic renal disease and/or IgA nephropathy, however, the patient required a kidney biopsy, but was unable to undergo the procedure because of her anemia, thrombocytopenia and refusal to receive whole blood if needed. The patient's desired hemoglobin in order to undergo biopsy was set at 10 g/dL, and iron deficit was calculated as 677 mg. The patient was administered intravenous iron sucrose along accordingly along with epoetin, which resulted in gradual improvement in anemia during hospitalization. Decision to biopsy was deferred to her outpatient care provider.

Discussion:

Atypical HUS responds best to supportive care with blood transfusions and dialysis, if accompanying symptomatic uremia is present. Definitive therapy is with eculizumab. Patients who will not receive blood for religious purposes, however, present a challenge to providers in the acute setting of HUS, as gradual hemolysis can result in tissue hypoxia, hemodynamic instability and even death. Should patients have concurrent iron deficiency, however, even in the setting of active hemolysis, replacing iron can result in meaningful hemoglobin recovery. Iron deficit is calculated by the following equation: Body weight (in kg) x [target Hb - actual Hb] + depot iron (which is 500 mg if patient >35 kg).

Iron deficit as a clinical tool is seldom discussed in the literature, with a particular paucity in studies pertaining to atypical HUS. One potential explanation for this absence is that atypical HUS is an already rare diagnosis, and is a disorder of peripheral red blood cell destruction rather than a disorder of decreased hemoglobin-to-oxygen binding, as is seen in iron deficiency. Regardless, the utility of iron replacement is evident in the presented case of atypical HUS, and should be explored further in larger scale retro- and prospective studies.

Conclusions:

While disease-directed therapy in atypical HUS (i.e. eculizumab) is required to effectively manage acute, complement-mediated hemolytic anemia and renal failure, correction of the calculated iron deficit in co-existing iron deficiency anemia, if present, can result in gradual but marked improvement in hemoglobin. Conversely, patients with atypical HUS who are actively hemolyzing with a normocytic anemia should still be evaluated for iron deficiency and undergo iron transfusions for any calculated deficit.

Disclosures

No relevant conflicts of interest to declare.