Chronic Fatigue: Unveiling Pancytopenia and Hemolysis Causes

Abstract

Case description

A 33-year-old woman with a history of anemia presented with fatigue, 61 lbs unintentional weight loss, shortness of breath on exertion over the last few months. She denied heavy menses, bleeding, fever, night sweats, pain in her chest, abdomen, or joints. There was no anemia workup or recent labs. She denied family history of malignancy or autoimmune diseases. Physical exam revealed conjunctival pallor, bruising and splenomegaly. Labs showed pancytopenia (WBC 6.8 g/dl, HGB 3.6 g/dl, HCT 12.5 g/dl, Plt 75 × 10e3/mcL, MCV 100 fL.) There was evidence of hemolysis: T bili 2.8 mg/dL (indirect 2.4 mg/dL), undetectable haptoglobin, and LDH 4893 u/L. B12 was undetectable and normal folic acid. Peripheral smear (post transfusion) had dacrocytes, schistocytes, anisocytosis with no blasts. Infectious workups including HIV, parvovirus, EBV, CMV, Hepatitis A, B and C were negative. Pan-CT revealed marked splenomegaly with no lymphadenopathy. Hematology was consulted; bone marrow biopsy showed hypercellular marrow with progressive trilineage hematopoiesis and decreased megakaryocytes with no signs of dysplasia or lymphoma, suggesting pernicious anemia (PA). Intrinsic factor antibodies were positive. Patient received B12 injections with a plan to follow up with hematology outpatient.

Discussion

PA is a form of megaloblastic anemia caused by vitamin B12 deficiency due to the destruction of gastric parietal cells leading to intrinsic factor deficiency.1 Hematologic abnormalities were reported in at least two thirds of PA patients; however, pancytopenia and hemolysis in this patient are only seen in 5% and 1.5% of cases, respectively.2,3 This case demonstrates an unusual presentation of PA and highlights the importance of recognizing its varied and often subtle manifestations. Untreated PA can lead to severe and potentially irreversible complications including peripheral neuropathy, subacute combined degeneration of the spinal cord, and cognitive disturbances. PA is also considered a precursor to neoplastic lesions with a 2.84 fold higher risk of developing gastric carcinoma compared to individuals without PA.4,5 Severe cases of B12 deficiency can lead to ineffective hematopoiesis and intramedullary hemolysis, mimicking thrombotic microangiopathy. In those cases, failure to recognize B12 deficiency as the cause has lead to treatment with more aggressive and sometimes unnecessary measures such as steroids, polyvalent immunoglobulins and plasmapheresis.3 Treatment involves high-dose oral or parenteral B12 supplementation, which can lead to rapid hematologic improvement and eventual resolution of neurological symptoms if treated early.6 Regular monitoring of B12 levels and clinical symptoms is essential to ensure adequate management and prevent relapse.

Conclusion

Pancytopenia and hemolysis may be some of the unusual presentations of PA; early recognition and treatment can lead to resolution of symptoms and prevention of chronic neurological sequelae.