Background: Autoimmune hemolytic anemia (AIHA) is a decompensated acquired hemolysis caused by host's immune system acting against its own red cell antigens. Serologically, it can be divided to warm hemolytic anemia, cold hemolytic anemia, paroxysmal cold hemoglobinuria and mixed AIHA. Pathogenesis of AIHA comprises of a series of complex interactions between genetics, environmental either conferring to protective or deteriorating effects. Among these, climatic changes appears to be key as it involves many triggers such as viral infections, temperature and other host factors. We reviewed a large national hospitalization database to determine whether rates of autoimmune hemolytic anemia have a seasonal variation over the past decade. Methods: We examined the Nationwide Inpatient Sample (NIS), a nationally representative survey of hospitalizations conducted by the Healthcare Cost and Utilization Project in collaboration with participating states. It is the largest all-payer inpatient dataset in the United States and includes a 20% sample of United States community hospitals that approximates 20% of all US community hospitals. The Nationwide Inpatient Sample (NIS) database was used to estimate annual number of hospitalizations from 2000 - 2012. Identification of autoimmune hemolytic anemia related hospitalizations was based on the designation of the prior validated International Classification of Diseases (9th Edition) Clinical Modification (ICD-9-CM) diagnosis code 283 as the principal discharge diagnosis. The frequency of hospitalization per month cumulative over 13 years was calculated and divided by number of days in that month to determine the mean hospitalizations per day for each month. All calculations were carried out using the weighted estimates approximating nationwide population estimates. Results: An estimated 48,416 hospitalizations with primary diagnosis of autoimmune hemolytic anemia occurred in the US from 2000 to 2012 as per NIS database. More specifically, the mean number of hospitalizations per day in each month is shown in Fig. 1. The mean number of hospitalizations each day was highest in November (141 per day) and thereafter the hospitalization rate dropped to a nadir in May (122 per day). There was a significant rising trend of admissions from June towards winter months with peaks in November as depicted in the Fig.1. In general, the number of hospitalization was maximum in the winter months and minimum in summer months as demonstrated in Fig.2. Conclusion: We identified for the first time in United States an impressive pattern of seasonal variation in hospitalizations for autoimmune hemolytic anemia with a notable increase in winter and fall and a significant drop during summer months. The seasonal pattern may reflect viral or other triggers for immune system activation. Further efforts need to be made to identify triggers and methods to determine the relationship of these variations and reduce this predictive burden on the overall health care system. Figure. Figure. Disclosures No relevant conflicts of interest to declare.
Alternative splicing is an epigenetic mechanism that plays a role in the development and function of antigen-specific lymphocytes. One such is the zinc-finger-RNA-binding-motif-and-serine/arginine-rich-2 (ZRSR2), which is clinically implicated in myelodysplastic syndrome and leukemia. Here, we present a case of a young male with myriad autoimmune conditions and adenocarcinoma of the colon in the setting of ZRSR2 mutation.A 28-year-old male with common variable immunodeficiency disease, atopic dermatitis, autoimmune gastroenteropathy, inflammatory polyarthropathy, primary bone marrow failure, colon cancer, and family history of Lynch syndrome was admitted to our hospital for an acute flare of autoimmune enteropathy secondary to subtherapeutic tacrolimus levels.He initially developed pancytopenia at the age of 26 years. Workup for HIV, hepatitis, cytomegalovirus, human-herpesvirus 6, parvovirus was negative. Partial thromboplastin time (PTT), international normalized ratio (INR), d-dimer, ferritin, iron profile, antinuclear antibodies (ANA) screen was unremarkable. Direct, indirect, and super-combs antibodies were undetectable. Chromosomal study for Fanconi-related chromosomal breakage and telomerase gene panel was negative. Flow cytometry did not reveal an abnormal clone. Bone marrow biopsy showed markedly hypocellular marrow with reduced trilineage hematopoiesis and 1% blasts with normal cytogenetics, immunohistochemistry, fluorescence in situ hybridization (FISH), and negative for myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria (PNH). Cincinnati inherited children's bone marrow transplant (BMT) panel was negative. He was diagnosed with aplastic anemia and was treated with antithymocyte globulin, cyclosporine, prednisone, and currently tacrolimus. At the age of 26 years, he was diagnosed with colon cancer. Immunohistochemistry was positive for MLH1, but the confirmatory genetic testing for Lynch syndrome was negative. He underwent total proctocolectomy and ileostomy and is currently in remission. Next-generation sequencing of bone marrow revealed a germline homozygous ZRSR2 mutation.ZRSR2 spliceosome mutations are more common in males as it's an X-linked gene. They are seen in myelodysplastic syndrome, leukemia, increased autoimmune phenomenon, and 35 cases of colon cancer associated with this mutation are reported. In the setting of aplastic anemia and lynch negative colon cancer, we suspect our patient could have aplastic anemia due to an autoimmune phenomenon, underlying common variable immunodeficiency disease (CVID), or the new ZRSR2 mutation could be playing a role. Further studies and research is warranted to determine its true association with the disease entities. The underlying contributing factor is ZRSR2 mutation.
Myosin heavy chain 9 (MYH9)-related hereditary macrothrombocytopenia is caused by mutation of the MYH9 gene encoding the heavy chain A of non-muscle myosin of class II. We present a case that emphasizes the importance of awareness of rare disorders which could potentially avoid over-investigation, especially in benign conditions. A 72-year-old Caucasian female presented for preoperative evaluation for cataract extraction. She was noted to have thrombocytopenia of 30 K/uL along with elevated creatinine. She denied any acute symptoms except for a prolonged history of easy bruising. Physical exam revealed bruising over the extremities. Upon further questioning, she was previously investigated for thrombocytopenia and had multiple diagnostic as well as therapeutic interventions including bone marrow biopsies, steroids, intravenous immunoglobulins with no improvement. Her family history is consistent with low platelet counts for at least three generations. Peripheral blood smear showed large platelets, normal red and white blood cells with Döhle bodies. Further genetic testing revealed an inherited MYH9 mutation which is autosomal dominant. MYH9-related disorders are characterized by macrothrombocytopenia, often associated with glomerulonephritis, sensorineural deafness, cataracts, and cytoplasmic inclusion bodies within leukocytes. Management is mainly conservative and directed towards the prevention of iron deficiency anemia in young females. The use of desmopressin, in combination with tranexamic acid, is recommended in a perioperative setting. Our case emphasizes the importance of history-taking skills that could potentially minimize further diagnostic or therapeutic interventions in this benign genetic disorder.
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