RESUMEN
A 57-year-old gentleman presented to the hospital with progressive fatigue and dyspnea on exertion three months after recovering from COVID-19. He was noted to have severe anemia with reticulocytopenia. After excluding vitamin deficiencies and heavy metal toxicities, a bone marrow aspirate and biopsy were performed, which showed erythroid predominant trilineage maturing hematopoiesis with 79% ring sideroblasts and no dysplasia. SF3B1 mutation was negative. He was diagnosed with sideroblastic anemia and became transfusion-dependent. He was treated with an erythropoiesis-stimulating agent and luspatercept with transient improvement in anemia. After 12 months of treatment, anemia spontaneously improved. Repeat bone marrow biopsy showed hypercellular marrow with 39% ringed sideroblasts. We suspect that this possibly was a delayed manifestation of COVID-19 infection.
RESUMEN
Pure red cell aplasia (PRCA) is a rare disorder mainly affecting the erythroid precursor cells. It presents with severe isolated reticulocytopenia with relatively normal counts in the myeloid and megakaryocytic lineages. It has been attributed to numerous congenital and acquired causes. DNA Methyl Transferase 3 Alpha (DNMT3A) mutation has been typically associated with myeloid and lymphoid malignancies. There is a scarcity of data regarding the association of DNMT3A mutation with PRCA. We report a case of a 73-year-old man who initially presented with anemia and reticulocytopenia. After a thorough evaluation and eventual bone marrow biopsy, he was diagnosed with PRCA. Further genetic testing identified a DNMT3A mutation. We are reporting this rare case to highlight the fact that DNMT3A mutation can also present as isolated PRCA in and of itself without the co-occurrence of leukemia, lymphoma, or myelodysplastic syndrome (MDS).
Asunto(s)
Síndromes Mielodisplásicos , Aplasia Pura de Células Rojas , Anciano , ADN , Humanos , Masculino , Mutación , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/genética , Aplasia Pura de Células Rojas/complicaciones , Aplasia Pura de Células Rojas/diagnóstico , Aplasia Pura de Células Rojas/genética , TransferasasRESUMEN
Erythroblastic synartesis is a rare cause of acquired dyserythropoiesis. Only 9 cases have been previously reported. We hereby report 3 cases of patients diagnosed with erythroblastic synartesis associated with monoclonal immunoglobulin and an overt malignant lymphoid disorder. A different B-cell clone may produce the monoclonal immunoglobulin, forming a biclonal disorder. In light of these data and literature review, treatment targeting the paraprotein seems to be efficient to control synartesis and correct anemia. In the case of monoclonal gammapathy associated with chronic lymphocytic leukemia, therapeutics should be adapted to control both chronic lymphocytic leukemia and monitored monoclonal immunoglobulin titer.
Asunto(s)
Leucemia Linfocítica Crónica de Células B , Trastornos Linfoproliferativos , Paraproteinemias , Anticuerpos Monoclonales , Eritroblastos/patología , Humanos , Leucemia Linfocítica Crónica de Células B/patología , Trastornos Linfoproliferativos/complicaciones , Paraproteinemias/complicacionesRESUMEN
Vitamin B12 deficiency is classically associated with megaloblastic anemia. Possible cobalamin deficiency is not investigated once hemolysis is seen. Around 2.5% of cases can present as pseudo-thrombotic microangiopathy (TMA). A swift identification of this means the difference between an easy solution and a protracted one for the patient. A 74-year-old man with no past medical history presented with exertional dyspnea, fatigue, and increasing anorexia over two weeks. Physical examination including a neurological examination was normal. Laboratory tests revealed pancytopenia, unconjugated hyperbilirubinemia, elevated LDH (lactate dehydrogenase), low haptoglobin, and fragmented red blood cells (RBCs) on the peripheral smear, but normal FDP (fibrinogen degradation product) and fibrinogen. The absolute reticulocyte count was reduced as opposed to the expected elevation. Vitamin B12 levels were undetectable, and severe cobalamin deficiency from pernicious anemia was found to be the paramount etiology. Cobalamin deficiency causing pseudo-TMA baffles most physicians. Advanced pernicious anemia is thought to cause intramedullary hemolysis, resulting in peripheral pancytopenia. The fragile RBCs are easily sheared, producing schistocytosis without platelet microthrombi. In contrast to hemolytic anemias, reticulocyte count is low given the unavailability of B12 for erythropoiesis. Reticulocytopenia is a universal finding in cases of pseudo-TMA. Around 38.8% of cases with pseudo-TMA are misdiagnosed as thrombotic thrombocytopenic purpura and treated with plasma product therapy. Keeping an eye out for reticulocytopenia in cases of hemolysis could mean a world of difference for the patient.
RESUMEN
Autoimmune haemolytic anaemia (AIHA) is an uncommon condition characterized by increased destruction of erythrocytes associated with reticulocytosis in the great majority of cases. We present the case of a 68-year-old woman with jaundice and malaise. Investigation revealed AIHA with reticulocytopenia. The patient failed to respond to prednisolone or to rituximab. Azathioprine and epoetin beta were subsequently started, the prednisolone dose was increased, and the patient began to respond after 1 month. In AIHA, reticulocytopenia is a very rare presentation and a sign of great severity and poor outcome. The scarcity of therapeutic options in refractory cases poses a major challenge for physicians. LEARNING POINTS: Autoimmune haemolytic anaemia is a rare disorder characterized by decompensated acquired haemolysis caused by the host's immune system acting against its own red cell antigens.Concomitant presentation with reticulocytopenia is very rare and a sign of great severity and poor outcome.Treatment options in refractory cases still greatly rely on individual experience and expert opinion.
RESUMEN
Eight patients were observed with a rare combination of thymoma and pure red cell aplasia of bone marrow (PRCA), of which seven women were between 44 to 68 years old. The diagnosis of PRCA was established before the detection of thymoma in 1 patient, simultaneously in 3, after - in 4. Seven patients underwent timomectomy. The weight of removed thymomas was from 200 to 780 grams. Morphological type A thymoma variant (spindle cell) was installed in 2 patients, type B1 - in 2, type B2 - in 2, type B3 - in 2. Complete remissions were obtained using cyclophosphamide and cyclosporin in 5 patients, lasting from 6 months to 7 years. The results of immunological studies with the identification of non - hemolytic antibodies to the proteolytic antigen (Pr1d) on the erythrocyte membrane in 4 patients are presented. Of these, two studied patients simultaneously detected antibodies to the Pr1d antigen and the interspecific antigen of mammalian erythroblasts (IAME). It is shown that the lifespan of red blood cells are not changed. The direct Coombs test was negative in 5 patients, but with the help of aggregate hemaglutination test and enzyme immunoassay, antibodies were detected on the surface of erythrocytes. The pathogenesis of this combination of diseases remains unclear and needs to be elucidated.
Asunto(s)
Médula Ósea/patología , Inmunosupresores/uso terapéutico , Aplasia Pura de Células Rojas/tratamiento farmacológico , Timoma/cirugía , Neoplasias del Timo/cirugía , Adulto , Anciano , Animales , Ciclofosfamida/uso terapéutico , Ciclosporina/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Aplasia Pura de Células Rojas/etiología , Timectomía , Timoma/complicaciones , Timoma/tratamiento farmacológico , Neoplasias del Timo/complicaciones , Neoplasias del Timo/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Correct diagnosis of inherited bone marrow failure syndromes is a challenge because of the significant overlap in clinical presentation of these disorders. Establishing right genetic diagnosis is crucial for patients' optimal clinical management and family counseling. A nondysmorphic infant reported here developed severe transfusion-dependent anemia and met clinical criteria for diagnosis of Diamond-Blackfan anemia (DBA). However, whole-exome sequencing demonstrated that the child was a compound heterozygote for a paternally inherited pathogenic truncating variant (SPTA1c.4975 C>T) and a novel maternally inherited missense variant of uncertain significance (SPTA1c.5029 G>A) within the spectrin gene, consistent with hereditary hemolytic anemia due to disruption of red blood cell (RBC) cytoskeleton. Ektacytometry demonstrated abnormal membrane flexibility of the child's RBCs. Scanning electron microscopy revealed morphological aberrations of the patient's RBCs. Both parents were found to have mild hereditary elliptocytosis. Importantly, patients with severe RBC membrane defects may be successfully managed with splenectomy to minimize peripheral destruction of misshapen RBCs, whereas patients with DBA require lifelong transfusions, steroid therapy, or hematopoietic stem cell transplantation. As suggested by the WES findings, splenectomy rendered our patient transfusion-independent, improving the family's quality of life and preventing transfusion-related iron overload. This case illustrates the utility of whole-exome sequencing in clinical care of children with genetic disorders of unclear presentation.
Asunto(s)
Anemia/diagnóstico , Anemia/genética , Proteínas Portadoras/genética , Proteínas de Microfilamentos/genética , Anemia de Diamond-Blackfan/diagnóstico , Anemia de Diamond-Blackfan/genética , Anemia Hemolítica Congénita/genética , Proteínas Portadoras/metabolismo , Errores Diagnósticos , Eliptocitosis Hereditaria/genética , Membrana Eritrocítica/fisiología , Eritrocitos/patología , Exoma/genética , Femenino , Humanos , Lactante , Proteínas de Microfilamentos/metabolismo , Mutación/genética , Linaje , Calidad de Vida , Espectrina/genética , Espectrina/fisiología , Secuenciación del Exoma/métodosRESUMEN
Acquired pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) are rare complications of immunosuppression in pediatric solid organ transplant patients. We report a 14-month-old female child who developed Coombs positive hemolytic anemia and reticulocytopenia while on tacrolimus after cardiac transplantation. She was successfully treated with rituximab after failing treatment with corticosteroids and intravenous immunoglobulins. Clinicians should consider PRCA differential diagnosis in a patient presenting with reticulocytopenia and hemolysis. In addition, the coexistence of PRCA with AIHA, and the response to therapy with rituximab, supports a common immune-mediated pathogenesis for both disorders.
Asunto(s)
Anemia Hemolítica Autoinmune/tratamiento farmacológico , Trasplante de Corazón , Inmunosupresores/efectos adversos , Aplasia Pura de Células Rojas/tratamiento farmacológico , Rituximab/uso terapéutico , Tacrolimus/efectos adversos , Anemia Hemolítica Autoinmune/inducido químicamente , Femenino , Humanos , Lactante , Aplasia Pura de Células Rojas/inducido químicamenteRESUMEN
AIM: Transient erythroblastopenia of childhood (TEC) is an uncommon, benign normocytic anaemia of unknown cause, characterised by reduced or absent mature erythroid precursors in otherwise normocellular bone marrow and a complete spontaneous recovery. We present epidemiological data on paediatric TEC cases in a single centre over 30 years and compare them with published data. METHODS: In this retrospective study, epidemiological data on children diagnosed with TEC between 1978 and 2008 were collected and compared with published data. RESULTS: A total of 36 children (median age 19 months, 56% male children) were diagnosed. At presentation, median haemoglobin was 44 g/L with absolute reticulocyte count 0 × 10(9) /L; seventeen (47%) patients were neutropenic and 23 (64%) had platelet counts of more than 400 × 10(9) /L. The majority (78%) presented from 1983 to 1997, and 78% of articles reviewing 10 or more TEC patients were published between 1983 and 1992. CONCLUSION: Transient erythroblastopenia of childhood is now diagnosed less frequently in our institution than in the last two decades. Although the aetiology remains largely unknown, it is possible that changes in causative environmental factors contribute to making TEC a rare disease. Clinicians need to be aware of TEC in order to prevent unnecessary diagnostic and therapeutic measurements.