Vitamin B12 deficiency is classically associated with megaloblastic anemia and neurologic or neuropsychiatric manifestations; however, in rare cases, it may present with pancytopenia and laboratory features that mimic hemolytic anemia. Pernicious anemia is a common cause of vitamin B12 deficiency classically described in older adults of Northern European descent; however, it can occur across all ages and ethnic backgrounds, and demographic assumptions should not delay diagnosis. We report a 35-year-old African American man with no significant past medical history who presented with progressive weakness, decreased appetite, and fatigue. Initial laboratory evaluation revealed profound macrocytic anemia, thrombocytopenia, elevated lactate dehydrogenase, indirect hyperbilirubinemia, and low haptoglobin. Despite these findings, the reticulocyte response was inappropriately low, the direct antiglobulin test was negative, and the peripheral blood smear demonstrated no schistocytes, consistent with ineffective erythropoiesis rather than true hemolysis. Further evaluation revealed severe vitamin B12 deficiency with normal folate levels and positive intrinsic factor antibodies, and biopsy findings consistent with autoimmune metaplastic atrophic gastritis supporting a diagnosis of pernicious anemia. Treatment with intramuscular vitamin B12 resulted in rapid clinical and hematologic improvement, emphasizing the reversibility of hematologic manifestations with prompt therapy. This case highlights pernicious anemia as a reversible cause of pseudo-hemolytic anemia and underscores the importance of recognizing its distinguishing features to avoid unnecessary interventions such as plasma exchange or immunosuppressive therapy.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR::ABL1 translocation and usually presents with leukocytosis. While somatic mutations can occasionally occur within CML, co-mutations in SF3B1 have rarely been reported. We describe a case of concurrent CML and MDS with mutated SF3B1, presenting with macrocytic anemia without leukocytosis. Whole-genome sequencing using Nanopore technology was performed to identify the t(9;22) breakpoint. Probes were designed to target the BCR::ABL1 translocation and the SF3B1 mutation. Single-cell DNA sequencing suggested that the SF3B1 mutation likely preceded BCR::ABL1 and blunted the expected granulopoiesis, thereby explaining the myelodysplastic syndrome phenotype without leukocytosis. This case illustrates how single-cell analysis can reveal meaningful clonal interactions that would not be evident with traditional bulk sequencing.

Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by macrocytic anemia and physical malformations. The only available curative treatment for patients with DBA is hematopoietic cell transplantation (HCT). Previous studies have included umbilical cord blood transplantation (UCBT) alongside other graft sources. We conducted a retrospective analysis of 41 pediatric patients with DBA who underwent related or unrelated UCBT between 1994 and 2023, using data from the Eurocord/EBMT registry. Twenty patients received related and 21 received unrelated single UCBT. Most patients received myeloablative conditioning and were transplanted after 1999. In related UCBT, median follow-up was 144.8 months, neutrophil engraftment at day +42 was 100% and 5-year overall survival (OS) was also 100%. In unrelated UCBT, median follow-up was 34 months, neutrophil engraftment at day +42 was 90%, and 5-year OS was 66%. The incidence of acute graft-versus-host disease (GvHD) was considerably higher among unrelated UCBT recipients. The incidence of chronic GvHD was similar between the two cohorts; however, extensive disease was more common after unrelated UCBT. UCBT from an HLA-identical sibling should be considered for DBA patients given the favorable short- and long-term outcomes. For the remaining patients, unrelated UCBT could be considered after individualized risk-benefit assessement.

Thrombotic microangiopathies (TMA) are characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. As a rare but reversible cause, vitamin B12 and folate deficiency may present as thrombotic microangiopathy (pseudo-TMA) with hemolytic uremic syndrome (HUS)-like clinical features, posing a significant diagnostic challenge. A 56-year-old woman developed severe macrocytic anemia, thrombocytopenia, acute kidney injury, and laboratory signs of hemolysis. Investigations revealed marked folate deficiency, pronounced macrocytosis (MCV>120 fL), low haptoglobin levels, and markedly elevated lactate dehydrogenase. ADAMTS13 activity was reduced but not consistent with classical thrombotic thrombocytopenic purpura, while complement studies demonstrated secondary, consumptive activation. Infectious, autoimmune, malignant, and drug-related causes were excluded. The patient required transient continuous renal replacement therapy, plasma exchange, and corticosteroid treatment, followed by high-dose folate and vitamin B12 supplementation. After vitamin replacement, a rapid reticulocyte response, resolution of hemolysis, and complete hematologic remission were observed. This case highlights that folate and vitamin B12 deficiency can cause reversible pseudo-TMA with HUS-like presentation. Early recognition and targeted vitamin supplementation are essential, as they may prevent unnecessary invasive or costly therapies. Orv Hetil. 2026; 167(14): 556-559.

BACKGROUND Superior sagittal sinus thrombosis is an uncommon but serious cerebrovascular disorder, often linked to a hypercoagulable state. One less common etiology of hypercoagulability is elevated homocysteine levels due to vitamin B12 deficiency caused by pernicious anemia, a process that usually also results in concurrent megaloblastic anemia. We describe a patient who developed superior sagittal sinus thrombosis despite normal hemoglobin and hematocrit values. CASE REPORT A 52-year-old man presented to the emergency department with first-time tonic-clonic seizure. Brain magnetic resonance imaging revealed thrombosis of the superior posterior segment of the superior sagittal sinus. Additional studies demonstrated deep vein thrombosis in the right peroneal vein. Extensive evaluation for potential prothrombotic causes revealed an elevated homocysteine level and vitamin B12 deficiency. The patient had serologic evidence of pernicious anemia; antibodies against intrinsic factor and gastric parietal cells were present. Despite the pernicious anemia diagnosis, his hemoglobin level was normal. High-dose oral vitamin B12 was administered to correct the deficiency and alleviate the hypercoagulable state. The patient was initially anticoagulated with a heparin infusion to treat the superior sagittal sinus thrombosis; therefore, intramuscular injections of vitamin B12 were avoided during hospitalization. He was ultimately discharged home with prescriptions for apixaban and intramuscular injections of vitamin B12. CONCLUSIONS Patients presenting with thrombotic events should be thoroughly evaluated for an underlying hypercoagulable state to ensure appropriate treatment and prevent complications. This case highlights the importance of considering hyperhomocysteinemia induced by vitamin B12 deficiency as a cause of thrombosis, even in patients with normal hemoglobin levels.

Vitamin B12 deficiency is a common and reversible cause of megaloblastic anemia, but in severe cases, it may mimic thrombotic microangiopathy (TMA), a presentation known as pseudothrombotic microangiopathy (pseudo-TMA). This rare entity is frequently underrecognized and may lead to inappropriate therapies if not promptly identified. We report the case of a 62-year-old man who presented with abdominal pain, distension, and constipation, initially raising concern for intestinal obstruction or malignancy. Laboratory evaluation revealed macrocytic anemia, thrombocytopenia, elevated lactate dehydrogenase, and indirect hyperbilirubinemia. Further assessment demonstrated a low reticulocyte count, absence of significant schistocytosis, markedly reduced vitamin B12 levels, and elevated ferritin. Autoimmune testing confirmed pernicious anemia as the underlying etiology. Treatment with intramuscular hydroxocobalamin resulted in complete clinical and hematologic recovery. This case demonstrates the value of recognizing pseudo-TMA and considering vitamin B12 deficiency in patients with TMA-like features and unexplained gastrointestinal symptoms.

Limited data exist on the prevalence and treatment of macrocytic anemia associated with selenium deficiency. We analyzed data from 21 patients receiving parenteral nutrition (PN). Twelve patients (57%) showed macrocytic anemia, and all 12 had serum selenium levels below the detection limit. Selenium supplementation therapy (sodium selenite, 100 µg/day for 10 days) was administered to a total of 14 patients (aged 79-103 years, PN duration 10-55 months), comprising these 12 patients and two additional anemic patients who presented with marked macrocytosis. After supplementation, serum selenium levels increased transiently but remained below the reference range. Mean corpuscular volume (MCV) showed a transient decline after selenium supplementation, followed by a gradual recovery. The nadir of MCV occurred 10.8 months after supplementation, after which MCV began to increase, indicating a U-shaped trajectory over time. No significant change was observed in hemoglobin levels. Macrocytic changes observed during PN were common manifestations of selenium deficiency and improved with short-term selenium supplementation.

Methylmalonic acidemia with homocystinuria (MMA-HC) is a rare inherited metabolic disorder characterized by diverse and nonspecific clinical manifestations. Here, we report the first case of MMA-HC presenting in the postpartum period, aiming to enhance clinicians' awareness and diagnostic capabilities regarding this condition. This will help prevent misdiagnosis and missed diagnosis, thereby enabling timely and effective treatment for patients. A 17-year-old woman who underwent cesarean section presented with encephalitis-like symptoms shortly after childbirth, including fever, headache, psychiatric disturbances, and limb weakness, accompanied by a progressive macrocytic anemia that worsened significantly from the late prenatal to the early postpartum period, along with markedly elevated red cell distribution width (RDW) and leukopenia and severe hyperhomocysteinemia. Genetic testing confirmed cblC-type MMA-HC. A metabolic crisis was triggered after administering valproate for seizures. The patient was effectively treated with a multidisciplinary approach, highlighting the importance of careful clinical monitoring and systematic metabolic screening in peripartum women presenting with progressive hematological abnormalities and encephalopathic symptoms. It further validates the critical role of early diagnosis and multidisciplinary comprehensive treatment in managing complex inherited metabolic disorders, thereby contributing to enhanced overall diagnostic and therapeutic standards.

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke in young adults and may present with nonspecific symptoms, leading to delayed recognition. Although CVT is associated with multiple acquired and inherited prothrombotic states, presentation as the first manifestation of acute myeloid leukemia (AML) is distinctly uncommon and poses diagnostic and therapeutic challenges, particularly when intracranial hemorrhage is present. We report the case of a 34-year-old woman with no significant past medical history who presented with sudden severe headache, vomiting, photophobia, and right-sided blurry vision. Initial noncontrast computed tomography (CT) of the brain demonstrated a right lateral occipitotemporal intraparenchymal hemorrhage with surrounding edema and hyperdense dural venous sinuses suspicious for venous thrombosis. CT venography confirmed extensive dural venous sinus thrombosis involving the straight sinus, right transverse and sigmoid sinuses, posterior superior sagittal sinus, with extension to the right internal jugular vein and involvement of the vein of Galen. Laboratory evaluation revealed leukopenia with severe neutropenia, macrocytic anemia, and borderline thrombocytopenia; peripheral smear showed circulating blasts, prompting hematologic workup. Bone marrow examination demonstrated marked blast infiltration with immunophenotypic features consistent with AML without maturation. This case underscores the importance of evaluating for underlying hematologic malignancy in patients presenting with extensive or unprovoked CVT, especially when cytopenias or abnormal peripheral blood findings are present, and highlights the need for early multidisciplinary management when thrombosis coexists with intracranial hemorrhage.