Visceral leishmaniasis misdiagnosed as an upper respiratory infection and iron-deficiency anemia in a 20-month-old male patient: a case report.

BACKGROUND: Visceral Leishmaniasis should be suspected in every patient with a history of splenomegaly, fever, and pancytopenia. It is one of the most dangerous forms of infection and prompt recognition is the key to positive outcome. CASE PRESENTATION: A 20-month-old Caucasian male patient was brought to our hospital as an outpatient with the complaint of persistent fever, which did not improve with empiric antibiotic treatment (> 96 hour after the initial dose). The antibiotic treatment had been prescribed by primary care physician at polyclinic, who also referred the patient to hematologist due to anemia, who prescribed iron supplement. Despite multiple subspecialist visits, bicytopenia was, unfortunately, left unidentified. Upon physical examination no specific signs were detected, however, spleen seemed slightly enlarged. Patient was admitted to the hospital for further work-up, management and evaluation. Abdominal ultrasound, complete blood count and c-reactive protein had been ordered. Hematologist and infectionist were involved, both advised to run serology for Epstein-Barr Virus and Visceral Leishmaniasis. The latter was positive; therefore, patient was transferred to the specialized clinic for specific management. CONCLUSION: Both in endemic and non-endemic areas the awareness about VL should be increased among the medical professionals. We also recommend that our colleagues take the same approach when dealing with bicytopenia and fever, just as with pancytopenia and fever. The medical community should make sure that none of the cases of fever and pancytopenia are overlooked, especially if we have hepatomegaly and/or splenomegaly.

A New Case of Association of Megaloblastic Anemia and Pancytopenia of Infants.

BACKGROUND: Vitamin B12, or cobalamin deficiency, an infrequent clinical entity in pediatric age, is found almost solely in breastfed infants whose mothers are purely vegetarian, non-supplemented or with pernicious anemia. Megaloblastic anemia in infants presents with generalized weakness or irritability. METHODS: Diagnosis is usually centered on complete blood count, vitamin dosing, and peripheral smear, which may show macrocytes, hypersegmented neutrophils, reticulocytopenia and a raised mean corpuscular volume (MCV ˃ 100 fL). Pancytopenia has also been noted. RESULTS: We report an exclusive breastfed nine-month-old female child who presented with irritability, developmental delay, and difficulties in introducing new foods. Her initial blood count revealed pancytopenia. Vitamin B12 levels were found to be reduced. Maternal levels of Vitamin B12 were also found to be borderline low. The child was treated as per protocols, and improvement was evidenced with the return of hematological parameters to the regular and gradual advancement of milestones. CONCLUSIONS: We aim to underscore the importance of megaloblastic anemia as an important and rare cause of anemia in infancy.

Nitrous oxide-induced polyneuropathy, pancytopenia and pulmonary embolism: a case report.

BACKGROUND: Nitrous oxide is a medical and household gas that has seen its use drift to recreational purpose among the young population in recent years. Significant neurological, hematological and psychiatric side effects, generally related to an induced functional vitamin B12 deficiency, have been described separately in the literature. CASE REPORT: A 22-year-old woman of North African origin experienced an exceptional combination of polyneuropathy, bilateral pulmonary embolism and severe pancytopenia related to vitamin B12 deficiency and hyperhomocysteinemia induced by recreational nitrous oxide use. After treatment with vitamin B12 supplementation and intensive rehabilitative management, the patient progressively regained the ability to walk and her biological parameters gradually returned to normal. The pathophysiological mechanisms related to a decrease in vitamin B12 activity are the reduction of products needed for synthesis of deoxyribonucleic acid, carbohydrate or fatty acids, and the increase of hyperhomocysteinemia. Other mechanisms involving a direct action of N2O are also suspected. CONCLUSION: This case report brings elements to support our knowledge about pathological pathway, recovery and prognosis of recreational N2O abuse complications. The general and medical population should be aware to the serious consequences of this type of consumption.

Vitamin B12 deficiency presenting with a pancytopenia in pregnancy.

Vitamin B12 deficiency is a significant public health problem globally. Although it is a well-known cause of macrocytic anaemia and in advanced cases, pancytopenia, there remains a relative paucity of cases reported in pregnancy. It is associated with an increased risk of pregnancy complications and adverse birth outcomes such as neural tube defects, preterm birth, low birth weight, neurological sequelae and intrauterine death. It has a predilection for individuals aged >60 years. It has been implicated in a spectrum of neuropsychiatric disorders and it may also exert indirect cardiovascular effects. Severe vitamin B12 deficiency may present with haematological abnormalities that mimic thrombotic microangiopathy such as HELLP syndrome (haemolysis, elevated liver enzymes and low platelets) or it may present as pseudothrombotic microangiopathy (Moschcowitz syndrome) characterised by anaemia, thrombocytopenia and schistocytosis. It can also closely mimic thrombotic thrombocytopenia purpura, hence posing a diagnostic challenge to the unwary physician. Serological measurement of vitamin B12 levels confirms the diagnosis. Oral supplementation with vitamin B12 remains a safe and effective treatment. The authors describe the case of a multiparous woman in her late 20s presenting with a plethora of non-specific symptoms at 29+5 weeks' gestation. Her haemoglobin was 45 g/L, platelets 32×109/L, vitamin B12 <150 ng/L and serum folate <2 µg/L. She was not a vegetarian, but her diet lacked nutrition. Following parenteral B12 supplementation, her haematological parameters improved. The pregnancy was carried to term. Due to the plethora of non-specific symptoms, the diagnosis can be challenging to establish. Adverse maternal or fetal outcomes may occur. Folic acid supplementation may mask an occult vitamin B12 deficiency and further exacerbate or initiate neurological disease.

Pancytopenia due to Restrictive Food Intake in an Autistic Adult.

Autism spectrum disorder (ASD) is a neuro-behavioral syndrome that develops in childhood and can be comorbid with restrictive and avoidant food intake disorder. This case details a young man who was hospitalized with pancytopenia due to restrictive nutritional intake related to his severe ASD. He was found to have undetectable vitamin B12 levels. His blood counts improved with transfusion, nutritional supplementation, and dental care. This report illustrates the importance of understanding ASD and potential medical complications of related behaviors.

Methotrexate Cutaneous Ulceration: A Systematic Review of Cases.

BACKGROUND: Methotrexate cutaneous ulceration is a rare methotrexate complication, and has only been described in case reports and case series. OBJECTIVE: To document patient characteristics, morphologic features, and mortality risk factors for methotrexate cutaneous ulceration. METHODS: A systematic literature review of PubMed and Embase (last date 1 November 2021) was performed with data collected from case reports and case series. This study was limited to cases of cutaneous ulceration; presence of oral ulceration was collected from within these cases. RESULTS: 114 cases (men = 57.9%, mean age = 61 years) of methotrexate cutaneous ulceration met inclusion criteria. Psoriasis (69.3%), rheumatoid arthritis (18.4%), and mycosis fungoides (6.1%) were the most common indications for methotrexate use. Morphologies included erosions localized to psoriatic plaques (33.3%), epidermal necrosis/necrolysis (35.1%), localized ulceration (16.7%), and skin-fold erosions (5.3%). Methotrexate dose preceding toxicity varied greatly; median 20 mg/week, interquartile range 15-40 mg/week, range 5-150 mg/week. Most patients had risk factors for serum toxicity (baseline renal dysfunction = 37.8%, concurrent NSAID use = 28.1%, inadequate folic acid use = 89.1%). Thirty percent of cases involved mistakenly high methotrexate doses. Fourteen patients (12%) died. Absence of folic acid use (69% vs. 100%, p value < 0.001), pancytopenia (33% vs. 86%, p value < 0.001), and renal dysfunction at presentation (47% vs. 92%, p value < 0.001) were associated with increased mortality. LIMITATIONS: Selection bias present due to abstraction from case reports and case series. CONCLUSION: Methotrexate cutaneous ulceration is commonly preceded by dosage mistakes, absence of folic acid supplementation, and concurrent use of nephrotoxic medications. Renal impairment, pancytopenia, and absence of folic acid supplementation are key risk factors for mortality from this adverse medication reaction. Providers should regularly monitor methotrexate dosing adherence, drug-drug interactions, and perform routine laboratory evaluation. Index of suspicion for this toxicity should remain high given the varied clinical presentation and high mortality.

Long-term eltrombopag for bone marrow failure depletes iron.

Eltrombopag (EPAG) has been approved for the treatment of aplastic anemia and for immune thrombocytopenia, and a subset of patients require long-term therapy. Due to polyvalent cation chelation, prolonged therapy leads to previously underappreciated iron depletion. We conducted a retrospective review of patients treated at the NIH for aplastic anemia, myelodysplastic syndrome, and unilineage cytopenias, comparing those treated with EPAG to a historical cohort treated with immunosuppression without EPAG. We examined iron parameters, duration of therapy, response assessment, relapse rates, and common demographic parameters. We included 521 subjects treated with (n = 315) or without EPAG (n = 206) across 11 studies with multiyear follow-up (3.6 vs. 8.5 years, respectively). Duration of EPAG exposure correlated with ferritin reduction (p = 4 × 10-14 ) regardless of response, maximum dose, or degree of initial iron overload. Clearance followed first-order kinetics with faster clearance (half-life 15.3 months) compared with historical responders (47.5 months, p = 8 × 10-10 ). Risk of iron depletion was dependent upon baseline ferritin and duration of therapy. Baseline ferritin did not correlate with response of marrow failure to EPAG or to relapse risk, and timing of iron clearance did not correlate with disease response. In conclusion, EPAG efficiently chelates total body iron comparable to clinically available chelators. Prolonged use can deplete iron and ultimately lead to iron-deficiency anemia mimicking relapse, responsive to iron supplementation.

Retrospective Analysis of Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia Treated with FLAG at a Comprehensive Cancer Center.

BACKGROUND: FLAG ± Ida (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin), is a salvage chemotherapy regimen for relapsed or refractory (R/R) acute myeloid leukemia (AML), with complete remission (CR) rates historically ranging from 52% to 63%. We review the outcomes for patients with R/R AML treated with FLAG ± Ida at the University of California Davis Comprehensive Cancer Center. PATIENTS AND METHODS: Adult patients (≥ 18 years) with R/R AML who received FLAG or FLAG + Ida from January 1, 2012 to October 31, 2016 were identified via chart review. Outcomes evaluated were CR, CR with incomplete hematologic recovery (CRi), overall response rate, overall survival (OS), relapse-free survival, and adverse events. RESULTS: Forty-two patients were included. The median age was 52 years (range, 23-73 years), and 57% were male. Sixteen (38.1%) patients had relapsed disease, and 26 (61.9%) had refractory disease. Most (n = 35; 83.3%) patients had European LeukemiaNet intermediate-risk AML. Responses were CR in 20 (47.6%) and CRi in 6 (14.3%). The median OS was 10 months (range, 0.8-51 months), and the median relapse-free survival was 12 months (range, 1-51 months) for responders. The median OS for patients who achieved CR was not reached, and the estimated 48-month survival rate was 56%. The median OS after CRi or no response was 3.47 and 2.17 months, respectively. The median OS was not significantly different when censored for stem cell transplant following chemotherapy, nor with use/deferral of idarubicin. The most common adverse effects were pancytopenia and infection. CONCLUSION: Patient outcomes after treatment with FLAG ± Ida for R/R AML remain similar to prior reports, confirming its role as a salvage regimen for these patients.

Meropenem-induced pancytopenia in a preterm neonate: a case report.

BACKGROUND: A post-marketing surveillance study has reported an association between meropenem use and the incidence of hematologic abnormalities, including leukopenia, thrombocytopenia, hemolysis, and neutropenia, but the precise incidence in neonates is unknown. Here, we report meropenem-induced pancytopenia in a preterm neonate. CASE PRESENTATION: A preterm newborn Pakistani received intravenous meropenem 40 mg/kg every 8 hours to treat Klebsiella pneumoniae in blood cultures and suspected meningitis. The baby developed severe thrombocytopenia, with a platelet count of 22 × 103 cells/mm3, low hemoglobin level of 9.7 g/dl, and low absolute neutrophil count (ANC) of 816 cells/mm3 on days 3, 14, and 17 of meropenem therapy, respectively. Based on the blood culture and institutional guidelines, meropenem treatment was continued with monitoring and supportive care for a total of 19 days. After discontinuation of meropenem, the baby was monitored continuously for hematological changes, and low counts persisted for 3 days. ANC improved to > 1500 cells/mm3 on the fourth day, and the platelet count reached > 150 × 103 cells/mm3 for the first time on the seventh day of meropenem discontinuation. All subsequent complete blood count (CBC) reports showed improving trends. The baby was discharged on the 48th day of life (DOL), with follow-up monitoring of CBC. The baby was kept on iron supplements, and hemoglobin level of 11.2 g/dl was observed on the 59th DOL. CONCLUSION: Neonatal pancytopenia may lead to serious health complications; therefore, clinicians and pharmacists need to vigilantly monitor CBC in this vulnerable population, even when administering meropenem in septic doses for the recommended duration.

Megaloblastic anaemia in a 9-weeks old infant: A case report.

Megaloblastic anaemia due to vitamin B12 and folic acid deficiency is uncommon in infancy and rarely reported in infants below 3 months of age. We hereby report a case of megaloblastic anaemia in a 9-weeks old infant having fever from 7th week of life. Blood picture showed pancytopenia and diagnosis was confirmed on bone marrow biopsy and serum level of vitamins. Patient positively responded to vitamin B12 and folic acid supplementation. Infants with pancytopenia even younger than 2 months, should also be investigated for vitamin B12 and folate deficiency. Mother of the baby was not antenatally investigated for anaemia. Prompt antenatal diagnosis and treatment of mothers can reduce the incidence in the infants.

Autophagy in endothelial cells regulates their haematopoiesis-supporting ability.

BACKGROUND: Endothelial cells (ECs) function as an instructive platform to support haematopoietic stem cell (HSC) homeostasis. Our recent studies found that impaired bone marrow (BM) ECs are responsible for the defective haematopoiesis in patients with poor graft function (PGF), which is characterised by pancytopenia post-allotransplant. Although activated autophagy was reported to benefit ECs, whether EC autophagy plays a critical role in supporting HSCs and its effect on PGF patients post-allotransplant remain unclear. METHODS: To evaluate whether the autophagy status of ECs modulates their ability to support haematopoiesis, human umbilical vein endothelial cells (HUVECs) and primary BM ECs derived from healthy donors were subjected to knockdown or overexpression of Beclin-1 (an autophagy-related protein). Moreover, BM ECs derived from PGF patients were studied. FINDINGS: Beclin-1 knockdown significantly reduced the haematopoiesis-supporting ability of ECs by suppressing autophagy, which could be restored by activating autophagy via Beclin-1 upregulation. Moreover, autophagy positively regulated haematopoiesis-related genes in HUVECs. Subsequently, a prospective case-control study demonstrated that defective autophagy reduced Beclin-1 expression and the colony-forming unit (CFU) plating efficiency in BM ECs from PGF patients compared to matched patients with good graft function. Rapamycin, an autophagy activator, quantitatively and functionally improved BM ECs from PGF patients in vitro and enhanced their ability to support HSCs by activating the Beclin-1 pathway. INTERPRETATION: Our results suggest that the autophagy status of ECs modulates their ability to support haematopoiesis by regulating the Beclin-1 pathway. Defective autophagy in BM ECs may be involved in the pathogenesis of PGF post-allotransplant. Rapamycin provides a promising therapeutic approach for PGF patients. FUNDING: Please see funding sources.

Cytopenias among patients with rheumatic diseases using methotrexate: a meta-analysis of randomized controlled clinical trials.

OBJECTIVE: To conduct a systematic literature review and meta-analysis to estimate the incidence of anaemia, leucopoenia, neutropenia and thrombocytopenia associated with MTX plus folic acid among patients with rheumatic diseases. METHODS: We searched MEDLINE, PubMed and EMBASE through August 2016 for all randomized controlled clinical trials with a MTX monotherapy arm. We excluded randomized controlled clinical trials for cancer and included only double-blind studies that reported on haematologic adverse events. Studies were excluded if patients did not receive folic acid or leucovorin supplementation. Full text articles were assessed by two independent reviewers. Incidence estimates were calculated using random-effects models. RESULTS: Of 1601 studies identified, 30 (1.87%) were included, representing 3858 patients; all had RA. Seventeen trials reported on anaemia (n = 2032), 17 reported on leucopoenia (n = 2220), 16 reported on neutropenia (n = 2202) and 12 reported on thrombocytopenia (n = 1507). The incidence for any anaemia was 2.55% (95% CI 0.60-5.47%), any leucopoenia 1.17% (95% CI 0.16-2.80%), any neutropenia 1.77% (95% CI 0.33-4.00%), and any thrombocytopenia 0.19% (95% CI 0.00-0.86%). Four cases of severe anaemia were reported, as defined by authors, along with three cases of severe neutropenia. No cases of severe leucopoenia, severe thrombocytopenia or pancytopenia were reported. CONCLUSION: Cytopenias are an uncommon side effect of low-dose MTX with folic acid supplementation among RA patients. Further research is needed to reach a more precise estimate.

Hypotension: an unusual presentation of vitamin B12 deficiency, with complete recovery following cyanocobalamin therapy.

Vitamin B12 deficiency and its sequelae are well described and reported, especially in vegetarians. However, its association with haemodynamic instability is not well identified. We report a case of a young man, previously healthy, presenting with fever, hypotension requiring vasopressors and pancytopenia. Extensive workup was unrevealing for possible infective, inflammatory or endocrine causes except for vitamin B12 deficiency. Fever and haematological parameters stabilised after adequate supplementation of cyanocobalamin (vitamin B12).

Hematologic Manifestations of Nutritional Deficiencies: Early Recognition is Essential to Prevent Serious Complications.

Nutritional deficiencies, including deficiencies of vitamin B12, copper, and vitamin C, may result in cytopenias and hematologic symptoms. Early recognition of these deficiencies is imperative for prompt treatment and improvement in hematologic and other manifestations. We describe 5 cases which illustrate the hematologic manifestations of nutritional deficiencies and challenges to initial diagnosis and management. Supplementation of the deficient vitamin or micronutrient in all of these cases resulted in rapid resolution of cytopenias, hemorrhage, and other associated hematologic symptoms. We also review other nutritional deficiencies that manifest with hematologic symptoms and compile recommendations on treatment and expected time to response.

A Rare Cause of Pancytopenia in an Exclusively Breastfed Infant.

Vitamin B12 (B12) deficiency in infancy can present with nonspecific symptoms. We report a 5-month old exclusively breastfed full-term infant with emesis, lethargy, progressive pancytopenia, hemolysis, hypofibrinogenemia, elevated lactate dehydrogenase and a hypercellular bone marrow with dyserythropoiesis. The B12 level in the serum was undetectable. The infant's lethargy resolved within 48 hours of intramuscular B12 injection, followed by rapid improvement of pancytopenia. The asymptomatic mother had a normal hemoglobin and mean corpuscular volume, but undetectable B12 level and positive antibodies to intrinsic factor, consistent with pernicious anemia masked by folate supplementation in the mother but causing symptoms in her infant.

A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence.

A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5-10% of BVD-vaccinated cows. Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date. To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders. After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle. We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months. The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections.

Renal failure and progressive pancytopenia.

Hyperparathyroidism may be a precipitating factor to the development of myelofibrosis; however, this is extremely rare with only a few documented case reports of myelofibrosis caused by secondary hyperparathyroidism. We describe a case of a 24-year-old female who had a failed live donor renal transplant and secondary hyperparathyroidism. While on haemodialysis she became increasingly pancytopenic despite erythropoietin injections and adequate iron, vitamin B12 and folate replacement. Her secondary hyperparathyroidism evolved to tertiary hyperparathyroidism despite vitamin D supplementation and phosphate binders. In order to determine the cause of her pancytopenia, a bone marrow biopsy was performed that confirmed myelofibrosis due to her secondary hyperparathyroidism. Following a successful parathyroidectomy in a tertiary hospital, her pancytopenia resolved and she is now awaiting a second transplant.