Cobalamin deficiency presenting with thrombotic microangiopathy (TMA) features: A systematic review.

INTRODUCTION: Cobalamin deficiency may result in hematologic characteristics similar to thrombotic microangiopathy (TMA). To facilitate diagnosis, we reviewed reported cases of acquired cobalamin deficiency presenting with TMA features (c.def-TMA). METHODS: A literature search identified reports of c.def-TMA. Deficiency was defined as B12 levels of <118 pmol/L. Corrected reticulocyte counts and reticulocyte production indexes were calculated. Clinical features were presented as proportion abnormal and results summarized as medians and interquartile ranges (IQR). RESULTS: Patient level data was extracted from 41 identified cases. Median age (years) was 43 (30-55) with 21/41 (51%) being female. Cobalamin deficiency was noted in 35/40 (87.5%) but fold increases in MMA and HC were 30 and 6, respectively. The etiology was pernicious anemia in 28/41 (68%) cases. Anemia was both universal and severe, with hemoglobin levels of 55 g/L (4.7-6.6). Hypersegmented neutrophils were noted in 23/37 (62%), schistocytes in 29/38 (76%) and median LDH levels 3981 U/L (2004-5467). The RPI was <3.0% in all patients. Thrombocytopenia occurred in 33/41 (80.5%) with a median platelet count of 91 × 109/L (42-112). Plasma infusion or exchange was initiated in 14/41 (34%) with associated complications in 2 cases. CONCLUSION: Reticulocytopenia (RPI of <3.0%) was a universal finding that aids in differentiating c.def-TMA from other causes of hemolysis. C.def-TMA was associated with severe anemia, generally mild-moderate thrombocytopenia, and significant elevations in LDH.

George Minot and Pernicious Anemia.

George Minot (1885-1950) was born in Boston, Massachusetts. He was great grandson of James Jackson, co-founder of Massachusetts General Hospital in 1821. Graduating from Harvard College he enrolled at Harvard Medical School and obtained his MD in 1912. As a house pupil (intern) at the hospital he became interested in diseases of the blood and began taking meticulous histories of dietary habits of patients with anemia.

Patient journeys: diagnosis and treatment of pernicious anaemia.

BACKGROUND: Instigating a patient support group for patients with pernicious anaemia (PA) revealed dissatisfaction with its current diagnosis and treatment. The authors investigated the clinical features, patient experience of diagnosis and treatment of PA in the UK. METHODS: A total of 889 patients registered with the PA Society support group completed an online survey or postal questionnaire. Outcome measures included clinical features, length of time to diagnosis and patient satisfaction with current treatment RESULTS: One-third of patients experienced symptoms for up to 1 year before diagnosis; 14% waited more than 10 years for a diagnosis. Neurological features were highly prevalent, the most common being memory loss and poor concentration. Nearly two-thirds of respondents were dissatisfied with current treatment; 10% used a non-licensed form of B12 to supplement their prescribed injections. CONCLUSION: The diagnosis and treatment of PA should be subject to a thorough review. This article discusses the patient survey and results and makes recommendations for how the diagnosis and treatment of PA may be evaluated.

Modulation of serum gastric parietal cell antibody level by levamisole and vitamin B12 in oral lichen planus.

OBJECTIVES: The objective of this study was to test the efficacy of three different treatment modalities on the reduction of serum anti-gastric parietal cell autoantibody (GPCA) level in GPCA-positive oral lichen planus (OLP) patients. MATERIALS AND METHODS: Of 147 GPCA-positive OLP patients, 100 were treated with levamisole plus vitamin B12, 10 with vitamin B12 only and 37 with levamisole only. The serum GPCA levels in 147 OLP patients were measured at baseline and after treatment. RESULTS: Treatment with levamisole plus vitamin B12 for a period of 2-50 months and treatment with vitamin B12 only for a period of 4-44 months could effectively reduce the high serum GPCA level to undetectable level in 100 and 10 OLP patients, respectively. However, treatment with levamisole only for a period of 2-50 months could not modulate the high mean serum GPCA titer to a significantly lower level in 37 OLP patients. A 92% GPCA recurrence rate was found in 25 OLP patients receiving no further vitamin B12 treatment during the GPCA-negative remission period. CONCLUSION: For GPCA-positive OLP patients, treatment modality containing vitamin B12 can effectively reduce the high serum GPCA level to undetectable level. OLP patients with underlying autoimmune atrophic gastritis trait should receive a maintenance vitamin B12 treatment for life.

Use of hyperbaric oxygenation as an adjunctive treatment for severe pernicious anaemia in a bloodless medicine patient.

Severe anaemia in patients who cannot receive blood transfusion is an indication for the use of hyperbaric oxygen therapy (HBO). Most reports of the use of HBO for anaemia involve patients with acute blood loss. This report details a case of HBO used for a patient with severe pernicious anaemia. A 35-year-old Jehovah's Witnesses believer presented to a hospital with fatigue, dyspnoea and haemoglobin of 26 g/L. She was diagnosed with pernicious anaemia. As she could not receive blood transfusion due to her religious beliefs, vitamin B12 supplementation and HBO were administered and resulted in significant improvement in her condition. The mechanisms of action of HBO, including increased systemic plasma oxygenation, can alleviate signs and symptoms of anaemia regardless of its aetiology. HBO administration can greatly enhance the plasma arterial oxygen content, leading to clinical improvement in patients with anaemia who cannot receive blood transfusion.

Pancytopenia and TTP-like picture secondary to pernicious anaemia.

A 21-year-old man presented to the emergency department with generalised weakness, weight loss and decreased appetite for few weeks. He had evidence of severe pancytopenia and haemolysis. His peripheral smear with many schistocytes was suspicious for thrombotic thrombocytopenic purpura (TTP). He was supported with blood transfusions and daily plasmapheresis. His platelet counts worsened despite 4 days of therapy. Bone marrow biopsy was significant for hypercellular bone marrow with megaloblastic changes. Further workup revealed normal ADAMTS13 level, low vitamin B12, positive intrinsic factor antibodies and high methylmalonic acid. Diagnosis of pernicious anaemia was established and he was started on daily treatment with intramuscular vitamin B12 which subsequently improved his symptoms and haematological parameters. This report highlights the importance of checking vitamin B12 level in patients presenting with pancytopenia and TTP-like picture before making a diagnosis of TTP.

[Pernicious anemia in an adolescent with type 1 diabetes mellitus]. / Maladie de Biermer chez une adolescente diabétique.

The most frequent organ-specific autoimmune diseases associated with type 1 diabetes mellitus in children are hypothyroidism and celiac disease. Among adults, other associations exist, notably with pernicious anemia, which is extremely rare in children. We relate the observation of an adolescent with type 1 diabetes mellitus and hypothyroidism, admitted for severe anemia in addition to chronic anemia caused by autoimmune gastritis. Blood cell count showed severe aregenerative anemia with pancytopenia, with signs of non-autoimmune hemolysis. Vitamin B12 levels were low, bone marrow aspiration revealed erythroid hyperplasia, and anti-intrinsic factor antibodies were positive, providing the diagnosis of pernicious anemia. Treatment with intramuscular vitamin B12 produced brisk reticulosis after 6 days, with a subsequent rapid resolution of the anemia. Follow-up of type 1 diabetes mellitus in children requires screening for organ-specific autoimmune diseases; in case of unexplained anemia, autoimmune gastritis must be suggested. It can evolve into pernicious anemia.

Autoimmune gastritis in type 1 diabetes: a clinically oriented review.

CONTEXT: Autoimmune gastritis and pernicious anemia are common autoimmune disorders, being present in up to 2% of the general population. In patients with type 1 diabetes or autoimmune thyroid disease, the prevalence is 3- to 5-fold increased. This review addresses the epidemiology, pathogenesis, diagnosis, clinical consequences, and management of autoimmune gastritis in type 1 diabetic patients. SYNTHESIS: Autoimmune gastritis is characterized by: 1) atrophy of the corpus and fundus; 2) autoantibodies to the parietal cell and to intrinsic factor; 3) achlorhydria; 4) iron deficiency anemia; 5) hypergastrinemia; 6) pernicious anemia may result from vitamin B12 deficiency; and 7) in up to 10% of patients, autoimmune gastritis may predispose to gastric carcinoid tumors or adenocarcinomas. This provides a strong rationale for screening, early diagnosis, and treatment. The management of patients with autoimmune gastritis implies yearly determination of gastrin, iron, vitamin B12 levels, and a complete blood count. Iron or vitamin B12 should be supplemented in patients with iron deficiency or pernicious anemia. Whether regular gastroscopic surveillance, including biopsies, is needed in patients with autoimmune gastritis/pernicious anemia is controversial. The gastric carcinoids that occur in these patients generally do not pose a great threat to life, whereas the danger of developing carcinoma is controversial. Nevertheless, awaiting a consensus statement, we suggest performing gastroscopy and biopsy at least once in patients with autoantibodies to the parietal cell, iron-, or vitamin B12-deficiency anemia, or high gastrin levels. CONCLUSION: The high prevalence of autoimmune gastritis in type 1 diabetic patients and its possible adverse impact on the health of the patient provide a strong rationale for screening, early diagnosis, periodic surveillance by gastroscopy, and treatment.

Pernicious anemia associated with cryptogenic cirrhosis: Two case reports and a literature review.

RATIONALE: Pernicious anemia (PA) is an autoimmune gastritis that results from the destruction of gastric parietal cells and the associated lack of an intrinsic factor to bind ingested vitamin B12. While an association between PA and various liver diseases has been rarely reported, reports of associated diseases include primary biliary cholangitis, autoimmune hepatitis, and Interferon-treated hepatitis C. We present 2 cases of PA associated with cryptogenic cirrhosis (CC), which has not been previously reported in the literature. PATIENT CONCERNS: A 42-year-old man presented with fatigue, pallor, and sustained abdominal distension that had persisted for 15 days. An 87-year-old man was admitted to the hospital for an unsteady gait and loss of appetite that had persisted for 20 days. DIAGNOSES: Symptoms, laboratory tests, and imaging findings for both patients were indicative of PA and CC.Both had neurological and psychiatric symptoms during hospitalization that were ultimately linked to a vitamin B12 deficiency but not hepatic encephalopathy. INTERVENTIONS: Both patients received intramuscular injections of vitamin B12. OUTCOMES: Hemoglobin levels of the 2 patients increased gradually, and their neurological symptoms were alleviated. LESSONS: PA associated with a liver disease is rare, and the underlying mechanism can only now be clarified. We speculate that autoimmune dysfunction and chronic vitamin B12 deficiency caused by PA might be unique causes of liver cirrhosis. Additional investigations are needed to verify these findings.

An acute transfusion reaction.

We present the case of a 67-year-old man who suffered an acute anaphylactic reaction during red cell transfusion due to the presence of anti-IgA antibodies. The incidence and clinical relevance of anti-IgA antibodies in IgA deficiency is reviewed, and the wider investigation and management of acute transfusion reactions is also discussed. This case highlights the need to consider the potential risks of blood component transfusion against the purported benefit.

The Lived Experience of Anemia Without a Cause.

This article explores anemia without an obvious cause from two perspectives: a patient and the evidence. Although evidence is required to drive favorable patient outcomes, the focus on evidence often hides the patient experience during diagnosis and treatment. Knowledge of experience with evidence can provide a deeper perspective for clinical decision making and meet nursing's ethical mandate to relieve suffering. Although one patient experience does not reflect every patient experience, this patient's experience demonstrates how difficult and dark anemia can be.

Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia: a case series.

BACKGROUND: Hyperhomocysteinemia has been suspected of favoring thrombosis. Several case-control studies and even a meta-analysis have confirmed a link between venous thrombosis and hyperhomocysteinemia. Homocysteine is due to genetic and acquired factors (poor diet in folate and vitamin B12, older age, renal impairment, thyroid diseases, and malignancies) induced by the intake and the concentrations of vitamin B9 or B12 in the majority of cases. CASES PRESENTATION: We report the cases of four Moroccan patients who presented with acute vein thrombosis of different sites: a 34-year-old man, a 60-year-old man, a 58-year-old man, and a 47-year-old woman. All patients had a low level of cobalamin with marked hyperhomocysteinemia with normal serum and red cell folic acid. Venous thrombosis revealed pernicious anemia in all patients. Their low levels of cobalamin, atrophic gastritis, and positive results for gastric parietal cell antibodies confirmed the diagnosis of pernicious anemia. There was no evidence of immobilization, recent surgery, malignancy, antiphospholipid antibody, myeloproliferative disorder, or hormone replacement therapy. No deficiencies in protein C and protein S were detected; they had normal antithrombin III function and factor V Leiden; no prothrombin gene mutations were detected. Treatment included orally administered anticoagulation therapy and cobalamin supplementation. The outcome was favorable in all cases. CONCLUSIONS: These reports demonstrate that pernicious anemia, on its own, can lead to hyperhomocysteinemia that is significant enough to lead to thrombosis. Understanding the molecular pathogenesis of the development of thrombosis in patients with hyperhomocysteinemia related to Biermer disease would help us to identify patients at risk and to treat them accordingly. The literature concerning the relationship between homocysteine and venous thrombosis is briefly reviewed.

Pancitopènia en un lactant secundària a anèmia perniciosa materna / Pancitopenia en un lactante secundaria a anemia perniciosa materna / Pancytopenia secondary to maternal pernicious anemia in an infant

Introducció. L’anèmia megaloblàstica és una causa poc freqüent de pancitopènia en lactants. La seva principal etiologia és el dèficit matern de vitamina B12 en recent nascuts alimentats exclusivament amb lactància materna, toti que en alguns casos aquest déficit pot ser secundari auna anèmia perniciosa materna.Cas clínic. Lactant de 3 mesos que va consultar a urgènciesper vòmits i estancament ponderal de 3 setmanesd’evolució. En l’analítica sanguínia destacava anèmia (hemoglobina 6,5 g/dL), trombocitopènia (12 x10E9/L) i leucopènia (5,5 x10E9/L) amb neutropènia severa (0,11x10E9/L). Els nivells de vitamina B12 van resultar ser de60 pg/mL. Davant la confirmació d’anèmia megaloblàstica,es completà l’estudi amb una analítica sanguínia i gastroscòpia materna que mostraren una anèmia perniciosa, prèviament desconeguda, causant del dèficit de cobalamina ala pacient. Es va iniciar suplementació amb vitamina B12endovenosa, comprovant-se bona resposta reticulocitària,augment de leucòcits i manteniment de xifra normal deplaquetes i hemoglobina.Comentaris. Les alteracions neurològiques secundàries aldéficit de vitamina B12 poden arribar a ser severes, i enalgunes ocasions fins i tot irreversibles. La importància delseu diagnòstic és la instauració de suplementació precoçper a corregir el dèficit i així millorar el pronòstic. (AU)

Introducción. La anemia megaloblástica es una causa poco frecuente de pancitopenia en lactantes. Su principal etiología es eldéficit materno de vitamina B12 en recién nacidos alimentadosexclusivamente con lactancia materna, aunque en algunos casospuede ser secundario a una anemia perniciosa materna.Caso clínico. Lactante de 3 meses que consultó a urgencias porvómitos y estancamiento ponderal de 3 semanas de evolución. Enla analítica sanguínea destacaba anemia (hemoglobina 6,5 g/dL), trombocitopenia (12 x10E9/L) y leucopenia (5,5 x10E9/L) con neutropenia severa (0,11 x10E9/L). Los niveles de vitamina B12 resultaron ser de 60 pg/mL. Ante la confirmación de anemia megaloblástica, se completó el estudio con una analítica sanguínea ygastroscopia materna que mostraron una anemia perniciosa, previamente desconocida, causante del déficit de cobalamina a la paciente. Se inició suplementación con vitamina B12 endovenosa,comprobándose buena respuesta reticulocitaria, aumento de leucocitos y mantenimiento de cifra normal de plaquetas y hemoglobina.Comentarios. Las alteraciones neurológicas secundarias al déficitpueden llegar a ser severas, y en algunas ocasiones incluso irreversibles. La importancia de su diagnóstico es la instauración de suplementación precoz para corregir el déficit y así mejorar el pronóstico. (AU)

Introduction. Megaloblastic anemia is a rare cause of pancytopeniain infants. Its main etiology is maternal vitamin B12 deficiency inexclusively breastfed newborns, although in some cases it may besecondary to maternal pernicious anemia.Case report. Three-month-old infant who consulted the emergencydepartment for vomiting and a three-week failure to thrive. Laboratory evaluation was significant for anemia (hemoglobin 6,5 g/dL),thrombocytopenia (12 x109/L) and leukopenia (5,5 x109/L) withsevere neutropenia (0,11 x109/L). Vitamin B12 levels were foundto be 60 pg/mL. Upon confirmation of megaloblastic anemia, thestudy was completed with a blood test and maternal gastroscopythat showed a previously unknown pernicious anemia causingthe patient's cobalamin deficit. Vitamin B12 supplementationwas started intravenously, proving good reticulocyte response,increase of leukocytes and normalization of platelet and hemoglobin values.Comments. Neurological alterations secondary to vitamin B12 deficit can be severe, and sometimes even irreversible. The importance of its diagnosis is the establishment of early supplementation to correct the deficit and thus improve the prognosis. (AU)

Coexistence of pernicious anemia and myasthenia gravis--a rare combination of autoimmune diseases in Taiwan.

About 5-10% of patients with myasthenia gravis concomitantly have other autoimmune diseases. However, the coexistence of myasthenia gravis and pernicious anemia is rare. Here, we report a 73-year-old Taiwanese woman who developed myasthenia gravis 5 months after the onset of pernicious anemia. Her myasthenic and pernicious anemia symptoms markedly improved after pyridostigmine, prednisolone and hydroxocobalamine treatment. It is important to recognize concurrence of myasthenia gravis and pernicious anemia in the same patient because the therapeutic results for both diseases are rewarding.

[Management, prevention and control of pernicious anemia]. / Manejo, prevención y control de la anemia perniciosa.

Pernicious anemia is the most frequent cause of megaloblastic anemia in our area, and it is the result of a vitamin B12 deficiency due, itself, to the decrease or absence of intrinsic factor (IF) because of gastric mucosa atrophy or autoimmune destruction of IF-producing parietal cells. With the existence of a severe gastric atrophy, there is a decrease in acid and IF production and a further change in vitamin B12 absorption. Fifty percent of the cases are associated to anti-IF antibodies, which presence in other autoimmune diseases is exceptional. In patients with pernicious anemia, measurement of anti-IF antibodies has high specificity (95%); however, measurement of anti-parietal cells antibodies has low specificity. The first-choice treatment is administration of vitamin B12 intramuscularly. The regimen is the administration of 1 mg of vitamin B12 daily for one week, weekly thereafter for one month and, then, every 2-3 months for life.

Advances in mechanisms, diagnosis, and treatment of pernicious anemia.

Pernicious anemia (PA) is an entity initially described in 1849 as a condition that consisted of pallor, weakness, and progressive health decline. Since then several advances led to the conclusion that PA is an autoimmune disease characterized by the deficient absorption of dietary cobalamin. It is currently recognized as the most common cause of cobalamin deficiency worldwide. We hereby review the current understanding of the disease and its neurological, hematological, and biochemical manifestations with emphasis on the diagnostic approach, treatment, and monitoring strategies. We propose an algorithm for the diagnostic approach considering the current performance and limitations of the available diagnostic tools for evaluation of cobalamin status and the presence of autoimmune chronic atrophic gastritis (CAG). Patients with PA require lifelong treatment with cobalamin replacement therapy. The current widely available treatment can be provided through enteral or parenteral cobalamin supplements, with comparable efficacy and tolerability.