Pernicious Anemia Patients Research Articles

Pernicious anemia is a common cause of cobalamin deficiency-caused megaloblastic anemia in Hainan, China

ABSTRACT Background Pernicious anemia (PA) is believed to be highly prevalent in Western countries but has rarely been reported in China. The study explores whether PA, an autoimmune disease, is an uncommon cause of cobalamin (vitamin B12) deficiency anemia in China. Methods Clinical and hematological data were collected from 90 cobalamin deficiency-caused megaloblastic anemia (MA) patients between July 2014 and December 2021. Through anti-intrinsic factor antibody (IFA) and anti-parietal cell antibody (PCA) testing, PA was distinguished from other causes of cobalamin deficiency leading to MA. Meanwhile, 30 healthy controls (HCs) were included to estimate the positive rates of IFA and PCA. Results Of the 30 HCs, only one tested positive for IFA, and all 30 tested negative for PCA. Among the 90 patients with cobalamin deficiency-caused MA, 76.7% were positive for IFA, and 47.8% were positive for PCA; a total of 76 patients (84.4%) were diagnosed with PA. The mean follow-up time was 41.0 ± 16.3 months. During the follow-up period, no case relapsed among the continuous cobalamin-supply treatment patients, while 24.4% of patients relapsed due to the interruption of maintenance cobalamin-supplement therapy (the median recurrence time was 54.0 ± 17.7 months). Conclusions The proportion of PA in cobalamin deficiency-caused MA patients in Hainan province was higher than 80%, which was more common than expected. Therefore, screening for IFA, PCA, endoscopic biopsy, and thyroid-related parameters are recommended for all cobalamin deficiency-caused MA patients. Furthermore, maintenance cobalamin-supplement therapy is important for PA patients.

Iron deficiency in pernicious anemia: Specific features of iron deficient patients and preliminary data on response to iron supplementation

While vitamin B12 (B12) deficiency is considered as the hallmark of pernicious anemia (PA), iron deficiency (ID) is also prevalent. Indeed, this auto immune gastritis is responsible for parietal cell atrophy and increase in gastric pH, leading to impaired iron absorption. We compared PA patients' features according to their iron status at PA diagnosis, and we assessed the iron status recovery after oral or intravenous iron supplementation. We prospectively included patients presenting with a newly diagnosed PA in a tertiary referral hospital between November 2018 and October 2020. Iron status was assessed at PA diagnosis then regularly during a standardized follow-up. In case of ID, the decision of treatment with oral and/or intravenous iron supplementation was left to the clinician convenience. We included 28 patients with newly diagnosed PA. ID was observed in 21/28 (75.0%) patients: from the PA diagnosis in 13 patients, or during the follow-up in 8 patients. Iron deficient PA patients had higher plasma B12 (p=0.04) and lower homocysteine levels (p=0.04). Also, ID was independently associated with the 'APCA (anti-parietal cell antibodies) alone' immunological status (absence of anti-intrinsic factor antibodies) after adjustment for age, gender and B12 level (aOR 12.1 [1.1-141.8], p=0.04). High level of APCA was associated with lower ferritin level. After 3 months of supplementation, 3/11PA patients normalized the iron status with oral iron supplementation, versus 7/8 with intravenous iron supplementation (p=0.02). The high frequency of iron deficiency in PA highlights the interest of regular assessment of iron status in this condition. ID was associated with a profile including APCA alone and less pronounced B12 deficiency. Intravenous iron supplementation seemed to be more efficient than an oral supplementation in these preliminary data.

Exploring the Association of Helicobacter pylori With Anti-intrinsic Factor and Anti-parietal Cell Antibodies in Pernicious Anemia: A Systematic Review.

Pernicious anemia, historically tied to vitamin B12 malabsorption due to intrinsic factor secretion impairment, has evolved in understanding, especially concerning its association with autoimmune gastritis. This systematic review dives deep into the multifaceted relationship between Helicobacter pylori (H. pylori) infection, autoimmune gastritis, and the presence of anti-intrinsic factors and anti-parietal cell antibodies. Comprehensive database searches revealed a higher prevalence of H. pylori infection in pernicious anemia patients, with some studies suggesting a consequential increase in the aforementioned antibodies. Interestingly, eradication of H. pylori displayed potential therapeutic effects; patients showcased reductions in antibody titers, improved histopathological findings, and reversion of atrophic changes in gastric corpus. Such outcomes highlight the conceivable benefits of considering H. pylori infection during the evaluation and management of pernicious anemia and autoimmune gastritis. However, disparities across studies make direct comparisons challenging. It's essential to approach the potential role of H. pylori in these conditions with caution. Further research is warranted to cement conclusions and refine clinical management strategies. This review seeks to prompt new investigative avenues into the intricate link between H. pylori, autoimmune gastritis, and pernicious anemia, ultimately enhancing patient care.

Elevated IL-19 Serum Levels in Patients With Pernicious Anemia and Autoimmune Gastritis.

Pernicious anemia (PA) is a megaloblastic anemia consisting of hematological, gastric and immunological alterations. The immunopathogenesis of PA is sustained by both autoantibodies (e.g. intrinsic factor (IFA) antibodies and anti parietal cell (PCA) antibodies and autoreactive T cells specific for IFA and the parietal cell proton pump ATPase. Iron deficient anemia (IDA) is a microcytic anemia and represents the most common cause of anemia worldwide. Our work aimed to investigate serum levels of several interleukins (IL) of the IL-20 cytokine subfamily in patients with PA, with IDA and in healthy subjects (HC). We compared serum levels of IL-19, IL-20, IL-26, IL-28A and IL-29 in 43 patients with PA and autoimmune gastritis, in 20 patients with IDA and no autoimmune gastritis, and in 47 HC. Furthermore, we analyzed the IL-19 cytokine production by gastric lamina propria mononuclear cells (LPMC) in eight patients with PA and four HC. We found that patients with PA have significantly higher serum levels of IL-19 (163.68 ± 75.96 pg/ml) than patients with IDA (35.49 ± 40.97 pg/ml; p<0.001) and healthy subjects (55.68 ± 36.75 pg/ml; p<0.001). Gastric LPMC from all PA patients were able to produce significantly higher levels of IL-19 (420.67 ± 68.14 pg/ml) than HC (53.69 ± 10.92 pg/ml) (p<0.01). Altogether, our results indicate that IL-19 serum levels are significantly increased in patients with PA but not with IDA and that IL-19 is produced in vivo in the stomach of PA patients. These data open a new perspective on PA pathogenesis and suggest that IL-19 may represent a novel important tool for the management of patients with PA.

Evaluation of vitamin D, vitamin B12 and Hemoglobin HbA1c levels in patients with type 1 diabetes mellitus

We aimed to evaluate the Vitamin D, Vitamin B12 and Hemoglobin A1c Levels in patients with T1DM. This study is a retrospective cross-sectional study. We classified patients as &lt;7.0% (good glycemic control) and ≥7% (poor glycemic control) based on HbA1c levels. Moreover, we divided the patients into four groups based on serum vitamin D concentrations. This study included 468 patients (257 females and 211 males) with T1DM. The present study revealed that the prevalence of vitamin D deficiency among children with T1DM was very high (49.57%). We found that the vitamin D, vitamin B12, ferritin, HGB and RBC levels were significantly lower in women than in men. The overall prevalence of poor glycemic control was 6.4%. When the groups we divided according to HbA1c levels were compared; we found that the fasting blood glucose and vitamin B12 were significantly lower, while insulin and Mg levels were significantly higher in the good glycemic control group compared to the poor glycemic control group. We found that as vitamin D increases, HbA1c, insulin and creatinine levels decrease, and vitamin B12 levels increases. The negative correlation of vitamin D levels with insulin levels (r:-0.320, p&lt;0.01) and HbA1c levels (r:-0.187, p&lt;0.01) was statistically significant . Our findings showed that, keeping the vitamin D levels high in T1DM patients is important in regulation of glycemic control. Considering the frequency of pernicious anemia in patients with T1DM, it is important to follow vitamin D, vitamin B12 and HbA1c levels in these patients.

Familial Risks between Pernicious Anemia and Other Autoimmune Diseases in the Population of Sweden.

Background Pernicious anemia (PA) is an autoimmune disease (AID) which is caused by lack of vitamin B12 (cobalamin) due to its impaired uptake. PA is a multifactorial disease which is associated with a number of other AID comorbidities and which is manifested as part of autoimmune polyglandular syndrome. Due to the shortage of family studies on PA, we planned to address the problem by assessing familial risks for concordant PA between family members and for discordant PA in families of other AID patients. Methods We collected data on patients diagnosed with AIDs from the Swedish hospitals and family data from a population register. We calculated standardized incidence ratios (SIRs) in families for concordant and discordant risks. Results The number of PA patients in the offspring generation (for which the familial risk was calculated) was 7701; 278 (3.6%) patients had a family history of PA. The population prevalence of PA was 0.9/1000. The familial risk for PA was 3.88 when any first-degree relative was the proband, equal for men and women. The familial risk was two times higher between siblings than between offspring and parents which may be due to complex genetic background. Associations of PA with 14 discordant AIDs were significant; these included some AIDs that have previously been described as comorbidities in PA patients and several yet unreported associations, including rheumatoid arthritis and other AIDs. Conclusions The familial risks for PA were high suggesting multifactorial genetic etiology. The results call for further population-level studies to unravel mechanisms of familial PA which may help to understand the etiology of this disease.

150 Patients with Pernicious Anemia Profiled: Contribution of Helicobacter Pylori, Autoimmune Disease, Thyroid Disease, and Paraproteinemia

Background/Purpose The recognition of the contribution of Helicobacter pylori (H. pylori) (Carmel et al Am J Gastroenterol 2001 96: 63.), plasma cell dyscrasias (Baz et al Cancer 2004 101:790.), autoimmune polyendocrine syndromes (APS), and other autoimmune disease to vitamin B12 absorption and pernicious anemia has lead to an appreciation of a more varied presentation of the disease. The purpose of this study is to document the spectrum of the disease as manifest in a cohort of patients diagnosed with pernicious anemia in a rheumatology clinic. Methods A retrospective chart review of history and physical, laboratory and x-ray studies was conducted among patients diagnosed with pernicious anemia over a 10 year period. Pernicious anemia was diagnosed on the basis of having had a low vitamin B12 level and the presence of intrinsic factor (IF) and/or anti-parietal cell antibodies (APA). Results A total of 150 patients, 106 female and 44 males ranging in age from 32-101 (mean 77.8) were diagnosed. Initial referral was based on acute fracture in 41, rheumatoid arthritis-30, arthritis-30, osteoporosis-16, pain-15, autoimmune disease-9, systemic lupus erythematosus-7, psoriasis-2. There was a history of major osteoporotic fracture in 55, heartburn-73, past peptic ulcer disease-16, thyroid disease-42, type 1 diabetes-12, and vitiligo-2. Fifty patients were taking a PPI. 101 patients had a sensory deficit at the level of the ankle including 38 with findings of glove and stocking sensory loss. Seventy one patients had IF antibodies, 53 had APA, and 26 had both IF and APA antibodies. Only 25 patients were anemic with 2 patients having an MCV &amp;gt;100 fL and 5 with a low iron. Folic acid was 8 ng/mL&amp;lt; in 9 patients with a predominance of IF antibodies (p=0.039). Vitamin D was &amp;lt;12ng/mL in 13. H. pylori was diagnosed based on urea breath test in 21 patients at the time of initial evaluation (Group 1). Paraproteins were identified with immunofixation in 19 patients, including 2 patients with myeloma (Group 2). Autoimmune disease diagnosis included rheumatoid arthritis-32, SS-a or SS-b positive Sjogren syndrome-9, systemic lupus erythematosus-3, psoriatic arthritis-4, CREST syndrome-2, spondyloathropathy-2, inflammatory bowel disease-2, PLA2R glomerulonephritis-1 (Group 3). Thyroid disease was present in 42 patients (Group 4) with the remaining 51 patients constituting Group 5. Mean age of the groups was 65.8, 77, 66, 71.3, and 71.7 years respectively. Twenty five patients had 1 disease associated with APS and 6 had 2 diseases. The diseases included as part of APS were: alopecia areata-1, vitiligo-2, primary Sjogren syndrome with SS-a and/or SS-b antibody-11, type 1 diabetes-12, Graves' disease-1, antithyroid antibody positive Hashimoto's disease-4. H. pylori breath test was given to 74 patients. There was a statistically significant increase of autoimmune disease present in the H. pylori positive Group 1 compared to 53 patients testing negative for H. pylori (p = 0.041). A history of major osteoporotic fracture was less common in the autoimmune Group 3 than Group 5 (p=0.0002). No other statistically significant differences were noted between Groups 1-5 or between patients with IF versus APA. Conclusion Pernicious anemia is more likely to be diagnosed in younger patients in the setting of autoimmune disease, especially primary Sjogren syndrome, elements of APS, and in those with H. pylori infection. In older patients fracture, neuropathy, and plasma cell dyscrasia are more likely clinical scenarios. The correlation found among pernicious anemia patients between H. pylori infection and underlying autoimmune disease supports the hypothesis that H. pylori can act as a trigger of an autoimmune response in a genetically predisposed host. Disclosures No relevant conflicts of interest to declare.

Diabetes mellitus and pernicious anemia: interrelated therapeutic triumphs discovered shortly after William Osler’s death

William Osler died on December 29, 1919, at the age of 70. Less than 1 year later, Frederick Grant Banting began a research project at the University of Toronto to find a treatment for diabetes mellitus. John James Rickard Macleod, director of physiology, gave him space, funding, and supplies. Charles Herbert Best, an undergraduate medical student, joined Banting. In 1921, Banting and Best isolated and purified insulin from pancreatic extracts of dogs. James Bertram Collip, a biochemist, helped in the purification process. The first American patient was treated with Toronto insulin in May 1922. Banting and Macleod were awarded the Nobel Prize in 1923 “for the discovery of insulin.” George Richards Minot, a young hematologist in Boston, had an obsessive interest in the effect of diet on anemia. In October 1921, Minot developed weight loss and was diagnosed with severe diabetes mellitus. By January 1923, the pioneering diabetologist, Elliott Proctor Joslin, began to treat Minot with insulin. Minot’s condition improved and he returned to work. In 1926, Minot and William Parry Murphy amazed the medical world when they eradicated anemia in 45 pernicious anemia patients by feeding them a half-pound of beef liver daily. Minot shared the 1934 Nobel Prize with Murphy and George Hoyt Whipple “for their discoveries concerning liver therapy in cases of anemia.” Minot remained on insulin the rest of his life. Osler described the clinical findings and blood picture of pernicious anemia nearly a half century before Minot but his observations were largely ignored. Osler had an intriguing connection to Banting. Had he lived, Osler would have been ecstatic over these two monumental therapeutic breakthroughs.

Role of Pernicious Anemia in Patients Admitted to Internal Medicine with Vitamin B12 Deficiency and Oral Replacement Therapy as a Treatment Option.

To determine the role of vitamin B12 deficiency in pernicious anemia and the efficacy of oral vitamin B12 replacement therapy given regardless of the etiology, and to compare the endoscopic and pathological findings in patients diagnosed with vitamin B12 deficiency. The study included 216 patients, aged 18 - 65 years, diagnosed with vitamin B12 level < 200 pg/mL between May 2015 and May 2016. Evaluation was made of the demographic characteristics of the patients, diseases, drugs used, dietary habits, previous use of vitamin B12 replacement therapy, family history of vitamin B12 deficiency, laboratory test values, and neurological symptoms present at the time of presentation. Endoscopy was applied to all the patients included in the study. Anti-parietal cell antibody (APCA) and anti-intrinsic factor antibody (AIFA) analyses were applied to all patients. Evaluation was made of a total of 216 patients diagnosed with vitamin B12 deficiency, comprising 145 (67.1%) females and 71 (32.9%) males. The mean vitamin B12 level of the patients was determined as 127 pg/mL at the time of presentation and 334 pg/mL after treatment. APCA positivity was determined in 40 (18.5%) patients, and AIFA positivity in 5 (2.3%) patients. Atrophy was determined endoscopically in 53 (24.5%) patients and pathologically in 90 (41.7%). Helicobacter pylori positivity was determined in 196 (90.7%) patients. A diagnosis of pernicious anemia (PA) was made in 4 (1.9%) patients (patients with AIFA positivity or APCA accompanied by corpus atrophy). APCA positivity was determined but not corpus atrophy in 36 (16.7%) patients and these cases were accepted as suspected pernicious anemia. In this study of 216 patients with vitamin B12 deficiency, stomach pathologies which could cause vitamin B12 deficiency (atrophic gastritis, HP, PA) and the responses to oral replacement therapy were investigated. As vitamin B12 absorption plays a role in the pathogenesis. Vitamin B12 deficiency can lead to atrophic gastritis, and this was determined with biopsy in 41.7% of the patients. APCA positivity was determined in 18.5% of the patients investigated with respect to autoimmune atrophic gastritis (pernicious anemia) and AIFA positivity in 2.3%. A diagnosis of PA was made in 4 (1.9%) patients from autoimmune marker positivity and the presence of corpus atrophic gastritis. HP was determined in 90.7% of the patients with vitamin B12 deficiency, and although no correlation was determined between HP and atrophy, HP positivity was determined in 84 (93.3%) of the patients with pathological atrophy. From the time of diagnosis, the patients in the study were prescribed 1,000 µg/day vitamin B12. At the 40-day follow-up examination, a significant increase was observed in the vitamin B12 levels of 92.5% of the patients. At the end of the study, as oral replacement therapy was seen to be effective to a great extent, even in patients with PA, it was concluded that for patients not responding to oral replacement therapy, it would be appropriate to apply parenteral vitamin B12 treatment. In developing countries such as Turkey, the role of HP infection in vitamin B12 deficiency must be kept in mind. The incidence of atrophic gastritis and pernicious anemia is higher than expected in vitamin B12 deficiency. Thus, it can be concluded that it is appropriate to investigate patients with vitamin B12 deficiency with respect to atrophic gastritis and PA, and oral replacement therapy should be the first stage in the treatment of vitamin B12 deficiency.

Receiving a Diagnosis of Pernicious Anemia: Exploring Experiences of Relationships With Health Professionals.

Objectives:Pernicious anemia (PA) is a chronic condition caused by vitamin B12 deficiency. This is a qualitative study using interpretative phenomenological analysis (IPA), which aimed to explore the patients lived experience of diagnosis and treatment.Methods:Eleven semistructured interviews were conducted in PA patients; these covered participants’ diagnostic and treatment journeys, the responses of others to their diagnosis, and the role health professionals have played in their medical care. Interviews were analyzed for recurrent themes using IPA.Results:Three superordinate themes were identified: “The struggle to achieve a diagnosis,” “The significance of a diagnosis,” and “Battling for sufficient treatment.” Participants were dissatisfied with their medical care due to diagnostic delay, insufficient treatment, and poor relationships with their health professionals. Many experienced, anticipated, and internalized stigma, which led to a reduced quality of life and withdrawal from the medical profession.Discussion:Participants’ interactions with their health professionals hindered their adaptation to their condition; this affected their psychological and physical well-being. Increased clinician awareness of stigma in the PA population symptoms and effective patient-centered communication is required.

Intrinsic factor Recognition Promotes Th17/Th1 Autoimmune Gastric Inflammation in Patients with Pernicious Anemia

Abstract The intrinsic factor (IF) is the major humoral autoantigen in pernicious anemia (PA)/autoimmune gastritis. Although many studies have examined the autoantibody response to intrinsic factor and H+,K+-ATPase, no information is available on possible pathogenic mechanisms mediated by IF-specific gastric T cells. The aim of this study was to investigate IF-specific T cells in the gastric mucosa of PA patients and define their functional properties. In vivo-activated T cells from the infiltrates of the gastric mucosa of PA patients were isolated and cloned. We investigated the ability of the gastric T-cell clones to proliferate and produce cytokines in response to IF, as well as their helper function for antibody production and their cytolytic potential. For the first time we provide evidence that gastric mucosa of PA patients harbour a high proportion (20%) of autoreactive activated CD4+ T-cell clones that specifically recognize IF. Most of these clones (94%) showed a Th17 or Th1 profile. Virtually all IF-specific clones produced TNFα, IL-21 and provided substantial help for B-cell immunoglobulin production. Most mucosa-derived IF-specific T-cell clones expressed perforin-mediated cytotoxicity and induced Fas-Fas ligand-mediated apoptosis in target cells. Altogether, our results suggest that chronic autoantigen-induced T cell– dependent B-cell activation is responsible for the local synthesis of IF autoantibodies found in the sera and indicate that activation of IF-specific Th17 and Th1 T cells in the gastric mucosa represent a key effector mechanism in PA suggesting that the Th17/Th1 pathway may represent a novel target for the prevention and treatment of the disease.

Intrinsic factor recognition promotes T helper 17/T helper 1 autoimmune gastric inflammation in patients with pernicious anemia.

The intrinsic factor is the major humoral autoantigen in pernicious anemia/autoimmune gastritis. Although many studies have examined the autoantibody response to intrinsic factor and H+,K+-ATPase, no information is available on possible pathogenic mechanisms mediated by intrinsic factor - specific gastric T cells. Aim of this study was to investigate intrinsic factor-specific T cells in the gastric mucosa of pernicious anemia patients and define their functional properties. For the first time we provide evidence that gastric mucosa of pernicious anemia patients harbour a high proportion (20%) of autoreactive activated CD4+ T-cell clones that specifically recognize intrinsic factor. Most of these clones (94%) showed a T helper 17 or T helper 1 profile. All intrinsic factor-specific clones produced tumor necrosis factor-α, interleukin-21 and provided substantial help for B-cell immunoglobulin production. Most mucosa-derived intrinsic factor-specific T-cell clones expressed cytotoxicity against target cells. Our results indicate that activation of intrinsic factor-specific T helper 17 and T helper 1 T cells in the gastric mucosa represent a key effector mechanism in pernicious anemia suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.

The risk of Clostridium difficile infection in patients with pernicious anaemia: a retrospective cohort study using primary care database.

Studies have found an association between proton pump inhibitor (PPI) use and Clostridium difficile infection. The purpose of this study was to determine whether the mechanism by which PPIs induce an increased risk of C. difficile infection is supported by the same mechanism acting in another cause of achlorhydria, pernicious anaemia. Using a database of anonymised primary care records between 1990 and 2013, we selected exposed patients with a diagnosis of pernicious anaemia treated with vitamin B12 therapy. Each exposed patient was matched by age, gender and general practice to up to 10 controls. Cox regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for C. difficile infection with pernicious anaemia, adjusted for potential confounders. We identified 45,467 exposed patients matched to 449,635 controls. The crude incidence rate of C. difficile infection was 1.85/1000 person-years for the exposed cohort and 1.09/1000 person-years for controls. Patients with pernicious anaemia had a greater risk of C. difficile infection than the controls (adjusted HR 1.57, 95% CI 1.40-1.76). Pernicious anaemia patients have an increased risk of C. difficile infection. This supports the theory that severe achlorhydria is the mechanism that increases the risk of C. difficile infection in long-term PPI users.

Chronic proton pump inhibition therapy in the diagnostic accuracy of serum pepsinogen I and gastrin concentrations to identify pernicious anaemia

BackgroundChronic use of proton pump inhibitors (PPIs) leads to increases in gastrin and pepsinogen-I serum concentrations. AimTo asses if chronic treatment with PPIs has an effect on serum gastrin and pepsinogen-I concentrations for the diagnosis of pernicious anaemia (PA). Materials and methodsSerum gastrin and pepsinogen-I were measured in 38 patients with PA and 74 without PA (controls); 17/38 PA patients and 36/74 controls were treated with PPIs. Receiver Operating Curves (ROC) were used to compare diagnostic accuracy of gastrin and pepsinogen-I for PA in patients under chronic treatment with PPIs and in untreated patients. ResultsPPI treatment increased pepsinogen-I in patients and in controls, while gastrin increased only in controls.In untreated patients, a pepsinogen-I <8.3ng/mL had 95.2% sensitivity and 100% specificity, whereas a gastrin >115pg/mL had 100% sensitivity and 92.11% specificity for PA diagnosis. In PPI-treated patients, a pepsinogen I<24.1ng/mL had a lower sensitivity (82.4%) but retained 100% specificity, however the best cut-off point for gastrin, 610pg/mL, had a very low sensitivity (58%). ConclusionsPPI chronic treatment decreased the diagnostic accuracy for the studied biomarkers, particularly of gastrin. In PPI-treated patients, serum pepsinogen-I concentrations >24.1ng/mL allowed rejecting a PA diagnosis with 100% specificity.

Cost of detecting gastric neoplasia by surveillance endoscopy in atrophic gastritis in Italy: A low risk country

BackgroundAtrophic gastritis (AG) is at increased risk of gastric neoplasia, thus surveillance gastroscopy has been proposed. AimsTo assess cost of detecting gastric neoplasias by surveillance endoscopy according to identified risk factors in Italy. MethodsPost-hoc analysis of a cohort study including 200 AG-patients from Italy followed up for a mean of 7.5 (4–23.4) years was done. Considered risk factors were: age >50years, extensive atrophy, pernicious anaemia, OLGA-OLGIM scores 3–4 at diagnosis. The number of 4-year-surveillance endoscopies needed to be performed to detect one gastric neoplasia (NNS) was calculated. ResultsIn 19 patients neoplasias (4 gastric cancers, 8 type 1 gastric carcinoids, 7 dysplasias) were detected at the 361 surveillance gastroscopies, corresponding to NNS of 19 and a cost per gastric neoplastic lesion of €2945. By restricting surveillance to pernicious anaemia patients, reduction of NNS and cost per neoplasia to 13.8 and €2139 may be obtained still detecting 74% of neoplasias. By limiting the surveillance to pernicious anaemia patients and OLGA 3–4, 5 (26.3%) neoplasias would have been detected with a corresponding NNS of 5.4 and a cost per lesion of €837. ConclusionRisk factors may allow an efficient allocation of financial and medical resources for endoscopic surveillance in AG in a low risk country.

Schistocytosis in B12 Deficiency (B12D) Reduces the MCV and Raises the RDW in the Absence of Iron Deficiency: a Cause of Unnecessary Plasmapheresis (PP)

Background:RBC size variation and microcytes in B12D are often ascribed, but rarely shown, to be due to co-existing Fe deficiency. Schistocytes (aka poikilocytes) were included in early descriptions of pernicious anemia (PA). As it also causes thrombocytopenia, B12D may be confused with thrombotic thrombocytopenic purpura (TTP). Because of the urgency of PP for TTP, it has sometimes been initial therapy for B12D with schistocytes.Purpose:Here we describe 3 PA patients, and review reports of 15 other severely anemic B12D cases, with schistocytes. As they are smaller than mature RBC, they may normalize the MCV, while raising the RDW. We wished to determine whether primary lab studies help to distinguish B12D from TTP.Case Reports:These patients presented with symptoms of severe anemia:Ferritins were normal or high, haptoglobins <30, anti-intrinsic factor and parietal cell antibodies present, and complete response to B12 therapy occurred. Significant numbers of schistocytes were present in all, as was a distinctive population of minute, hypochromic schistocytes (MHS).Review:We found 15 reports of individual B12D patients with schistocytes, published between 2003 and 2015. All but 2 vegans had PA, 6 being anti-IF Ab+. Median & median ages were 52 & 53, [Hb]’s 5.9 & 6.0, MCV’s 120 & 117 (3 normal), platelets 97 & 85, WBC 3200 & 3120, LDH’s 4050 & 5860; reticulocyte levels were all low for severe anemia. Iron deficiency anemia was not found; ferritin and/or Fe/TIBC were reported normal in 4. Six legible blood smear microphotographs were included, confirming schistocytosis. Five patients had one or more PP before B12 deficiency was discovered. All 15 responded completely to B12. MHS were also observed on 4 of the 6 legible microphotographs, and noted by authors. For comparison, our survey of 36 reported TTP legible blood smears failed to detect MHC.Conclusions:Schistocytes are observed in some severely anemic B12D, may account for as much as 6.7% of RBC, and alter their indices. Schistocytosis and thrombocytopenia suggest TTP, and may lead to unnecessary PP. But such patients' low reticulocyte counts and very high LDH levels are not typical of TTP. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Single nucleotide polymorphisms related to vitamin B12 serum levels in autoimmune gastritis patients with or without pernicious anaemia

BackgroundAutoimmune gastritis may present as pernicious anaemia arising from vitamin B12 malabsorption, but also with iron deficiency anaemia due to iron malabsorption. These different clinical presentations might have a genetic basis. Single nucleotide polymorphisms associated with vitamin B12 levels have not been investigated in autoimmune gastritis. AimsTo determine the frequency of single nucleotide polymorphisms related to vitamin B12 levels in autoimmune gastritis patients, with or without pernicious anaemia, compared to healthy controls. Methods14 single nucleotide polymorphisms associated with vitamin B12 levels were selected from literature. 83 autoimmune gastritis patients (43 with and 40 without pernicious anaemia) and 173 controls were enrolled. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping was performed using Sequenom MALDI-TOF mass spectrometry iPLEX platform. ResultsTCN2 (rs9606756) GG genotype, related with lower vitamin B12 levels, was found in 3 (3.6%) autoimmune gastritis patients (2 with pernicious anaemia), but in none of controls (p=0.02). FUT6 (rs3760776) AA genotype was present in four (4.8%) autoimmune gastritis patients (all pernicious anaemia) and three (1.7%) controls (p=0.007). ConclusionA genetic variant of TCN2 (rs9606756) related to lower vitamin B12 levels was more frequent in pernicious anaemia patients compared to controls, showing the plausibility of genetic factors determining the possible clinical manifestation of autoimmune gastritis.

Myelodysplastic Syndrome and Polymyalgia Rheumatica Associated With Pernicious Anemia

An 83-year-old man who had been treated for pernicious anemia (PA) developed myelodysplastic syndrome (MDS) and polymyalgia rheumatica (PMR). While PA patients are at an increased risk of malignant tumors, association with MDS is rarely reported. PA patients are also associated with various autoimmune conditions; however, association with PMR has not been reported. Derangement in the immune system associated with PA and subsequent MDS was assumed to have contributed to the development of PMR. J Hematol. 2015;4(2):181-183 doi: http://dx.doi.org/10.14740/jh204w

Pernicious Anemia in Patients with Primary Biliary Cirrhosis, Autoimmune Hepatitis, and Chronic Viral Hepatitis

Backgrounds: Cases of Pernicious Anemia (PA) with Autoimmune Liver Diseases (ALDs) or chronic viral hepatitis have been uncommon. There have been few articles regarding the associations between these diseases. Methods: A review of concomitant cases of PA in patients with ALDs, such as Auto Immune Hepatitis (AIH) or Primary Biliary Cirrhosis (PBC), and patients with chronic viral hepatitis with or without Interferon (IFN) treatment were conducted. Results: Six cases of concomitant PA and ALDs (five were PBC and one was AIH) and seven cases of chronic viral hepatitis (six were due to HCV, one was due to HBV; five cases were of IFN-induced PA and two were of PA without IFN treatment) have been reported. In these concomitant cases, serum vitamin B12 deficiency was documented in all 13 cases and serum Intrinsic Factor Antibodies (IFA) were positive in 11 of 12 cases, excluding one case in which detection of IFA was not mentioned. Conclusions: Although concomitant cases of PA in patients with ALDs or chronic viral hepatitis have been rarely reported, PA should be considered in cases of progressive macrocytic anemia in these patients.

High Percentage of Regulatory T Cells before and after Vitamin B12 Treatment in Patients with Pernicious Anemia

Introduction: In some previous studies, vitamin B₁₂ treatment showed immunomodulatory effects and restored the immunological abnormalities in patients with pernicious anemia (PA). In the present study, peripheral blood T cell subsets, including regulatory T cells (T_regs), were examined before and after vitamin B₁₂ treatment in PA patients. Patients and Methods: The percentages of CD4, CD8, Th1, Th2 and T_regs were examined in 23 PA patients before vitamin B₁₂ treatment, in 23 other PA patients after vitamin B₁₂ treatment and in 28 healthy controls. Results: The mean percentage of CD8+ T cells was significantly higher in the control group (23.0%; 95% CI, 20.4-25.6%) than in the pre- (16.0%; 95% CI, 12.1-20.0%) and posttreatment groups (15.2%; 95% CI, 11.8-18.6%; p < 0.05). The CD4/CD8 ratio was significantly lower in the control group (2.01; 95% CI, 1.66-2.34) than in the pre- (3.45; 95% CI, 2.55-7.80) and posttreatment groups (2.97; 95% CI, 2.22-3.72; p < 0.05). There was no significant difference in the mean Th1/Th2 ratio among these groups. There were significant increases in the mean percentage of T_regs in the pre- (6.29%; 95% CI, 5.04-7.54%) and posttreatment groups (7.77%; 95% CI, 6.34-9.20%) compared with the control group (4.18%; 95% CI, 3.92-4.47%; p < 0.05). Conclusions: The percentage of T_regs was significantly higher in PA patients than in normal subjects, and this high T_reg percentage was not different before and after vitamin B₁₂ treatment. Other immunological alterations also did not recover after vitamin B₁₂ treatment, so that these immunological changes appear to be the cause of PA and are not induced by vitamin B₁₂ deficiency.