scholarly journals Time to Abandon the Serum Cobalamin Level for Diagnosing Vitamin B12 Deficiency

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2447-2447 ◽  
Author(s):  
Sven R Olson ◽  
Thomas G. Deloughery ◽  
Jason A Taylor

Abstract B12 deficiency is a common, reversible cause of macrocytic anemia and neurological symptoms. Suspected B12 deficiency can be evaluated both directly and indirectly using a variety of assays. The serum cobalamin level, despite highly variable sensitivity and specificity, is often the sole test relied upon to diagnose B12 deficiency, despite being influenced by many common medical conditions. B12 levels tend to fall late in deficiency, making it less useful in detecting acute fluctuations in body stores. In addition, assay methodology has proven problematic, with high rates of falsely normal cobalamin levels using newer chemi-luminescent technologies. Most assays also tend to measure total serum cobalamin, notwithstanding the fact that 80% of cobalamin circulates in biochemically inert form. These factors make it difficult to establish thresholds for "normal" serum cobalamin. B12 status exist along a continuous spectrum ranging from subclinically low vitamin concentrations, as observed in vegans who maintain a system of enterohepatic circulation, to fulminant deficiency with severe clinical signs and symptoms. Serum cobalamin <200 pg/mL is a threshold commonly used to delineate true deficiency, though such low levels are infrequently observed. Methylmalonic acid (MMA), a molecular intermediate in a unique metabolic pathway requiring cobalamin as a cofactor, can be also be used to assess B12 status. MMA reflects tissue availability of biochemically active cobalamin rather than total cobalamin, with an excellent sensitivity. Fluctuations in MMA occur rapidly, and are detectable in the setting of subtle neurologic, psychiatric or hematologic signs and symptoms when corresponding serum cobalamin levels may remain normal. False positive MMA can be seen in renal dysfunction, though typically to a far milder degree than true deficiency. To explore the operating characteristics of these serum tests in detecting clinical B12 deficiency, we retrospectively identified all MMAs measured at our institution over the 2015 calendar year and compared any elevated values with corresponding serum cobalamin levels drawn within the same week. 34 of 42 (81%) elevated MMAs were associated with a serum cobalamin level within our laboratory's reference range, and six (14%) of these were actually greaterthan the upper limit of normal. Acknowledging the limited size of our data set, this translates to a 19% sensitivity of serum cobalamin for detecting elevations in MMA and, by extrapolation, detecting clinical B12 deficiency. This sensitivity is far lower than that commonly reported in the literature. Despite the superior test characteristics of MMA, serum cobalamin is often the first and only test performed to evaluate B12 status due to "economic" reasons or force of habit. If only the cobalamin level were relied upon, many patients would go untreated for a curable disease. While the cost difference of serum cobalamin and MMA assays at our hospital ($7.00 and $18.00, respectively) is not negligible, the time and expense of repeated cobalamin measurements or other testing necessary to accurately diagnose B12 deficiency is arguably greater. The mass of accumulated data shows that serum cobalamin is an insensitive assay for B12 deficiency and should be abandoned. MMA is superior for detecting diminished functional B12 stores; increased utilization of this test will result in more accurate and cost-efficient diagnosis of true B12 deficiency. Disclosures Taylor: Baxalta/Shire: Consultancy, Research Funding; Novo Nordisk: Research Funding; Kedrion: Research Funding; CSL Behring: Consultancy, Research Funding.

Author(s):  
Aryati Aryati ◽  
Dwi Retno Pawarti ◽  
Izzuki Muhashonah ◽  
Janti Tri Habsari

Allergic rhinitis is an allergic disease that is most often found beside bronchial asthma and eczema with the prevalence of is about33.3%, 9.8% and 11.2% respectively. The main examinations of allergic rhinitis are Skin Prick Test (SPT) and specific IgE, becausethe sensitivity and specificity of specific IgE examination depend on the examination method. To know the diagnostic value of specificIgE immunoblot examination by determination and were compared with ELISA in patients with allergic rhinitis. The cross-sectionaldesign of the study is con-ducted on patients at the Outpatient Clinic Department of ENT-Head and Neck from May until October 2014.Patients were grouped as diagnosis of allergic rhinitis and non-allergic non-infectious rhinitis based on clinical signs and symptoms,physical examina-tion, positive in SPT examination with or without an increase in total serum IgE and/or blood eosinophils. SpecificIgE immunoblot was conducted by using Foresight®, Acon Laboratories and the ELISA method using Allercoat™. The sensitivity andspecificity of inhalant allergen -specific IgE immunoblot Foresight® method was 73.9% and 42.9%, respectively. The sensitivity andspecificity of inhalant allergen -specific IgE ELISA method was 67.4% and 57.1%, respectively. The results of these two methods havea correlation coefficient 0.531 with p=0.000. The sensitivity and specificity of ingestan allergen specific IgE immunoblot Foresight®method was 41.3% and 85.7%, respectively. The sensitivity and specificity of ingestan allergen specific IgE ELISA method was 17.4 and78.6%, res-pectively. Results of these two methods have a correlation coefficient 0.375 with p=0.003. Based on this study of specificIgE immunoblot and ELISA methods, both have diagnostic sensitivity and specificity, which are almost the same. The sensitivity ofimmunoblot method inhalant allergens are superior to ELISA. The Immunoblot method ingestan allergen specificity is superior toELISA.


2019 ◽  
Vol 6 (2) ◽  
pp. 559
Author(s):  
P. Sudhakar ◽  
P. Ajitha

Background: The Yale observation scale (YOS) is an illness severity helps to diagnose bacteremia based on simple noninvasive clinical signs and symptoms. The aim of the present study was to assess the utility of YOS as a predictor of bacterial infection in febrile children aged 3 to 36 months.Methods: This prospective observational study was conducted on 200 children aged 3 to 36 months presenting with fever, at the Institute of Child Health and Hospital for Children during the period from April 2016 to September 2016. Rectal temperature was taken for all children. Clinical examination was done as required based on the YOS and scores were given accordingly at the time of initial presentation of the child before invasive investigations. All the observation was assessed statistically and receiver operating characteristics (ROC) curve was performed to analyze the sensitivity of the YOS.Results: Highly significant correlation (p=0.0001) was found to exist between the age of the child, duration of the fever, higher body temperature >104, WBC count, ANC and improved condition of patient with higher YOS. ROC curves showed that the sensitivity and specificity of YOS at the best cut off value of 14.5 was found to be 97% and 79.6% respectively.Conclusions: YOS is very good tool for predicting bacteremia in young febrile children based on simple non-invasive clinical signs and symptoms. The findings ruled out by YOS aids in the immediate and early management of bacterial infections before the arrival of the results of the biochemical diagnostic tests.


2018 ◽  
Vol 119 (6) ◽  
pp. 629-635 ◽  
Author(s):  
Sadanand Naik ◽  
Namita Mahalle ◽  
Vijayshri Bhide

AbstractThe prevalence of a sub-clinical vitamin B12 deficiency in the vegetarians is high. Total serum vitamin B12 concentration alone does not reliably reflect vitamin B12 status. Holotranscobalamin (holo-TC) II is a bioactive B12 fraction promoting specific uptake of B12 by cells and the circulating concentration reflects the intake of B12, whereas total homocysteine (tHcy) indicates the metabolic ability. In this study, we investigated the diagnostic value of circulating holo-TC, B12, folate and homocysteine in vegetarians who were at risk of B12 deficiency. B12-related biomarkers were measured in 119 young, healthy graduate vegetarians. None was folate deficient. As per reported definition, half were B12 deficient; 70 % of males and 50 % of females had low plasma holo-TC concentrations; and 92 % of males and half of females had hyperhomocysteinaemia. None had any clinical signs of B12 deficiency. Receiver operating characteristic curve analysis demonstrated similar AUC at the B12 concentration of 100 and 150 pmol/l when holo-TC (0·777 and 0·784) and homocysteine (0·924 and 0·928) were used as variables. Cut-off value of 100 pmol/l resulted in the highest sensitivity of 77·78 % and specificity of 71·05 % with a predictive value of 19·6 pmol/l for holo-TC and a sensitivity of 82·72 % and specificity of 89·7 % with a predictive value of 21·7 µmol/l for homocysteine. The combination of B12, holo-TC and tHcy improves the diagnostic accuracy at these cut-offs, and we suggest that for the young Indian vegetarians the cut-off for plasma B12 and holotrancobalamin is 100 pmol/l and 19·6 pmol/l, respectively, and for homocysteine it is 17·6 (females) and 27 µmol/l (males) for identifying B12 deficiency.


2017 ◽  
Vol 4 (4) ◽  
pp. 1341 ◽  
Author(s):  
Sadhan Kumar Cheekuri ◽  
Alok Mohanty ◽  
T. Ganesh ◽  
R. Kannan ◽  
Robinson Smile

Background: Appendicitis is the most common acute abdominal condition requiring emergency surgery, with a lifetime risk of 6%. Appendectomy continues to be one of the commonest procedures in general surgery, accounts for approximately 1% of all surgical operation. Despite the increased use of ultrasonography, computed tomography scanning and laparoscopy, the rate of misdiagnosis of appendicitis has remained constant (15.3%). The aim of this study was to whether Serum Bilirubin can be considered as a new laboratory marker to aid in the diagnosis of acute appendicitis and if so, does it have the predictive capacity to warn us about complicated appendicitis.Methods: This was prospective observational study done in Mahatma Gandhi Medical College and Research Institute, Pondicherry between November 2014 and August 2016. About 110 patients of acute appendicitis who had undergone appendicectomy were studied. Data was collected and analyzed critically.Results: Males 66 (60%) outnumbered females 44 (40%) and overall mean age was 26.61±12.37 years. Of the 110 patients, 9% were normal appendix, 59.09% were confirmed as acute appendicitis while 31.81% were diagnosed with complicated appendicitis on biopsy. The Sensitivity and Specificity of serum bilirubin as a marker in predicting Acute appendicitis and complicated appendicitis was 47.6% and 90.9% respectively. Similarly, the Positive predicative value and Negative predicative value for the same was 88.5% and 61.5% respectively with odds ratio 12.4 with significant p value <0.0001.Conclusions: Serum bilirubin is easily available test and cheap and can be estimated from the sample of blood drawn for routine blood investigations. Patients with clinical signs and symptoms of appendicitis and with hyperbilirubinemia should be identified as having a higher probability of complicated appendicitis. Hence, serum bilirubin levels have a predictive potential for the diagnosis of severity of acute appendicitis and need for early appendicectomy. If total serum bilirubin is added to already existing laboratory tests, then the diagnosis of complicated appendicitis in clinically suspected cases can be made with fair degree of accuracy, the need for CECT and MRI can be reduced and unnecessary delay in appendicectomy can be avoided.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3773-3773
Author(s):  
Fabrizia Bamonti ◽  
Nicola Fracchiolla

Abstract A diagnosis of macrocytic anemia, a common blood disorder presenting in many forms, requires additional tests to determine the underlying cause. In particular, the prevalence of a sub-clinical functional Vitamin B12 (B12) deficiency in the general population is higher than expected. Treatment of B12 deficiency is important to prevent neurological and/or hematological complications but requires a reliable diagnosis. Total serum cobalamin concentrations may not reliably indicate B12 status. Several recent studies have reported that holotranscobalamin (HoloTC), the bio-available cobalamin fraction, would be an early indicator of B12 status with improved accuracy compared to total serum B12. We evaluated the diagnostic value of measurements of a macrocytic anemia panel (total B12, HoloTC, Folate and Homocysteine) in order to characterize populations at risk of metabolic cobalamin deficiency. Our observational study included 66 myelofibrosis patients (MF), 56 neurological patients (26 probable Alzheimer’s disease, AD; 17 Mild Cognitive Impairment, MCI; 13 Vascular Disease,VaD), 20 vegans (V) and 16 apparently healthy volunteers (C) matched for age and sex. Serum concentrations of B12, Folate, and HoloTC were determined by microparticle enzyme immunoassay (MEIA); plasma Hcy levels were measured by fluorescence polarization immunoassay (FPIA) all on the Abbott AxSYM analyser. Hyperhomocysteinemia (>12 micromol/L) was present in 33.3% of MF (median 10.4, range 3.9–30.9); 38.5% of AD (median 11.4, range 7.1–46.5); 41.2% of MCI (median 12.0, range 8.3–16.4); 69.2% of VaD (median 15.0, range 6.6–23.6); 76.5% of V (median 14.2, range 5.9–31.5) and 33.3% of C (median 10.0, range 5.7–15.8). Low levels of B12 (< 180 pmol/L) were found in 10.6% of MF (median 471, range 137–959); 11.5% of AD (median 275, range 78–695); 11.8% of MCI (median 259, range 127–648); 15.4% of VaD (median 283, range 114–591); 10.6% of V (median 231, range 172–883) and 11.1 % of C (median 237, range 177–795). Low levels of HoloTC (< 35 pmol/L) were found in 43.9% of MF (median 46, range 14.9–123); 46.1% of AD (median 43, range 6.0–185); 52.9% of MCI (median 37, range 12–114); 23.1% of VaD (median 56, range 31–105); 82.3% of V (median 15.3, range 4.1–197) and 33.3 % of C (median 45, range 29–75). Vegans showed HoloTC levels significantly lower than all the other groups (p<0.02, Mann Whitney U test). Folate levels were considered not to add information in this context. Our preliminary findings clearly showed that HoloTC together with Hcy can help detect subjects likely to develop neurological and/or hematologic complications, and thereby likely to benefit from early tailored pharmacological treatment. In conclusion, HoloTC determination may be included as a complementary or alternative diagnostic strategy. Anemia Panel Results In At-Risk Groups Group Hcy>12μmol/L(%) B12<180pmol/L (%) HoloTC<35pmol/L (%) MF 33.3 10.6 43.9 AD 38.5 11.5 46.1 MCI 41.2 11.8 52.9 VaD 69.2 15.4 23.1 V 76.5 10.6 82.3 C 33.3 11.1 33.3


2017 ◽  
Vol 4 (9) ◽  
pp. 3024
Author(s):  
Ramaswami Y. B. ◽  
Prakash H. S. ◽  
Raghavendra Prabhu T. C. ◽  
Faiyaz Abdul Jabbar

Background: Appendicitis is one of the commonest causes of abdominal pain requiring emergency surgery. Diagnosing acute appendicitis clinically still remains a common surgical problem as the clinical signs and symptoms of other abdominal pathologic conditions mimic the diagnosis of acute appendicitis. Delay in diagnosis and surgery for this condition may lead to various complications like perforation, abdominal abscess etc. By knowing perforation prior to the exploration, we can manage the condition very effectively in terms explaining the prognosis of disease, morbidity of surgery, wound infection, and requirement of emergent nature of surgery. Aim of the study is to determine of role of hyperbilirubinemia as a new diagnostic marker to predict gangrenous/perforated appendicitis.Methods: It’s a retrospective study was conducted in the department of surgery, MMCRI, Mysore during the period of January 2015 to December 2015 total of 100 patients with clinical as well as ultrasonographic diagnosis of acute appendicitis or appendiceal perforation were made. The serum bilirubin test was carried out in all the patients pre-operatively.Results: In the study, the total 100 patients enrolled for the study, hyperbilirubinemia (> 1.2 mg/dL) in present study was found in 47 patients with 19 acute and 28 patients perforated appendicitis of all the 100 patients while 53 patients had normal bilirubin levels (≤ 1.2 mg/dL) 51 patients acute and 2 patients perforated appendix.Conclusions: Total serum bilirubin appears to be a new promising laboratory marker for diagnosing appendicular perforation. The patients with clinical signs and symptoms of appendicitis and with hyperbilirubinemia without elevation of liver enzymes should be identified as having a higher probability of appendicular perforation, suggesting total serum bilirubin levels have a predictive potential for the diagnosis of appendicular perforation.


2016 ◽  
Vol 12 (3) ◽  
Author(s):  
Ann Tammelin

Swedish nursing homes are obliged to have a management system for systematic quality work including self-monitoring of which surveillance of infections is one part. The Department of Infection Control in Stockholm County Council has provided a simple system for infection surveillance to the nursing homes in Stockholm County since 2002. A form is filled in by registered nurses in the nursing homes at each episode of infection among the residents. A bacterial infection is defined by antibiotic prescribing and a viral infection by clinical signs and symptoms. Yearly reports of numbers of infections in each nursing home and calculated normalized figures for incidence, i.e. infections per 100 residents per year, as well as proportion of residents with urinary catheter are delivered to the medically responsible nurses in each municipality by the Department of Infection Control. Number of included residents has varied from 4,531 in 2005 to 8,157 in 2014 with a peak of 10,051 in 2009. The yearly incidences during 2005 - 2014 (cases per 100 residents) were: Urinary tract infection (UTI) 7.9-16.0, Pneumonia 3.7-5.3, Infection of chronic ulcer 3.4–6.8, Other infection in skin or soft tissue 1.4–2.9, Clostridium difficile-infection 0.2–0.7, Influenza 0–0.4 and Viral gastroenteritis 1.2–3.7. About 1 % of the residents have a suprapubic urinary catheter, 6–7 % have an indwelling urinary catheter. Knowledge about the incidence of UTI has contributed to the decrease of this infection both in residents with and without urinary catheter.


Healthcare ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 498
Author(s):  
Mark Reinwald ◽  
Peter Markus Deckert ◽  
Oliver Ritter ◽  
Henrike Andresen ◽  
Andreas G. Schreyer ◽  
...  

(1) Background: Healthcare workers (HCWs) are prone to intensified exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the ongoing pandemic. We prospectively analyzed the prevalence of antibodies against SARS-CoV-2 in HCWs at baseline and follow up with regard to clinical signs and symptoms in two university hospitals in Brandenburg, Germany. (2) Methods: Screening for anti-SARS-CoV-2 IgA and IgG antibodies was offered to HCWs at baseline and follow up two months thereafter in two hospitals of Brandenburg Medical School during the first wave of the COVID-19 pandemic in Germany in an ongoing observational cohort study. Medical history and signs and symptoms were recorded by questionnaires and analyzed. (3) Results: Baseline seroprevalence of anti-SARS-CoV-2 IgA was 11.7% and increased to 15% at follow up, whereas IgG seropositivity was 2.1% at baseline and 2.2% at follow up. The rate of asymptomatic seropositive cases was 39.5%. Symptoms were not associated with general seropositivity for anti-SARS-CoV-2; however, class switch from IgA to IgG was associated with increased symptom burden. (4) Conclusions: The seroprevalence of antibodies against SARS-CoV-2 was low in HCWs but higher compared to population data and increased over time. Screening for antibodies detected a significant proportion of seropositive participants cases without symptoms.


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