scholarly journals Folate Deficiency in Chronic Liver Disease

Blood ◽  
1965 ◽  
Vol 25 (4) ◽  
pp. 443-456 ◽  
Author(s):  
FREDERICK A. KLIPSTEIN ◽  
JOHN LINDENBAUM

Abstract Fifty-five patients with liver disease of varied etiology and severity have been studied. Serum folate concentrations were subnormal and folic acid clearances rapid, when studied, in 19 actively imbibing alcoholic cirrhotics who had a megaloblastic anemia. Eleven patients, from both the nonalcoholic and alcoholic groups, had rapid folic acid clearances, with subnormal serum folate levels in seven, in the absence of morphologic evidence of folate deficiency. Serum B12 concentrations were uniformly normal or elevated. Dietary deficiency appeared to be the major cause of folate deficiency; all 19 patients who had megaloblastic changes were considered to have an inadequate dietary intake. Increased requirement for folate due to hyperactivity of the bone marrow secondary to gastrointestinal bleeding. hypersplenism, or hemolysis appeared to contribute to the development of abnormal folic acid determinations in many patients in both the alcoholic and nonalcoholic groups. Two of 10 patients studied had malabsorption of folic acid. Such factors as the presence of ascites, an expanded plasma volume, a Patent portacaval shunting procedure, the type of alcoholic beverage imbibed, and the severity of impairment of liver function did not appear to be of significance in the development of folate deficiency.

Blood ◽  
1967 ◽  
Vol 29 (5) ◽  
pp. 697-712 ◽  
Author(s):  
FREDERICK A. KLIPSTEIN ◽  
FREDERICK G. BERLINGER ◽  
L. JUDEN REED

Abstract Two patients have been described who were found to have a megaloblastic anemia due to folate deficiency while receiving treatment for pulmonary tuberculosis with isoniazid and cycloserine. In an additional 120 patients studied with tuberculosis, serum folate concentrations were subnormal in 7 of 12 inadequately nourished and in 5 of 24 well-nourished patients with untreated tuberculosis, in 15 of 29 patients taking isoniazid and cycloserine, but in only 2 of 55 patients receiving other combinations of drugs for tuberculosis. In vitro studies showed that isoniazid had a depressant effect on the growth of L. casei but only when added in a concentration that greatly exceeded the pharmacologic dose; cycloserine had a similar effect at a concentration that was only threefold greater than that usually found in patients receiving therapeutic doses of this drug. Serum concentrations of vitamin B12 were normal in both patients described with megaloblastic anemia as well as in all 36 patients with untreated tuberculosis and were in the indeterminate range in 14 and subnormal in 3 patients who were receiving drug therapy. The addition to medium in vitro of cycloserine, but not of isoniazid or pyrazinamide depressed the growth of L. leichmannii. These results confirm previously reported observations by others which indicate that folate deficiency is a frequent occurrence in patients with untreated tuberculosis. They suggest that abnormal folate determinations in these patients are due principally to inadequate dietary intake. In addition, the significantly greater incidence of abnormal folate determinations that was observed in adequately nourished patients taking cycloserine and the results of the in vitro studies suggest that this drug can be responsible for folate deficiency in some instances. The mechanism for this is unknown.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4655-4655
Author(s):  
Peter J. Miller ◽  
Elizabeth B. Agnew ◽  
Mary Ann Knovich ◽  
Andrew M. Farland ◽  
Johanna Waldron ◽  
...  

The utilization of folic acid during erythropoiesis is widely known and accepted in medical literature and deficiency is known to cause a characteristic megaloblastic anemia resulting from the inhibition or ineffective synthesis of DNA. Although the resultant megaloblastic anemia may take considerable time before evidence or symptoms present, there are more acute changes visualized on peripheral smear that are representative of a functional folate deficiency. In addition to erythrocyte macrocytosis, hypersegmentation of neutrophils can also be seen. Often times, despite these visualized changes measurement of serum folate and/or total red cell folate yields a result within the accepted “normal” range of the assay. It has been demonstrated that these visualized characteristics represent a functional folate deficiency and can be overcome with folic acid supplementation regardless of the measured folic acid levels indicating a yet to be understood mechanism of folate utilization. Here, we sought to measure the folic acid levels in the earliest erythrocyte progenitors in peripheral circulation, the reticulocytes. Methods Reticulocytes were isolated using anti-CD71 (the transferrin receptor) coated magnetic beads. After separation, a sample slide was made utilizing methylene blue for visual confirmation of reticulocyte isolation. The reticulocytes were then lysed with citric acid and a Nanodrop-1000 spectrophotometer was used to determine absorbance at 413 nanometers. This absorbance was used to determine the sample hemoglobin concentration from a simple calibration curve. The sample folic acid level was then determined using the lysing method utilizing mouse monoclonal anti-folate binding protein, paramagnetic particles coated in anti-mouse IgG, human serum albumin and milk folate binding protein. Results were calculated as nanogram of folate per gram of hemoglobin. Results Twenty-five samples from normal individuals, not taking folate supplements, were analyzed. The range of results was 2.51 to 17.38 with a mean level of 9.61. Conclusion This protocol effectively and efficiently allows for isolation of reticulocytes in numbers high enough for measurement of folate in nanogram per gram of hemoglobin. By this method we show the normal reticulocyte folate level to be approximately 3-15 ng/g of Hgb. This figure is consistent with the normal red cell folate concentration. Further analysis is planned for comparing these results in patients with a suspected functional folate deficiency but “normal” red cell folate levels. Efficient isolation of reticulocytes and measurement of folate levels will allow us to probe the underlying cause of acute folate deficiency seen in very sick patients. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1967 ◽  
Vol 30 (3) ◽  
pp. 341-351 ◽  
Author(s):  
MIRIAM B. DAHLKE ◽  
ELIZABETH MERTENS-ROESLER

Abstract A high incidence of subnormal serum folate levels in pediatric subjects receiving diphenylhydantoin is reported. The effect is observed shortly after the onset of therapy and is not related to dosage of drug. An adult epileptic, who presented with a megaloblastic anemia secondary to a diphenylhydantoin-induced folate deficiency, demonstrated normal serum and erythrocyte folate levels only after folic acid was administered orally in amounts of 600 µg. per day. The folate deficiency was due to malabsorption of folic acid induced by diphenylhydantoin. Folic acid tolerance tests performed at 0, 4, 12, 16 and 20 hours after diphenylhydantoin showed a progressive rise in serum levels as diphenylhydantoin was withheld for longer periods prior to the test dose of folic acid. Further evidence of improved absorption was an associated rise in urinary folates. In addition, the patient demonstrated a convincing hematologic response to ingested conjugase, in the form of chick pancreas. The hematologic response was observed, despite prior demonstration of conjugase activity in the patient’s intestinal secretions. Attempts to show inhibition of chick pancreas conjugase activity by diphenylhydantoin in vitro were unsuccessful. Several explanations for these conflicting observations are offered.


2018 ◽  
Vol 6 (1) ◽  
pp. 1
Author(s):  
Binoy Yohannan ◽  
Kristi McIntyre ◽  
Mark Feldman

Treatment of cancer patients with olaparib (PARP inhibitor) is associated with an increased risk of anemia, which is seen in a majority of treated patients. However, symptomatic anemia requiring transfusion is rare. Olaparib-induced anemia can be secondary to bone marrow suppression, hemolysis or folate deficiency. We report a case of new onset severe folic acid deficiency anemia in a patient with breast and relapsed fallopian tube cancer being treated with olaparib. Complete blood count on admission showed a hemoglobin of 4.2 g/dl and serum folate was undetectable (< 1.6 ng/ml; reference range 7-31.4 ng/ml). This is the second report of olaparib-induced folate deficiency anemia. She received three units packed red cell transfusion and parenteral folic acid supplementation and improved symptomatically. This case highlights the importance of recognizing folate deficiency as a reversible cause of anemia with PARP inhibitor therapy.


Blood ◽  
1969 ◽  
Vol 34 (2) ◽  
pp. 191-203 ◽  
Author(s):  
FREDERICK A. KLIPSTEIN

Abstract The response to therapy with oral tetracycline has been assessed in three subjects with tropical sprue, all of whom presented with a megaloblastic anemia due to combined folate and vitamin B12 deficiency, and all of whom were shown to have normal absorption prior to treatment of a physiologic dose of 25 µg. of folic acid, as tested by assay of the fecal excretion of a tritium-labeled test dose. Treatment was associated with clinical and intestinal improvement and a hematologic response in all three subjects. The serum folate concentration rose to normal in one subject and the absorption of a pharmacologic dose of folic acid was normal when tested by microbiologic assay at the termination of the 20 day treatment period in all three. In contrast, both the absorption and serum concentrations of vitamin B12 remained subnormal. These observations confirm the fact that folate deficiency can be present in some subjects with tropical sprue in whom the absorption of a physiologic dose of folic acid is normal. They suggest that in this circumstance folate repletion and the hematologic response secondary to tetracycline therapy in tropical sprue is mediated by a factor other than the absorption of crystalline folic acid; it is likely that this factor is increased absorption of dietary polyglutamate forms of folate.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 46-46
Author(s):  
Lindsey A Hildebrand ◽  
Brett Dumas ◽  
Charles Milrod ◽  
James Hudspeth

Introduction: Folate deficiency is a known cause of megaloblastic anemia. Serum folate level is therefore a common component of the workup for megaloblastic and other anemias. Following mandatory fortification of grain products with folic acid in the US in 1998, folate deficiency has become relatively rare in both the general population and in hospitalized patients. Some authors have suggested that serum folate levels should be tested rarely if at all in countries with mandatory folic acid fortification given low rates of deficiency, high cost per diagnosis of deficiency, and low rates of supplementation for those found to be deficient. However, given persistent racial, ethnic, and socioeconomic disparities in folate deficiency, these conclusions may not apply to all populations. In this study, we examine the rate at which serum folate testing detected folate deficiency in an urban safety net hospital and the characteristics of patients found to be folate deficient. Methods: All serum folate tests performed on inpatients and emergency department patients in 2018 at a large safety net hospital in Boston were reviewed. Serum folate levels under 4 ng/mL were considered deficient per WHO criteria. We reviewed the charts of all patients found to be folate deficient, collecting demographic data; data concerning social determinants of health; and clinical data such as hematologic lab data, stated reason for testing, and pertinent disease states such as malnutrition and substance use. We also noted whether the medical team acted upon the folate deficiency. Finally, we performed a cost analysis. Results: Out of 1368 patients whose serum folate was tested, 76 patients (5.5%) met criteria for folate deficiency. Of those patients, chart review found that hematologic abnormality was a documented cause of testing for 63%. Overall, 79% of folate deficient patients were anemic, but only 20% had a macrocytic anemia. 42% had a documented diagnosis of malnutrition. Common social determinants in patients found to be folate deficient include birth outside of the US (25%), homelessness (12%), and alcohol use disorder (29%). Of those found to be folate deficient, 93% were either started on folic acid supplementation or had already been prescribed supplementation prior to testing (5%). Given that our institution charges $71 per folate test, the expected charges per deficient test would total $1278. Discussion: While the decreased incidence of folate deficiency after fortification has led many to conclude that serum folate tests have limited utility, our data show that this conclusion may not apply to all populations. The 5.5% rate with which testing detects folate deficiency at our institution, with 46% of 2018 income from Medicaid, was markedly higher than the 0.4% rate reported in a similar study done at nearby hospital that derived 14% of 2018 income from Medicaid (Theisen-Toupal et al. J Hosp. Med. 2013). Comparisons to other studies are limited, as the cutoff for folate deficiency varies significantly between institutions. However, the markedly higher frequency with which folate deficiency was detected at our institution as compared to others suggests that folate testing may still have a role within safety net and many public hospital systems. In addition, serum folate testing may be more cost effective at such hospitals. At our hospital, the charge per deficient folate test was $1278, while previously published data from the nearby hospital described above showed a charge of over $35,000 per result under 4 ng/mL (Theisen-Toupal et al. J Hosp Med 2013). In addition, our results showed that deficient folate results usually prompted change in management. At our hospital, over 90% of folate deficient patients were prescribed a folic acid supplement at discharge, while prior studies reported rates of supplementation in the range of 0-65% (e.g. Ashraf et al. J Gen Intern Med 2008). This may reflect greater cognizance among our providers of nutritional deficiencies associated with social determinants of health common to our patient population. As our results indicated high rates of anemia, malnutrition, immigrant status, and substance use disorders among folate deficient patients, future research may include comparisons between patients found to have normal vs low folate levels. Identifying correlations between folate deficiency and other patient characteristics may help to target testing towards those most likely to benefit. Disclosures No relevant conflicts of interest to declare.


1965 ◽  
Vol 51 (6) ◽  
pp. 441-455
Author(s):  
Giancarlo Bignotti ◽  
Sergio Tognella ◽  
Gian Piero Gennari ◽  
Vincenzo Grifoni

Basal serum folate activity, serum folate clearance and folate output in the urine after folic acid loading, urocanic acid and formiminoglutamic acid output in the urine after histidine loading were determined on 27 patients with malignant blood diseases in therapeutic remission. The mean values for basal serum folate activity and for serum folate activity and urinary folate output after folic acid loading were significantly lower than normal, both in chronic myeloid leukemia and in Hodgkin's disease. On the contrary, in chronic lymphatic leukemia only after folic acid loading urinary folate output was significantly lower than normal. The median values for urinary excretion of histidine derivatives after histidine loading was higher than normal in Hodgkin's disease and in chronic lymphatic leukemia. Folate deficiency was observed in 16 out of the 27 patients under study. Comparative analysis of multiple test results showed different response patterns which can be attributed to different types of deficiency, namely tetrahydrofolate deficiency from primary folate deficiency and possibly tetrahydrofolate deficiency from folate metabolic abnormalities. Folate deficiency appeared to correlate with the activity of disease when expressed by such parameters as performance status and erythrocyte sedimentation rate. This applies to all patients as a group, and, as far as performance status is concerned, to the chronic lymphatic leukemia patients as a subgroup. Folate deficiency did not appear to correlate with other parameters of disease nor to induce, in the majority of patients, the typical hematologic features. Folate deficiency in malignant blood diseases is likely to be somehow related to the abnormal cell proliferation, through several possible mechanisms which are analysed and discussed.


2020 ◽  
Vol 7 (5) ◽  
pp. 1013
Author(s):  
Anjana Murthy K. ◽  
Ashwini Malladad ◽  
Mallesh Kariyappa

Background: Severe acute malnutrition is the important health issue children affected in India. It is often associated with Iron, Vitamin B12 and Folic acid and other micronutrient deficiencies. These reports of declining trend of Iron and folic acid deficiency with implementation of national anemia control programme. Estimation of Serum Folate and Vitamin B12 levels in SAM children aged 6-60 months with anemia was the objective of the study.Methods: A hospital based observational study on 80 children admitted to nutritional rehabilitation center were suffering from severe acute malnutrition (SAM) in the age group of 6-60 months enrolled in the study during the period November 2018 to May 2019 .Data was collected using a predesigned and pretested Proforma, containing details of feeding, socio-economic and development history. Blood samples were sent for measurement of plasma vitamin B12 and serum folate levels. Statistical analysis was done using SPSS version 20.0.Results: Out of 80 children, majority were between the age group of 24-60 months and majority were boys (53.8%). Mean Vitamin B12 and folic acid levels being 384.61 and 8.95 respectively. 45% and 3.8% had vitamin B12 and folic acid deficiencies respectively. Majority of neurological changes and developmental delays were noted in B12 deficient group. Of the 36, B12 deficient children, majority had moderate anaemia (40.2%), normal total count (41.7%), 60% had neutropenia, 44.4% had lymphocytosis, majority had normocytic (30.9%) anemia.Conclusions: There was a moderate to high prevalence of vitamin B12 deficiency among malnourished children. Folate deficiency was found only in few. Efforts should be directed to prevent its deficiency in pregnant and breastfeeding women and their infants with special attention on malnourished children.B12 and folate deficiency shall be considered in all cases with SAM irrespective of blood indices. Treatment will have impact on prognosis of child.


Anemia ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
M. Premkumar ◽  
N. Gupta ◽  
T. Singh ◽  
T. Velpandian

Background. Pancytopenia has multiple etiologies like megaloblastic anemia, aplastic anemia, leukemia, and various infections. We investigated the clinical, etiological and hematological profile including bone marrow morphology of patients with pancytopenia in relation to their vitamin B12 and folic acid status at a tertiary care referral hospital in north India.Methods. A total of 140 consecutive patients with pancytopenia were selected from June 2007 to December 2008. Bone marrow examination and other tests were carried out as warranted, including serum cobalamin and folate assays using liquid chromatography mass spectroscopy (LC MS/MS).Results. The study population consisted of 92 males and 48 females with a mean age of 32.8 years. Megaloblastic anemia 60.7%, aplastic anemia (7.8%), and leukemia (9.2%) were common causes. Infectious causes (16.4% of all cases) included leishmaniasis, HIV–AIDS, malaria and tuberculosis. Severe cobalamin deficiency (B12 < 100 pg/mL) was seen in 81% of all patients including 91.6% of patients with MA. In contrast, only 7.14% of all pancytopenic patients were folate deficient. Folate deficiency (<5 ng/mL) was seen in just 5% MA patients. Combined cobalamin and folate deficiency was seen in 5 patients (3.51%).Conclusion. Cobalamin deficiency was found to be more common in our setting and is largely underdiagnosed in the age of folate supplementation. Infectious diseases like tuberculosis, leishmaniasis, and increasingly HIV are important and treatable causes of pancytopenia. This is in contrast with the developed nations where the bulk of disease is due to malignancy or marrow aplasia.


2020 ◽  
pp. 1-8
Author(s):  
Dolores Busso ◽  
Guadalupe Echeverría ◽  
Alvaro Passi-Solar ◽  
Fernanda Morales ◽  
Marcelo Farías ◽  
...  

Abstract Objective: To analyse serum folate levels in women of childbearing age in the Metropolitan Region (MR) of Chile. Design: Cross-sectional design as part of the 2016–2017 National Health Survey (Encuesta Nacional de Salud, ENS 2016–2017), using a household-based multistage stratified random sample. Serum folate levels measured by electrochemiluminescence immunoassay in fasting venous blood samples were classified as deficient (<4·4 ng/ml), normal (4·4–20 ng/ml) or supraphysiological (>20 ng/ml). Setting: The MR of Chile. Participants: Women of reproductive age (15–49 years, n 222) from the MR participated in the ENS 2016–2017. Results: The mean, median and range of serum folate were 14·2 (se 0·4), 13·9 and 2·1–32·2 ng/ml, respectively. Folate deficiency was detected in 0·9 % of women, while 7·0 % had supraphysiological levels of the vitamin. No significant effects of age, educational level, marital status, parity, smoking status or nutritional status on serum folate levels were detected by univariate or multivariate analyses. Intake of folic acid supplements showed a significant association with serum folate levels, but only 1·2 % of women used supplements. Conclusions: Folate deficiency in women of reproductive age living in the MR of Chile is almost inexistent according to the ENS 2016–2017, suggesting that the current population-wide mandatory folic acid fortification of flour is an effective and equitable measure to prevent folate deficiency. These results support the option of maintaining current folic acid fortification in Chile, particularly based on the low adherence to supplementation regimes evidenced in other populations.


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