Vitamin B12 and folate coenzymes deficiency are known to cause delayed in DNA synthesis and eventually results in macrocytic anemia Green and Dwyre, ; Lanier et al.
Second, oxidative stress has been identified as an pivotal pathophysiological mechanism in chronic viral hepatitis B Uchida et al.
Because red blood cell is thought to be tightly related to whole-body antioxidant capacity Tsantes et al. Oxidative stress decreases the RBC capacity to deform, reduces blood flow in microcirculation and compromises oxygen supply to certain tissues Mohanty et al. Moreover, There are various factors that affect erythrocyte morphology in liver disease, such as etiology, severity of hepatic impairment, and use of drugs. There are many complicated mechanisms that affect the shape of red blood cells.
These mechanisms may allow to perform effectively their independent or collaborative functions. The MELD score is approved for assessing the degree of liver diseases. These variables include prothrombin time, INR, serum bilirubin and creatinine level. MELD score changes with variations in these variables.
Higher MELD scores associate with increased risks of death and hepatic events in cirrhosis. However, there was no remarkable difference with creatinine and eGFR. Therefore, macrocytic anemia may not be relevant to renal injury in patients with decompensated HBV associated cirrhosis. Several study limitations are noted. First, the main limitation of this study lies in its retrospective observational nature, the cross-sectional nature of our study does not permit the determination of causality between MCV and MELD.
Second, this study included only Chinese participants, and therefore these findings may not be generalizable to other biogeographic ethnic groups. Third, we did not perform an analysis on the data of folate, serum vitamin B12 and reticulocyte count, which could provide a better understanding of macrocytic anemia in cirrhotic patients.
Macrocytic anemia was highly correlated with the degree of hepatic dysfunction and may be a reliable predictor for mortality in patients with decompensated HBV associated cirrhosis. Moreover, further large-scale, well-designed and multicenter studies need to be conducted to confirm our conclusions, it is important to evaluate and investigate this association and to gain insight the underlying mechanisms.
The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation. The studies involving human participants were reviewed and approved by the research protocol with a waiver of written informed consent by the Ethics Committee of the First affiliated hospital of Dalian Medical university. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
T-YZ designed the study. Q-WC and FL interpreted the data. YZ designed the experiments, improved the manuscript. All the authors have read and approved the final manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Bambha, K. Bourlon, M. Cancer Med. Carter, B. The most common cause of B12 deficiency is pernicious anemia due to impaired intrinsic factor secretion usually secondary to the presence of autoantibodies—see Autoimmune Metaplastic Atrophic Gastritis Autoimmune Metaplastic Atrophic Gastritis Autoimmune metaplastic atrophic gastritis is an inherited autoimmune disease that attacks parietal cells, resulting in hypochlorhydria and decreased production of intrinsic factor.
Pernicious anemia can develop even in the absence of old age. Other common causes are malabsorption due to gastritis, gastric bypass, or tapeworm infection. Dietary deficiency is rare but can occur in patients eating a vegan diet. Folate deficiency is exceedingly rare in countries where cereals and grains are fortified with folic acid. However, folate deficiency can occur in patients with restrictive diets, chronic alcohol use, or anorexia.
Malabsorptive conditions such as celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption Diagnosis is clinical and by small-bowel biopsy.
Symptoms depend on the length and When folate requirement is increased, including during pregnancy and in patients with chronic hemolysis ie, hemoglobinopathies folate deficiency may occur. Other causes of megaloblastosis include drugs generally antineoplastics such as hydroxyurea , or immunosuppressants that interfere with DNA synthesis and rare metabolic disorders eg, hereditary orotic aciduria.
Megaloblastic states result from defective DNA synthesis. RNA synthesis continues, resulting in a large cell with a large nucleus. All cell lines have dyspoiesis, in which cytoplasmic maturity is greater than nuclear maturity; this dyspoiesis produces megaloblasts in the marrow before they appear in the peripheral blood. Dyspoiesis results in intramedullary cell death, making erythropoiesis ineffective.
Because dyspoiesis affects all cell lines, reticulocytopenia and, during later stages leukopenia Overview of Leukopenias Leukopenia is a reduction in the circulating white blood cell WBC count to read more and thrombocytopenia Overview of Platelet Disorders Platelets are cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes, Macro-ovalocytes enter the circulation.
Hypersegmentation of polymorphonuclear neutrophils is common. Howell-Jolly bodies residual fragments of the nucleus are usually present. If iron deficiency or impaired iron utilization is present simultaneously, macrocytosis may not develop. Megaloblastic anemia develops insidiously and may not cause symptoms until anemia is severe. Gastrointestinal manifestations are common, including diarrhea, glossitis, and anorexia.
This case was presented at a medical clinic in the John Hopkins Hospital on March 8, A man, aged 50, showed a clinical picture of advanced hepatic cirrhosis together with signs strongly suggestive of pernicious anemia.
The liver was markedly enlarged and nodular. The skin was moderately jaundiced icteric index, There were in addition glossitis, combined sclerosis and a macrocytic type of anemia. The hemoglobin. Arch Intern Med Chic. Certain medical conditions require at-risk medications. Physical exam may reveal nonspecific anemia findings conjunctival pallor , neurologic deficits if vitamin B12 deficient impaired proprioception or vibration, positive Romberg sign , and stigmata of underlying diseases glossitis from autoimmune atrophic gastritis, hepatosplenomegaly from familial hemolytic anemias, hypopigmentation from vitiligo, or jaundice and spider angiomata from alcohol abuse.
Initial evaluation of macrocytic anemia includes a thorough history and physical followed by limited labs PBS, reticulocyte count, and serum B If the PBS is normal, no megaloblastic RBCs, order additional testing for liver and thyroid diseases aminotransferases and thyroid stimulating hormone , the most common causes of non-megaloblastic anemia.
If hyperproliferative, look at the B12 level. Both or MMA only are elevated in vitamin B12 deficiency; homocysteine is elevated in folate deficiency.
Normal values may warrant hematology consultation for bone marrow studies. Specialist consults are recommended in patients with abnormal myeloid morphology on PBS disordered immaturity, hypo-granulated or hypo-segmented neutrophils, or additional cytopenias.
Work-up for specific causes of megaloblastic anemia should be based on presentation. Antibodies for intrinsic factor or parietal cells are indicative of pernicious anemia.
The Schilling test, once used to measure vitamin B12 uptake before and after administration of intrinsic factor, has fallen out of favor. Treat macrocytic anemia by replacing folate or vitamin B12 and targeting the underlying cause. Give folic acid orally, 1 mg to 5 mg daily, and encourage diets with foods rich in folate fortified cereals, leafy vegetables. Patients who are taking folate antimetabolites or pregnant women especially those with a history of neural tube defects or taking antiepileptics should take daily supplements to prevent deficiencies.
It is important to not overlook vitamin B12 deficiency as a cause for macrocytic anemia, treatment of folate deficiency but not vitamin B12 deficiency will resolve the anemia but not the neurologic effects.
Prescribe micrograms oral vitamin B12 daily for 1 month followed by to micrograms daily or administer micrograms intramuscular B12 every week for 4 weeks then monthly to replace vitamin B12 stores, the latter of which is preferred for patients with pernicious anemia or altered gastrointestinal anatomy.
Reticulocytosis will improve within 1 to 2 weeks, and anemia should resolve after 4 to 8 weeks. There is no need to monitor RBC indices or recheck folate or vitamin B12 levels and their metabolites during active treatment, though some physicians check yearly complete blood counts in patients taking long-term vitamin B12 therapy.
Neurologic symptoms from vitamin B12 deficiency take longer. Macrocytosis related to alcohol use resolves with abstinence. Other non-megaloblastic anemias improve when the underlying conditions are treated. In other instances, macrocytosis is indicative of medical compliance ex. Folate deficiency anemia Anemia due to liver disease Hypothyroidism Myelodysplastic syndrome Alcoholism. With early identification and treatment of underlying cause, the prognosis for macrocytic anemia is excellent.
Specialist referral is rarely needed unless anemia is resistant to therapy or there is evidence of underlying myelodysplasia or leukemia.
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