Research Article: Cobalamin and Folic Acid Status in Relation to the Etiopathogenesis of Pancytopenia in Adults at a Tertiary Care Centre in North India

Date Published: April 1, 2012

Publisher: Hindawi Publishing Corporation

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.

Partial Text

Pancytopenia is diagnosed when there is a reduction in all three hematopoetic cell lines. This is seen as reduction in the white cell count, hemoglobin, and platelet count which is most often the result of bone marrow infiltration or failure, anticancer chemotherapy, hypersplenism, systemic diseases, and infections like HIV, tuberculosis, leishmaniasis, and so forth [1, 2]. While there are several published studies on the hematological diagnosis of pancytopenia on basis of bone marrow morphology, few have attempted to explore the underlying etiology and clinical course of the disorders leading to this condition. In this study, we hoped to evaluate the demographic, nutritional, socioeconomic and age patterns of the myriad disorders which cause pancytopenia and develop an approach to the diagnosis of this condition in our patient population.

This prospective study comprised of adults drawn from the outpatient/inpatient/emergency/referral services of Maulana Azad Medical College, Lok Nayak Hospital and other associated hospitals, a tertiary care referral centre in New Delhi, north India. The period of observation was from June 2007 to December 2008. Overall, 160 consecutive patients were recruited in the study with written informed consent. Of these, 20 patients were excluded due to one or more exclusion criteria. The inclusion criteria for the study were

The study population consisted of 140 patients with a mean age of 32.8 years with range of 18–80 years. There were 92 males and 48 females in the study group (M : F ratio 1.9 : 1). More than half (59%) of all patients belonged to a younger age group (18–30 years) including 56% of all females and 55% of all males. Most of the patients (76.4%) belonged to a lower socioeconomic status based on occupation, income, and education. In our study, MA was the largest group comprising 60.7% of all cases. Aplastic anemia accounted for 7.8% while leukemia (including acute myeloid leukemia, acute non myelogenous leukemia, undifferentiated leukemias, chronic myeloid leukemia in blast crisis, and one case of lymphoma) accounted for 9.2% cases, respectively (see Table 1).

Six broad diagnostic groups could be identified in pancytopenia. Megaloblastic anemia constituted the largest group comprising 60.7% of all cases. Aplastic anemia (7.8%), leukemia (9.2%), and infections (16.4%) were the next most common causes.

Pancytopenia has multiple etiologies. Data regarding pancytopenia in an adult Indian population is lacking which prompted this study. People in India and other developing nations continue to suffer from vitamin deficiencies which cause anemia and pancytopenia. These are easily preventable if diagnosed and treated early. Better health awareness will reduce the burden of disease. Infectious diseases like tuberculosis, kala-azar, and increasingly HIV are important and treatable causes. This is in contrast with the developed nations where the bulk of disease is due to malignancy or marrow aplasia. A careful and individualized approach to the diagnosis and management of this condition is needed (See Figure 5). The role of dietary deficiency of cobalamin cannot be emphasized enough, even in nonvegetarian patients as subclinical deficiency is common in the Indian population and manifests with both hematological and neurological consequences. Our study revealed that multifactorial causation for pancytopenia in our patient population is probable and occult cobalamin deficiency may contribute to the burden of hematological disease in patients with other primary diagnoses. Therefore B12 status needs to be assessed either clinically or by laboratory methods in high risk groups, and also in case of poor response to primary therapy. Cobalamin (either oral or parenteral) and folic acid therapy should be considered in addition to treatment for the primary diagnosis, depending on the clinical scenario. Concerns raised about the risks of unmasking undiagnosed B12 deficiency in the age of folate supplementation are compelling especially in the Indian population. Further recommendations regarding folate or B12 supplementation in the general population can only be made after more population-based studies are completed.




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