title: Folate and homocysteine status and haemolysis in patients treated with sulphasalazine for arthritis.
abstract: In an attempt to estimate the frequency of folate deficiency and haemolysis in a group of 25 outpatients with arthritis treated with sulphasalazine (SASP), haematological measurements, including plasma total homocysteine (tHcy) which is a sensitive marker of folate deficiency, serum folate (S-folate), erythrocyte (RBC) folate, S-cobalamin and routine indices of haemolysis were performed. No patient had been taking folate-containing vitamins for at least 8 weeks prior to the study. Compared to a group of 72 healthy hospital staff, the median plasma tHcy was significantly higher in the patient group (8.8 mumol 1(-1) vs. 6.8 mumol 1(-1); p = 0.003). Five patients (20%) had plasma tHcy levels that exceeded the upper normal limit of plasma tHcy (median+2 SD of the reference group). Median S-folate was significantly lower in the patient group (6.0 nmol 1(-1) vs. 8.5 nmol 1(-1); p < 0.001), and 11 (44%) patients had depressed S-folate. Only three (12%) patients had RBC folate values below the reference interval. There was no difference in the levels of RBC folate between the two groups. A comparison of S-cobalamin levels in the two groups disclosed a significantly lower level in the patient group. However, no patient had cobalamin deficiency as assessed by S-cobalamin and S-methylmalonate measurements. Thus, it is unlikely that any patient had increased plasma tHcy due to cobalamin deficiency. Of 24 patients having a HbA1c measurement performed, 12 (50%) had decreased levels indicating chronic haemolysis. Only seven (28%) patients had reticulocytosis. HbA1c was positively correlated to haptoglobin levels (r = 0.77; p < 0.001) and negatively correlated to the percentage of reticulocytes (r = -0.50; p = 0.02). The percentage of reticulocytes was negatively correlated to haptoglobin levels (r = -0.42; p = 0.04). The chronic haemolysis of the patients' blood due to SASP might explain the similar RBC folate values in the two groups because of a relatively higher folate content of young erythrocytes. In conclusion, our results support previous findings of folate deficiency and haemolysis occurring in a considerable fraction of patients receiving treatment with SASP. Measurements of plasma tHcy suggest that a substantial number of patients may have folate deficiency at the tissue level.
authors.affiliation: Department of Haematology and Internal Medicine, Aalborg Hospital, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Krogh Jensen
authors.forename: S
authors.initials: S
authors.lastname: Ekelund
authors.forename: L
authors.initials: L
authors.lastname: Svendsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001168:Arthritis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000503:physiopathology; D003093:Colitis, Ulcerative / Q000150:complications; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005494:Folic Acid Deficiency / Q000175:diagnosis; D006461:Hemolysis / Q000187:drug effects*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D013167:Spondylitis, Ankylosing / Q000188:drug therapy / Q000503:physiopathology; D012460:Sulfasalazine / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D006710:Homocysteine; D012460:Sulfasalazine; D005492:Folic Acid