Folate and homocysteine status and haemolysis in patients treated with sulphasalazine for arthritis

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 mu mol l(-1) vs. 6.8 mu mol l(-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 l(-1) vs. 8.5 nmol l(-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 HbA(1c) measurement performed, 12 (50%) had decreased levels indicating chronic haemolysis. Only seven (28%) patients had reticulocytosis. HbA,, 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.