No abstract

DEPRESSION of the haemopoietic system with leucopenia and thrombocytopenia is a well-recognised hazard of the use of antimitotic agents in the treatment of malignant disease. During a study of the causes of thrombocytosis, however, we observed that a rise in the platelet count appeared to be frequent following methotrexate therapy. We report our findings on the effect of methotrexate on the platelet count, and, in particular, on its effect in producing a thrombocytosis. PATIENTS AND METHODSThe case records of 39 patients who had received methotrexate (amethopterin) as therapy for malignant disease were examined. Serial platelet counts were performed, at intervals of not more than 3 days, before, throughout, and after the period of therapy.Methotrexate was administered by intra-arterial infusion after cannulation of the regional artery supplying the site of the tumour (18 patients) by intravenous injections (19 patients) or orally (2 patients). The total methotrexate dose by intra-arterial infusion ranged from 150 mg. to 640 mg. given over a period of 3 to 16 days, mean 7.0 days; by the intravenous route, 15 mg. to 150 mg. over 3-27 days, mean 8.5 days; and the oral dosages were 70 mg. and 110 mg., over 15 and 25 days, respectively. The length of therapy exceeded 10 days in only 9 patients.The malignant conditions treated were carcinomas of breast (13); mouth, fauces or tongue (7); larynx (4); skin (4); oesophagus (3); vulva (3); jaw (2); parotid gland (1); bronchus (1); ear (1). Although many patients had recurrent carcinomas, especially of the squamous epithelial type, none had evidence of disseminated disease beyond the regional lymph nodes clinically, and none had a leucoerythroblastic blood picture before therapy. Bone-marrow biopsy was not carried out as a routine procedure.Platelet counts were performed by the method of Oettle and Spriggs (1951). The normal range of the platelet count in our laboratory is 150-270,000 c.mm. RESULTSPhase of thrombocytopenia- Table I shows that a reduction in the platelet count of more than 25% of the pre-treatment level occurred in 31 of the 39 patients. It is also apparent that the platelet count fell slightly earlier after both the start and the end of the course of intra-arterial, than after intravenous, administration of methotrexate, presumably because of the higher dosage in the intra-arterial treated group.

In seven hypertensives receiving beta-blocker drugs, an additional reduction in standing blood pressure occurred between 60 and 90 minutes after 40 mg phentolamine by mouth. The occurrence of the postural hypotensive effect was delayed in relation to the reported time of peak plasma concentration of unchanged phentolamine. Supine blood pressure and heart rate were unaffected. Phentolamine has no clinically useful anti-hypertensive effect in conjunction with beta-blockers in patients with essential hypertension.