A Coagulation Defect Produced by Nitrogen Mustard

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Abstract
Observations on 5 human subjects with neoplastic disease and on normal rabbits indicated that a N mustard (methyl-bis-beta-chloroethyl)-amine hydrochloride) produces a coagulation defect identical with that caused by radiations. Two patients were given 0.1 mg./kg. body wt. on 4 consecutive days; the 3d received 4 injns. of the same dose at intervals of 12 hrs.; the 4th was given 4 injns. of the same dose at intervals of 7 hrs.; and the 5th was given 2 injns. of 0.3 mg./kg., 6 hrs. apart. The total doses were 25.4, 26.8, 22.4, 20.0, and 38.0 mg.,resp. After 2 wks. all patients developed a moderate anemia, severe leucopenia, thrombocytopenia, prolonged bleeding time, cutaneous petechiae, and ecchymoses. The whole-blood coagulation time was definitely prolonged or was incoagulable after 1 day. There were gastrointestinal and cerebral hemorrhages, and 2 patients died. The clotting time was reversed to normal in 24 hrs. by intraven. injn. of 2 mg./kg. of toluidine blue or protamine. The dose was repeated every 24 hrs. The same reversal occurred in a test tube. The prothrombin time of all subjects was normal.

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