Roles of prothrombin activity, heparin-protamine titer and platelet concentration in bleeding of leukemia.

EUKEMIA imivolves mans’ tissues and may often become complicated by imifection, bleeding, malmiutrition an(l mechanical intem-feremice with orgamis. Stud!ies have beemi made imi this laboratory on the nature of the hemorrhagic diathesis as it OC(tIPS ili leukemia. This report pertaimis chiefly to heparin-protamimic titration, to prothroml)imi activity of plasma and to platelet concentration. i)ata omi plasma fibrinogemi in bleedimig leukemic patiemits are also presented. Howell’s suggestiomi that the dlelayed! (lottimig of 1)100(1 IIi shock was the result of circulating heparimi’ was substantiated by the quamititative isolatiomi by Jaques and! Waters of hepariii from dogs that had! heemi anaphylactically shocked.2 They imidicated also that heparin existed! iii extremely low comicemitratiomi. Later, Volkert and Hertel3 m’epOrte(l that a varial)le compomiemit of the amitithrombic complex described by Astm’up amid 1)am’ling4 acte(! like hepariti, and that this componemit i .as reflected! in elevated amitithrombimi levels imi some cases of leukemia. rFheim. observations, however, were miot related to bleeding in particular. Barnard!5 Claimed! to have had similam’ experience, hut data were miot presemited. Kleimi and Seegem’s6 explained the amitithm’ombic effe(t of lieparimi on the basis of its interferemice with the thrombin-fibrimiogemi reactiomi, rather than by destnictio,i of thrombimi. Allen amid his associates,7’ 8 usimig the method of ,Ja(1ues and Waters2 imiitially reported an increase imi heparin III (logs that had! beemi treated with large (loses of m’oemitgemi rays. They considered the associated bleedimig to be cause(l 1)y “heparimiemia,” amid! t he comicomi t ant t h rombocyt opemiia to be of secondary import aiice. The observation by (‘hargaff amid ()lson, ’ that the affinity of protamine for heparimi could be used to assay its anticoagulant effect imi vivo, was applied by Allemi audI his associates to study the naturally-occimrm’imig (omicemitratiomi of ‘‘heparin-like substamices’’ in idiopathic and leukemic thrombocytopemiic purpimra.’ Smith and Allen amid their co-workers made a similam’ studly of the ((Micemitratiomi of these substamices aftem mmitrogemi mustard poisomiimig.’’ Other workers’2’ #{176} failed to verify the comiclusiomis of Allemi and his associates imi regard to “heparinemia” in im’m’adiate(l (logs, amid feel that tlimomboeytopemiia is the basic defect. The obscurity of t he sigmiificamice of heparimi-protamine t it rat iomis prompted a