Document Lpr5wvVyBxz954E6KgpL8Ypw

APRIL 1979 Chromosome Analysis in Two Unusual Malignant Blood Disorders Presumably Induced by Benzene By H. Van den Berghe, A. Louwagie. A. Broeckaert-Van Orshoven, G. David, and R Verwilghen T w o patients with presumably benzeneinduced malignant blood disorders with preleukemic phases were cytogenetically m o n i t o r e d t h r o u g h t h e courses of t h e i r diseases. P a t i e n t 1, in addition t o a familial chromosome translocation [t(3;161], developed karyotypic abnormalities in 100 % of the marrow cells, including t w o transloca- tions: t ( 9 : l a l a n d t(4:15). M o n o s o m y of chromosome 7 characterized t h e cells of p a t i e n t 2. C y t o g e n e t i c monitoring of t h e patients a t various phases of their diseases served as a n important indicator of the transformation o r progression of t h e preleukemia into frank leukemia and of the unusual behavior of such leukemic cells. IT IS GENERALLY ACCEPTED that chronic exposure to benzene (benzi;) may induce leukemia in man. Early reports on benzene leukemia in the nineteenth century were follo\ved by an abundant literature on the subject. On the basis of the clinical and hematologic picture, so-called preleukemic phases have been delineated, of which some are nonproliferative (e.g., leukemoid reactions). Chromosome studies have concentrated mainly on the clastogenic effects (i.e., chromosome breaks and other structural changes) of benzene on 1ymphoc)rtes in vivo and on a few cases of leukemia (without banding). The exact significance of the chromosome aberrations induced in lymphocytes or bone marrow cells by benzene (or othcr environmental agents) is not well understood, and !he cytogenetic abnormalities reported in bknzene leukern% seeiri t o h d i c a t e that these changes may not be different from those found in other acute myeloproliferative or lymphoproliferntive disorders.' This report deals with 2 patients in whom presumably benzene-induced malignant conditions with preleukemic phases were cytogenetically monitored from shortly after the onset of symptoms until death. Some unexpected and unusual dynamics of the malignant cells were revealed. MATERIALS AND METHODS Palient 1 Paticnt I,a 25-yr old drartsnnn on steel plates Tor about 4 yr, used petrol to clean the rnctal sheets. Thc solvcnt. intended for use only as a motor car fuel. contained 2.2% benzene, 7.63toluene, and 8.7% xylene. I t was riscd in a small unventilated room. and inhalation of the petrol vapor was sufficient to cause nausea. His past history \vas negative. From the Divisioris of flirtitan Generics and Henrnrology. Dcparrnierrrs of Hrottoti Biology and Medical Research, Uniwrsity of Leiiven. Lritverr. Belgiirnr. Subrrrirred July 25. 1978: accepred Novi~rirber17. 1975. Supporred in parr by a grarrt front ihe ASLK Caricer Fiord. Be1giio)i. G. David is at1 Aspiran1 Of NFWO-Belgiirnr. Address for reprinr rrqirests: H . Vnn den Berghe. Dibsisionof Hiinran Gerierics. Mi,rderbroederssrrOaf 12, 8-3000Leirven. Ue/,qiiitrt. 8 1979 by Grirrre & Stratton. Inc. ISSN 0006-~971/79/SJ04-0004S01.00/0 559 -- First episode. In September. 1975. the patient complained of slight pyrexia. tiredness. a bleeding .-e tendency. and diffuse arthralgia. He was treated for a few days with an antibiotic for a sore throat and Kg improved when treated with triamcinolone (4 mg/day). ~uz g - . When first seen by US (September 18, 1975). all therapy was withdrawn. H e showed only a few 57. arid the Spleen was palpable under the costal margin. The blood picture (Table IA) was !&.:mainlycharacterized by marked leukocytosis (up to 110,0OO/cu mm) and a marked shift to the left. The 53.-..-. granulocytes showed marked toxic granulation. with a normal leukocyte alkaline phosphatase (LAP), g.;which became supranormal during the further evolution of the condition. Plasma acid levels and lactic dehydr0genaSe activity were markedly increased. All other biochemical data in blood and urine were normal. A slight increase in serum immunoglobulin levels was noted. The leukocyte count decreased sponlaneously during the following weeks; in fact, leukopenia Anemia appeared during the first month of observation, but the thrombocyte count remained ring that time. Bone marrow (September 24, 1975) showed marked granulocyte hyperplasia with a left shift and marked toxic granulation (Table I B). Erythroblasts and megakaryocytes were well represented. Within 1 w k the bone marrow became hypocellular. although the erythroblasts were still present in significant numbers. During October and November, 1975. progressive normalization of peripheral blood and bone marrow occurred. X left shift in the peripheral blood and a slight increase of 1. Leukocytes - ( x tOq/lirer) - -~ Myeloblasts Myelocytes Nonsegmented . neutrophils Eosinophils Table 1 A. Patient 1 :Hematologic Investigation: Blood 1919 13 1975 2/10 24/10 8.8 13.5 4112 16 811 17.3 1976 2914 1115 10 8.2 1215 7 - - -11-0 -2.9 6.9 12 13 23 154 137 15 53 64 62 a 1- 6 9 13 6 24 36 5 4 76 66 30 15 16 - 6 7 4 6 29 4 6 1 ,g. 1 . R - b a n d e d k a r y o t y p e o f p a t i e n - I >ho*Li c ~e ( 3 1 I I , ~ 1 oi t~ II ,VI le i i r e d a n o m a l y (t19:1Ol] in a m a r r o w c 1 4 - i g 2 R - b a n d e d k a r y o t y p e 0 1 p a r i e n t 1 0 'a rele e x n m t n e d / / I I n c w a l s o c o n r a i n i n g a r ( 4 151 i n a d c ~ t i o nI > t h e a n % l o c c7 I 1 1 . M 1.3 II ir 1 I !i n 1,. .. I " as8 " a o l e Z A . p1: -ib Igid,I <- e u ~ o c y t e s 0' orerr Myelobiasrc. Mvelocyies Nonsegmerited .ieuiropnlis Eosinophils aasoohtls - Lymphocyte> Monocires R e r i c u ~ o c y t o s ~(sk i Thromboc)res I Y 1 0 ' / i ~ t ~ l L D H ( u n i t s , I terl Uric acld (mg,'dll NAP score T a b l e 26. Pairerr Myeloblasts Promyelocyies NIE Myelocytes N/E .M e t a m y e i o c y t e s N I E Bands N/C Segmented neutrophils NIE Lymphocytes Monocytes Plasmocytes GranulocytesJerythroblasts Megakaryocytes Cellularity - L- pulmonary infiltration. diRuse edema, hemorrhages, and marked splenomegaly (3000 g ) 5.b 1 I L , 1 1 infarctions were found. Leukemic proliferation was present in most organs. Patient 2p Patient 2, a 67-yr-old retired carpenter, suffered from gastric ulcers during 1953-1 957 time his wife died from leukemia. He also had recurrent episodes of depression. During 111. .'r life as a carpenter he had been using glues containing benzene for many years. Beginning :'- 'I he complained of tiredness, nocturnal sweats, and loss of appetite. Medical examination revealed anemia and bone marrow compatible with megaloblastic anemia. Vitamin B,, >va! ..,im tered without success. At the end of June. 1976. he \vas markedly anemic. and an increased leukocyte count ( 2 3 with a marked shift to the left was present (Table 2A). T h e LAP score was increased t r > I t ) Jul! 1976) (normal 14-100). Plasma uric acid was 8.4 mg/dl, iron was. 199 pg/dl, and TIBC was 444 gg/dl. All (ithci s e r u ~ chemistries were normal. The bone marrow showed increased cellularity due to inyeloiu hvperplasia with only occasional erythroblasts and megakaryocytes. All myeloid maturation stages were oreseni however, degranulation was marked, and Dohle bodies were present. Monocytosis (Table 29) i v a ~ observed on one occasion (August 13. 1976). Because of the high LAP score and the absence of a Phi chromosome. C M L was rejected, a n d 2 provisional diagnosis of a leukemoid biopsy, during the following months reaction failed to was made. reveal any Extensive investigations. infection or malignancy. Pinecnlduidnigngthleymrepshulnto<oc. the Lowenstein culture (it was later known that all remained negative for acid-fast bacteria), a I - trial with tuberculostatic drugs was inaugurated, without clinical benefit. The patient came u d e r \ - care early in August, 1976. His condition was essentially unchanged since June, 1976. T h e anemia U J S marked. and repeated transfusions were necessary. I n rhe absence of any cyrosraric or onfrbroirL. irenrnienf. the leukocyte and thrombocyte counts dropped progressively. On August 23, hypocellular bone marrow was found, and after September 4 all bone marrow samples were entirely aplastic. The serum LDH level reverted to normal, and it was thought that the earlier increase i n LDH was duc to inefficient proliferation of the bone marrow. Fig. 3. A-banded karyotype of a marrow cell of patient 2 showing the monosomy of C J \ : J ~ ' ' ~ some 7. -3ble 3 c u -B ?rlA -B PHA B - F-A hl \$ h( h' \' h' h! B - PHA M B - PHA M 8 - PHA M -8 ?HA M -B ?HA -B PHA M -0 ?HA -0 ?HA M AL. ous iich mal 376. ime nisnm) Y I. iUT;. sia. ent: w2s id a ode s of -mo our 1V3' 31, liar due B 710- CHROMOSOMALLY MONITORED BENZENE LEUKEMIA - 563 The clinical course was mainly influenced by a variety of infections and hemorrhagic complications requiring intensive treatment with antibiotics and transfusions of packed erythrocytes and thrombocytes. Nevertheless, the patient's condition deteriorated progressively, and he died from G I hemorrhages (Table 1). A last bone marrow examination on September 20, 1976, showed normal cellularity. toxic granulations in the myeloid cells. and an appreciable quantity of erythroblasts and megakaryocytes. Numerous mature plasmocytes were observed for the first time. At autopsy.three recent gastric ulcers proved to be the direct cause of the GI hemorrhages and death. Extensive pulmonary infection due to Aspergillus and Gram-negative bacteria and marked arteriosclerosis were present. The bone marrow showed normal cellularity. and the atrophic spleen (87 g) showed slight extramedullary hematopoiesis and siderosis. Cytogenetic Investigations Chromosome preparations were made from bone marrow and blood cultures of approximately 48 h r and were processed for R banding (acridine orange fluorescence). Blood cells were also grown in the p e n c e of PHA for 72 hr to determine the karyotype in the normal lymphocytes. Y-chromosome loss was evaluated by screening of 100 metaphases with Q banding. The results of the investigations a r c shown in Table 3. Patient 1 had a familial translocation (FT)characterized by exchange of the long arm of chromosome 3 and the short arm of chromosome 16 [t(3;16)(ql 1:pl I)]. This chromosome anomaly was found to be present in the patient's lymphocytes and skin fibroblasts as \vel1 as in the cells of several members of his family. The bone marrow and peripheral blood cells grown without PHA a t the first investigation D.I~ PniIlt 1 14-75 24- 75 LOCI75 60C175 em 75 22 & I 7 5 300~175 20 Nov 75 18 D u 75 .- 29 An 76 2 9 b 76 29-16 Table 3. Summary of the Cytogenetic Investigations M I 8 z PHA Chromosome C w n i ~ 4 4 45 46 47 a48 Number of Normal Cells. Numba 01 Abnumal Cells' Krryotwe (R Bandand M +B - P H A B PHA -B PHA M M M M M M M -B PHA 17- -3 5 - 2 23 No mitoses - -No mitoses 10 -2 a - 1 zo -1 16 -3 13 2 12 1 1 14 1 -4 11 2 16 2 0 1 0 46.XY.FT.119:1011p24?:p12) 0 10 46.XY.FT.119: lOl1p24?:p121 24 0 46.XY.FT.numal 0 10 46.XY.FT.119: 101(p24?:p121 0 1 0 46.XY.FT.Il9:l O l l p 2 4 I : ~121 6 17 46.XY .FT.namd/46.XY.FT. l(9: lOllD24?:P12b 2 18 46.XY.FT numalI46.XY.FT. t(9:101(D24?:P12) - -1 17 46.XY.FT.num81146.XY.FT. r~9:lO~lP247:Pl2) 0 16 46.XY.FT.119:1011~247:pl21. 114:l5llp 13:a 141 0 16 46.XY.FT.119:101lp24?:1~21. 1(4;1511D13;914)1 0 15 46.XY.FT.119: lOl(P2471~21. lt4: 151IP13:ql41 0 2 0 46.XY.FT.119:1011~247:~121. t14:1511p13:q141 814-4-5- No molosos No m m s e i NO m ~ t o s ~ i 13No m~tolei No m ~ i o ~ i 29- 1 0 0 -2 4 12 14 4 14 5 0 46.XY.namd 0 46.XY.num.l . :j -.'U. e 564 VAN DEN BERGHE ET AL. showed an acquired translocation in addition to the constitutional one. Part of the short m n c chromosome IO was deleted and translocated on the short a r m of chromosome 9. Le.. t(9;10)(p24'!:plI At that time. 11% myeloblasts were present in the marrow. and the WBC was 31,OOO/cu mni. w::, many immature elements. Twelve days later, when the bone marrow had become hypocellular \vithoui blast excessgnd the WBC had spontaneously dropped to 21OO/cu mm. marrow and blood culturcs failcd to show any mitoses. On October 22 the cellularity and cytology of the bone marrow normalized. but the 10 metaphases examined all showed the abnormal karyotype. On October 30 the same result was obtained. On November 20. cytogenetically normal cells showing only the FT appeared in the bone marrow (265%).for the first time. but their number decreased again in December 1975. and January, 1976. Further cytogenetic monitoring was then temporarily suspended because the patient was in good condition and had gone back to \rork. When he returned a few months later and was found 10 be overtl! leukemic, the acquired karyotpic anomaly persisted, and an additional one had developed. consistine e.' . an almost complete exchange betwen the long arm of chromosome I5 and the short a r m of chromaso;4. i.e., t(4:15)(ql3;q14). Two cells with 47 chromosomes showed an extra minute marker. Only one cc;I was found in which the additional translocation was not present. Patient 2. on July 1, 1976. had chromosome 7 monosomy in the blood a n d bone marrow. in which only I normal cell out of 15 was found. On Auglrst 12 the same anomaly was found in loo% of the cellj. No mitoses were round in the bone marrow of August 23 o r in the blood of August 23 and September 1. .41 that time the marrow had become aplastic. the WBC was 12OO/cu mm. and almost exclusively lymphocytes were present in the blood. Only four metaphases were found in the marrow ofSeptember 3. They were completely nornral. On September 20. when the cellularity of the marrow had become normal again, all metaphases showed a normal karyotype. DISC USSlON I t is very likely, although difficult to prove, that a causal relationship existed between the hematologic disorders and the professional activities of both patients. In the first patient it \vas proved that he had used solvents containing Iaree quantities of' benzene. The second patient apparently had been using glues contain- ing benzene for many years. The use of glues containing more than 19 benzcne is unlawful in Belgium. The nieasure. however, has not always been strictly enfi3:csd. and two other carpenters ;ire currently being treated for aplastic anemia ir r ' department. W e may surmise that the patient had been exposed to benzene 1- 1 the law was passed and t h 3 t the possibility of exposure existed even after that .... :. Both patients initially presented with so-called preleukemia, as manifestea by an - increased WBC with imn?:iture elements in the blood and a n elevated nuniber of blasts in the marrow. This preleukemic state, moreover, was characterized by n clonal type of chromosomal anomaly that was present in 100%of the bone m a r r w and blood metaphases in patient 1 and in 95% of the bone marrow metaphases in patient 2. Clonal proliferations in man, a s a rule, a r e malignant in nature. Exceptions to this rule may be endothelial cell proliferation in atherosclert\sij.' nocturnal paroxysmal hemoglobinuria (NPH),' and some benign gamrnapa:t:j. particularly in elderly Ataxia telangiectasia appears to be the cjnl! exception in which a consistently d e m o n s t r a b l e k a r y o t y p i c ch:lngC [t( 14;14)(ql2;q32)] is present many years before malignancy develops.e Thc significance of clonal abnornialities in some patients with polycythemia veri myelofibrosis is still obscure. O n the other hand, there is convincing evidence that many leukemias may be preceded by a preleukeniic stage, such as pancytopeniL1 Or aplastic anemia, in which consistent chromosomal abnormalities exist in the marrow. Not only is the proportion of these preleukemias presenting chroiiw; .*d anomalies with clonnl chiiracter siniilar to that found in AL, but during thc lcukcmia thc same karyotypic anomaly that was demonstrated in the preletl:.. liC phase charac . E '' . h t .r during the le Ikci ' a. The rnaligj a n . I the absence ( I' .!I . . r ~ t : ! i ~ r q IOO,OOO/CL rim ::ici. , ::I returned to l t o r r j ; i ;I ~ : :i picture agair , '24 i .]I: ::x( cells began tc a p ):: I :II i h e abnormal. I-e:ict, :.tic pa clinical and iytcl::: ,.: r:mi sign that t h e disi: i:x rna) number of bone r . 1 , ~':'c.ii n relapse occurred In patient 2 t h : C I : ) U ~ ; Cc however, disappe:ir.t d '.otai bleeding and infw.i:ius cor started to recover .I .id was on two occasions. F'roni tE rejection of the pre,,;umabl, tion of normal hern;.ropie 1, and of plasrnocy,osis in rejection may have xcurrt partial and of short durati whose death from conlplic: Spontaneous regression no cases with abnormal ka! documented. The chromo. frcquently associated with regularly found in ;icutc le was found i n patient 2, i! anomaly in A,ML; onl!. trP Chromosome studies in been reported,'-" but we techniques. One case oi candidate) is mentioned b (one benzene-induced prci Unfortunately, no bandin whether a (9;22) or anotbc tion, in benzene-induced anomalies that occur non liferalive disorders would significance of these anc unlikely, indeed, that thc also appear in benzene lex SIS, and questions about cancer and specific chrom Paticnt I was a carrier -- . translocation. Whetllrr r & -CHROMOSOMALLY MONITORED BENZENE LEUKEMIA z2x e?: -rY= $ phase characterizes the leukemic cells. Further karyotypic evolution may [I( 1 during the leukemic phase.' The malignant process in our 2 patients showed a remarkable natural histor \ I --;4- ,:".-g- the absence of any antitumor treatment, the WBC of patient 1 dropped from ~o~,OOO/cmum' to about 2000/cu mm within 1 wk, the myeloblasts in the r n n r r c i' returned to normal, and after a hypoplastic phase the marrow showed a n c r 7 L s ~ --picture again, with the exception of an increased number of eosinophils. Nc rniLil --Ls- 25- cells began to appear in the marrow, in which initially 100%of the metaphases were i2.:,;?- abnormal. Hence, the patient spontaneously went into a seemingly corndc:e clinical and cytologic remission, allowing the patient to return to work. The on y ?$- sign that the disease may not have disappeared totally was that a substantial -i .i. number of bone marrow metaphases was still abnormal; indeed, 3 mo later a fatdl relapse occurred. In patient 2 the course of the disease was very similar. His aneuploid cell clone. however, disappeared totally, leaving an aplastic marrow. The patient died from GI bleeding and infectious complications at a time when his bone marrow had already started to recover and was accompanied by plasmocytosis and normal metaphases on two occasions. From these observations it can be concluded that spontaneous -- I _. rejection of the presumably malignant cells occurred, with (temporary) regenera- tion of normal hematopoiesis. T h e concurrent appearance of eosinophilia in patieqt - --_ - 1, and of plasmocytosis in patient 2,'may lead support to the hypothesis that this * .. rejection may have occurred on an immunologic basis. However, rejection was only -. partial and of short duration in patient 1; it may have been complete in patient 2, - ' - whose death from complications prevented further follow-up. Spontaneous regression of leukemia in man has been repeatedly observed,' but no cases with abnormal karyotype. studied ith banding techniques, have ever been documented. The chromosomal anomaly found in patient 1 is not known to be - frequently associated with any particular malignancy, but such translocations are - regularly found in acute leukemia. The chromosome 7 monosomy, however, which , was found in patient 2, is the second most frequently encountered chromosome anomaly in AML; only trisoniy 8 is more frequent.' Chromosome studies in benzene-induced malignant hematologic disorders have been reported,'-'' but we know of no cases that have been studied w i t h banding lechniques. One case of monosomy C (statistically monosomy 7 is a strong .andidate) is mentioned by Aksoy,14 who also stressed the finding i n two instances (one benzene-induced preleukemia and one benzene-induced leukopenia) of a Ph'. %Unfortunately, no banding or pictorial material was presented, and i t is unknown whethera (9;22) or another type of translocation was present. The clear demonstra%v.. tion. in benzene-induced malignancy, of a Ph' or other structural chromosome F anomalies that occur nonrandomly in human myeloproliferative and lyrnphopro- ;jiferative disorders would be of utmost importance for a better understanding of the of these anomalies in malignant processes. It would seem rather 5 unlikely, indeed, that these characteristic chromosome anomalies, if they should alsoappear in benzene leukemia, would be of primary importance to leukemogene- $sis*and questions about the relationship between individual etiologic agents in S,.-c.anccrand specific chromosome anomalies would losc somc of their interest."-'* :-' I was a carrier of an apparently balanced and familial (3;16)(ql 1;ql I ) ~..~ t r a n s l o c a Wh .hether malignancy occurs inore frequently in individuals with .e% I .J r.b 566 VAN DEN BERGHE ET AC. constitutionally abnormal karyotype other than trisomy 31 or occurs in clusters in families in which constitutional chromosome anomalies have occurred remains an ope*question.' REFERENCES I. Sandberg AA: The Chromosomes in Human Cancer and Lcukemia. New York. Elsevier North-Holland. 1979 2. Benditt EP, Benditt JM: Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Sat1 Acad Sci USA 70:1753-1756, 1973 3. Oni SB. Osunkoyo BO, Luzzato L: Paroxys- mal nocturnal hemoglobinuria: Evidence for monoclonal origin of abnormal red cells. Blood 36:145. 1970 4. Waldenstrom J: Studies on conditions asso- ciated with disturbed y-G rorms (garnmapathies). Harvey Lcct 5621 I , 1961 5. Michaus JL. Heremans J F Thirty cases of monoclonal Ig disorders other than myeloma or macroglobulin. Ani J Med 46562, 1969 6. McCa\\ BK. Hecht F. Harnden DG.Teplitz RL:Somatic rearrangement of chromosome 14 in human ~ynlphos!,tes.Proc xall Acad Sci USA 72:2071-20-5. 1975 7. Boyd \V: The Spontaneous Regression of Cancer. Springfield. 111. CC Thomas, 1966 8. First \Vorkshop on Chromosomes in Leu- kcniia. Cancer Res 38:867. 1978 9. Pollini t.Colombi R: I1 danno cromosomico midollare nell'zncmia aplastica bcnzo!ica. Med J Lavoro 55:241. 1964 10. Forni .A. .\lore0 L: Cytogenetic studies in a case of benzene leukemia. Eur J Cancer 3:25 1- 255. 1967 I I . Forni A. hloreo L: Chromosome studies in a case of benzene-induced erythro-leukemia. Eur J Cancer 5:459-463. 1969 12. Hartwich G.Schwanitz G . Becker J: Chro- mosomen Aberrationen bei einen Benzol- Leukamie. Dtsch Med Wochenschr 94:1228- 1229, 1969 13. Erdogan G,Akso! hf: Cytogenetic studies in thirteen patients \r.ith pancytopenia and leukemia associated with long term exposure to benzene. New Istanbul Contrib Clin Sci 10:230. 1973 14. Aksoy M: Leukemia in workers due to occupational exposure to benzene. N e w Istanbul ContribClin Sci 12:3-14. 1977 IS. Rowley JD: Do human turners shot\ : chromosome pattern specific for each ctiologic agent? J Natl Cancer lnst 52315-320. 1974 16. Rowley JD: Are chromosomal changes relatcd to etiologic azcnts. in Proceedings of the 1I t h Canadian Cancer Conference. 1976. pp 124- 133 17. Rowley JD: Arc nonrandom karyotypic changes related 10 etiolo_eicagents'? in Mulvihil! J J . Miller RW. Fruumcni I1 Jr (eds): Progress :- Cancer Research and Thcrap!. VOI 3. Gcnetica Hunian Canccr. \.ark. Raven Prcss. 19- pp 125-1 36 18. Mite1nian-F. \lark J. LevanG, Levcn A T Tumor etiology and chromojonre pattern. Science 176:1340-1 34 I. I972 '. Effect of A I W e studied t h e inter with human platelet activated by IgG a r tained from 3 patient fusion purpura syn heparin-plasma buffe complement activatic platelet function. Wit ment activation was immune alteration \ P1*' antibody was p r e s e n c e of c o m p t e : both platelet lysis a ( r e l e a s e r e a c t i o n ) in were observed. Plat by "Cr loss, r e q u i r e body than was n e c e s PLATELET IM. may be medi immune complexes immune alterations of IgG-coated plat result.'%'2CompIer: lysis of human pl;! alteration mediated man.'4.'' We studied the conditions in whici antibody) obtained We studied the nat component require antibodies can me platelets. - From ihe Hernololog. phia. PO. Subnilired July 7. 19; Supporred by Anrenr and by Speciol Fello* h k e t n i a Soriety o/Ai Presetired in parr be$ 1978. Address for rcpn'm r (he Uniwrstry of Petmsi 0 1979 by Grime & 5