From www.bloodjournal.org by guest on December 22, 2014. For personal use only. HISTORICAL Paroxysmal A Classic nocturnal svn(Irorne 1 1(1(1 anol 191 such a l)tt ient iii in 1866, Strul)ingm35 in the new entity, the citation ease ft-oni 1882. afldl characteuized INtSe(l io)i15 i)itP(тАЩi \Vt5 has 0)1тАЩ fullsтАЩ denouistuated cited the iii believed an(I тАШ тАШ(lit-o)ni(тАЩ hidтАЩtD( тАШтАШ. . lтАЩronii I loslat well that andi sixty ihe later. andl a by the dliSof a(тАЩouracy of Although Str#{252}- case othelтАЩWise as was theories exceptional been Paul regal-died! dlisease proposed years re- case by be the ol)seu\тАЩations. a somewhat- l)tol)osedl )gl( )h )iIill tтАЩit-hi(тАЩfll( of cold! com- almost- t li(тАЩ Ziskinid I I ivisli , )V grant record of t lie fnтАЩotn ml aine(l Library s \Vashiingt ol fronii t lie m\ t banks on, t I). i\ ones found the 1\I ichuehi nuen- in the I )onat тАШ тАШ has litera- Ic anemia amended i stuck. t lie ) of amid it le observations, hemolyt type. (hleniatology al his epo)nynl vho that. тАШтАШ тАШsplenonuegalic тАШ the audi \IauтАЩchiafaтАЩa, propose(1 he had iafaтАЩa ane- of hemo- hemosideritutliiIt published LttldтАЩli lтАЩ an(l uтАЩhich (hisease , ( тАШemit me I lospit of t he . rnii to forтАЩ in t lie Medic:tl IтАЩniiversit I)r. ( liarl C.. itles listed t lie Milan; auul amounts ,J. II . Prat 1)eiatnтАЩt miiemit of t I)iagnost-ic \Eechicinie, Tufts 8(11001. to majonтАЩit lahorat lnigl:tnid 1928 in entity cases the lonтАЩintmtia ty)d,тАЩтАЩ lse:trchi Nei )d(тАЩ(hi(тАЩ:tl ;ided Lii macv t lie l)atieu1t henolyt-ic тАШacquiue(1 тАШ I))тАЩ hat-ge I)elтАЩPetual sinuiliauтАЩ calling )5i( of repo)rtedl disease with -ie\тАЩetтАЩal \Itt(i1iItImt\тАЩa-\liOh1(тАЩli . uvtts anemia a ca-se chau-Iictetizedl a newтАЩ seoтАЩondl tinue sanue uepo)ut-edl case second id :: I ioтАЩlieli t1 anal (тАШohlege hdтАЩfllOlVt flue 07 #{176}- uuтАЩit ii Forghiere, clearly it- has was ioleuutified \IiuxтАЩIuiafaтАЩaтАЩs at NazatтАЩi vhuich A hue ha(l stuidiod tiouuing type,тАЩтАЩ utine.t that dtlle(l this, in igluo)redl. sidet-in t uut.e.1 excellent dlescription of his patienttests, he dhiffet-entiated some luem()gloh)iuultia, Marchiafavadlescrih)ed syn(lrome might- subject clinical as an (lefinite a hemoglobinui-ia of his called! first been published as u-ecogniZe(l occasionally nau-ciu mimt., \\i(lmtl-Al)imlflhi t he analysis 19 1 1 , \lauтАЩchuiaft-a In latet . A.U.S. have Gull65 l)auтАЩoxysmal and l928.#{176}Actually, the dhsease uтАЩas f-hat Charles Stewarttuu diescribed it by a careful 136 BтАЩ provocative ltl)Oti heeuu henoglobiuuuuia I)letelY cases.)m of entity in possil)le lie M.(1., to first uecognizel papeu on the Strul)ingтАЩs in 1882, commonly \Villiam uтАЩas investigation. of eaulier olcoituct I)ings Althouigh o)thieuтАЩ fou-ms pathOgOтАЩuUтАЩsiS It is eveuu olisease of (тАШlinioal classic his I 793. (oL., helievedi a clinical as LiтАЩ. hemoglobinuria, generally l#{176},)th century. 1)ort a is redтАЩo)gnizedl in the knouvu Hemoglobinuria I-I. CRosulY, WILLIAM AHOXYSMAL )iIidтАЩhlCII Nocturnal Description by Paul Strubing a Bibliography of the Disease By P REVIEW I.uis Itunid ani(l he personiniel t heir count Chicago; Marval, t he (/ of esv bibliography. I ibranтАЩv v of (he t on t norтАЩ arid t hose t he aut atice 270 Aires; in lick, amid providing (тАШonicernie(l Dr. Jean ion Army 1)ivisionn public:ttionis lionтАЩ niiversitats-Bibliot Buenios my lтАЩounidat 1)ai Reference assist For from I I . I loud . t lie which Medical the mm! with could riot- be I am in(lel)te(lto Got tigeti ; l)r. Reniato , Favre-Gilly, Lyon. From www.bloodjournal.org by guest on December 22, 2014. For personal use only. WILLIAM From time to time instance has been the to describe first the right disputed.2тАЩ ft has disease, of the been was 271 CROSBY of paternity H . the H. Italian protest-ed! not- the who have reviewed Marchiafava and to it in their paper.) Hmans van den hemolytic Bergh process was anism in vitro was Biffis8 published patient occurred patient was in Holland, and suggested the literature, Nazari wтАЩere reported due only aware a case to a defective potentiated by carbonic a case report in 1915, only in the evening CalabresiтАЩ7 made in 191 He cell and acid. noting or at the noted the common many cases had when been the in America67 mans slight van been found Almost in the oxysmal and that which vork which, f-he mech- hemoglobinuria also pointed in his out that his taken Dacie up was 15, 45, 66, scant- he red the cell the studied have had clinical picture There have hemoglobinuria, All syndrome. not been it been hitherto published upon by after constitutes 146 until the latter in Holland,5587 the finding of Hy- normal, hemolysis. a normal globulin.28 and that It has plasma The conremark- uтАЩas invoked to explain the sleep the respiratory (тАШenter increasing hemolysis. a theory dlesirable identified today, 129, f-he plasma in increased of hemolysis nowтАЩ been reported and f-he disease It- seems 117, confirmed accelerator and 89, by Jordon is acted coagulation 68, only thrombosis attention independently in England.35 appreciated f-hat the red cell is dlefective, plasma in vitro results defective тАШ case have evolved at least 123 cases has become a wтАЩell to call attentid)n to the of parknown early and especially td) review StrubingтАЩs wтАЩould be regarded! as a significant * Other globinuria that hemolytic hemoglobinuria. thrombosis of acidity on the hemolyfic mechanism of hemoglobinuria at night.35 67 1)uring and carbon dioxide is retained, thereby contribution. history and may piecemeal, cases the idlen- iefeuence metabolism, demonstrated by changes in the plasma Neither Marchiafava for It is nowтАЩ recognized was that of the the which 70 20th century. nocturnal much * 68 тАШ acidification тАШ venous in this disease.5тАЩ 6, 7. the hemolysis received prol)lem Bergh den of nocturnal of published. threat of Ham st-itut-ent69 able effect occurrence is depressed phenomenon occurrence most serious The mechanism 1930тАЩs, not similar to that of Marchiafava and Nazari. In 1925, Enneking47 unaware of the Italian reports, published a carefully studied that the disease be called тАЬparoxysmal nocturnal hemoglobinuria.тАЭ had The this ol)hque demonstrated the He noted an that that night. In 1927, Scheel,тАЩ28 in a study dealing with pigment that f-he nocturnal hemoglobinuria was accompanied hemoglobin, l)ilirul)in and urinary uroi)ihnogen. Micheli has of it and red was to that neither he nor Micheli wrote a definitive Chauffai-d and Troisier24 in 1908 had published wтАЩho three years later was described by Marchiafava authors in this Marchiafava i-ecognize it as an entity diescription. a i-eport of the same patient and Xazari. (Of the many first and tity. hematologists that early of reports nocturnal was that of ParoxYsmal henioglobinuria. reporteol hienioglobinuria The in 1832 by first Johns are idenitifiable Elhiotson, of interest case of of lonidon.nui as background paroxysmal The for cold disease the hemoits this From www.bloodjournal.org by guest on December 22, 2014. For personal use only. 2 72 early As as published I 794, an thra.тАЭ It The em-ises lasted! became crisis was much of any the in spade only appearance тАШiVilhiam sтАЩere IV. ( in leaf-her practicing at Archangel, of blood from the had nocturnal with systemic a l)u-anny though of and sedliment- regularly, to) tinge the red! at- the the colour, second! mention made uтАЩas first d!ischarge, less severe uu-as very urine made time was of the ure- hemosympof fulness crises the A . if- returned continuing of a deep No of making perfectly influence free of cold nor or chills. of Lond!on About in flue exciting reported an incontestable time a numheiof cases that English cause who, showed : instead! days, blood.тАЭ uill6i 18(16. wтАЩorker cold case ordls discharge l)ut тАШ (тАШolouued; of published! тАЬThe variety. quantity of fever globinuria surgeon periodhical hemoru-hage, of three slightly association colorтАЩ : тАЬThe diminished the a Scottish patient, a 51 year old Russian, three days and were associated! his тАШof natural тАШ L HEMOGLOBINURIA in the hadтАЩk and lower abdomen, torpor, and a sense severe crises the urine was dlark all olay. Between dlescrihed! it- was Stewart, of a singular that urine NOCTLтАЩRNA L (тАШhaties тАШAcoтАЩount тАШ t-oms, such as pain in the head. During during YSMA is possible globinuria. if, BOX PA in literature. was exposure the course Gull uvet f-hat- his case was тАШiтАЩhe patient and! wтАЩo)rk, hemoluemoglobinuria of nocturnal cold! of believed td) his d)f case of this uvass a cold.тАЭ frequently was (!renched uvith wтАЩater Sd) that he became uтАЩet- to) the skin. Gull gives an exceptionally fine history and! olailv notes of the patientтАЩs hospital course. Through these recthe pidтАЩtut-e of no(тАЩturnal hemoglobinut-ia emerges clearly (lespite the er- FOflCOli5 case was It \uтАЩas foinud to Perhial)s Because (lue of the seetiis to to тАЬWhile noted!, contain the that haematin a cold response unilikely ani uuтАЩas diagnosis. morning hieniagglutinin, quinine, diagnosis. this for case TeniporarтАЩ u-urine f-hat was passe(! which was passed at the attacks is usually were written iniprovememit in prevented off as of typical f-lie one etrly or during noon by quinine. This malaria. cold of paroxysmal hemoglohinuria (agglutiniimi type) under large (loses of quinine was demonstrated years later, 1873, h)V Rohsert I)ruitt , an lтАЩnsglishi physician iтАЩho тАШas himself afflicted by the disease,mtt Elhiotsoni reported oh)servations in his patient ivhich rather ehiminiate malaria as a diagnosis. тАЬThis nian was labouring umider frequent. chills, but had not regular aroxsnias of ague.тАЭ Elliotsoni also S1)Oke of the тАЬaguish fever. . which he suffered whenever the east wind blovs, or he is eXpOse(I to cold ani(1 vet three attacks in a single (Ity. I)espite lтАЩiliotsonmтАЩs I)riority, l)arxYsniial descript iomi scril)e(l a 10 year mal cold crises. vithi of hoтАЩnioglobimmuria, I)resslerтАЩs careful Tens and years 1)ressler ivhi() was since is a niiucli rel)eate(1 physical mi England later his ProIablY exaniinations a spate of an(l cases the hiterature.m49 \Iost of these were cold henioglobiniuria reported by Gull was among England to the (тАШonitinemit-, anid durinig t he niext hemoglol )i nuria were reported. In many of absensce of red grounds, Gull pignuent-at ion the cells earlsтАЩ in t lie suggested of the reports, therefore, тАЬhaernatinuria.тАЭ urine in all of cases the in agglutinin original 1S54. type nose amid ears ol)servat-ion the had during than He de- of paroxys- hemolytic Elliot-soniтАЩs, urinialyses. paroxysmal them. Interest- thirty years 1868, apparently with published hemoglobiniuria hemoglobinuria, used In these of was hemoglobin and urine, with patienit credited was yanois of the piece of clinical better the is generally report afflicted lie developed report occasion of WUrt.zburg hemoglobinuria. child old Oni one ....тАЬ mistaken the Popper represented but in almost for term appeared the case the disease 1(X) cases of paroxyтАЩsmnal I)ressler 1)100(1. тАЬchromaturia.тАЭ proposed found On that hcmoglobinuria.mum in of nocturnal spread from the the paroxysmal an same From www.bloodjournal.org by guest on December 22, 2014. For personal use only. WILLIAM H. 273 CROSBY the latter part. of the day was healthy, and so it continued for as many as eight (lays. Such is the usual clinical history of these intermittentattacks.тАЭ StolnikowтАЩ of St. Petersburg, Russia,tm36 pul)hished one of the early reports in 1880 but made no mention of f-he nocturnal pattern of the hemoglobinuria. However, on one in color, it- is noted day containing : тАШ The a quantity urine accumulated! of uric dluring salt acid! hut no the night- formed was elements red [casts or blood cells]. Thete w-as a faint oxyhemoglobin spectral absorption st-ripe. The morning portion of the ui-inc was a deep strawтАЩ coloi and! showed no hemoglobin in the spectroscope.тАЭ Stolnikow usually collected all of his patientтАЩs urine each olay a single as i)inuria was specimen, missed. hemoglobinuric so that He crisis. did, On the nocturnal howтАЩever, the set tenth day of March, he notes, for instance, тАЬtemperature The pallor of the mucous membrane yesterday is very ness The and headache fender in the right during the a murmur at f-he apex and! Stolnikow noted exposure his that patient wтАЩith the right dluinine cold hemoglobinuria and! something to pei-iod. in 1880, that suggested wтАЩith did) II. bloodl day of the crisis, enlau-gedl. The liver tongue is fuzzy. Borborygmi 20. The heart- uuтАЩas enlarged, cc. of perfectly nothing effect. to black wit-h d!id not the He although he believed kidlney d!isease as an that his patient efiologic factor was in f-he the he noted! might (тАШOncept for that have pai-- jaundice w-hich an enlightened! published a uepoit offer urine.тАЭ crisis. be- of Lyon He do a diagnosis dlestuilcfion, Lepine9m third! is dlistinctly 1500 had without тАШ Also spleen jugular; to yond тАШparoxysmal hemoglobinuria,тАЭ not a тАЬtypical case.тАЭ He eliminated ticulai- the evening 38.8; this morning 37.4. marked, as it- uuтАЩas yesterday ; weak- to percussion though not enlarged. The lower ahd!omen. Pulse 88. ltespiiations was t-ieated night. chai-acteristic of the hemoglodlescripf.ion of a typical a good d!own of a case in which the typical pattern of noctuu-nal hemoglobinuu-ia is mentioned! : тАЬIt is only at nightf-hat- f-he urine was blood-colored . ai-ound 1 1 : 00 oтАЩclock or midnight, the urine was l)loodl-coloted and! not the otheu- specimens. The coloring uuтАЩas, moreover, as . I have said!, onstu-ate! not intense. an colored are positive.) of hemafuria, dlilutc jouity of cases is the only six the ui-inc in the My . . . examination cells. 1ed! entiu-ely . ft-ce seveial . . uтАЩenal is the patient There tul)ules. result had are at The times urine He of cold. by the an kidney, concluded, But- i-epeafed, d!emwhich au-c (They were guaiac specimens of hemoglobin.тАЭ is in i-eality that hemoglobinuria dells are lost as such ted [f-he cuisis] cause. hours. of not- contended that flue veuy micioscopic absence probably Lepine in l)ed On absolute . тАЬIn wтАЩe need unusual and! form aie lysed flue immense not- l)elicve in ma- that this his paroxysms at midnightuuтАЩhen he had been least two d!istinct types of paroxysmal hemoglobinuria.тАЭ Paul wright * Strubing* uuтАЩho Paul reported seen his case in 1882тАЩ; the patient was in Novembet-, 1880, in flue Medical uuтАЩas first Strubimig was borni in 1852 and sтАЩa1d in 1876. Ins 1889, he became in 1900, professor of internal subjects as laryngospasm and director medicine. ozena. took his medical of the His nose later and degree at the throat cliniic published work a 29 year old caitClinic of Professor Uuiiversit-y at was the of Greifs- University confined and to such From www.bloodjournal.org by guest on December 22, 2014. For personal use only. 274 PAHd)XYS.\-IAL NOCTURNAL service, (lt-enchuings тАЬFlue especially uvith of an overhuentedi in observed! Mosleu 1876, he OтАЩO)lOF change up and by The enlarged, l)inous urine flue evening urine, he nate. pain the neigluborhoodl pain in the liver fote the eyes, area, at-tacks, time, this his extraordinary fatigue on exertion, d!eveloped!, well and . . . wтАЩetc he was he urinate voided once or pathological The most constant increased palpit-ation, after habit-s complaint by was percussion ; lesser sometimes a glitter be- After an attack the exhaustion. a very severe attack wтАЩcie very regular, once there is a daily ; after in 24 hours. attack, 36.6 to which and and! 1880, on. hemogloday or in . accustomed! which vertigo, stools . not percussion. dhisfurl)ed without any urge to) unhe had in the morning naturally cor- at-tack. bowтАЩcl 2-3 an b)etween His muscled liver from November, He void!e(! (kirk was not-ed! d!uu-ing the . fol!owing of breath, ears, to pu-od!rome spleen, shortness wтАЩith was his to) percussion f-here tempeuature At . getting Clinic unless which the tender daily. nights of in the h)ladd!er. association tint This after no lymphad!cnopat-hy, Medical examined those of is tend!er in the тАЬIn the till morning the symptoms buzzing area se\тАЩete on intensity f-he kidney and at of in pressure enlarged uuтАЩas ditlieflY wтАЩifh easy black. d) passc(! colou. strength to an a wтАЩell tongue, urine night, intensity physical records only in flue mot-ning. No before an attack. Although the responded his titine yellowтАЩ of exhaustion, a normal treated the slept- The pallor, was (luring usual a yellowgiay spleen.тАЭ examination so)mcwhat time the dIal-k-brown the in of the dlusky spleen looked morning lost- primarily physical with this twice the assumed patient тАЬThe sometimes in attained! the 1)uring flue latest neighborhood! man . urine itself ShOwed! at d!etailcdl young l)d)diy his he complains in the to) had! Now pain himself tuaccs his present illness to his milithe heavy i1usicai exertion and! the many After his d!iscluarge fuom the military service negaud! had bedтАЩome pale and! the past year hue had noon тАЬDuring olegree. that OfllV (тАШomplexion any patient of (iueifsuvalol. tary HEMOGLOBIXURIA the and patient 37.2. No never felt eui.iption a chill of hives was or heat. The observed usтАЩit-h at-tack. тАЬ\Vith of oтАЩold in the J)iuning heatedl regau-d! cOuld! summer the Strubing oluring the uvete as frequent just- light praying bath) pi-ecipitated that noted subsequent dlescnihed ately after by Fleisehuen- the тАШтАШbehino! Ot.lr exercise But backтАЩтАЩ attacks, (!osed just or wore but himself and a dhrect that severe as those in the open air at bodly wтАЩot-k with overwot-k . ether uтАЩouulo! was salts . wтАЩithout attacks the winter. with over- noting any of giving an produce come effect the (insteao! these wтАЩhich тАЬdisagreeable often there with iron . between hemoglobinunia) excess himself go into as would! he atta(тАЩks stated! he distinguished! (march Alcoholic noctut-nal he his uuтАЩhole no aft adтАЩk.тАЭ heavy night. exertion. which ind!ivid!ual patient- and! winter clothing effect of the cause The 00)1(1 of last in the thiosse l)teoipitate patient pn-ecipit-ating demonstrated. be severe body (letnimental him a cold! to) the not attack episodes emotionsтАЭ could! no discernible cause. and! pro)d!ucco! ano! immedhi- on an also The attadтАЩk From www.bloodjournal.org by guest on December 22, 2014. For personal use only. WILLIAM unequalled nocturnal in severity hemoglobinunia Strubing the studied w-hich has lasted been his patient H. four noted diligently 275 CROSBY to five nights. in several later and described (This effect reports.t6тАЩ 77 the of iron 82. , significant in 141) facts about disease: After 1. that was especially severe at-tacks blood cells were dissolved a penetrating observation argued about ingтАЩs . - 1911. Marchiafava Free in found urine the sediment in the were urine found except тАШas identified plasma believed contemporary, Lepine (above), Although he failed to identify a fine-grained, yellowish-brown 2. тАЬ. in the was the blood vessels for the time. The He that construed in the this kidney as or the evidence urine. of hemoglobinuria hemolysis occurred in the This was still kidney. Strtib- believed that hemolysis occurred in the urine. the pigment, Strubing described the hemosiderinuria: detritus and fine-grained casts of the same color. yellow-browni a rare red. and not mechanism in one after renal a very epithelial severe attack. cells.тАЭ The No red cells were hemoglobin in the by spectroscopy. StrUbing pointed out that glohinuria. The only way that in the dlevelopment sleep was the (letermining factor hemoglobinuria was to be found 3. in other than of hemomorning urine was by having the patient wakened at some other hour. He reasoned that a dissolution of red cells took place during sleep; that the process was a slow and gradual one, for there were never signs of violent hemolysis such as chill, fever, and flushing; that the hemoglobin was excreted by the kidneys into the urine. His further reasoning is made more interesting by our recent knowledge of the mechanisms of this disease. He postulated that the red cell must be defective, the product of a disordered blood-producing organ. He knew that all red cells are somewhat sensitive to the hemolvt-ic action of carbon dioxide and suggested that these slowing Particular acid (from the hemolysis of patient acid manner,68 ducing cells the circulation of previous these and might be during sleep (layтАЩs abtiormal sodium He hemoglobinuria even but was enough was Were accumulation would cells. did not. give senisitive. anud the exert-ion) red bicarbonate but- Strubing nocturnal abnormally provide the attempted to unsuccessful. acid.) This not heard of this so, he of carbon proper acid provoke concluded, dioxide the and lactic environment- a crisis by for giving (A crisis cani 1)e produced theory of nocturnal acidity again unitil 1937, fifty-five- the in this proyears later.35 67 4. Strilbinig speculated alout the spleen. At this time a conniection between the spleen and abnormal hemolvsis had not l)eens accept-ed. тАЬBecause of our uncertain knowledge about the function of the spleen, we niay only hi-тАЩ1)othesize about the s)lenoniegaly and its Part Hi our syn(lron7ue. A close coninection between the individual attacks and the spleen is provc(l by the apearansce of Pains iti the splensic area after ani at-tack and after several attacks the appearance of a slight but definitely Pall)al)le enilargenient and increase(l tenderness of the spleen.тАЭ 5. \IansтАЩ patients iтАЩit Ii noct urnial henioglobiniuria develop serious t-hrombot ic phenonuienia at some time (luring the course of their illness. Although this did not happen to StrubinsgтАЩs Patient , he suggested that the nianiy sniptonis which develo1)ed Iurinig this attack might тАЬSenisationi chest , time of the symptoms breath) stroma the cough, Landois, be due iveakniess, aini attacks mi to such the the t-o the and to the concerninig a process. exhaustion, area number bowel liver arid inconnpat He short-ness of the spleeti of stools which were due to anemia and those which were due in the blood might somehow circulation chest), soniehow of and to some the symptoms a sense a1)doniinial from StrUbing loss (pain). transfusion t-o t-he His lungs crisis: in Furthermore, cells during (weakness, (cough based dogs.#{176}5 and thie shortness oppression of mi on experiments The violent the the hetweeti suggested that free re(l and a partial obhiterationi was in of a severe apprehension distinguished of red reasoning react ion of pain. other process. He a formation of fibrin (hyperperistalsis), spleen ible noted 1)reatli, is increased.тАЭ resulting cause of cell of the by picture From www.bloodjournal.org by guest on December 22, 2014. For personal use only. 276 PAROXYSMAL ivhichi occurred LanidoisтАЩ in aniinuals to be a magnifications Strubing the animals ol)st ruct were lтАЩ ed have to fibri The . HEMOGLOBINURIA (hienuoglobinuuria-, of the founid t lie NOCTURNAL process some vahidit ins his arid mesenteric St ri) hingтАЩs The si flll)le headache whirls nnost pat ient 5 W t h their attacks occasionally progresses to cerel)ral casionally becomes a full-blown portal thrombosis. of red cell stronnata or to sonic other mechianisni are plagued 1)5тАЩ thironsibosis of a minor and nuiajor hyperpnea) lie ol)served their of of y (hiarrhea, which speculat aniply doubt degree , is abdominal this is due but the fact without vessels borne out. with experience The Whether to nsortein, blood been hiemoglobinuria thrombosis. is in Post I)ulmonary ions has nocturnal appeared patient. cramp oc- to the development that these 1)at-ients question. COMMENT It is seen from the luemoglobinut-in above accoutut acoтАЩutтАЩately was that svndhud)me the olescnibed fifty nocturnal of h)aioXYsmal years it before was accepted!. differentiated his dhsease fu-om other types of pau-oxysmal hemoglobinuu-ia wтАЩhich had been idientified! at that time. He identified it wтАЩith other cases of the same svn(!rome descu-ibedl by other authors uuтАЩho had not recognized the significance of their (!escniptions. How then did f-his d!isease fail to be accepted? Strfibing We have examined! answet-, the writings mu(тАЩh \Vithd)tlt paroxysmal had! been in identified! as a(тАЩdтАЩepfeo! GullтАЩs somewhat kid!nev function as of malaria in spite of the d!iscussid)n is given to ( mauтАЩch hemoglobinuria theories regarding ma! that mentioned! (Old was !) carbon at face value StolnikowтАЩs Chvostek . however, almost gave and! . of quinine. with those fascinated!, uvas dlioxide this LepineтАЩs theory of d!efcct-ive case is d!ismissed as a case of feveuтАЩ and the failute case, which is identified! StrQbei-gтАЩs an ieport Chvostek and! remarked! very He dliscussed LepineтАЩs in hemoglobinunia kid!ney dhsease. a for a comprehensive reviewтАЩ of all of the cases (almost 100) each of those which we have hemog!obinuuu-ia this al)sendтАЩe contemporaries StrQbingтАЩs I-fe revicwтАЩedl an(! fullsтАЩ but accepted! the huemoglobinuria. for of published! J)auoxysmal thoтАЩorv moi-e 1894. dlafe noctu ease dO.5C arid to paroxysmal to GullтАЩs as briefly pUl)hisheo! many Chvosteknut hemoglobinut-ia wтАЩhich of sti(тАЩdтАЩess. a page The longest of Fleischer by to StrubergтАЩs theii description d!iseasc entity (lisdтАЩIissid)Ii. the Perhaps tinue uтАЩhcn first is Stt-(ibingтАЩs name seems careful work dhiseases foi himself vain for clinictm57; has of medical this plished too mitch. Masiusnt) thirty This before iecognizc his may d!isease disease dlefect than luereditary immoutalifv. It know remains synonymous nocturnal to) two) causes. name. works. it, flue with hemoglobinuria a mou-e These uтАЩas first Belgian has toget f-hat wтАЩe look from BiermerтАЩs pernicious anemia. peu-haps, titled! described. observers her achieved cases serious a StrfibingтАЩs little or, by an ad!eduately spherocytosis anemia,тАЭ mattets among at The Bestowing While by lumping pernicious uve nd)w MinkowтАЩski.156 good Biermer, тАЬprogressive is shared! this laid! he a dlistinn.тАЩti\тАЩe attention it might have caughton. is doubtful. The work contains in whichi years as anemiaтАЭ his to his dтАЩontempouary, them anenuia, huaol called luemoglobinut-in, give unnoted, тАЬBiermeiтАЩs wтАЩo)rld dlesctil)ed of focusing naming a measui-e even 1871, gone med!ical a(lequiatelv to way anol But and first failuie pel-nicious Strubing nesic it was a sui-ei- several ofтАЩ the failutтАЩe the flaw-it work in If aphyp- accomof Vanlair This was in named! their From www.bloodjournal.org by guest on December 22, 2014. For personal use only. WILLIAM disease тАЬmicrocythemia,тАЭ But it didnтАЩt onstrated catch red normal spherical. spherical cells by proposed! way тАЬred! cells on the due to destruction only was a new was advanced!. disease but it was backedi was either ignored fifty Masius: It years to or water the patientтАЩs scale.тАЭ an entirely observation elapsed before seems intellectual well indeed must be blood rival claims to its d!iscovery between 1915 Yet- this wтАЩith work Vanlair almost leap they were declined to iigid. For a theory the right climate, Given 1927 of hemolysis in three find!ings in 1882, it may and the disanewitness simultaneous labot-atoi-ies be said that about 1936. the climate not- propitious. was StтАЩuiut 1 . The tention raphy 2. huisfot-v of pau-oxysmal fh outstanding wтАЩork of l)articUlau to the attention earhieu- dhifferentiatcd the disease which part of disease obscu-vat of his basis repou-ts huave ions now played nocturnal from the in the Strubing as is is ieтАЩiewтАЩed, and centut-y. A bibliog- StrObing identified 19th reviewed!. a dhisease entity in flue disease with great 1882 but at- failed to calling accuracy, by sleep in ptecipitating the paroxysms. hemoglobinuu-ia and by pI-ovodтАЩativc tests d)thiem paioxysmal hemoglobinunias. On the he proposed! been hemoglobinuria published Paul luemoglobinuria name. He described cited! BY noctuuтАЩnal is called! to fouu- case iepotfs of the d!isease is appended. 1)aroxYsmtil noctut-nal give it a dhisf-mcfive He too and wтАЩit-h them. right. and cells, due to that at that time, appear in several places at once. Witness the recent simultaneous covery in several laboratories of folic acid, the vau-iants of Mediterranean mia, and the Hh antigens. Or, coming back to noctui-nal hemoglobinunia, development of the mechanism When Sti-ubing reported his were of disease red it. may the them and anemia one paper not same fault- ; in one the contemporaries ordicred, тАЬclimateтАЭ up make concept the so it- was caught possessed the lnhappily, injuring patients jaundice In this experiment. Strubing, p1-ogress both papers contemporaries. also there uтАЩas jaundice was entirely newтАЩ and! wтАЩit-h As that in their pnimai-ily dem- Masius showтАЩed newтАЩ nosologic involving designation. and! wтАЩould found! i-ed cell dlestruction, jaundice. All of this clinical they cells a grand тАЬon a d!isease rejected. of ideas f-hat cells hut wтАЩith by or yeaus distilled a catchy Vanlair blood; spheu-ical and red present-ed up flue the paper. patientтАЩs adding that of excessive hemolytic evolution flourish, in their dealt is evident that ahead of their leap. The cells even a remai-kable to destructionтАЭ rfhis because i.e., was of these 277 CROSBY a characteristic, too, heating They were in which, destruction, certainly ! This, small, H. shown theories to regard!ing ie remarkably the pathogenesis of the accurate. BIBLIOGRAPHY Each reported case is indicated by an asterisk. An asterisk iti parentheses indicates that the particular patient had 1)een reported before. Titles without asterisks are research, reviews, historical notes, or cases erroneously diagnosed as )aroXysrnal nocturnal hennoglohinuria. It is 1)elieved that this list is complete to January, 1950. AsnuctiтАЩr, I., Michelischeri KtтАЩHn.snAx, F., Flaemoglobinurie AND DENтАЩKS, Deutsche H.: Kasuistischer Arch. f. khins. Beitrag Med. 190: zur 156. Marchiiafava1943.* From www.bloodjournal.org by guest on December 22, 2014. For personal use only. 278 2 P.-IJtOXYSMAL An.nтАЩERnN, j) .M,,jtN t) ALTS(titтАЩLE, M. cause, L. synudronie I)., ANt) , тАЬMarchiafstva tipo S ARNr)AL, 6 BARTA, 0. : IтАЩini Scanudinav. BIFFIS, K. dice) J. : StudsтАЩ : 1tU(1e 91, ISO, S. Blood f. laeger M., m3 BRIt.E, _,_ hull. mm Axm) , med. et ANt) 20 (тАШ.-sn (Ic anid n.. erit , Haemoglobinurie. Acta 1915.* icterus (acholuric jaun- 1946. of a case of Marchiafava-MichehiтАЩs dтАЩun cas (he miualadie (Ic \1archiafava-ImIicheli. s#{233}rologique med. G. P. : Renal et th#{233}rapeutique d. hop. function de (he Paris during 65: ha maladie 1030, chronic de 1949.* anemia in man. af I)arOXтАЩsfliatisk llaenioglobinuri niit(I. : Cmi nouveau #{188}1 . : La ANI) GAiтАЩBE, R. : Deux cas (IтАЩhi#{233}moglol)inurie hop. (Ic Paris 53: 197, 1937.* cas (lтАЩani#{233}mie hi#{233}molvtique avec hi#{233}nuoglobiniurie IIARRmStтАЩE, avec J., d. hiSl. t ia di med. ANt) (Ic nocturnal hienioglobinuria Lab. & Cliti. \Led. J. B0UwENS hi#{233}nuoglobimiurie malat ssf Marchiafavatypen. VAX nocturne Paris t)ER et paroxystique. et h#{233}mosid#{233}ri- isтАЩit.h hemolytic 1941.* : Anemic h#{233}mo- 26: 1434, G. BOEN, h#{233}mosid#{233}rinurie permanente. 70, 1937.* 53: тАШtlarchiiafava-\Iichseli \Iilano, . Casa Edit rice Giuseppe l937.* I). : Su . I 64, treatment (Ii . un (тАШas() ( тАШ -lтАЩтАЩ (тАШhill . 60: (Ii anieniiia eriiolit ica riniiico 21 ( E(oN Haemoglo- (*O) cliniotue, \IanтАЩchii:if:tv:i-\Iichieli t il)o paroxysmaler .1., BF:ssrs, \I., IтАЩтАЩruvi, .J., RM)1n.-1)UvAL, ANt) I)0NNET: A POl)OS (IтАЩUti tiouvetiu nialadie (l(тАЩ тАШslarchii:sf:Lv:t-)blichieli тАШ Sersiaine d. hop. Paris 25: 1759, 1949.* U., Nt) 1)E(тАЩon.t.E, 1.тАЩ. : Sopra Uli CtS() (Ii amieniia ennolitica cots emoglobinuria C.Ror.1, (тАШson.o, 1946.* paroxvsmatisk 1941.* P., Soc. - LsBRESn tm9 mit F. : Haemolytic 1: 812, et m#{233}m.Soc. 938, 1luLnF:sr.Nn, niini. Prinicipato, (тАШ:55 81: J. therapeutique Tilfaelde 103: 16 CAIN, .., CтАЩnтАЩTAx, II.. lvtique jet (rig#{234}mie Bull. et nuтАЭmn. Soc. tm7 nathig 1929.* kryptogener niurie. Presse nio(l.46: 1329, 1938,(*m3) BtF:n.n .,A.,. тАШtNI) \1ETTnER, S. It : Paroxysmal anemia (Marchiafava-Micheli sтАЩnoIrome). ni 18 serology BRADLEY, P. : Et Ugesk. med 160, 1940.* L0uTIT, Lancet Bull. E., emosiderinuria 1: 192, 1947. 2: BREN1STRrP, 12 AND P. : Etude Marchiafava-Michieli. in BRAnnEY, obscure (*tmO) %ERNANT, ANt) et of e(I e din. Anaemi 273: 266, 3: 1 12, 1950 . 1940.***** 1941. emoglobinuria haemolytica Riforma E., the Oti 1950 115, hemoglobinuria 502, . acquired. haematol 957, pat. interniiittierender 1931 B. s#{233}rologique Sanig2/: 10 DooD, and Acta disease. voni 224, emolitico. E., congenital BOU5SER, 9* Fall 77: P. : SullтАЩittero a BOORMAN, 102: u. Phvsiol. . cons 18: hemoglohinuria 68: haemolytisk f. laeger Arch. massive Med. with anemia Ter. iaraglionsoтАЭ I). : Splenomegahia 1)1tth. Ansat Arch. med. S Ugesk. it)l like H. : Acute тАЬE. uif kronisk GOROc, ANt) 7 I3ERO%nARK, Arch. Tilfaelde Hacnuoglobiniuri. l)inurie. [Hemolytic : forms D. Micheli.тАЭ P. : 1тАЩt I., \A. and GinLIo.kN, HEMOGLOBINURIA jaundice an(l anemia. Arch. mit. ANt) \iAt,E, L. : Anemia emohitica with 4 ALZONA, M. AN(тАЩHEvuTz, (Marchiafava-Michehi 3 NOCTURNAL , (Id unidollo osseo. Rifornna ni)e(l A . : A niennia ernol i I ica- cots ensiosideri . 642, 1939,* tipo \l:trcliiafava-tlichieli 39: 489, niuria 1947 Perl)et con reperto . ua \linierv:o . nned . 8: 1110, 192$. 22 lтАЩ . : Les (тАШti.uiitom., (I(тАЩ тАШtl:irclii:if:iy:i? 23 CnrMBoN, P. : La It i qiue ani(тАЩniiies hiumainie. 21 Cinsrran, A., ANt) (1. ni#{233}d.liSp. ne 25 (тАШn v. t.LEitt, I. : I.e 26 (тАШutossv, W. 11.: hiemoglobinsunia. 26a - : The relat nsoct unnral ion avec i(тАЩtenтАЩigenies hi#{233}mnoglobiniunтАЩie S(тАЩniiainie (I. liSp. Paris 25: maladie (he \IanтАЩchiiafava-\Iichseli, Lyon Thesis, TRomsmF:R. Paris enioglol 2: l9-1. .J. : I)eux 411, 0 nm ne. ori . dтАЩictcre Siena, 1916. the heunolvtic J. Chins. Inivestigation of I he clot 1 insg mechanism miniuria -dies тАШтАШ1st nialadieтАЭ majeure (he Ia nialadie laniolvtique. Bull. et h#{233}mom#{233}uii.Soc IOOS.* Observations hemiiogloi forme cas sonit 1949. 3468, J. Chirs . 28: Invest mechianiism 776, 1949. anal t lie hsemol igat ions 29: 807, ins tic 1950. paroxysmal system nocturnal in paroxysmal From www.bloodjournal.org by guest on December 22, 2014. For personal use only. WILLIAM 27 CROSBY, \V. 1)ased 28 on the AND ability nocturnal and its relation amid! Stefaninsi, I. 279 CROSBY hemoglobinuria. of thrombin to activate the Vi. : Paroxysmal nocturnal DAMESHEK, hemohysis 28a : Paroxysmal H. H. to the coagulation : Pathogenesis hemolytic test factor. for The Blood transfusions reactioni. the Blood hemoglobinuria. mechanism. plasma of A specific 5: disease 1950. 843, mechanism of 5: 822, 1950. Fed. Proc. 26, 9: 1950. CROIZAT, 29 P., clinique GtтАЩIcFIARD, A., et chimique L., REVOL, dтАЩun 80 31 _ : H#{233}moglobinurie de : Diagnosis 32 nocturne ha quest-ion. and 32a : Practical 32b : The & 33 AND -тАШ 4: 1183, 1949. London, 1950. of hemolysis Haematology. Bact. of cold 62: 241, Etude MEUNIER: Lyon cells ins nocturnal 1948.* (*33) maladie de anatonio- Med. 179: 313 haemoglohinuunia. Marchiafava-Michehi ; #{233}tat 1949. in chronic haemolvsins in sera transfusion in nocturnal hemolytic containing anemia cold with nocturnal haemagglutininis. J. Path. 1950. D. : Blood FIRTH, ou 4: 577, dтАЩh#{233}mat. Blood lresence red 7: 65, paroxystique Rev. mechanism hemoglobinuria. A7.D de Marchiafava-\Iicheli. and 329, 1948; Sang 19: 218, 1948.* DAdE, J. V. : Transfusion of saline-washed (Marchiafava-Michehi disease.) Cliii. Sc. actueh R., CREYSSEL, de maladie cas haemoglobinuria. Brit. M. J. 1: 626, 1943.* 34 AND -, of binuriaтАЩ). M. C. G. ISRAELS, _, of the Marchiafava ANn) MOLLISON, 36 turnal 37 -, anaemia (Fanconi type). wit-h mi one case a relationship haeunoglobinuria (Marchiafava-Michehi Arch. Dis. Childhood 19: 155, 1944.* family, nocturnal 85 A. : Refractory GILPIN, one AND P. Lancet 1: 479, L. : Survival haernoglohinuria. of N. : The J. Path. 38 DAMESHEK, W. : Paroxysmal drome). Bull. New England 39 -, AND NEBER, J. : Transfusion pathogenesis and treatment disease or members anaemia тАШnocturnal nocturnal erythrocytes with haemogho- haemoglobinuria from a donor with noc- on in-vitro hiaemolysis nuocturnal in haemo- 1943. nocturnal hemoglohinuria M. 4: 224, Center reactions by in three haemolytic 1949. of pH 375, 55: incidence F. : Paroxysmal transfused influence & Bact. Its chronic 1938.* 1: 390, Lanscet AND RICHARDSON, globinuria. J. WInKINsoN, ty)e. to to (mIarchiafava-Michehi a plasma washed red syn- 1942.** constituent i)lood of whole cell transfusions. Lanscet 1: 913, blood. Their Blood 5: 129, 1950.* ANt) SCHWARTZ, 40 41 Typ 42 G., DAMM, DAVIS L. DEnoN, E. L., human I. Un cas L., ANI) ila AND for de MONdтАЩOURRiER, L., 693, vom 143.* net- gain 1951). with or h#{233}nioglohinurie 1939. hemolitica 4.9: 401, inagglutinsable deficit et of red cells h#{233}mosid#{233}rinunie; (*m42) crSnica hennoglohin#{252}nica tipo 1942.* H. AND et m#{233}m. Soc. FEILLARD, Bull. Marcliiafava-Micheli. avec Thesis, Anemia med. of 29: 1938. Hfimoglohinurie E. : Studies measurement Investigation G.: 562, 1948.* J. 50: 589, H. HAMILToN, Paris Semana P., I)EssAussE, drome A method J. Clin. BoxndHhI, 73: M. Edinburgh H. F. dтАЩan#{233}mie h#{233}molytique Marchiafava-Micheli. n#{228}chthichen Wchnschsr. (he Marchiafava-Micheli. DEMARVAL, paroxysmalen anaemias. subject. P. : Sur syndromes. : Zur med. SHEETS, counts. syndrome тАЬ Deutsche J. : Haemolytic eryt-hrocyte its the haemolytic M. RATSCHOтАЩ.%тАЩ, Marchiafava. 42,t DEG0wIN, 43 S. 0. : The AND U.: RENNER, Med. d. un cas de Paris Sur hop. (he syns- 66: 899, 1950.* iI DONATI, A.: Anemia fava-Michehi. 46 EASTWOOD, тАШ7 ENNEKING, splensomegalica Folia C. J.: G., AND hiol. din. SMYTH, Een bijzondere u. geneesk. 69: 1526, 1925.* con emoglobinuria-eniosideninuria 2: 229, 193o.* G. G. E.: Haemolytic vorm van paroxysmale anaemia. haemoglobinurie. tipo Lancet Marchia- 2: 895, 1932.* Nederl. tijdschr. From www.bloodjournal.org by guest on December 22, 2014. For personal use only. 280 PAROXYSM.-tL 48 hтАЩNNEKnNo, J. : 1тАЩinie 49 iaroxysmalis lтАЩvANs, U. msodturnns) . Khin. S. : Chronic lseniiolvtic 50 neue NOCTURNAL VnтАЩehrsschr. amiemia. ANt) lIRom1Fn:n.o, Michehi svmsdronse. dauernsder Tr. Roy. J. 65 FLYNN, J . F . : (тАШlironic A. : The crvl)togensic GIFFnN, 68 (mNEsTm, 11. Paris Marchiafava-Michehi Mont . with avec content 2) 1941 . 32: 432, in )mlarchiiafava- 1938. Ansaeniie Khins. Wchtsschr. anaemias. Quart. J)aroxysmah nut 14: J. nocturnal lang- 1078, 1935.* Med. 16: 245, hemoghobinuria. Maladie de 6tm) jaunsdice. 31-32: . of (Case 505(1 treatment. (henionsstrations Arch. particuhi#{232}re med anid fat oliagnosis haeniohytischser (**t3. forme pelhier of l946.* hs#{233}moglobinurie-hCniosidCriniurie. 1938. J. : 1тАЩise H. J. : Flemoglobinunia GLASER, anemia ins hieniolytic R01)iER, ANt) vons hiaemolvtic Thesis, 95, & IIvg. Fall effect 77: 544, in 10: Ilaenuosideninurie. ic Z. : hienioglobiniunia j., Med. acquire(1 henuolvt tIed. Its Trop. 255, l945.* hCniolvt ique Marchiafava-Micheli. 57 Soc. unsd M. Soc. 35: 11 . : lтАЩansCmie (A1тАЩBE, NIe(l. (Ilaemoglohitsuria (*47) on the advances J. тАШmhmsm.&n, \V. : IтАЩins I) FuSHER, Iowa recetst Quart. Ilaensioglobinsunie 64 J. Irit. H. J. : Pseu(lo-methaemoglol)in. ,A.,tx 63 FAtKuwncz 1928. Ar-hi. aniemias, Med. 70: 244, 1949.* N. II. : \lethiaemall)Umits. im FAnRt:Y, Haenioglobirsurie 7: 2045, Observations transfusion. _, 52 59 initermittieren(her 1-he (liet- anl(h nlultil)le red cell AND DUANE, U. : Ilemolvtic Californsia 56 Form HEMOGLOBINURIA Inst. Med. 31: dтАЩh#{233}moglohinurie: 39, 573, Ia 1923.* maladie de 1947.* dar(liovascular-renal disease. Am. J. 4: 594, Med. I948.* 60 GoNzAnEs Rev. Micheli) isocturna (Eniferuiiedad 25: 51, l947.* a lтАЩ#{233}tude (Ic lтАЩhCnioglobinsurie A. : Anemic (.11тАЩuCHARD, hemolitica hCmolytique ; a l)rl)O5 (lтАЩuni cas avec inC(hit-, paroxystioue. hCmoglohinunie hтАЩonigiise tul)erculeuse hiologi ques , ha flC1)h nit e et ha niyosite nied. 169: 42 ars(1 65, 1943. ANt) FERoI,nI, J. : Maladie (he Marchiafava-Michehi doncel)tion niosologique de lтАЩaffections. Sang 17: 64 ANt) 65 Gumn, W. 66 11AM, - G. : I.dt maladie (he тАШmIar(тАЩhiiafava-тАЩmlicheli W. : A of intermittent C., case ANt) Report autopsy. Me(h. J. 217: : Studies mal on ANt) 69 on ANt) 70 on with med. 1943 (cited Hosp. anemia only hiCmoglohinunique; myosite Lyon, GuyтАЩs with occasiomial l),тАЩ GuichardтАЩ2). Rep. 13: 381 paroxysmal , hsensoglohinunia arid nsocturnal hemoglobirsunia. acid-base e(iuihih)nium. New relation to cells. I. Chronic 1866.* nocturnal 67: 735, 1941.* with paroxysmal insvest-igatiors Arch. Inst. destruction of red special Med. 64: aspects of the ivith Study England to serum 495, II. iaroxysvith (*71) niechanisni ins P:troXтАЩsmal 19:39. Chronsic heniolytic ininiunsological complemetit. smiths of hemolysis, 1939.**** liennolvtic cells. blood anemia nsechsansisni 1271, 18: : certain reference hsemiiolvtic of Inivestigation hieniioglohinsunia L. P., A.: Chronic hemo1тАЩtic Ansi. J. M. Sc. 192: 30l, 1936.** IIF:RNSTEIX, ANt) hierusoglobiniunia. U.: (Typus ANI) ivith Lyon . ansemia aspects J. Chiri. of the vith hemolytic Investigation 18: 1939. nocturnal 72 llta;(;nJs, nOtion cases. nio(тАЩturnial 71 IIAMBIIRiER, -, five Studies -: J . documents assocines 1946. 439, hemolytic blood : an henisoglobitsunia. 1)aroxysnial mechanism 657, of ned 2, 11 . : Imnnnmunsologicah 4 . (тАШlimi. I)uNot.F:, nsoct,urnal case Med. hsenioglobinsunia observations et nsunique 1927.* Marchiafava- 19:37. (lestructioni nsocturnial a lot. hemolvtic anscmia of hemolvsis ins 1)15, . Thesis, (he (hu syndrome, hCmoglohi haeniatinunia. M. : Chronnic of Arch. 67 IIAM,T. H. : (тАШhronsic of the mechsamiism 68 11. lIoRAdтАЩK, hemoglohirsunia. complete тАШmlarchiiafava- Paris (maladie anatomo-pat 63 (he chimi. es)an. J. : Constributioms 6m (EX, 62 V. : Anemia C.&n,vo, Michehi). I)ie (-hronsisclse Manchniafava). MAuER, of C.: hsaeniohytische 1-lelvet. The MarchiiafavaтАЩs тАЬheat med. resistanceтАЭ ansennia. Am. Ansaemie acta 10: 27, nut Sc. tiaechstlichen with paroxysmal Ilaenioglobinsunie 1943. of ervthrocytes. .J. M. anemia 207: A specific 624, 1944. test for the recog- From www.bloodjournal.org by guest on December 22, 2014. For personal use only. WILLIAM U. 74 HEGGLtN, Anaemie AND C. : Uber MAtER, vom Typus den 281 CROSBY Haemolysemechansismus KIm. Marchiafava-Michelis. L. : Niichtliche 75 HEILMEYER, H. Himoglohinunie hei Wchnschr. der 20: haenuolytischen 956, (Marchiafava-An#{228}mie). 1941. Khin. Wchnschr. 22: 307, 1943. 75,, 1)ie -: 76 h#{228}molтАЩtisehieui AN!) _, Ans#{228}unien. Sang F. : then WENGELER, 610, M. The D., ANn) VAN Rev. n)EN med. syndrome. A. I3ERGH, 31: 63, : Les hCmoglohinunies. 80 HITZENHERO,ER,: Naechthiche B. sn HOFFMAN, nocturnal Med. Marchiafava-Anaemie. it-Ied. Welt 17: J., K., glohitsunie. M. adult. St-rashourg med. Haemoglohunsunie. ANI) ANt) FRENREISZ, Wchnschr. C. G., ANt) : Etudes 7: 137, crises 362, 1926. Wien. me(1. hCmoglobinuriques. Wchmuschr. hemolytic with experimental 81: anemia with studies. J. 1189, l931.* paroxysmal & Chin. Lal). 85, 27: Ilaemolytischer J. F. : Haemolytic (Case PLAS, F., AN ; #{233}tudehistologique. uh)er Haemoglohimiunie. . tij(lschr. V. Acta nied. : Illeniolytic mit miaechthicher Haemo- mit (sphierocytic) jaundice in the 3) Semaine Utrecht geneesk. 81: Scansdiniav. mтАЩit-h de maladie A. : A POPO5 dтАЩun cas d. hop. Paris 25: 2143, Thesis 1935.* HAIEN;uE, anemia 1949.* Ikterus Anaemie 1934.* L., N . M , 8.80, 1938.* IтАЩhCmoglobiniunie. Moscow 1505, haemoglobinunia. 1 , 1948.* 17: avec ST. : Haemolytischie 13: Nederl. sur KoNcniAu.0vSKAYA med. 89 LASCH,: report WILKINSON, J. Med. Haemoglobinunie. : 86: U. : Chronic Case JACQ1тАЩET, 1., DROBERT, de 1nlarchiafava-Michehi JORt)AN, F. L. J. : Studie 86 B. KRMKE, Xliii. Quart. 87 aminenniawith J. Med. A. : Ict-#{232}re hCmolytique hemoglohOnunia. 83 IsRAELS, haemolytic Quart-. 817, l94:3.* 28: 82 IGLA1тАЩER, 90 1950. von l9ll.* 7) 88 105, L. K. : Chronic MALLEY, Marchiafava-Michehi 78 HYMANS 82 Ffllle l943.** 77 HICKEY, 84 21: zwei 2024, 1937. 9.5: :319, 1938. nocturnal 1949. (*16) (*85) hemoglohunsunia.] Haeunoglobiniunie. Wien. nied. Khins. Wchnschir. 81: 193l.* LEMIERRE AND Cited KOiRtnSKI,: by Guichsard and Feroldi,63 PrOt)al)bтАЩ refers GeuxтАЩs to case H. : Contribution nuC(l.et chin. 4: 722, 91 LEPINE, 92 LEscn-nER, F. 335, 53 Lou,m.u N . : Sull , i\-1ACKENZIE, differemutial 190, 1935.* J., r,ar MANINu, med.) 8: 41, 35: Anuemia 1931. -тАШ Rev. mens. de : Atypical haemolytic anaeniiias. Quart J. Med. 8: AND chinico tica con enuoglobiniuria-ennosicleninu na tipo Niarchi afava. l933.* of obscure of S. ANt) CRLтАЩK, etiology. Chin. hsemnoghobinsunias. NEVERRE, G. (S. I)()I)()5 (hтАЩuns (тАШaS chez Soriderfonun haemolytischser Einse . With notes Misc. Mary Sun ha l)no(ltsdt I тАШensfant ion ) . AlgCnie Amiaemie. oni the I. classification Bassett Flosp. dтАЩhCnioglobinunie unC:I, \Iiimsch. rv- 5! : 354, med. : l947,* 87: Wchinsschr. aroxysmnah deghi uioctunnsah itteni emohitici. hennoglo- Gior. din. l927.* 98 NIARCIIIAFAVA, 100 paroxystique. U - C. Chronic hiemolvtic anieniia with Anns. Inst. Med. 23: 1)35, 1945.** L.: Contnibuto ansatomo-chimsico alle studio birsunia. -: lтАЩhCtnoglobimiunie h940.** 96 Mrt-tsтАЩrtnt, med. enuohi l3l3, diagniosis amsoxie II.тАЩ \In.тАЩr:, 1207, 49: G. тАШs-I. : Ilemoglobinsisnia and (luCe тАШanemia med. 94. \IAt.i1EJA(тАЩ, тАШ C. U. OSBORN, ANt) de 1939. Riforma 94 0., a lтАЩCt-ude I880.* I. : Aiscniia enuolitica cons emosideninunia perpetua. Pohicli niico (sez. med.) 38: 105, 109, 1928.* emolitica cons emosi(lenimiunia l)erpetua. Pohichinico (sez. (*98) A.: (sez. med.) NAZARI, Nuovo 18: 241, contnibuto 1911. (*24) allo studio (legli itteni cronici cmohit-ici. Poli- From www.bloodjournal.org by guest on December 22, 2014. For personal use only. 282 PAROXYSMAL J. : The MARKS, 101 NOCTURNAL Marchiafava-Michehi J. Med. PanoxтАЩsniale binunia). Quart. tm02 MEYER, A. : Die 103 MEYER, H. : Khinischie 104 MIc1IELI, hamburg 105 _ (Ii Tonimso 7: : Anemia enuohitica 148, 106 : Anemia 112 Bull. NEBER, J., ANt) cd)nsgenital 9: by NEssurr, lie Ot,nvARnтАЩs, : The use S., /5: 1tm7 IтАЩANTON, 1, hsaemolvtic lichen med. insiproved di med. -emosideni Bnit. Sc. M. 2574, 35: with ennoglohinunia 57: tipo emosiderinuria 90, 1931.6 mu the 1945.* special reference polmonare. to Haemato- Bull. Hae- . PerPetila differentiation ons pathogenesis. -Iar- tipo Marchiafava-Michieli con techniques nunia 2: 84, J. 6: 137, 1947.6 cons emosiderosi emohitica cronica notes I)rat.) 1930. Clin. denuonistration of a hovinse ANt) WATKINS, F. : Et t)E 244:3, N., P. P., tilfaelde af (Tipo Mar- of acquired New England and M. Center J, circulating antibodies in 2: 371, 1947. Am. J. M. Sc. haemoglohinunia hemolytic anemia 74, 1942.* 203: paroxvsmatica (Case nocturna. 3) Nord. 1942.6 A. MArTI.ANt)-JoNEs, to zur ANt) G., pernicious chronsischen ALDRICtI, C. ANI) Arch. f. kIm. A. : Chronic (IтАЩlarchiafava-Michiehi A. : I)e ziekte old van G. : The RtDD0CII, anaemia. Lancet h#{228}moIтАЩtischen Deutsche thsromhocvtopensia mi a five-year lioninNsoN, J. H. : tniniary excretion RonHARt, of albumin medium. Blood C. H. : Acute porphyria. H#{228}nuglobirsunie. PIERcE, m18,. 1946* Accad. (sez. erythnocytes, Roma W. : Newer anemia; nail hemoglobinunia 11) anemia disorders A. : Beitrag 117,. PETERsEN, It) cons Accad. 1)AMESHEK, B. med. 381, 1947. - the ins emolitica hennolytic 166, ANI) 114 35: l)erPetU2t. emoglobinunia transsfused anuaemia. (Ii anemia l946.* caso di roy. 54, cons of Uns caso :385, terzo A. : Un haemoglo- Haemoglohinunie. Pohichinico 101 , 1931 (*98) haemnoglobinunia. survival G. : Sopra (hiafava). 113 12: of nocturnal 19: 353, 11)38. , M . : Arseniia NAZARI, 4: Sang haennolytic 29: paroxysnnaler enuosiderinunia perpet-ua. emohitica L. : The matologica Praxis von Form con ennosideninsunia hCrnolytiques. of acquired logica MORTAR Marchiafava. Typus nieueni ernohitica IIaeniatologica P. cases 110 MONTALt)O, I con J. A. : A case 109 \1ottisoN nocturnal 1928,(*98) (splenomegahia) chiafava. 108 Mun.NE, In di anemia caso 107 zmi einer (paroxysmal i9:3. F. : Un 1928. : Spl#{233}nsonnCgalies syndrome 18: 105, 1949.*** H#{228}moglohinunie Beitrage Thesis, HEMOGLOBINURIA Med. 196: hemolytic anemia syndrome) . child. J. of carbonic Nederl. 486, of some msacht- 1949.6 with Report Pediat. 22: msnshy(lrase. Marchiafava. relationship 1: 529, 1924.** An#{228}mie mit l)arox\тАЩsmaler paroxysmal of a case 30, 1943.6 J. Chins. tijdschr. v. noctur- with Path. 3: geneesk. marked 142, 1950. 90: 1866, 1946.6 i19: . (тАШhirotsiso-hie hiaenuolvt mlar(-hiiafava-\hidhieli m20 ROSENTHAL, IтАЭ. : then kIm. Med. BoтАЩnin, 0.: Med. 110: 122 11 USCICA, 123 -: ansaenuie des тАЬIctCre 77, 1913.6 G.: Enuosideniniunia 124 SALAH, [sic] n25 SALN, 66: SAXL, chir. 38: M., AND syndrome). E. B.: 566, P.: 792, niet haennoglobiniunie. (Ziekte Hiimoglobinurie. vans Ztschr. h#{233}molysiniqueтАЭ in ansemia prat.) con (Chiauffard). (splensomegahia) 38: Deutsche Arch. f. f. kIm. emolitica-Splenectonuia 1509, 1931.6 emosiderinunia-splenectomia. Arch. 1932(6122) GInANEM, M. I).: Nocturnal Report of two cases. J. Roy Zunu Begniffe тАЬIlaemoglohinsunia 1927,* Discussion. nacht-ehijke 1950. (*119) paroxysmaler 1932.6 (Nota preliminsare). Polichinico (sez. Anemia (splensome:.alia) emolitica ital. 126 119: 449, Zur Frage ische I . .Annsterdann Thesis, einse neue Form voni Wieni. med. Wchnschsr. haemoglohinunia Egyptian M. paroxysmalis.тАЭ 78: 553, 1928.* (Marchiafava-Michsehhi A. 32: 548, 1949.6* Acta med. Scandinav. Soc. From www.bloodjournal.org by guest on December 22, 2014. For personal use only. WILLIAM 127 SCHALLY, A. 128 248, 128* 128b inies i)ij 88: 572, een VAN hijder de ziekte H. B., Syndrome 95, SHIRCORF van J. StsTo, mag. Haemo- f. laegevidensk. 86: A. case Trop. Mededeehinigeni T., AND haemagglutinsv. geneesk. door haemagglutinines. uit het Sittardsche E. SCO\%тАЩEN, with F. : The haemolytic emoglobinuria med. of 19: Zieken- Marchiafava-Micheli anaemia. J. Med. Quart. 7: caso di 42: anemia (sez. ed emosiderinuria 508, 55: anatomo-patologico Marchiafava- treated with sulphathiazole. 1949.* emohitica prat.) tipo 1938.* haemoglobinuria & Hyg. Pohichinsico 82, recurrent Med. E. : Un D., WASSERMAN, Am. con 1302, emoglobinuria-emosiderinuria tipo 1948.6 dellтАЩittero ternuituating STnrnn, Axn Pat-h. 18: of a emolitico. ANI) Policlinico : ther Splenomegahie. (sez. med.) P. A. N., heniohitica tipo khins. 22: con C. Marchiafava-Michseli. N(; , 1. : Paroxysmale 138 STRtBn 139 TRESTmNI, S. : Ln VAN AND globinsunie I #{149}( тАШRI: Thesis, 141 , , DEN l. setneiologico M., dтАЩansemie hCmolytioue P. hsro-ytcs F., ADAMS, in M., 5: 1643, 223 and (Case 1938.6 231, 1880. Icterus 0. hemoglobinuria mit 2) G. : Anemia paroxistica Santa Fe, Argentina 9: 5, 1942.6 I)cutschse me(i. Wchrsschr. 8: 1 1811(117, 1882.6 nsue(l. tipo (he Marchiafava--Iichehi mt by )bloscow 19: (тАШomit mтАЩazionse Soc. med. J. F.: The cdl emosideriniuria 19: 235, 11)39.* i ni de hiaemiiolv (-hsanтАЩactenize(l mmcl urnal urethra Hamoglobinurie ANm) B0NAzZoLA, y A. et 43, (henio- t ischse della hiemnolvsis niilza, SmKoutAv AND d. liSp. de Paris iron metabolism J. une(hianite II.: Sun (syndrome 55: 49:3, an(1 acid Clin ansd(тАЩn . hiCmoglobinsunie hsemoglobinsuuтАЩia. t oest ravascular 1941 volunie di l92S. Ii., RUBENS-DUVAL et mCm. ANI) Ross, aroxysmal A., hiCmosidCninsunie avec Bull. H. (he rued, trop. ichse fact on(тАЩn (helLs 465, JUSTIN-BESAN#{231}ON. \Iarchsiafava-Michschi). \%TA(;LtтАЩ7Y, 12: e cinc. cases.) the acholurischen cons emoglobinsunia . hemo- 1794. n#{228}chthicher 45: 42: 551), 1935.* L. : I.e svndronue ,[ Elms from 1: 332, perrnanente aniemiiia syndrome) Cuore 1906; Soc. belge (her h)ltSnsitt 19.14,6 F. ?mI. : [Chroniic : Ii sigmiificato adrensahinsa. 143 VIu.LARET, med.) BERCtIE, Aniri. J . : St udie CтАЩmlarchsiafava-?tlichiehi 43: 1590, emolitica (sez. nocturne). N t)E N IIR() Leuveni di anemia caso med. med. 6 other blood 1949.6 Wchmsschr. chronischens BUSANICHE, Rev. Soc. Haenuoglobinsunie. Policlinico Nlarchiafava. 140 \ALCKE, 0., H., of mit des hiensiosideniniuria with on 3: 855, Petersburg Wchnschr. PRoso, cronica Anamie Formens anemia iniformation Commentaries Monatschr. St. Berl. STRmNGmIINI, Medical eflVOrhene Hemolytic discharge hannolytische Med. : Ilaemnoglobinunie. H. STRA(#{149}SS periodical DuncanтАЩs I. : Die HorunloER, Marchiafava-Micheli). 136 STor.NnKow RosEsT11An, N. 757, l948.* (Tabular singular successfully. W. (T:p IA. R., Clirs. J. C. : Accounit 135 STEWART, eryt door tijdschr, mi vitro Haeniolvsis H. con e din. 0. : A Soc. glohinuria. cas in vitro Nederl. 1915.(*8) 134 STATS, 142 E. : Haemohysis miltverwijdening. emohitica P. : Studio 389, тАШ-- Norsk \-Iarchiafava-Micheli. haemoglobinuria Pat. Marchiafava. \тАШA J. R. van Marchiafava-Micheli. nocturnal Arch. 132 Stn.vnsTRoNI, I I O. A. (IC ziekte van A. : Anemia Tr. Roy. 137 ved ROBB-SMITH, of Micheli. 136. paroxysmalen l938.** 130 SEGA, D.Sa kryptogenuetischen 1935.6 haemolvse. 1944.6 : Over 529 SCOTT, 133 der 697, 127: BEIтАЩRDEN, ann (;unstige uitwerking hiuls 1: 15, 1944. (*128) 13t Aetiologie Med. CROSBY 1925.* SCHOONHOVEN AN zur Zfschr. f. kIm. : Galdefarvestofdanneise 0. SCHEEL, : Beitrag 0. glohinurie. 283 H. - Invest un (he 1939.6 fragility igat ion of 28: 816, 1949. 146 ._, ANt) IImeKF:Y, M. 1seuiiolysis 1948. 1).: ins paroxтАЩsnial Susceptibility nocturnal of red cells hienioghobinunia. amid seruns J. factor Chini. in thie niechianiisnii of Inivestigat ions 27: 559, From www.bloodjournal.org by guest on December 22, 2014. For personal use only. 284 PAROXYSMAL 146 WEIR, J. Mayo 117 Wtrrs, F. : Recurring Chin. L. 8: NOCTURNAL acute 110, 1933.6 J. : The hemolytic crisis haemoglohiniunias. REFERENCES F. : then henioglobinunria. nias Lanscet WHICIt NOCTURNAL 148 CinovosTEK, wit-h Proc. Staff Meet., (*57) )aroxysnnal ADDtTIoNAm HEMOGLOBINURIA Wesen Do NOT 2: 115, 1936.6 CONCERN PARoxYsMAL HEMOGtOBINURIA den paroxysmaler Hamoglobinurie. Leipzig und Wien, 1894. 149 DICKINSoN \V. II. : Notes on four cases of intermittent haennatunia. Lancet 1: 568, 1865. Eini Fall 160 DREssn.ER: ISi Ansat. 1)RITr-rтАЩr, PhтАЩsiol. U. R. : Two 481), 1873. 162 EndioTsox, 163 hARLEY, J,: G.: 166 LANDOtS, ans(i II.: 14.: 166 MnNKowsKI, 1)ie 0.: Irobilinunie, тАШ PonтАЩnтАЩEio, of of two treatmenst. On the einse M.: I)ie f. inn. progressive Nervoese rind Ii wit intermittenit Chromatunie. Me(l. ague. Times Lancet or des 1865. winter hsaematuria. Gaz. 1: 500, with haematunia, Arch. path. 1: 408. and 461 1832. remarks their UOti 1: 568, intermittent tтАЩber united of Lancet Transfusions Konig. 11.: Albuminunie hiaemat-inunia. heart cases Blutes. hsereditflre, Splersomegahie (1. (heutsdhs. 167 MCI.t.ER, irsterrnittirensder h)iseases Notes pathology Hss.umi, A. von 6: 264, 1854. cases of intermitt-enst unsd Med. 18: Leipzig, unter them Bil(le Nierensiderosis 316, perniciose Lancet- 2: 368, 1865. 1875. eines ehronischen verlaufende Affect Icterus ion. mit Verhandl. 1900. Aniimie. haemoglohinurie. Ztschr. Zurich, f. prakt. 1877. Heilkunde 14: 659 and 673, 186$. 169 Vsn..un, Belgique C. F., AND MAStUS, 5: 515, 1871. J. B.: Dc Ia microcyt-hemie. Bull. Acad. roy. ole med. de From www.bloodjournal.org by guest on December 22, 2014. For personal use only. 1951 6: 270-284 Historical Review: Paroxysmal Nocturnal Hemoglobinuria: A Classic Description by Paul Str├╝bing in 1882, and a Bibliography of the Disease WILLIAM H. CROSBY, LT. CoL. 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