Platelet Thrombosis Syndrome

By PHILIP S. VASSAR, M.R.C.S., L.R.C.P. (LOND.), AND DAVID M. SPAIN, M.D.

This paper reports the clinical and pathologic manifestations of seven cases of platelet thrombosissyndrome. Evidence is presented to indicate that vascular damage precedes the formation ofplatelet thrombi. It is suggested that the syndrome may be secondary to a variety of underlyingdisease entities.

T HE PURPOSE of this paper is to reportthe clinical and pathologic manifesta-tions of seven cases of the platelet

thrombosis syndrome. In 1925 Moschowitz'first described a rapidly fatal disease charac-terized by fever, anemia, petechiae, neurologicsigns and autopsy findings of generalizedcapillary and arteriolar hyaline thrombi. Sincethen approximately 45 cases have been re-ported,2-30 most of them within the past 10years. Many synonyms for the disease havebeen suggested, such as "thrombotic thrombo-cytopenic purpura,""' "thrombocytic acro-angiothrombosis,"8 "thrombotic microangio-pathic hemolytic anemia,"26 "disseminatedarteriolar and capillary platelet thromboses,""'7and "generalized blood platelet thrombosis."''4Much of this nomenclature is either cumber-some or suggests features of the disease thatare not invariably present. We believe the term"platelet thrombosis syndrome" to be themost satisfactory until the nature of the entityis more fully elucidated.

CASE REPORTSCase 1. A 21 year old white male student was

admitted to the Presbyterian Hospital on May 8,1936, with a six months' history of increasing weak-ness and anemia following an upper respiratory in-fection. The only significant feature of his previoushistory was albuminuria for the past five years.Physical examination revealed jaundice, pallor,petechiae, retinal hemorrhages, hepatomegaly, bloodpressure 150/76, and temperature of 100 F. Hemo-globin was 25 per cent, red blood cells 1 million,reticulocytes 43 per cent; anisocytosis, poikilocytosis,and polychromatophilia were present. Red bloodcell fragility began at 0.425 and was complete at0.350. White blood cells numbered 3400 (neutrophilsFrom the Department of Pathology, Columbia

University, College of Physicians and Surgeons, NewYork, N. Y.

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49, lymphocytes 32, monocytes 8, eosinophils 2,basophils 2, and myelocytes 6). Platelets numbered9,000.* Capillary fragility was 30 cm. Hg. Bleedingtime was 7 to 40 minutes. Coagulation time was 3.5minutes. Urine showed 3 plus albuminuria, occa-sional red blood cells, white blood cells and casts.Nonprotein nitrogen was 48. Serum bilirubin (in-direct) was 4 mg. per 100 cc. Serum proteins were6.1 Gm. per 100 cc. (albumin 4.2, globulin 1.9).Bone marrow aspiration revealed hyperplasia withprevalence of erythroblasts in all stages.Throughout the three month hospital stay the

anemia proved refractory to multiple transfusions,iron and liver therapy. On August 1, 1936, the redblood cells were 1.66 million, serum bilirubin was11.3 mg. per 100 cc. and blood urea nitrogen 73 mg.per 100 cc. The patient died with a terminal septi-cemia from an abscess in the buttock. The grossfindings at autopsy revealed ascites, hydroperi-cardium, bilateral hydrothorax, splenomegaly (500Gm.), hepatomegaly (2000 Gm.), scattered petechialhemorrhages, abscess of buttock, abscesses of heart,adrenal, kidney and prostate, infarct of spleen, achronic gastric ulcer, edema of the lungs, and avegetation on the aortic valve.

Case 2. t A 44 year old white male iron-worker wasadmitted to the hospital on Nov. 12, 1937, with ahistory of exposure to lead. For the preceding threeweeks he had complained of severe headaches,weakness, tinnitus, deafness in the right ear andepigastric distress following meals. On the day beforeadmission he had a transitory episode of aphasia.Physical examination revealed pallor, mental con-fusion and a right facial weakness, blood pressure130/90, and temperature 99 to 100 F. Hemoglobinwas 42 per cent, red blood cells 2 million withanisocytosis, poikilocytosis and marked basophilicstippling; reticulocytes were 19 per cent. Erythro-cyte sedimentation rate was 38. White blood cellsnumbered 11,300 (neutrophils 78, eosinophils 5,basophils 3, monocytes 8 and lymphocytes 6). Plate-lets numbered 46,000. Red blood cell fragility began

* The direct method of counting platelets was usedon all occasions.

t Cases 1 and 2 have been reported briefly by I.Gore.

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PHILIP S. VASSAR AND DAVID M. SPAIN

at 0.450 and was complete at 0.30. Bleeding time wastwo minutes, clotting time 4 minutes, 45 seconds.Capillary fragility test was normal. Serum proteinswere 6.9 Gm. per 100 cc. (albumin 3.7, globulin 3.2).Nonpr6tein nitrogen was 33. Serum bilirubin was2.5 mg. per 100 cc. The Kline test was negative.The cerebrospinal fluid was normal. Urine containeda trace of albumin and many red cells.A few days after admission petechiae and scleral

icterus were noted. He finally became comatose withoccasional tonic and clonic convulsions. The anemiafailed to respond to transfusions, and bleeding fromthe gums, hematuria and temperature of 104 F.were present. He expired five days after admission.Gross findings at autopsy revealed scattered pete-chial hemorrhages, edema of the lungs, a spleen of280 Gm., a liver of 1800 Gm., and a chronic gastriculcer. Chemical analyses revealed excessive amountsof lead in viscera and bones.

Case S. A 32 year old white housewife was ad-mitted to the hospital on Oct. 27, 1940, with ahistory of transient rash on the hands two monthspreviously. Four days before admission she developedsevere epigastric pain, weakness and petechiae ofthe skin; these symptoms had persisted. She wasmildly disoriented on the day of admission. Physicalexamination revealed pallor, petechiae, scleralicterus, blood pressure 105/80 and temperature of101.6 F. During the examination she became un-conscious and had a convulsion. Hemoglobin was 7Gm. per 100 cc., red blood cells 2.15 million; aniso-cytosis, poikilocytosis, polychromatophilia and nu-cleated red cells were present. White blood cellsnumbered 21,640 (neutrophils 77, lymphocytes 20,myelocytes 2). Platelets numbered 50,000. Nonpro-tein nitrogen was 39. Serum bilirubin was 4.8 mg.per 100 cc. The Kline test was negative. The urinecontained albumin and red cells.

The patient never regained consciousness anddied four hours after admission. Gross findings atautopsy revealed scattered petechial hemorrhages,a spleen of 140 Gm., a liver of 1420 Gm., and twoacute ulcerations of the stomach.

Case 4. A 16 year old white schoolgirl was ad-mitted to the hospital on April 26, 1942, with ahistory of headaches associated with double visionfor the preceding 10 days. On the day of admissionshe experienced a sudden left hemiparesis. Physicalexamination revealed a left hemiparesis, a systolicmurmur at the apex, blood pressure 118/70, andtemperature of 99 F. Hemoglobin was 11.6 Gm. percent, red blood cells 4.3 million with anisocytosis andpoikilocytosis. White blood cells numbered 5,750(neutrophils 71, lymphocytes 21, monocytes 5,eosinophils 3). The platelets numbered 270,000.Nonprotein nitrogen was 39 mg. per 100 cc. Thecephalin flocculation was 2 plus. Prothrombin timewas 52 seconds. Serum proteins were 7.6 Gm. per100 cc. (albumin 4.8, globulin 2.8). The erythrocyte

sedimentation rate was 60 mm. in 1 hour. TheKline test was negative. The urine examination wasnegative.

During the hospital stay of eight weeks therewas a constantly elevated erythrocyte sedimentationrate, a mild anemia and nonspecific electrocardio-graphic changes of myocardial damage. The pro-thrombin time gradually decreased to normal byJune 15, 1942. Repeated platelet counts were per-formed, the lowest count recorded being 143,000.On May 21, 1942, the patient experienced a suddenarterial occlusion to the right lower leg; return ofweak pulsations followed paravertebral sympatheticblock. On June 16, 1942, she became unconscioussuddenly and experienced several convulsive epi-sodes. She died the following day without regainingconsciousness. The gross findings at autopsy re-vealed a vegetation on the mitral valve, a spleenweighing 160 Gm., with two infarcts, a liver of 1400Gm. and mottled myocardium and kidneys.

Case 5. A 40 year old white housewife was ad-mitted to the hospital on Nov. 4, 1947, with a 10weeks' history of weakness and nausea. More re-cently she had experienced severe headaches andmental confusion. Physical examination revealedslight icterus, retinal hemorrhages, blood pressure100/60 and temperature of 100 F. Hemoglobin was7.3 Gm. per 100 cc. and red blood cells numbered2.25 million with anisocytosis, poikilocytosis andbasophilic stippling. White blood cells numbered6,500 (neutrophils 57 and lymphocytes 43); therewere 4 nucleated red blood cells per 100 white bloodcells. Reticulocytes were 10 per cent. The cephalinflocculation was 4 plus, the thymol turbidity 3 plus.Red blood cell fragility began at 0.60 and was com-plete at 0.325. Serum icteric index was 9 units.Serum bilirubin was 1 mg. per 100 cc. There wereno isoagglutinins at 37 C. Platelets numbered10,000. The Kline test was negative. No anti-Rhagglutinins were demonstrable; there were ques-tionable blocking antibodies (repeated). The urinecontained albumin and red cells.

Soon after admission, aphasia, mental confusionand severe weakness of the extremities were promi-nent features. The hemoglobin fell to 4.6 Gm. per100 cc.; the white count rose to 11,500 (neutrophils79, lymphocytes20, and monocytes 1). Despite multi-ple blood transfusions, folic acid and liver extract,the anemia remained refractory and she died fourweeks after admission. The gross findings at autopsyrevealed many scattered petechial hemorrhages andsplenomegaly (320 Gm.).

Case 6. A 44 year old Mexican man was admittedto the hospital on May 10, 1952, with a long andcomplex history of variable neuromuscular com-plaints over the preceding seven years. One year agohis blood pressure began to rise and reached 200/100.Three months ago he became ataxic, with vertigo,headaches, nausea and vomiting, diplopia and

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666PlLATE:LET THROMBOSIS SYNDROME

anesthesita of the left si(le of his face. Physical ex-amination revealedl fltaccidity of the extremities,ataxia, (lvSarthria and hvpertensivye retinopathy,apical murmur suggestive of Austin-Flint, 1)10(1opressure 200/100 and temperature of 99.2 F. Hemo-globin was 14 Gm. p)er 100 cc. The erv-tlhro(.Nvtessedimentation rate was 715 ImlI. in 1 hour. Whiteblood cells numbered 7,100 (neutol)phils (68 andlynml)hioctes 25). The urine contained 4 p)lus a]-buinni and 10 to l5 red 1)lood cells and 20 to 30white blo)0( cells per higlh power fiel(l. Nonproteinnitrogen Wa1s 61 Ilg. )er 100 cc. The cephalin floc-culation was negative. Serum proteins were 6.8 Gm.per 100 cc. (albumin 3.5, globulin 3.3). The cere-brospinal fluid was normal.He deteriorated rapidly with rise in temperature,

aphasia and stupor, tand expired May 18, 1952. Thegross findings at autopsy revealed vegetations ofthe mitral and aortic valves, a spleen weighing 1 10GI1., ta liver weighing 1900 Gm., each kidney weigh-ing 170 Gm., finely granular, mottled an(l henmor-rhagic, and cerebral l)etechiae.

Case 7. A 37 year ol0( housewife wats admitted tothe hospital on Aug. 6, 1952, with a three months'history of progressively severe hea(laches, vertigoan(l (liplopia. Two days before admission she ex-periencecl two brief convulsive episo(les ln(l hald beendisoriented and restless since. Physical examinationrevealed scattered petechiae, retinal hemorrhages,blood pressure 200/150 and temperature of 102 F.Hemoglobin was 8.7 Gm. per 100 cc. ancl rec bloo10cells numbered 3.27 million. Red blood cell fragilitybegan at 0.44 and was complete at 0.30. The erythro-cyte sedimentation rate was 83. Platelets numbered24,000. White blood cells numbered 8,400 (neu-trophils 94 and lymphocytes 6). Later the whiteblood cells numbered 35,000 (neutrophils 97 andlymphocytes 3). Nonprotein nitrogen was 31 Ing.per 100 cc. Prothrombin time was 22.4 seconds.The Coombs test was negative. Serum bilirubinwas 0.3 mg. per 100 cc. The urine contained albuminand red cells.

Massive hematuria commenced soon after ad-mission. An electrocardiogram revealed recentmrvocardial damage. Her condition rapidly (lete-iiorated, svith furtherI convulsive episodes, and sheefxpired on Akug. 10, 1952. The gross findings atautopsy revealed hypertrophv of the left ventricle,focal mvocardial infarct, vegetations on the mitralvalve, splenomegaly (380 Gm.) with scattered in-farcts, hepatomegaly (2200 Gm.), hemorrhagickidneyes andl hemorrhagic cvstitis.

SUMMARY OF CLINICAL FEATURESThe average age of these patients was 33

years. There appeared to be no obvious sex orracial predilectioin. The average duration ofthe entire illness was 17 weeks; occasionally,however, vague prodromal symptoms were

present for several \weeks before the onset ofthe acute illness. Case 1 had anl unusually longillness lasting nille months; case 6 presents(lifficulty in dlifferelitiating the lengthy historyof neuromutscular (lisorders from the morerecent ceiitral nervous system disease.

Fever, in the 99 to 102 F. range, \vas aconstant feature. Hemorrhagi( manifestations,iioted in five cases (onlsisted of purpura, retinalhemorrhages, hematuria or bleeding gums andepistaxis. In cases 4 anid 6 11o hemorrhagicmanifestations were present,; iii case 4 nothrombocytopenia was detected; and in case 6platelet counts were not performed. Pallor,weakness and easy fatigability were notable inthe five cases with severe anemia, four of whomwere jaundiced. Six patients had neurologicfindings such as headaches, drowvsinless, mentalconfusion, convulsiolls, focal paresthesia andparesis. In cases 6 and 7 hypertension wasmarked but, apparently, preceded evidence ofthe final illness, at least in case (6. Laboratoryexaminations revealed a severe normochromicanemia in five eases and minimal anemia incases 4 and 6. Anisocytosis, poikilocytosis,reticulocytosis, and nucleated red cells werefrequently present. Serum bilirutbin levels wereelevated in four cases. Coomb's test wasnegative in case 7, but blocking antibodieswere questionable in case 5. Red blood cellfragility studies were normal in four casesexamined. Elevation of the erythrocyte sedi-mentation rate was a common finding. Therewas a leukocytosis with a "left shift" in fourcases; in case 1, however, persistent leukopeniawith "left shift" was present. A severethrombocytopenia was present in five cases; aplatelet count was not performed on case 6.Of unusual interest is the fact that plateletcounts in case 4 were repeatedly within normalrange with anl unexplained transient prolonga-tion of prothrombin times. The Kline orWassermann test was negative in all cases.Positive cephalin flocculation and thymolturbidity tests were found in two of three casesexamined. The blood proteins wvere estimatedin four cases, hyperglobulinemia being presentiii two (the cephalin flocculation and thymolturbidity tests were negative iii one, and notperformed in the other). Of the four patients-

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IPHILIP' S. VASSAR AND I)AVID 74. SPAIN 6

without concomitant renal disease, two hadincreased nonprotein nitrogen blood levels andhematuria. Of the three cases with concomitantrenal disease, two had elevated nonproteinnitrogen blood levels; all three had albuminand red cells in the urine. The cerebrospinalfluid of three patients was normal. Electro-cardiographic studies wNere performed on threecases and evidence of acute myocardial damagewas found in two.

FIG. 1. Photomicrograph (hematoxylin and eosin,X 250) showing myocardium with characteristichyaline thrombi in capillaries.

SUIMMARY OF POSTMORTEM FINDINGS

Significant gross findings were scant. Oc-casional areas of hemorrhage, vegetations on

the heart valves, focal areas of visceral necrosis,particularly in the brain, and splenomegalywere the only gross features that could be

related specifically to the syndrome.Microscopically, the most characteristic

finding was the widespread presence of hyalinethrombi in the small arteries, arterioles, andcapillaries. (See fig., 1.) These platelet thrombiwere present in the kidneys and myocardiumin all cases. Involvement of these organs was

usually widespread. Markedly dilated, thin-

walled vessels contaiming thrombi wvere charac-teristically seen in these two organs. (Seefig. 2.) Oni the basis of serial sections in casesstudied by Orbisonll33 these dilated vessels wereconsidered to be aneurysmal dilatations andwere regarded as evidence for primary vasculardamage. In the myocardium many arteriolesand capillaries were filled with platelet thrombiin various stages of organization. These wereoften associated with minimal to albun(lanit

FIG. 2. Photomicrograph (hematoxylin and eosin,X 500) showing dilated vessel (aneurysm) withhyaline thrombus in the myocardium.

endothelial proliferation. (See fig. 3.) Inadjacent areas, the myocardium exhibited fociof necrosis and fibrosis. In addition to the myo-cardial changes, hyaline thrombi were found onthe aortic and mitral valves in three cases.These vegetations differed in no respect fromthe usual picture of thromboendocarditis.Bacteria were not present, and there was noassociated inflammatory process. There waseosinophilic degeneration of the valve substanceadjacent to the thrombi. (See fig. 4.) It ap-peared that this eosinophilic degeneratedmaterial was extending from the valve surface.Others have reported similar findings on theheart valves.

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PLATELET THROMBOSIS SYNDROMEl

In the kidneys, the cortical vessels were

commonly the site of platelet thrombi forma-tion. Especially affected were the afferentarterioles with occasional extension of theprocess into the glomerular tufts. Foci ofcortical hemorrhage with red blood cells fillingthe tubules were occasionally observed. Inone case, intercapillary glomerular nephritis

FIG. 3. Photomicrograph (hematoxylin and eosin,X 250) showing organization of thrombus and endo-thelial proliferation in myocardial vessel. Anothervessel shows eosinophilic degeneration which extendsinto surrounding tissue.

FIG. 5. Photomicrograph (hematoxylin and eosin,X 250) showing organizing thrombus with endothelialproliferation in vessel of pia arachnoid.

was present. What the relationship is betweenthe glomerular nephritis and this syndromeis not clear. Two other cases with markedypertension had advanced arteriolar nephro-

sclerosis. Endothelial proliferation in theglomerular tufts was present in still anothercase. In none of the postmortem material was

there anything suggestive of the changes seenin lupus erythematosus.

Brain examinations were performed in threecases but the presence of neurologic manifesta-tions in all but one of the seven patientswould indicate that the brain was involved tothe same degree as the kidneys and the heart.

FIG. 4. Photomicrograph (hematoxylin and eosin, The same dras the kiney andth deaX 180) showing aortic valve leaflet with eosinophilic The brains that were examined contained wide-degeneration and attached hyaline vegetation. spread involvement of numerous vessels with

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PHILIP S. VASSAR AND DAVID M. SPAIN66

platelet thrombi. As in the other sites, endo-thelial proliferation was present. (See fig. 5.)In one case where the lesions were most wide-spread, there were numerous gross areas ofencephalomalacia. Vessels in the pia arachnoidwere similarly involved.Next in frequency of involvement were the

pancreas, adrenals, spleen, and gastrointestinal

w-^w _

FIG. 7. Photomicrograph (hematoxylin and eosin,X 250) of large pulmonary vessel with small hyalinethrombi attached to intimal surface.

FIG. 6. Photomicrograph (hematoxylin and eosin,X 250) showing adrenal cortex with thrombi incapillaries just beneath the capsule.

tract (six out of seven cases). However, thenumber of vessels implicated was considerablyless than in the previously mentioned sites.There were numerous thrombi in the adrenals,limited almost entirely to the vessels im-mediately beneath the capsule. (See fig. 6.)Occasionally vessels outside of the capsulecontained thrombi. Focal hemorrhages werepresent. In the pancreas, the involvement wasdiffuse and generally located in those vesselsin the interlobular connective tissue. Nosecondary changes were present in the pancreas.In the spleen, only few vessels were involved.Splenomegaly was present in four cases. Therewas considerable congestion and in two casesthere were splenic infarcts. There was no

FIG. 8. Photomicrograph (hematoxylin and eosin,X 250) of vessel in myocardium with prethromboticlesion and superimposed endothelial proliferation.

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PILATE'LET THROMBOSIS SYNDI)lIt 1.

concentric perivascular fibrous proliferation.Megakarvocytes were infrequent.

In the gastrointestinal tract, the vessels illthe submucosa were the ones usually onitaininigthrombi. Foci of hemorrhage \were observed.Three cases revealed gastric ulcers (twochronic and one acute). It is possible that thedevelopment of these ulcers was related to thevascular occlusions.

Particularly significant was the limitedinvolvement of the lungs and liver. Of themajor organs, these were the least frequentlyinvolved and wheni thrombi were present, it\vas onily- ill an occasional v-essel. In the liver,the usual site was the vessels in the portalregion, whereas ill the lung there was no

characteristic site. The involvement of onevessel in the lung was of coiisideral)le interest.It was a (onsiderably larger vessel than thoseusually seen with platelet thrombi. Attached toits intimal surface at several separate pointswere small hyaline thrombotic masses. (Seefig. 7.) The lumen was not obliterated. Thistype of involvNemenit would tend to support theview that the vascular change is primary.M.legakaryocytes were present in the lungs inthree cases.

Other sites ill which vessels containedthrombi were the thyroid, pituitary, gall-bladder, larynx, diaphragm, urinary bladder,peripheral nerves, tonsils, and striated muscle.It is interesting that striated muscle has onlybeen rarely implicated.The bone marrov in all cases was uniformly

hyperplastic. Abundant megakaryocytes verefound and the changes in the marrow wereconsidered consistent with those seen charac-teristically in secondary anemia. The vesselsin the marrow did not contain hyaline thrombi.A careful search was made for the pre-

thrombotic vascular changes described byGore.'7 In several instances, these changes wereunmistakably identified (fig. 8) and wouldsupport the thesis that vascular changesprocede the formation of the thrombi. Thewidespread nature of the process withoutmarked localization to those areas mostsusceptible to stagnation of the circulation hasalready been referred to as an argumentagainst this syndrome originating primarily asan intraluminial phenomenon.

l)ISCUSSIONThe etiology of the entity is unknown. It is

not even clear whether this condition can beregarded as a primary one or secondary to a-variety of underlying diseases. The presenteviden-ce supports the view that the thrombifollow vascular damage and is ill keeping w-iththe observation of similar changes in knownhypersenisitive reactions. IPlatelet thrombiassociated with vascular damage have beenobserved in fatal cases of drug sensitivityreactions. 10, 13 Four of the cases in this studyhad associated processes which could haveproduced vascular damage (lead poisoning,glomeruloniephr itis, and malignant hyper-tension). In other reports, platelet thromboseshave been seen in llupus erythematosus andpolyarteritis.31 3'2 On occasion, platelet thrombiare seen in the myocardial arterioles ill rheni-matic heart disease. Thus, it is entirely possiblethat this syndrome is not a primary andindependent disease.

SUMMARY1. The clinical and necropsy findings in

seven cases of "platelet thrombosis syndrome"have been presented.

2. The findings of this study favor the viewthat vascular damage precedes the thrombusformation.

3. The view is presented that this syndromemay be entirely secondary to a variety ofunderlying disease entities.

SUMARIO ESPANOL

En este trabajo se informan las imanifesta-ciones clinicas y patologicas en siete casos delsindrome de trombosis de plaquetas. Se pie-senta evidenclia que indica que el dlano xvas.(ulaIprecede la formaci6nl del trombo de plaquetas.Se sugiere que el slindrome puede set secundarioa una variedad de enfermedades sutbyacenites.

REITFERENCEAS' MOSCHOWITZ, El.: An icute l)leioch1iioiii(nt anemiiia

with hyaline thrombosis of the terminal ar-terioles and capillaries. Arch. Int. Med. 36: 89,1925.

2 BAEHR, G., KLEMPERER, P., AND SCHIFRIN, A.:An acute febrile anemia and thrombocytopenicpurpura with diffuse platelet thromboses ofcapillaries and arterioles. TI. A. Am. Physicians51: 43, 1936.

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(iTLOW, S., AND GOLDMARK, C.: Generalizedcapillarv and arteriolar thrombosis. Ann. Int.Med. 13: 1046, 1939.

A-LTSCHULE, M.: A rare type of acute thromibo-(Vtopenic plurplula: widespread platelet thrombiin capillaries. New England J. Med. 227: 477,1942.

*!.:RNHEIM, ..: W\idespread capillary and arteriolarllatelet thronibi .J. Mt. Sinai Hosp. 10: 287,1943.

THOBOUGH, F. 11., MARKOWITZ, M., AND DAVID-SON, C. S.: An acute febrile illness characterizedby thrombocytopenic purpura, hemolytic ane-

ia and generalizedlplatelet thrombosis. Arch.Path. 41: 327, 1946.

7BIOWN,YE. B., AND NORMAN, J. W.: Multiplelplatelet thrombi, clinical-peathologic confer-ences. New York J. Med. 46: 2167, 1946.

S FiHTZGERALD, P. J., AUERBACH, 0., AND FRAME,E.: Thronmbocytic acroangiothrombosis. Blood2: 519, 1947.

' CARTER, J. R.: Generalized capillary and arterio-la.r platelet thrombosis. Am. J. M. Sc. 213: 585,1947.

10 ENGEL, (G. L., SCHEINKER, M., AND HUMPHREY,1). C.: Acute febrile anemia and thrombo-cvtopeleic purpura with vasothromboses. Ann.Int. Med. 26: 919, 1947.

1SINGER, K.. BORNSTEIN, F. P., AND WILE, S. A.:Thrombotic th rombocytopenic purpura. Blood2: 542, 1947.

'2-MIIUIR.HEAD, E. E,. GRASS, G., AND HILL, J. M.:D)iffuse platelet thromboses with thrombo-cytopeinia an(l henmolytic anemia. Am. J. Clin.Path. 18: 523, 1948.

18 EHRICH, W. E., AND SEWFTER1, J.: Throml)oticthrombocvtopenic uirpurI(a aused by iodine.Arch. Path. 47: 446, 1949.

G(;REEN, M. A., AND ROSENTHAL, S.: Generalizedblood pllatelet thrombosis: Report of three(ca.ses with necropsy findings. .1. Mt. Sinai Hosp.16: 110, 1949.

PAGFL, W .: Acronecrosis (lue to fibrin thrombianld endothelial cell thronibi. Am. J. M. Sc. 218:425, 1949.

" GOLDENIBERG, I'. T., THAYER,1J. E., AND HAST-INGS, L. P.: Feb)rile thrombocytopenic purpurawith hemlolytic aiemiia an(l platelet thrombosis.New Englai(l .J. Med 7C4: 2.52. 1950.

7 GoRE, I.: Disseminated arteriolar and capillaryplatelet thrombosis. Am. J. Path. 26: 155, 1950

18 SINGER, K., MOTULSKY, A. G., AND SHANBERGE,J. N.: Thrombotic thriombi)ocytop)enic purpura:Studies on the hemolvtic sNyndrome of the (is-ease. Blood 5: 434, 1950.

19 WYATT, J. P'., AND LFF, R. S.: Hemorrhagicencephalopatly (lue to dissemnincated thrombo-cytic thrombosis. AICh. Path. 49: 582, 1950.

20 ROTTER, E. J., AND ALTSHULE, M.: Wisconsin Clini-cal-Pathologic Conference. Wisconsin M. J.49: 1035, 1950.

21 SYMMERS, W. ST. C., AND BARROWCLIFF, D. F.:Platelet thrombosis sn(ldrome. J. Path. Bact.63: 552, 1951.

22MEACHAM, A. C., ORBLISON, J. L., HEINLE, R. W.,STEELE, H. J., AND SCHAEFER, J. ..: Thromboticthrombocytopenic purpura. Blood 6: 706, 1951.

23 TACKETT, H. S., AND JONES, R. S.: Thrombocyticacroangiothrombosis. Circulation 5: 920, 1952.

24 COMESS, 0. H., AND OYAMADA, A.: Uremia anddisseminated platelet-cell thrombosis. Arch.Int. Med. 89: 802, 1952.

25 RACKOW, F., STAINGOLD, L., AND WOOD, J. H. F.:Thrombotic throilmboceytopenic purpura. Actamecl. scan(linav. 143: 137, 1952.

26 SYMMERS, W. ST. C.: Thrombotic imiciroangio-patthic haemoly-tic(anaclia. Brit. M. J. 2: 897,1952.

27 GENDEL, B. J., YOUNG, J. M., AND KRAUS, A. P.:Thrombotic thiomhil)ocv'top)eniic purpura. Am.J. Med. 13: 3, 1952.

28 ERPSTEIN, F. H., DESCHAMPS, S. H[., AND CHI-FELLE, T. L.: Acute thIroimlbocytopenic purpurawith l)latelet throInm)i. Yale J. Biol. & Med. 20:570, 1948.

29 HANSER, A., 13;yF~lt, .A., AND BURGER, R. A.:Encephalopathy associated with acute diffuseplatelet thrombosis. Arch. Neurol. & Psychiat.65: 672, 1951.

30 3ARONDESS, J. .Ak.: Thrombotic thlriomiiboeytopenicpur)ura. Am. J. Med. 13: 294, 1952.

31 BEIGELMAN, P. M.: Variants of platelet thrombosissyndlrome. Arch. Pcath. 51: 213, 1951.

32 SYSIMERS, WV. ST. C., AND GILLETT, R.: Poly-arteritis Nodosa. Arch. Path. 52: 489, 1951.

31 ORBISON, J. L.: Morphology of the vascularlesions in thrombotic thrombocytopenic purpurawith demonstration of aneuriysms. Am. ,J. Path.27: 687, 1951.

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PHILIP S. VASSAR and DAVID M. SPAINPlatelet Thrombosis Syndrome

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1953 American Heart Association, Inc. All rights reserved.

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