Download - Value of the schilling hemogram in infections: Preliminary report based on 3500 cases

VALUE OF THE SCHILLING HEMOGRAM IN INFECTIONS

PRELIMINARY REPORT BASED ON 3500 CASES*

ARTHUR A. EISENBERG, M.D., AND HARRY S. NEMENS, M.D.

NEW YORK CITY

“KIinischer and h;immatoIogischer Be- fund miissen zusammengehen.“-NaegeIi.

T 0 paraphrase CIaude Bernard’s weII- known dictum : “true science teaches us to doubt and, in ignorance, to

refrain,” we may say that true science shouId teach us to doubt and try, whiIe ignorance teaches us to doubt and refrain.

About four years ago one of us (A. A. E.), feeIing that more information couId be obtained from bIood counts, if the Iatter were performed according to the method of SchiIIing, began to use this method routineIy.

In presenting this preIiminary report and our impression we are conscious of both quantitative and quaIitative inade- quacies, an entireIy insuffIcient number of cases representing the former, and an in- sufhcient number of counts on the same case constituting the Iatter; we feeI, however, that even a smaI1 number of cases, if suffIcientIy diversified, permits us, if not to draw concIusions, at Ieast to admit impressions.

The data herein gathered wiI1 probabIy make very IittIe impression on that type of cIinician, be he a surgeon or a physician, whose majestic seIf-assurance is ever un- rumed, come what may. In an exceIIent articIe by Yagudal there is this quotation of HeIIwig : “ FowIer’s opinion that it is diff%uIt to estimate the exact diagnostic vaIue of the Ieucocytosis, is at the present time as true as it was in Igoo.” Tt is hardIy possibIe to beIieve that any one couId, even with the most superficia1 knowIedge of clinica hematoIogy, make such a state- ment today; yet Yaguda quotes a number of men, some of them we11 known, whose opinion of the vaIue of bIood studies to

the surgeon is entireIy negative. We must, therefore, bow to the fact that there wiI1 aIways be a group of cIinicians who wiI1 refuse to accept the newer facts (we emphasize the word “ facts”) discovered by modern hematoIogy, and who wiI1 continue missing, now and then, an occasiona diagnosis, taking out an inoffensive anemic appendix which had never done anyone any harm, or Ieaving in the so-caIIed “siIent” suppurative appendices, or making sanguine prognosis onIy to find them- seIves confronted with the “sudden” death of that particuIar patient who “had been doing so we11 right aIong.”

There is, however, another group of chnicians who have not made a fetish of “cIinica1 judgment,” infaIIibIe and error- proof; who weIcome any heIp which has, as its soIe object, the desire to shed Iight, whenever possibIe, on an obscure diagnosis, or on an uncertain prognosis; to add an eIement of certainty when diagnosis is wavering, and to sound a warning when compIications arise before they manifest themseIves cIinicaIIy. To this group of cIinicians who are aIways on the qui vive, who form a weIcoming vanguard to a new fact or thought and who do not shut the windows to prevent a ray of Iight from entering the cIinica1 judgment, to this group we dedicate the resuIts of our investigations.

I. THEORETICAL

Adumbrating the summary at the end of the article we wish, at the outset, to point out the folIowing impressions which, we beIieve, are justifiabIe:

I. The quantitative and quaIitative studies of the “Stab-zeflen” or, as we, in

* From the Pathologica Laboratories of the Sydenham Hospital, New York City.

56

NEW SERIES VOL. XXI, No. 1 Eisenberg, Nemens-SchiIIing Hemogram A ,nericnn .Jr,l,rnnl of s”rgcT,y j -

common with many others, have desig- nated them, “band” or “staff” ceIIs, are the most important parts of a bIood count. It is in the recognition of the existence and of the importance of the band ceIIs, the immature neutrophiIes with non-segmented nucIei, that the SchiIIing2 count (the written record of which is caIIed “a hemogram “j differs from an ordinary count.

2. The band ceI1 count study is even more important in conjunction with the tota Ieucocyte count and, as has been again recentIy emphasized by MedIar,3 with the mature, i.e. segmented, neutro- phiIes, for it is the mutua1 reIationship of these three eIements: the tota Ieucocytic count, the number of the mature (segmented) and of immature (band) neu- trophiIes, that reflects, mirror-Iike, the hematoIogica1 reaction in the presence of infection.

3. By infection we understand not onIy diseases caused by bacteria and their toxins, but aIso a11 pathoIogica1 conditions in which there is abnorma1 cIeavage or breaking down and hyperabsorption of proteins, e.g. intestina1 obstruction, de- generated uterine myofibromata, uIcerat- ing maIignant neopIasms, etc.

4. In many. deep-seated infections, cen- tra1 pneumoma, deepIy buried retroceca1 appendicitis, etc., a properIy performed bIood count is of inestimabIe vaIue in that it pIainIy and unequivocaIIy points to the existence of a progressive infection, not onIy hours, but not infrequentIy, days, before the symptoms and signs permit one to form a definite cIinica1 diagnosis.

5. A SchiIIing hemogram is of the greatest vaIue in postoperative or metacritica recovery from a surgica1 or medica infection; the arising compIications are reflected first (and often considerabIy earIier) in the bIood count. We have seen patients who were discharged with a high band count (15-20 per cent*) onIy to return again within a few days, some with intestina1 obstruction or peritonitis, others with empyema. We have become used to

* The norma band cel1 count is 3-S per cent.

seeing patients who, whiIe “doing fine,” wouId suddenIy show an aIarming bIood picture whiIe, cIinicaIIy, the reason for it wouId become obvious onIy some time, hours or days, Iater.

6. We have Iearned to appreciate not onIy the quantitative but the quaIitative changes in the band ceIIs. In severe infections the usua1 form of the band ceI1 nu- cIeus is that of a sausage, very plump and Iarger than in moderate infection; very frequentIy the nucIeus is riddIed with vacuoIes, whiIe the cytopIasm is studded with the so-caIIed “toxic granuIes,” large, dark and pIeomorphic.

7. In a very smaI1 percentage of cases, not over I per cent, no hematoIogica1 expIanation of the surgica1 picture found at the operation couId be vouchsafed, this discrepancy consisting both of the absence of hematoIogica1 evidence of infection in the face of an adequate anatomica pathoIogy, and of the absence of definite pathoIogica1 changes in the presence of a suggestive bIood picture (here we might add that there may have been patho- IogicaI changes, but not demonstrated b\ Iaparotomy).

Theoretical Basis of the Schilling Hemo- gram. The epoch-making studies of Ar- neth (1904) which have estabIished the morphoIogica1 variabiIity of the nucIeus of the neutrophiIic Ieucocyte, have natu- raIIy focussed attention afresh on the significance of the bIood count.

True, Arneth’s4 own method has not and, probabIy wiI1 not, become an everyday Iaboratory procedure for several reasons. In the first pIace, Arneth’s count is too compIicated: there are five cIasses of ceIIs, according to the number of the nucIear Iobes, each of which has four or more con- figurations (“ sausage,” “ bean,” “ baI1 “), giving a tota of over twenty different neutrophile ceIIs; the amount of time con- sumed by such counts is not the onI), objection; during the Iast twenty-five years Arneth has engaged in probabl>- more poIemics than any other hematolo- gist, on pureIy theoretica grounds, and

58 ‘4 merican Journal of Surgery Eisenberg, Nemens-SchiIIing Hemogram JULY, 1933

IargeIy because he had gone too far in estimating the vaIue of his cIassification. SchiIIing, Weidenreich, Pappenheim and Tuerk are some of his adversaries. One of the most serious arguments against accepting Arneth’s teaching Iies in the fact that he disregards the degenerative (quaIita- tive) changes in the cytopIasm as we11 as in the nucIeus (the presence of toxic granuIes, vacuoIes, staining defects, etc.), in other words, he ignores a11 those changes which have been so we11 studied, recentIy, by GIoor.5 For other objections to the accept- ance of a11 of Arneth’s tenets the reader is referred to the numerous articIes by SchiIIing, GIoor and others.

In order to cIearIy understand SchiIIing’s conception of the bIood picture, it is usefu1 to recaI1 severa physioIogica1 data.

In the mammalian bone marrow circuIa- tion is cIosed (Doan, Sabin,6 Cunningham, Drinker). The ceIIs produced in the bone marrow are the erythrocytes, the thrombocytes (bIood pIateIets) and the granuIar Ieucocytes: the eosinophiIes, the basophiIes and the neutrophiIes; whiIe the erythrocytes are formed intravascuIarIy, the Ieucocytes are formed extravascuIarIy; after the maturation has progressed from the myeIobIast, through the promyeIocyte to the myeIocyte, and from the myeIocyte to the metamyeIocyte, the active migra- tion of Ieucocytes into the bIood vesseIs begins; in other words, normaIIy the metamyeIocyte is the first Ieucocyte to enter the vesseIs, due to the streaming of its granuIes; during this penetration a few metamyeIocytes change into the band ceIIs, of which a11 but 5-8 per cent mature into the segmented neutrophiIes (mature neu- trophiIic Ieucocytes) in the periphera1 circuIation, and thus a drop of bIood taken from the Iatter gives us the weII-known normal differentia1 formuIa of 70 per cent neutrophiles (62-65 per cent of segmented, and 5-8 per cent of band ceIIs), 20-25 per cent of lymphocytes, 1-2 per cent of eosinophiIes, 0.5 per cent of basophiIes and 3-4 per cent of monocytes (the Iym- phocytes being formed by the lymphatic

tissue, and the monocytes by the reticuIo- endotheIia1 tissue).

The deIivery of the ceIIs from the bone marrow to the bIood stream takes pIace, according to Shaw,’ in two tides, one beginning in the forenoon, reaching its height in the afternoon and decreasing earIy in the evening, whiIe the other tide begins Iate in the evening, reaches the maximum shortIy after midnight and the minimum in the morning; these diurna1 variations affect the tota count but not the differentia1 percentages. These facts shouId be carefuIIy evaIuated when check- ing up the bIood counts made on the same patient at different hours, in order to do justice both to the patient and to the one who examines the bIood.

The infectious agent apparentIy introduces either both a chemotactic and a maturation factor or a chemotactic factor onIy; in the former case a Ieucocytosis with a norma differentia1 count resuIts, whiIe in the second case there wiI1 be, after a transitory Ieucocytosis, a progressive Ieucopenia, due to the fact that a Iast- ing chemotaxis wiI1 graduaIIy Iead to exhaustion.

The exact mechanism of these two opposing factors is not yet known; it may be, as Noy and EppIer beIieve, that the stimuIus to the bone marrow Iies not in the direct chemotaxis by bacteria or their toxins, but in the increase of the body substances which normaIIy stimuIate the bone marrow; it may be that the norma spIenic inhibitory hormone reIaxes during the infective process, or it may be that with the increased phagocytosrs a new stimuIus for an increased production of the neutrophiIes is furnished; at any rate, whatever the stimuIus, it is a specific one for the neutrophiIes, since the baso- phiIes and, particuIarIy, the eosinophiIes promptIy disappear at the onset of infection, and reappear when the Iatter is gone.

What reguIates the dehvery of the Ieucocytes under norma conditions? It is assumed that normaIIy the production of the myeIoid Ieucocytes (the neutrophiIes,

N,-, sElllEs vOL. XXI, No. I Eisenberg, Nemens-Schilling Hemogram A merican Jour~~:~l 01 Surgery 59

basophiIes and eosinophiIes) is reguIated, directIy or through the sympathetic nervous system, by hormones; at Ieast one of them seems to be produced by the spIeen, and appears to be an inhibitory one; it is a matter of everyday cIinica1 observation that most of chronic spIeno- megaIies (Banti’s disease, maIaria, chronic tubercuIosis, syphilis, Gaucher’s and Pick- Niemann’s diseases, WerIhof’s disease, pernicious anemia, etc.), except the Ieuke- mias, are accompanied by Ieucopenia; some subacute spIenomegaIies (e.g. typhoid fever) are aIso characterized by Ieucopenia.

NaegeIi has recentIy expressed an opinion that the resuIting bIood picture, both quantitative and quaIitative, in infections, i.e. the toxic reaction of the bIood, depends IargeIy on the degree of mesenchyma1 affinity of the bacteria concerned in a gi\.-en infection, pointing out that whiIe the coccaI infections produce intense changes in the bIood pictures, infections which seem to have a marked prediIection for the ectoderma1 nervous tissue (neurotrophic or neurophilic infections), such as Heine- Medin disease, tetanus, lethargic encepha- Iitis, etc., are not reflected by any marked changes in the bIood picture.

A word in connection with the spIenic inhibitory hormone; it must be added that a11 other ceIIuIar eIements produced by the bone marrow: the erythrocytes and the thrombocytes (bIood pIateIets), are aIso under the spIenic contro1, and E. Frank stresses the finesse and deIicacy of the contro1 manifesting itseIf beautifuIIy in the fact that spIenectomy causes an increase onIy or especiaIIy of that bone marrow eIement, the insuffIciency of which constituted the most striking part of the preoperative hematoIogica1 picture; thus, in pernicious anemia it is the erythrocytes, in !\‘erIhof’s disease the bIood pIateIets (the thrombocytes), and in Banti’s disease the Ieucocytes which so strikingIy increase in numbers.

In passing we may mention Stephen’s opinion that it is the adrena cortex which, together with the spIenic hormone, controIs

the hemopoietic functions of the bone marrow.

FinaIIy, there arises the question of whether the spIenic hormone controIs the production of the ceIIs or their maturation and reIease into the periphera1 circuIation; it is quite conceivabIe that the Iatter two phenomena may be under the pIurigIandu- Iar contro1 of the endocrines, so that the spIenic hormone controIs the production of the immature Ieucocytes, and the endocrines their maturation to neutrophiIes, and the substances Iiberated by the dead, disintegrated neutrophiIes (which substances are probably chemotacticaIIy iden- tica with bacteria1 toxins) reguIate the outflow of new neutrophiIes to repIace them.

To transIate the foregoing physioIogica1 data into the cIinica1 hematoIogica1 picture, we may say that if the infection introduces both the chemotactic and the maturation eIements, we shaI1 have a Ieucocytosis and a norma differentia1 count, if the infection is slight; if the infection gains, the neutro- phiIes, both the band and the segmented ceIIs, wiI1 increase, as wiI1 the tota Ieu- cocyte count; if the infection becomes severe, the maturation of the band ceIIs into the segmented neutrophiIes wiI1 Iag, and the percentage of the band ceIIs wiI1 rise, and that of the segmented ceIIs wiI1 decIine; from now on, as the infection gains in severity, the Iagging maturation wiI1 manifest itseIf in the appearance in the bIood of ceIIs which are progressi\.-eIy Iess and Iess mature, i.e. there wiI1 appear, at first, the metamyeIocytes CSchiIIing’s “ jugendliche Zellen “), then myeIocytes and finaIIy promyelocytes, and, occasion- aIIy, even myeIobIasts, the Iatter event takes place but very seIdom since the patients usuaIIy die before this happens. At the same time that more and more immature ceIIs make their appearance, the signs of exhaustion begin to manifest themseIves by the decreasing total Ieuco- cyte count, and the worst hematoIogica1 prognosis is just this combination of the progressive decIine of the total count and

60 A merican Journal of Surgery E’ Isen b erg, Nemens-SchiIIing Hemogram JULY, 1933

the increase of the immature ceIIs : the band ceIIs, the metamyeIocytes and the myeIocytes.

Some infection, or rather infections in some individuals, the so-caIIed “over- wheIming” or “ fuIminating” infections yieIding onIy the chemotactic but not the maturation eIement, Iead to a very earIy exhaustion, the bIood showing a Iow tota Ieucocyte count and high increase in the band ceIIs. This may be preceded by a very transitory Ieucocytosis, aIthough in the most severe cases the bone marrow seems paraIyzed at the very outset of infection.

We beIieve that as Iong as the band ceIIs are under 13 per cent the infection is not suppurative, and if they are over 20 per cent, we are aImost aIways confronted with pus or very grave intoxication due to hyperabsorption of broken-down proteins (intestina1 obstruction, broken-down uterine myofibromata, etc.).

It is especiaIIy important to remember that no one count makes a hopeIess prqgno- sis; we have seen cases recover in which the band ceIIs were as high as 60 per cent, and we have seen many cases die in which the band ceIIs were onIy 30 per cent; it is the progressive rise of the band ceIIs that speIIs the patient’s doom, regardIess of the cIinica1 picture (see under IIIustrative Cases). A patient who, during the postoperative or the metacritica1 pneumonic course, suddenIy shows a rise in the band forms which persists or progresses, is deveIoping a suppurative condition (an abscess, peritonitis, obstruction or empyema) no matter what the cIinica1 picture is, because the Iatter aIways changes Iater than the bIood picture. We have seen this time and again, but we have never seen the reverse, i.e. the occurrence of the cIinica1 compIications before the warning is sounded by the blood picture. Moreover we have repeatedIy seen the patient Ieave the hospita1 quite we11 cIinicaIIy, but with 15-20 per cent of the band ceIIs, onIy to be readmitted a few days Iater with the afore- mentioned compIications. (See IIIustrative

Cases.) Another important point is to remember

that with the onset of a severe infection or compIication the eosinophiIes disappear, and that with the onset of an improvement they aIways reappear, a most favor- abIe sign.

FinaIIy, the bIood count in chiIdren, especiaIIy in very young chiIdren, requires a particuIarIy carefu1 observer, since the bIood making and reguIating apparatus in chiIdren is much Iess stabIe than in the aduIt.

2. ILLUSTRATIVE CASES

I. Appendicitis. This forms a Iarge part Of our S&3, comprising as it does 2 143

cases: they are cIassified pathoIogicaIIy as foIIows :

Cases A. Chronic appendicitis. . . 1192 B. Subacute appendicitis.. 234 c. Acute catarrhal appendicitis.. . . 3% D. Acute suppurative appendicitis (gangrenous,

with or without abscess or peritonitis). . 348 A. Chronic appendicitis shows a normaI count:

Average Total W.B.C. count.. . . 6500-12,000 8500

Total neutrophiIes. . 65-75 per cent 67 per cent of which

Band ceIIs.. . z-6 per cent 4.5 per cent B. Subacute appendicitis shows a sIight increase in

the tota Ieucocyte count but the band ceIIs are stiII normaI:

Average Total W.B.C. count.. 10,000-17,000 13,000

TotaI neutrophiIes. 58-83 per cent 70 per cent of which

Band ceIIs. 4-10 per cent 7.5 per cent c. Acute catarrha1 appendicitis show a detinite

increase in the tota Ieucocyte and neutrophiIe counts, and a sIight increase in band ceils.

Average TotaI W.B.C. count.. IO,OOO-23,000 I 8,000 TotaI neutrophiles. 65-85 per cent 77 per cent

of which Band cells.. . 8-18 per cent I I per cent

D. Acute suppurative appendicitis shows a striking increase in a11 figures:

Average TotaI W.B.C. count.. 14,000-30,000 19,000 TotaI neutrophiIes. . 75-94 per cent 84 per cent

of which Band ceIIs. IT-70 per cent 20.5 per cent

If the postoperative convaIescence is uneventful, the band ceIIs are the first to

NF.W SERIES Var.. XXI, No. I Eisenberg, Nemens-SchiIIing Hemogram A rnericnn Joul-n,4l 01 surgq 61

return to normaI; if a complication is showed: W.B.C. 16,000, neutrophiles 83 per setting in, the band ceIIs either remain

sustained or rise higher.

cent, of which band ceils were 20 per cent,

A gangrenous appendix was remo\-ed; tJi-o

CHART I. Acute gangrenous appendix in patient aged fifty-one years.

The foIIowing cases are seIected to weeks later, on October 4, W.B.C. were I~,OOO, emphasize some particular point in diagno-

sis or prognosis:

neutrophiles 76 per cent, band ceIIs 34 per cent; during this period the patient showed definite

CHART II. Acute appendicitis, pneumonia.

CASE I. No. 10667. A male patient, aged signs of peritonitis, which soon began to fifty-one, was admitted to Sydenham HospitaI September 21, 1929, with symptoms referabIe

improve, and a week Iater, on October 12, W.B.C. were 10,000, neutroph3es 72 per cent,

to the right Iower quadrant; his bIood count band ceils IO per cent. (Chart I.)

62 A merican ~~~~~~~ of surgery Eisenberg, Nemens-SchilIing Hemogram JULY, 1933

Comment: The tota W.B.C. and the tota CIinicaIIy, the patient’s condition remained neutrophiIe counts were of no heIp, but the the same. On ApriI 15, between the hours of band ceIIs showed a curve paraIIe1 to tempera- IO A.M. and 4 P.M. the patient was seen by three

CHART III. Acute gangrenous appendix, retrocecal.

ture, the two peaks coinciding on the same day (Oct. 3).

CASE II. No. 14966. This is a case of acute catarrha1 appendicitis compIicated by a postoperative Iobar pneumonia. On admission the bIood count showed W.B.C. 18,000, neutrophiIes 81 per cent, band ceIIs 7 per cent; two days Iater the temperature rose from 101’ to IO~OF., and his bIood count showed W.B.C. 18,400, tota neutrophiIes 88 per cent and band ceIIs 32 per cent. (Chart II.)

Comment: As in the preceding case, neither the tota W.B.C. nor the tota neutrophiIe count were heIpfu1, whiIe the band ceIIs rose and feI1 with the temperature.

CASE III. No. 17440. This is an extremeIy instructive case, one in which cIinica1 diagnosis compIeteIy faiIed to recognize the presence of an infection, whiIe the hematoIogica1 evidence was absoIuteIy cIear cut at the very outset.

A maIe patient, aged twenty, was admitted to the Sydenham HospitaI ApriI 12, rgsr, with cramp-Iike diffuse abdomina1 pains of forty- eight hours’ duration; there was a sIight fever, and a sIight spasm in the right upper quadrant.

BIood counts showed on ApriI 12: W.B.C.

18,ooo, neutrophiIes 80 per cent, band ceIIs 20 per cent; two days later: W.B.C. Ig,5oo, neutrophiIes 80 per cent, band ceIIs 36 per cent.

competent consuItants: an internist, a surgeon and a gastroenteroIogist ; their opinion was “hands off, no acute surgica1 condition present.” Three hours Iater, an interne noted the rigidity of the abdomen; immediate operation reveaIed a ruptured gangrenous retroceca1 appendix. AIthough cIinicaIIy he began to improve immediateIy after the operation, the band ceIIs persisted and five days Iater a mass was feIt in the Ieft flank, a11 this with no symp- tom or sign other than the sustained rise of the band ceIIs. ResoIution of the mass brought about a sIow but uneventfu1 recovery as we11 as a return of the bIood picture to normaI. (Chart III.)

Comment: WhiIe the temperature came down and the tota W.B.C. and neutrophiIe counts remained stationary, the band ceIIs remained sustained near 40 per cent, and came down when the totaI W.B.C. count went up, a most favorabIe prognostic point.

CASE IV. No. 13594. A maIe patient, aged twenty-eight, was admitted to the hospita1 on May 2 I, 1930, with symptoms of acute appendicitis. His bIood count showed: tota W.B.C. 60,000, neutrophiIes 91 per cent, band ceIIs 60 per cent, numerous toxic granuIes present. At the operation a gangrenous appendix with peritonitis was found. Three days Iater the

NE\\ SERIES var. XXI, NO. I E’ rsen b erg, Nemens-SchiIIing Hemogram ~~~~~~~~~~ ~~~~~~~~~ ,)I c~,~,.,-~ 63

blood count was: W.B.C. 44,000, neutrophiIes temperature, the totaI W.B.C. and neutrophile 62 per cent, band cells 50 per cent. Six days counts were going down, whiIe the band cells later the total W.B.C. count began to drop, were going up. (Chart VI.)

CHART IV. Acute appendicitis, peritonitis, in patient aged twenty-eight years.

whiIe the tota neutrophiles remained at go per cent and band ceIIs at 60 per cent, a most serious and unfavorabIe phenomenon. (Chart IV.)

Comment: Observe the steady decrease in the tota W.B.C. count and the persistent rise of the band ceIIs, a combination usuaIIy pointing to a fata issue.

CASE v. No. 8799. This is a very interesting case, iIIustrating the desirabiIity of examining the patients’ blood when they are ready to be discharged, especiaIIy after an infective process. In this case, had it been known that the patient still had 20 per cent of band ceIIs (and espe- ciaIIy, that they had just risen from 8 per cent), the patient certainIy wouId not have been discharged, but kept under observation. The patient had been operated on for acute catar- rha1 appendicitis, and was aIIowed to go home with a normaI tota W.B.C. and neutrophiIe count, as we11 as a norma temperature, but with band ceIIs 20 per cent. He was readmitted two days Iater, his tota W.B.C. and neutrophiIe counts rose moderately, but the band ceIIs went up to 70 per cent; he died three days Iater of intestinal obstruction. (Chart v.)

CASE VI. No. 14392. This case iIIustrates the fact that at times the band ceI1 count may be the onIy factor pointing to a grave prognosis. One can readily see from the chart that the

2. Cholecystitis. Of gaII bIadder disease

672 cases were studied hematoIogicaIly;

590 cases of chronic cholecystitis, and 82

I CHART v. Acute appendicitis. Home. Readmitted with

intestina1 obstruction. Patient aged forty-six years.

cases of acute choIecystitis. We have found that the presence or

absence of stones, adhesions, etc. does not

2m w

2ooo 40

1600 so

100 20

600 10

I : I : I : 1 : I : I

CHART VI. Acute suppurative appendicitis, abscess, CHART VII. Acute choIecystitis in patient aged sixty. peritonitis, in a patient aged sixty-two years.

64 American ~~~~~~~ of surgery Eisenberg, Nemens-SchiIIing Hemogram JULY. 1933

influence the bIood picture, and that the weeks later. An interesting feature is the fact

latter is affected onIy by the presence or that a11 four eIements: the temperature, tota

absence of infection. W.B.C. count, total neutrophile count, and the

_

In chronic disease the average count was: band ce1I.s rose and feI1 in a paraIIe1 course. (Chart VIII.)

TotaI W.B.C. count. . . gooo CASE IX. TotaI neutrophiIes. 6g per cent

No. 14476. This is a case of acute

of which suppurative ChoIecystitis in which the patient

Band celIs.. g per cent subsequentIy deveIoped peritonitis. It iIIus-

In acute gaILbladder disease the average trates very we11 the fact that whiIe the band

count was: ceI1 count was steadiIy and rapidIy rising, and

TotaI W.B.C. count......... 18,500 thus caIIing attention to the gravity of the

Total neutrophiIes. 82 per cent situation, the tota W.B.C. count remained of which unchanged, the tota neutrophiIe count was

Band ceils.. 22 per cent decreasing, and the temperature rose only

CASE VII. No. 7709. A femaIe patient, aged during the Iast three days. (Chart IX.)

sixty, was admitted to Sydenham HospitaI on Comment: Observe the false sense of security

February 3, 1928, with symptoms of acute conveyed by the tota W.B.C. and the total

gaII-bIadder disease. Her temperature was neutrophiIe counts.

104’~. and the bIood count moderatety high. Under conservative treatment she improved,

3. Intestinal Obstruction. These cases

and was discharged. (Chart VII.) show practicaIIy the same bIood picture

Comment: The total neutrophiIe count re- as is shown by pus infection; apparentIy

mained high, but the temperature, tota W.B.C. hyperabsorption of toxic products of pro-

and band ceI1.s graduaIIy came down to normaI. tein cIeavage affects the bIood-forming

This is a case which depicts the return to organs in the same manner as do bacteria norma of an infected gaI1 bIadder under con- and their toxins. servative treatment. In 81 cases studied by us the average

CASE VIII. No. 10382. In this case of bIood count was as foIIows: cIinicaIIy chronic ChoIecystitis in which operation was performed, the bIood picture pointed

TotaI W.B.C. count.......... 20,000

postoperativeIy to acute infection, which TotaI neutrophiIe count. . . 80 per cent

of which became Iocalized as a subphrenic absecss two Band cells.. . 30 per cent

NEW SEHIES VOL. XXI, No. I Eisenberg, Nemens-SchilIing Hemogram A mcricun Journal <,I Surgery 65

CASE x. No. 12426. In this case it is inter- after the crisis, the eosinophiIes do not esting to note that whiIe the tota neutrophiIe return, it means that there wiII be compIica- and the band cell counts reacted to the patient’s tions: empyema, puImonary abscess, etc.

CHART VIII. Cholecystectomy, subphrenic abscess.

condition, the tota W.B.C. count remained practicaIIy unchanged. (Chart x.)

CASE XI. No. 22186. The interest of this case centers in the fact that aIthough the clini- ca1 condition of the patient was not of sufficient severity to caII for surgica1 interference during the first five days of iIIness, and aIthough there was Ieucopenia during the first three days, the band cei1 count was persistentIy high: 40 per cent to 60 per cent, another instance of the grave significance of steadiIy decreasing tota and increasing band ceI1 counts. (Chart x A.)

4. Lobar Pneumonia. Of Iobar pneumonia 210 cases were studied. The average bIood count was as foIIows:

TotaI W.B.C. count.. 20,000 TotaI neutrophiIes.. 85 per cent

of which Uand ceIIs. 30 per cent

HematoIogicaIIy, a moderateIy high tota W.B.C. count, moderate tota neutrophiIe and a Iow band ceI1 count give a most favorabIe prognosis; the reverse: a Iow tota W.B.C. count together with high tota neutrophiIe and band ceI1 counts, is of III omen.

It aIso must be emphasized that if,

CASE XII. No. 16784. This case iIIustrates the cIose paraIIeIism between the temperature and the band cell curve, whiIe the tota W.B.C.

I

CHART IX. Acute gangrenous gall bladdrr, peritonitis.

and neutrophiIe counts appear irreguIar. AIso observe an unfavorabIe picture during the first three days of iIIness before the serum was given: Ieucopenia with high band ceI1 count,

66 ~~~~~~~~ ~~~~~~~ or surgery Eisenberg, Nemens-SchiIIing Hemogram Jury, 1933

and marked improvement after injection of going home, in spite of the fact that the band serum. (Chart XI.) ceIIs were 16 per cent. She was readmitted two

CASE XIII. No. 13488. A femaIe patient, weeks Iater, the band ceIIs stiI1 being 18 per

CHART x. Chronic appendicitis, rupture of wound, intestina1 obstruction, peritonitis in patient aged thirty-three years.

aged twenty-five, was admitted ApriI 23, 1930, cent, whiIe the tota W.B.C. and neutrophiIe with a diagnosis of bronchopneumonia; the counts had dropped. A smaI1 encysted empy- bIood count on admission was as foIIows: tota ema was discovered and treated surgicaIIy.

CHART x. A. IntestinaI obstruction in patient aged fifty.

-

W.B.C. 17,000, total neutrophiIes 74 per cent, (Chart XII.)

band ceIIs 14 per cent; after sIight transient rise of a11 counts, the temperature dropped from 5. Osteomyelitis. Fifty chronic cases

104’ to IOI~F., and the patient insisted on have shown nothing of consequence,

NEW S~KIES VOL. XXI, No. I Eisenberg, Nemens-SchiIIing Hemogram A mrrican Journd oiSurgcry 67

hematoIogicaIIy. On admission both ears were discharging,

Acute osteomyeIitis, 75 cases of which there was a sweIIing of the right thigh and an were studied by us, shows the following irregular fever. Blood count on admission

3000 __g!

ZSOO 50

3000 40

i

160 30

i

20

600

CHART XI. Lobar pneumonia in patient aged thirty-five.

average bIood picture :

TotaI W.B.C. count.. 20,ooo Total neutrophiles.. 75 per cent

of which Band cells.. zo per cent

showed: tota W.B.C. 12,000, total neutrophiIes 70 per cent, band ceIIs 22 per cent; the patient was observed for two weeks with a provisiona diagnosis of rheumatic fever, and at the end of this period there appeared signs of pus in

CASE XIV.

CHART XII. Bronchopneumonia, empyema.

No. 13076. J. R., aged two, was the right hip. The bIood count at that time admitted ApriI 12, 1930, with a history of Iobar showed the tota W.B.C. rs,ooo, total neutro- pneumonia two weeks prior to admission. philes 71 per cent, band ceIIs z$ per cent;

68 American Journal of Surgery Eisenberg, Nemens-SchiIIing Hemogram J-y, 1933

immediate operation reveaIed right pyarthrosis. suppurative osteomyebtis of the mandible it is The subsequent course was one of septicemia interesting to note that both the tota W.B.C.

with metastatic manifestations and, finaIIy, and neutrophile counts were going down, while

CHART XIII. Otitis media, septicemia, pyoarthritis of hip in patient aged two years.

SC 103

9600 7c 1OI

SWOl 6C 101

269oI M lo(

9iWMI 40 95

1600l~ SC or

1oaot 2c 9:

6OOl 1c 9

:I:I:J:j:/ :I: : I CHART XIV. Acute suppurative periostitis of mandibIe in patient aged twenty-tive.

meningitis. (Chart XIII.) the band ceI1 count steadiIy pointed to the Comment: Both the tota W.B.C. and neutro- seprence of pus, in spite of the fact that the

phiIe counts showed a sIight downward course, first incision did not revea1 the presence of pus. while the band ceIIs steadily increased, a (Chart XIV.) worthwhiIe point of differentiation between acute OsteomyeIitis and acute rheumatic fever, especiaIIy of the monoarthritic type. 6. Mastoiditis. Chronic infections of

CASE xv. No. 12716. In this case of acute the mastoid do not produce a character-

istic bIood picture; acute cases, 192 of it wouId have been impossible to determine the bvhich were studied by us, show the foIIow- presence of an infection for the total W.B.C.

ing average count. count ~vas ~S,OOO, and the total neutrophiles

CHART xv. Lymphatic Ieukemia, acute mastoiditis, in patient aged fifty-six.

TotaI W.B.C. count.. 16,500 TotaI neutrophiIe count.. 68 per cent

of which Band celfs.. . 15 per cent

were onIy 30 per cent; the reason for the former

w-as, of course, the Ieukemia, and the Iatter, 30 per cent of neutrophiIes, certainIy did not

CHART XVI. Chronic mastoiditis, sinus thrombosis in patient aged fourteen years.

CASE XVI. No. 8816. This case is of interest point to infection. It was the band ceIIs which in that a patient suffering from chronic saved the day, since of the 30 per cent neutro- Iq-mphadenosis deveIoped a suppurative mas- philes, 22 per cent were band celIs, i.e. over toiditis; according to the standard bIood count, 65 per cent of ali neutrophiIes. (Chart XV.)

70 American Journd of Surgery Eisenberg, Nemens-SchiIIing Hemogram JULY. 1933

CASE XVII. No. 7577. This is a case of chronic and acute mastoiditis which deveIoped sinus thrombosis; the tota W.B.C. count was rather Iow : between 10,000 and 18,000, the tota neutrophiIes ranged between 68 and 90 per cent, whiIe the band ceIIs were persistentIy high between 35 and 48 per cent. (Chart XVI.)

SUFMARY AND CONCLUSIONS

I. With due respect to surgeons who are cited in the Iiterature as expressing their opinions to the effect that the bIood count gives no usefu1 diagnostic information, we beg to differ with them and point out to them that they are missing much heIp by not famiIiarizing themseIves with the modern bIood count. The most experienced of them wouId save much diagnostic and prognostic grief by not ignoring the friendIy aid offered by the hematoIogist.

2. The oIder method of bIood counting which ignored the immature, non-segmented (staff or band) neutrophiIes, does not offer anything Iike the information, diagnostic and prognostic, conveyed by the SchiIIing method, ahhough the oIder methods of correIating the tota Ieu- cocytic (w.B.c.) with the totaI neutrophiIe count, the Gibson and the WaIker indices, are vaIuabIe.

3. The main practica1 feature of the SchiIIing count is the recognition of the non-segmented (band) neutrophiIe ceII which normaIIy constitutes from 4 to 8 per cent of a11 Ieucocytes.

4. If the infection is progressing, the most dependabIe hematoIogica1 sign is the increase in the percentage of the band ceIIs, regardIess of whether the tota Ieucocytic (w.B.c) count and the totaI neutrophiIe count rise or not; if the two Iatter counts are aIso high it is ever so much more favdrabIe than when they are Iow, as this wouId point to the exhaustion of the hemopoietic activity of the bone marrow; in other words, the steady rise of the band ceIIs points to invasive, progressive nature of infection, pus formation, and, if postoperative, to unfavorabIe termi- nation; if they rise during an “uneventfu1”

convaIescence, medica or surgica1, a com- phcation or a recrudescence is present, regardIess of the cIinica1 appearance, since the Iatter may be deIayed hours or days, as compared with the rise of the band ceIIs, e.g. an abscess formation foIIowing an operation, empyema foIIowing pneumonia, acute exacerbation of a chronic mastoid, etc. When such rise in the band ceIIs is accompanied by a falI of the totaI W.B.C.

or neutrophiIic count, or both, its unfavor- abIe significance is greatIy enhanced.

5. In especiaIIy severe infections there appear Ieucocytes more embryonic than band ceIIs, viz. metamyeIocytes, myeIocytes and even myeIobIasts.

6. The return of the eosinophiIes- which, as a ruIe, disappear with the onset of infections, is aIways a most favorabIe sign, particuIarIy in pneumonia-we have never seen pneumonia folIowed by empyema after a metacritical reappearance of the eosinophiIes.

7. Just why in some infections a11 three counts: the tota Ieucocytic (w.B.c.), tota neutrophihc and band ceII, are high, whiIe in others onIy the band ceII rises out of proportion to the former two counts, is not definiteIy known; the best expIanation is that the infection introduces two eIe- ments : the chemotactic eIement which caIIs forth the ceIIs from the bone marrow into the bIood stream and to the site of infection, and the maturation eIement which hastens the evoIution of the embryonic Ieucocytes to the stage of metamyeIo- cytes, at which IeveI the Ieucocytes migrate into the circuIation and continue their process of maturation; if the infective agent carries with it the maturation eIe- ment onIy, then the bone marrow wiII be forming ceIIs which wiI1 not be caIIed out into the bIood stream; in either case the totaI W.B.C. count wiII be Iow, and the phagocytosis wiII be inadequate. This conception may expIain why some diseases have, as their characteristic bIood picture, a marked Ieucocytosis with a high band ceI1 count, e.g. Iobar pneumonia, whiIe the characteristic bIood pictures of others, is a

~~~ sEHIEs vol.. XXI, N,,. I Eisenberg, Nemens-SchiIIing Hemogram A mcrican .JOUrnill ‘,(‘Surrq.ry 7 I

Ieucopenia with a high tota band ceI1 count is the ordinary bIood count, such as count, e.g. typhoid fever. has been done for the Iast thirty or forty

8. In the so-caIIed “incompIete” cIinicaI years, except for two things, both extremeIy picture of acute appendicitis, choIecystitis, 2mpIe : osteomyelitis, mastoiditis, and other surgi- a. The &mature (non-segmented, staff cal infections, as we11 as in pneumonia, or band) neutrophiIe ceIIs are separated typhoid, and other medica infections, the from the segmented or mature neutro- band ceI1 count is of greater importance, phiIes ithe famiIiarIy known “poly” of pointing to any of these infections, when yester-year), and, considered together with the cIinica1 picture b. The presence of occasiona metamye- and taking the pIace of the missing symp- Iocytes or myeIocytes shouId not be ignored, toms; taken without the cIinica1 picture the as it usuaIIy is, in non-Ieucemic cases, but high band ceI1 count points, non-specificaIIy shouId mean an even greater danger than and without IocaIizing it to a serious the rise of the band ceIIs; the more imma- infection, probabIy suppurative, if the ture the bIood ceIIs, the more severe the count is more than 15 per cent, and aImost infection. invariably so if it is more than 20 per cent.

We have seen centra1 deep-seated pneumonias, retroceca1 deepIy buried ap-

We wish to acknowIedge our sincere thanks

pendices, and other “atypica1” infections, to the members of the staff of Srdenham HospitaI for their generosity in pIacing the

giving a typica hematoIogica1 picture days records of their cases at our disposal. To Dr. before they became “ typica1” cIinicaIIy. Eugene E. Cahan of the Laboratory Staff we

9. In less than I per cent of cases of wish to express our deep gratitude for his

discrepancy, the Iatter consisted, in a very vaIuabIe cooperation and interest in the work.

Iarge majority of cases, in the bIood picture being one of infection, whiIe the operation failed to show an anatomica reason for it.

REFERENCES

The answer to that is, of course, that I. YAGUDA, A. Studies on SchiIIing count in appendi-

surgica1 expIoration of severa organs had citis. Am. J. Clin. Patb., I : 39. 1931.

missed the site of infection, and not that 2. SCHILLING, V. The BIood Picture. St. Louis. hlosby,

there was no infection, onIy an autopq 1929.

3. MEDLAK, E. M. A critica study of the polynuclear

could prove otherwise. In a few cases there count as advocated by SchiIIing. J. Lab. 8” Clin.

was a clear-cut cIinica1 picture of infection Med., 17: 169, 1931.

with a norma bIood picture, and the course 4. ARNETH, J. Die neutrophiIen weissen BIutkoerper-

then bei Infektionskrankheiten. Jena, Fischer,

of the patient’s sojourn in the hospita1 1904.

proved the correctness of the cIinica1 ARNETH, J. QuaIitative Blutlehre. Leipsig, Mink-

picture; for this we have no expIanation. hardt, 1920.

3, GLOOR, W. Die kIinische Bedeutung der quaIitxtiven

IO. FinaIIy, we wish to point out to those Veraenderungen der Leukozyten. Leipsig, Thieme,

who are habituaIIy hesitant in adopting 1929.

anything that is “new,” that in the first 6. SABIN, F., and DOAN, C. A. Bone marrow as an

organ. Proc. Sot. Exp. Biol. @ hfed., 25: 1.21, 1927.

pIace, the SchiIIing count is not new any 7. SHAW, A. F. B. The diurna1 tides of the leukocytes

Ionger; in the second pIace, the cIinician of man. J. Patb. W Bacterial., 30: I, 1927.

shouId clearIy understand that the SchilIing 8. NAEGELI, 0. BIutkrankfreiten und Blutdiagnostik.

Berlin, Springer, 193 I.

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