SCHILLING DIFFERENTIAL BLOOD COUNT IN APPENDICITIS*

J. VERNON LUCK, M.D.

LOS ANGELES, CALIF.

0 UR present standard cIassification of Ieucocytes was made by EhrIich after he discovered an aniIine dye

it beyond the average technician’s abiIity to do the count.

for which bIood ceIIs have a pronounced affinity. The successfu1 study of Ieucocytes data from this discovery. Before this time Ieucocytes were thought to originate from one common bIood forming system. Ehrlich and NaegeIi were the first to suggest that there were at Ieast two systems, the myelogenous and the Iymphatic. That there are two such systems is now a well- estabIished fact. Recently a third and entireIy independent system has been demonstrated which forms the monocytes (the Iarge mononucIears and transitionaIs). These ceIIs are said to originate from the reticula-endotheIia1 system of the spleen, Iiver, etc. The ceIIs from the myeIogenous system or bone marrow were at first a11 caIIed granuIocytes and those from the Iymphatic system caIIed Iymphocytes. Later EhrIich subdivided the granuIocytes into neutrophiIs, eosinophils, and baso- phils, thus originaIIy establishing the CIassification that is stiI1 standard. CIini- caIIy the neutrophiIs are by far the most important ceIIs in the bIood picture. A study of their nucIear changes has proved of the utmost clinica significance, espe- cialIy in the diagnosis and prognosis of infection. In Igod and rgo5 Arneth gave us an index by which the nucIear changes of the neutrophi1 might be interpreted. This count, being the first of its kind, aroused much new interest in the Ieucocytic bIood picture; however, it was so detailed and diffIcuIt that it proved of IittIe practica1 importance. In fact Arneth designated more than eighty ceI1 species, thus making

Many interesting investigations of the Ieucocytes foIIowed the introduction of the Arneth index. The Iimited cIinica1 significance of the EhrIich differentia1 was probabIy as evident then as it is now. It was obvious that the Arneth count wouId be of great practica1 vaIue if it couId be made Iess compIicated. Many attempts were made to simpIify it but none met with any degree of success unti1 Ig 12 when Victor von SchiIling at the First MedicaI University CIinic of BerIing gave us his modification of the Arneth index. SchiIIing’s method gives us far more information than that of Ehrlich, especiaIIy regarding the course of the various infections. Its introduction in this country has been rather slow, but wherever it has been properIy expIained and demonstrated it has been received with much enthusiasm.

The only essentia1 difference between the SchiIIing differentia1 and the oId differentia1 count as it was outIined by EhrIich is a division of the poIymor- phonuclear neutrophiIs into three cIasses : juveniIes, stabs and segments. The type of nucleus present is, for the most part, the basis for this cIassification. The poIy- morphonucIear neutrophiIs were so divided because their cIinica1 significance depends IargeIy on their degree of maturity or age, and this is mainly reflected by the type of nucIeus present. The onIy other differ- ence in the two counts is that the Iarge mononucIears and transitionals are com- bined and caIIed monocytes. There is no practica1 significance in separating these

* Read before a joint meeting of the Los Angeles County Media1 Association and the Los AngeIes Surgical Society, May 19, 1932.

275

276 American ~~~~~~~ of surgery Luck-BIood Count in Appendicitis FEBRUARY, ,933

two ceIIs. TabIe I gives a comparison of the two counts.

TABLE I

EhrIich SchiIIing

I. BasophiI 2. EosinophiI 3. NeutrophiI

A. MyeIocytes

B. PoIymorphonucIears

I. BasophiI 2. EosinophiI 3. NeutrophiI

A. Mydocytes

!

I. Jugediche (juveniIe)

B. 2. Stabkernige

\

(stab) 3. Segmentkernige

(seg.)

Lymphocytes Lymphocytes

Large mononudears TransitionaIs Monocytes

In Figure I are sketches of the four neutrophiIs. These are the ceI1.s with which

than the myeIocyte nucIeus. The juveniIe, Iike the myelocyte, contains nucIeoIi. This ceI1 is not normaIIy present in the aduIt bIood picture.

The stab type of neutrophi1 is the stage seen just before the nucIeus breaks up into segments that characterize the mature neutrophi1. The stab nucIeus is dark staining, narrow, often irreguIar in outIine, and assumes severa different shapes, e.g. v, s, u and 7. It contains no nucIeoIi. Two to 5 per cent of these ceIIs are present in the norma bIood picture.

The Iast neutrophi1, the segment, is a fuIIy matured ceI1, being characterized by the presence of two or more segments in its nucIeus. These segments are usuaIIy connected by a fine fiIament of nucIear materia1. Segments normaIIy constitute the Iargest part of the differentia1 picture, 63 per cent being norma in aduIts. These

TABLE II

we are most concerned in the SchilIing count. The sketches indicate the various nucIear changes of the neutrophi1 as it grows to maturity. The nucIeus of the youngest neutrophi1 or myeIocyte is most often kidney shaped, but may be round or ovaI; it contains nucIeoIi. The protopIasm is variabIe, but is most often a very paIe bIue with coarse neutrophiIic granuIes. This is an important ceI1 of the bone marrow where neutrophiIs originate, but is never normaIIy present in the bIood. It appears in the bIood during the most severe infections or toxic processes.

The juveniIe is next in Iine of deveIop- ment. Dr. SchiIIing describes it as having a sausage to aImost bean shaped nucIeus. It takes a sIightIy more intense staining

ceIIs have finer granules and are sIightIy smaIIer than the immature forms.

Notice again that the juveniIes, stabs and segments are divisions of the poIymor- phonucIears and that a11 neutrophiIs except segments are immature.

TabIe II is a norma SchiIIing hemogram. B represents basophiIs (I per cent), E =

eosinophiIs (3 per cent), M = myeIocytes (0 per cent), J = juveniIes (0 per cent), St = stabs (4 per cent), Seg. = segments (63 per cent), Ly = Iymphocytes (23 per cent) and Mon = monocytes (6 per cent). The neutrophiIs are a11 incIuded between the doubIe Iines. The dotted Iine is for descriptive purposes; it divides those ceIIs that are mature from those that are immature; the mature neutrophiIs

NEW SERIES VOL. XIX, No. 2 Luck-BIood Count in Appendicitis A rnericnn Journdl s,fSu~~rry Z-7” / ,

or segments to the right and immature ones : stabs, juveniIes and myeIocytes, to the left. If there is an increase in the neutrophiIs on the Ieft side of the dotted Iine it is spoken of as a nucIear “shift to the Ieft.” Arneth was the first to use the term “shift to the Ieft.” If there is an increase in the ceIIs to the right of the dotted Iine it is likewise caIIed a “shift to the right.” In aImost a11 infections or toxic processes there is an increase in the immature neutrophiIs; that is, there is a “shift to the Ieft.” The degree of this nucIear shift of the neutrophiIs has proved to be of the utmost cIinica1 significance, because it is one of our most accurate criteria of the presence and advancement of an infection or toxic process.

At the outset of an infection there is a mobilization of avaiIabIe mature Ieuco- cytes. As these are consumed by the septic process there begins a pathoIogic change in the neutrophiIs, and then a liberation of immature forms into the bIood stream. The first ceIIs to increase are stabs. SchiI- Iing beIieves that this resuIts from an inhibitory or paraIytic action of the toxins on the bone marrow, preventing the juve- niIe ceIIs from passing on to norma stabs and segments. This degenerative effect is thought to invoIve the neutrophiIs in both the bone marrow and periphera1 brood. The resuIting stabs show definite evidence of degeneration in that they are quite fragiIe and have a tendency to vacuoIization. Their nucIei are very intenseIy stained and assume many odd narrow shapes. These degenerative stabs are to be differ- entiated from the normaI stabs that are present up to 5 per cent in the norma bIood picture. The norma stab is the transitiona stage between the juveniIe and segment. The degenerative stab usuaIIy never reaches the segmented stage; that is, it deveIops to maturity without becoming segmented. A Ieucocytosis may be absent where there is an increase onIy in stabs; there may even be a Ieucopenia. SchiIIing designates this shift to degenerative stabs

without the presence of jul-eniles as a degenerative shift.

As the infection or toxic process advances

NEXlTROPNILS

MIMCYTN (0%)

SEYA (63%)

FIG. I.

F%YNOWNONUCLEAM

there is a demand for more Ieucocytes and as a resuIt bone marrow activity is stimuIated, giving an increasing “shift to the Ieft.” Evidence of this is seen in the rising Ieucocyte count and the appearance of juveniIe neutrophiIs in the periphera1 bIood. Due to the regenerative activity of the bone marrow, SchiIIing caIIs this a “regenerative shift.” If the infection stiI1 keeps the upper hand and continues to advance, the bone marrow in its effort to meet the demand for Ieucocytes may reIease its youngest neutrophi1, the myeIo- cytes, into the bIood stream. This gives a stiI1 greater “shift.” Thus we see that the “shift to the Ieft” foIIows the whole septic process in a definite and significant fashion. The shift to myelocytes is the worst infectious bIood picture seen, except in such rare conditions as the agranuIocytic and monocytic anginas. Something in the infection of these two conditions com- pIeteIy in hibits the entire myeIogenous system.

278 American Journal 0f surgery Luck-BIood Count in Appendicitis FEBRUARY, ,933

In TabIe III are Iisted a few representa- of the cases; the poIymorphonucIear count tive SchiIIing counts as observed by us was aIso misIeading severa times. For in simpIe acute appendicitis. The normal exampIe in Case I the white and poIymor-

TABLE III

SIMPLE ACUTE APPENDICITIS -

-

-.

-.

-.

-.

-.

-.

-.

-.

-.

-.

-.

-

-

_

-

x=

--

--

--

--

--

--

--

-

-

I Ii NeutrophiIs

B. E. LY.

27

Mon. Remarks Case W. B. C.

NormaI. . 7,500

I. Mrs. D.. . 8,150

2.Mrs.S ._....._. 9,200

3. Mrs.N . . . . . . . . 8,300

4.Mr.B . . . . . . . I3,I50

5. Mr. B.. . 12,500

6. Mr. G.. 23,100

7.Dr.D . . . . . . . . . . 14,900

8. Mrs.A ..___.... 15,000

g. Master H.. . . 13,900

IO. Master P.. 12,150

II. Mr. R .._.___. IS,r5o -____

12. Mrs. W.. I 6,800

M. J. St. i Seg. I I ~

I

I I j

0 2m5

6 m I 3 __-

0 0 --

20

‘3

I2

II

I2

5 Acute diffuse

I Acute diffuse ___- -

._

0 2 21; 63 -____ I___

85 ’

0 7 1 28 so

O/O ._

3 Markedly gangrenous 0 0 _ -_-‘-

88 j

0 4 27: 57 ~~-,~

88 j

0 I 0748 ---:-

91 i

TW 0 3 19’ 69

-_--_-.L_

0

__

._

Operation 18 hours later. See I next count.

Markedly gangrenous 0 Profuse drainage

I Acute diffuse __- ._

6 Acute catarrha1

0 0

0 0 --

I 0 --

0 I

--

7

26

/ 87 i

- 0 2 16; 69

-.-_: .- ‘3 0 Acute catarrha1

1 85 i

0 6 18 61 ---‘-

3 Acute diffuse I2 .-

0 0 __-

0 0

I 91

0 7m4 0 Beginning gangrenous 9 ._

.-

/ 74 :

0 0 0 3 18, 54 ~- __ ---_:_

25

12

0 Acute diffuse

5 PeritoneaI exudate on appendix I - hemogram is seen at the top of the tabIe. phonucIear counts were both practicaIIy First notice the wideIy variabIe tota norma despite the fact than an acute Ieucocyte count. It was far amiss as a appendicitis was found at operation. The criterion of the infection present in severa true state of the infection was accurateIy

1L’t w SERIES VOL. XIX, No. z Luck-BIood Count in Appendicitis A mcricnri J~l-t~.il 111 SU:ZU,, 279

indicated by the “shift to the Ieft.” Note next that eosinophiIs are absent in aImost every case. In the beginning of an acute appendicitis, as we11 as in other acute infections, eosinophiIs decrease or entirely disappear from the bIood picture. These ceIIs are of considerabIe cIinica1 signifi- cance; their presence during an infection is usuaIIy favorabIe and their absence unfavorabIe. “At the dawn of convaIes- cence,” as the attack is subsiding eosino- phiIs reappear in the picture and as compIete recovery is approached they may increase considerabIy above their norma percentage.

During the acute stage of appendicitis the foIIowing changes usuaIIy occur in the blood picture: (I) Increase in neutrophils, both reIative and absoIute, associated with a “shift to the Ieft,” which is in direct proportion to the degree and ad- vancement of the infection. (2) Decline or absence of eosinophiIs. (3) ReIative decrease in Iymphocytes and monocytes. SchiIIing, in his book “The Blood Picture,” terms this phase of an infection “the neutrophiIic battIe phase.” This is the stage of appendicitis that gives us the most concern. The information offered by the bIood picture is most often sought for during the “battIe phase.” During this acute stage when an accurate index of the presence and severity of the infection is so usefu1 and so much needed, the SchiI- Iing differentia1 count is found to be most enIightening.

Referring again to TabIe III note that myeIocytes are absent in every case. We have personaIIy never seen an uncompIi- cated case of simpIe acute appendicitis in which there were myeIocytes. These ceIIs are seen onIy in the severest infections or toxic processes. The appearance of I per cent or more of myeIocytes in the bIood picture during an appendicitis usuaIIy means that a peritonitis has deveIoped. The juvenile neutrophils varied from none, as in the acute catarrha1 appendi- citis of Case VII, to ro per cent as in Casev where the appendix was markedIy gan-

grenous and on the verge of perforating. Cases IX and x were in smaI1 chiIdren; notice that these counts both show a rather marked “shift to the Ieft.” In our ex- perience, counts on chiIdren show some- what more marked “shifts” for the same degree of infection than do those on aduIts.

If an acute attack of appendicitis sub- sides, with or without surgery, some interesting and definite changes can be observed in the bIood picture. Veq- often one of the first signs that the body is begin- ning effectiveIy to resist the invasion is a materia1 increase in monocytes. SchiIIing terms this the “phase of monocytic defense or subjection.” FoIIowing this, if the attack continues to subside, the Ieft shift recedes, then as recovery is approached the Iym- phocytes rise and eosinophils reappear. When these changes occur the “phase of Iymphocytic cure ” has been reached, meaning that the acute infection is entireI?; overcome. With compIete recover\- the norma blood picture returns with the exception of an increase in eosinophiIs and frequentIy aIso Iymphocytes for a time. FavorabIe changes in the bIood picture, then, are indicated by a recession of the Ieft shift, a decrease in poIymorpho- nucIears, an increase in monocytes and Iymphocytes and the reappearance of eosinophiIs. UnfavorabIe changes are indi- cated by an advancing “shift to the Ieft,” a rise in poIymorphonucIears, decrease in Iymphocytes and monocytes, and a decline or disappearance of eosinophiIs.

In TabIe IV are a few counts made on cases where a perforated appendix and various degrees of peritonitis were found at operation. Here again the Ieucocyte counts are wideIy variabIe. Frequently the Ieucocyte count rises as the infection advances, and in a certain way refIects the course of the infection; however, we must aIways remember that Ieucocytosis in inflammation is an index to the patient’s reaction and resistance and not to the severity of the infection. Through an excessive ceII consumption by a severe

280 American Journa.1 of Surgery Luck-Blood Count in Appendicitis FEBRUARY, rgss

septic process there may be a sudden transi- farther to the Ieft giving us an .accurate tion from a hyperleucocytosis to a hypo- understanding regarding the advancement Ieucocytosis. When this fact became known of the infection in spite of the variabIe and the tota white count Iost a great deaI of its often ambiguous tota white count. Exam- cIinica1 significance. Such drops in the pies of this are seen in Cases II, IV and VII.

Case W. B. C.

NormaI. .......... 7,500

I. Mrs. D ......... 7,800

2. Mrs. W. ....... 8,900

3. Mr. M ......... 8,400

4.Mr.P.. ........ 4,300

5. Mr. N. ......... 14,350

6. Mrs. B.. . . . . . 25,800

7. Miss M.. . . . 6,900

8. Mrs. S.. . . 34,750

g. Mrs.K . . . . . . . . . 10,150

IO. Mrs. K.. . . . .I 9,600

I-

-

:=

__

_.

-

B.

-

I Z=zz==

0 -

0 -

0 -

0 -

0 -

0 -

0 -

0 -

0 -

0

-

-

-

--

--

- ._

--

-_

--

- ._

-_

--

-

-

E.

-

3

0 -

0 -

0

0 -

0 -

0 -

0

0 -

0 -

2

-

TABLE IV

RUPTURED APPENDIX

NeutrophiIs

I I ;

I-Y. Mon. Remarks

M. J. St. i Seg.

0 0 4463 23 6 =~~/-~- 82 i- -

4 Patient recovered I 14 30 38 15 2 Stormy conva1.

--‘-:---- 72 j

/-- 4 28 31 j 13 20 4 Death one week postoperative

----____-

88 i Y-W Bacteriophage used; patient

I 11 24;53 II 0 recovered -.--‘---

78 i FataI prognosis; death three

2 25-z 20 0 -_---i

days postoperative ____-

91 i

,-- 0 19 29 43 9 O Patient recovered

- .- _‘_ 82: -

/-- 10 22 40 : 20 3 5 FataI prognosis; death next day

______~

8 52+ 8 IO 2 FataI prognosis; death eight

hours Iater

--I;;----

Good resistance; patient re- 0 18 31 i 44 5 2 covered

--_: _F-

82 ’ Shift receding.

,-- Operation postponed for 12 2 34 36 I 12 14 2 days

--_‘_--

83 Count made day of operation. ,-A WaIIed off

o 3 17 i 63 13 2 Abscess drained

Ieucocyte count are the resuIt of an over- When this condition obtains the prognosis wheImed or broken resistance, due usuaIIy becomes much worse and often fatal. to a massive, highIy viruIent infection. Many physicians have at times faIseIy Arneth has termed this condition in which interpreted the Iow Ieucocyte count of the ceI1 consumption exceeds the increased “agona1 ceI1 Iiberation” as a good omen. regeneration as “ agonaI ceI1 Iiberation.” This error has too often proved fata1, WhiIe this is occurring the nucIear shift especiaIIy when the physician was deaIing of the neutrophiIs moves farther and with appendicitis and peritonitis. The

NI..w SERIES VOL. XIX, No. z Luck-BIood Count in Appendicitis A lllericnll Jwrn:,I .,f SI.rg’Ty 781 l,

proper use of the bIood differentia1 wiII obviate this error.

It wiI1 be noted that I per cent or more of myelocytes are present in most of the cases listed in TabIe IV. The presence of any of these ceIIs indicates that the infec- tion is very severe. Percentages as high as those in Cases VI and VII usuaIIy predict a fata termination, especiaIIy if the sum of the immature ceIIs is 60 per cent or more.

Juvenile and stab ceIIs are, as wouId be expected, quite markedIy increased in peritonitis; the more severe the infection the more marked the increase.

Counts IX and x were made on the same patient. Notice the very marked “shift” in count IX. This confirmed the cIinica1 diagnosis of peritonitis. The patient was quite seniIe and such a poor operative risk that the operation was deferred. A second SchiIling count taken about ten hours Iater showed that the “shift to the Ieft ” was definiteIy receding, indicating to us that the infection was subsiding and probabIy waIIing off. The operation was then further deferred unti1 the “shift ceased to recede.” DaiIy counts showed a definite and steady recession of the Ieft shift for the next ten days. During the folIowing two days the shift receded no farther, so the patient was operated upon and a we11 waIIed off appendicea1 abscess drained through a smaI1 stab wound. Had this patient been operated upon when first seen a fata termination wouId probabIy have resuIted.

Let us emphasize here that the value of blood findings in many cases is greatIy enhanced by frequentIy repeated examina- tions. With daiIy counts the Ieft shift can be niceIy pIotted and a curve established that wiI1 reIate with remarkable accuracy the day by day progress of the infection.

In TabIe v are cases that were a11 orig- inaIIy diagnosed cIinicaIIy as acute ap- pendicitis. This diagnosis was questioned after obtaining a SchiIIing count due to the absence of a “shift to the Ieft” of any consequence.

In Case I there was a high Ieucocyte and poIymorphonucIear count. This was mis-

Ieading because there proved to be no demonstrabIe infection present in this patient. The SchiIIing count indicated the true condition of things. A cystoscopic examination revealed the cause of the troubIe to be a stricture of the right ureter due to pressure of a dispIaced eight months pregnant uterus. DiIatation of the ureter and manipuIation of the uterus promptly reIieved a11 of the symptoms that so cIoseIy simurated those of an acute appendicitis. Case II is simiIar except that the troubIe was due to a stone in the right ureter. It is surprising how such a stone or stricture will very often cause an increase in the tota Ieucocyte and the poIymorphonucIear counts, without de- monstrabIe infection being present. The same is frequently true of biIiary stones. The SchiIIing count is quite heIpfu1 in these cases, because unless there is an acute infection or toxic process accompanying the stone or stricture there wiI1 be no “shift to the Ieft” of any consequence.

Case III shows a typica count of early interna hemorrhage. These cases usuaIIy show a hyperleucocytosis and an increase in poIymorphonucIears associated with onIy a sIight “shift to the Ieft,” if any at aI1. There is frequentIy a persistence of eosinophiIs. The hyperIeucocytosis and increase in poIymorphonucIears is often misIeading in these cases. The SchiIIing count does much to cIarify this Ieucocytic picture and differentiate it from those of acute inflammation, e.g. acute appendicitis and acute saIpingitis.

We have seen severa cases Iike I\’ and v. Emergency operations were done for a supposed acute appendicitis. As you see there was no “Ieft shift” whatever. A sIightIy chronic appendicitis was found in both of the cases.

One of the most important uses of the SchiIIing method is to indicate in question- abIe cases whether there is or is not an infection present. We have thus far not encountered an infection of any severity in the absence of a “shift to the left,” regardIess of the cIinica1 symptoms or the Ieucocyte and poIymorphonucIenr counts.

282 American Journal of Surgery Luck-BIood Count in Appendicitis FEBRUARY, 1933

After using the SchiIIing count in a fairIy “with the diagnosis of tubercuIosis estab- large series we have concIuded that it Iished the method offers us the best singIe gives us much more information and is guide in determining the progress of the more accurate and dependabIe than the disease.” Further, “it is the most delicate oId differentia1 as outIined by Ehrlich, index we possess to interpret the phase especiaIIy in regard to the course of the and degree of focal activity.” Those

TABLE v

ALL DIAGNOSED ACUTE APPENDICITlS

Case W. B. C. B. E.

NeutrophiIs

NormaI. . . . . . . (

I. Mrs. W.. .

2. Mr.D . . . . . . . . . .

3. Mrs. T.. .

4.Mr.F . . . .._....

5. Mrs. S.. . .

6. Miss C.. , . . .

7. Mrs. F.. . , 10,900

8. Mrs. T.. . . . . . I17,ooo ~o~o~o~I++

I I Ly. Mon. Remarks

23 6 m- Stricture of right ureter due to

pressure of an eight mo.

r3 I pregnant uterus --

X-ray taken Iater showed stone IO 2 in rt. ureter

-~-

Ruptured tuba1 pregnancy, 8 o right

--

Chronic appendix (emergency 13 2 oper.)

--

14 5 Chronic appendix --

I2 3 Gastroenteritis --

18 0 Cyst of rt. ovary --

‘3 8 Hydrops of gaI1 bIadder

various infections. In the patients with appendicitis that were operated upon we were abIe to foreteI1 the pathoIogy present with greater accuracy than with the oId differentia1 count. The SchiIIing method has a wide range of usefuIness in many conditions besides appendicitis. It is espe- ciaIIy vaIuabIe in tubercuIosis. Bredeck, in an articIe on “The SchiIIing Blood Differ- entia1 in TubercuIosis,“l concIuded that

‘Am. Ret:. Tuberc., 20: No. I, 1929.

interested in tubercuIosis shouId read Bredeck’s articIe.

Expected changes in the bIood picture may be absent at times and for unknown reasons. On these occasions it is presumabIy our limited sphere of interpretation that is at fauIt and not the bIood. We shouId ever strive to remove these Iimitations.

May we emphasize in cIosing that the bIood picture shouId not be used aIone in making a diagnosis, but aIways in con- junction with compIete cIinica1 findings.