DETERMINATION OF THE TOTAL A M O U N T O F HEMOGLOBIN I N ANEMIA AND POLYCYTHEMIA

BY T. SJOSTRANU

Froiri thc Lnbornforg of Cliiricnl Physiologj at Karoliriskn S~ickhrtsrf. S/ork l io l r i i , SzL’ederi

(Received for publication August 9, 1949)

The clinical judging of cases of anemia and polycythemia has hitherto been based only on the relative hemoglobin values. These values, horn ever, are influenced by the plasma vol~inie, which latter can not always be supposed to conipensate the de- crease in erythrocytes in anemia, or to re- main constant in polycythemia. In these diseases it should therefore be of interest to complete the relative hemoglobin values with determinations of the total amount of hemo- globin.

The result of a series of determinations of the total amount of hemoglobin in a nun- her of cases of anemia and polycythemia are reported below, chiefly with the view of demonstrating the practical value of this procedure.

1Mk:THOD

The total amount of hemoglobui was determined according to Sjostrand (1918). that is by the administration of small amounts of carbon mo- noxide, and subsequent analysis of the carbon monoxide concentration in the alveolar air. The administered volume of carbon monoxide is propor- tionated so that the COHb concentration reaches a level about 2 7’ above the blank value. As the patient inhales 95 7‘ oxygen during the deter- mination, the oxygen physically dissolved compen- sates the decrease in Ol-capacity induced by the

experiment. After the determination, the COHb concentration in the blood may be lowered rapidly by the administratiou of oxygen in an open system. Thus determhations could be made also in greatly anemic subjects, witlhnt thc patient feeling any untoward effects.

In anemia, 6 - 7 nil of CO \\ere generally given. whereas in polycythemia 25-40 ml had to be ‘admi- nistered in order to alloa o f a sufficient exactness of the CO determination. -4 complete mixture in the body is not almays attained in 15 minutes in cases of polycythemia, and therefore 30 minute determinations were made in some such cases. In the calculations, the earlier. published corrections were used (Sjostrand 1948).

When calculating the expected hemoglobin amount in a given individual the mean values of the hemoglobin.aniount in “c of the body weight, published in an earlier article (Sjnstrand 1949), were used. These are for the adult woman 0.86 5- and for the adult man 1.16 %. In especially fat or especially thin individuals, this per cent value should be reduced or increased respectively, as is evident from the earlier published analysis of the relation between the amount of hemoglobin and the body weight. Here one can proceed from the ideal weight as calculated from the height.

The relative hemoglobin values were determined in finger “capillary” blood, and with the Sicca hemometer. 100 7 G corresponds to 15.4 g- of hemoglobin in 10 ml of blood. If the total amount of hemoglobin is divided by the hemoglobin per cent value, the blood volume is obtained. As the

21 5

Scan

d J

Clin

Lab

Inv

est D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y N

yu M

edic

al C

ente

r on

11/

22/1

4Fo

r pe

rson

al u

se o

nly.

216 T. SJOSTRAND

Hb 70 value obtained from finger blood is not re- presentative of the Hb concentration in the entire blood vessel system, such a determination will not be entirely accurate. In this way one can, however, obtain values comparable to one another from dif- ferent persons.

RESULTS

The relationship between the total and relative heinogobin values in hcinorrhagic anemia

In 2 cases of duodenal ulcer with large hemorrhages, the hemoglobin amount was determined the days immediately following the hemorrhage, and also during the restitu- tion. One case was treated with blood trans- fusions, the other was not.

I . . 0 , " . ' I

50 100 96 re1 Hb

Fig. 1. The relation between the estimated relative hemoglobin values and the corresponding values calculated from the determined total hemoglobin

amount on two cases of hemorrhagic anemia.

Fig. 1 illustrates the relation between the total hemoglobin values in % of the values

calculated for each individual, and the rela- tive Hb values (Haldane values), in the 2 cases of hemorrhagic anemia. It can be seen that the regression lines do not tend to- wards the zero point, which would be expec- ted if the relative values were a direct quanti- tative measure of the total decrease of hemo- globin. The displacement of the regression lines shows that the plasnla volume does not increase correspondingly to the loss of blood, but that the total amount of blood is smaller than before the hemorrhage. During resti- tution the normal relationship and blood amount are successively and parallelly re- attained. At a loss of about half the hemo- globin amount, the relative H b value was thus 62 % in one of the cases. This means that the total blood volume is nearly 20 70 smaller than the normal value as calculated from the body weight, i. e. about 1 liter. As the determinations were made during a period of 30 days, and the first values were obtained a couple of days after the hemor- rhage, it is evident that the decrease in blood volume is not only an acute occurrance in connection with the hemorrhage.

The repeated determinations of total hemoglobin have also possibilitated a deter- mination of the daily production of hemo- globin above the destruction. This was in one of the cases 4.0 g (the increase caused by transfusion of course being subtracted), and in the other 5.2 g. Such values may be of interest in many respects. They are a direct quantitative measure of the blood production, and might be used for a balance calculation of the production and desinte- gration respectively of the hemoglobin.

Scan

d J

Clin

Lab

Inv

est D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y N

yu M

edic

al C

ente

r on

11/

22/1

4Fo

r pe

rson

al u

se o

nly.

DETERMINATION O F THE TOTAL AMOUNT OF HEMOGLOBIN I N ANEMIA A N D POLYCYTHEMIA 2 17

The relationship betwecn the hemoglobin amount and the relative hemoglobin value i l k some cases

of chronic anemia

Fig. 2 shows the relationship between total H b and relative H b in four cases of chronic anemia. One of these was a hemolytic

100 %rel .Hb

Fig. 2: The relation between relative Hb-values and from the total hemoglobin amount calculated values on four cases of chronic anemias. 0 and .cases of pernicious zinemia, C) hemolytic anemia,

3 sideropenic anemia.

o--------. , ' ' 1 5 c,

anemia in a case of nephritis, and another a sideropenia. The two remaining were cases of pernicious anemia. As is shown by the figure these chronic anemias display a different characteristic as compared to the hemorrhagic anemias, in that the relative Hb-value very nearly corresponds to the decrease in total hemoglobin. The 2 cases of pernicious anemia, however, present a some- what greater total Hb-value than what could

be expected irom the relative Hb-value whereas the 2 other anemias showed a some- what lower value.

Earlier, Rowntree and Brown (1929) have stated that there is an increased blood volume in pernicious anemia, a statement, however, that is rejected by others.

The difference between the hemorrhagic and the chroiiic anemias as concerns the blood volume, explains the great difference in their respective effect on the general con- dition of the patient. The one case of perni- cious anemia was up and about with a relative Hb-value of 23 Oh, whereas both the hemor- rhagic cases displayed a very poor general condition with relative values of about 55 %. When the blood volume in this case of per- nicious anemia is calculated from the stated figures, it is found to be 930 nil. i. e. 26 "/o greater than the normal as calculated from the body weight. The differences of the blood volumes between the hemorrhagic and the chronic anemias respectively, is of deci- sive consequence to the adaptiveness of the blood circulation. The symptonis of an acute hemorrhagic anemia are chiefly caused by the change in blood volume, and the consequent circulatory disturbance. The diminution of the OL capacity of the blood conies only second in importance. In order to understand the variety of symp- toms in a case of anemia, and be able to evaluate the circulatory adaptability e. g. before a surgical intervention, it is thus of importance to complete the relative hemo- globin values with those of the total hemo- globin amount, and to calculate the blood volume in this way.

Scan

d J

Clin

Lab

Inv

est D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y N

yu M

edic

al C

ente

r on

11/

22/1

4Fo

r pe

rson

al u

se o

nly.

2 1 8 T. SJOSTRAND

Subj.

0 - n . . . . . . . . . . . B - e . . . . . . . . . . . W - e . . . . . . . . . . K - s . . . . . . . . . . . K-n . . . . . . . . . . . C - m . . . . . . . . . . . 0 - m . . . . . . . . . . R - n . . . . . . . . . . . R - n . . . . . . . . . . . R - n . . . . . . . . . . . E-n . . . . . . . . . . . A - n . . . . . . . . . . . E - d . . . . . . . . . . .

u - g . . . . . . . . . . .

- Sex

male male male male

female female female femrle female female female female female female

T a b l e I.

* After treatment with radioactive phosphorus.

?'hc rclatioitship between the total ltemoglobin outouiat and the relative Hb-values in polycythenzia

In Table I, the relative Hb-values, the total hemoglobin amounts, the blood volumes, and the increase of the latter as compared to the value calculated from the body weight, are collected from a number of cases of poly- cythemia. As can be seen, the total hemo- globin amounts are greater throughout, and often considerably greater than what is in- dicated by the relative values. The total blood volume is generally, but not always, considerably increased, the increase varying in amount from case to case.

The relative values show no simple cor- relation to the increase in total hemoglobin, and from a comparison in one and the same patient during treatment with radioactive phosphorus it was found that there was no simple and direct relationship between the total amount of hemoglobin and the relative Hb-values. (Se Fig. 3.)

- B

Hb opt. grams

I I50 a350 1690

1040 1090 1240 930

1055

2000

8 75 485 1270

980 1200

P

B - A n 'Vo of A

53 165 '45 I55 65 118 206 114 117

-6 I 08 113

63

120

Bloodvol. C I D Bloodvol.

- D - C

n o/o of C

4 0 9'

81

64 98 67

I I 2

2

18 0'

7' 62 42 42

An increase of the relative hemoglobin value of up to 110-120 % is now and then found without any increase in the total amount of hemoglobin, and it is evident that such a case is not one of authentic poly- cythemia. Sometimes such cases present great diagnostic difficulties, which is proved by the fact that of the cases hitherto sent to the laboratory with the diagnosis poly- cythemia, two showed no increase in the total Hb-values. In both cases, treatment with radioactive phosphorus had been insti- tuted immediately before admission. This treatment had no effect on the hemoglobin values.

The effect of treatment of polycythemia with radioactive phosphorus can be studied in Figures 3 and 4. In Fig. 3 it can also be seen that a spontaneous regression sud- denly appeared in one of the cases some time before the institution of the phosphorus

Scan

d J

Clin

Lab

Inv

est D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y N

yu M

edic

al C

ente

r on

11/

22/1

4Fo

r pe

rson

al u

se o

nly.

DETERMINATIOX OF THE T0'1 A L AMOUXT OF HEMOGLOBIN IN ANEMIA A N D POLYCYTHEMIA 3 19

tot, Hb

rel. Hb

4h0 2%o 54 Fig. 3. The ainount of Iienioglobin and the relative hemoglobin values 011 a case of polycythetnia.

treated ivith radioactive phospliorus.

treatinent. In the same patient the effect of repeated venesections was also followed, which proved verl; small. In this way deter- ininations of total hemoglobin possibilitate an exact control of the effect of the treat- ment, and a correct estimation of the proper time for instituting treatinent.

DISC LSSlON r . 1 lie investigation has examplified the

l-alue of deteriiiiiiatioiis of the total amount of hemoglobiii in cases of anemia and poly- cythemia. -4s to the :memias, the most 01)-

vious advantage here seeiiis to he that the determitiation possibilitates an estimation of the blood volume, and thereby the possi- bilities of the blood circulation to meet with different demands, perhaps especially in con- nection ivith surgical interventions.

In polycytliemia the determiiiatioii may I)c necessary for a correct diagnosis, as also for the judgiiig of the severity of the case. Deterinination oi the total aiiiount of hemo- globin also makes it possible to discover spontaneous regressions. and to i o l l o ~ the

Scan

d J

Clin

Lab

Inv

est D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y N

yu M

edic

al C

ente

r on

11/

22/1

4Fo

r pe

rson

al u

se o

nly.

220 T. SJ<jSTKAXL)

cu c) a W n

l o t . H b

b r e l H b

The hemorrhagic anemias showed higher relative Hb-values, than what could be cal- culatecl from the total hemoglobin amounts in relation to those calculated from the body weight. In the chronic group, however, two cases of pernicious anemia displayed a lower relative Hb-value. From this it could be calculated e. g. that, at the first examinations, one of the hemorrhagic cases had about i liter (nearly 20 %) smaller blood volume than normal, whereas one of the pernicious anemia cases had about 900 ml (26 %> greater blood volume than normal.

In the two hemorrhagic cases the amount of hemoglobin produced per day above the amount destructed was determined, and found to he 4.0 and 5.2 g respectively.

Fig. 4. The decrease of the amount of hemoglobin :itid the relative hemoglobin values on a case of pol ycythemia, treated with radioactive phosphorous.

effect of a treatment, and also to decide when it is most suitable to institute this treatment.

ri comparison was also made between the relative Hb-values and the total amounts of hemoglobin in a number of cases of poly- cyt heinia.

The relative Hb-values did not correspond to the increase of the total amount of hemo- globin. Also in the individual case, the rela- tive and total Hb-values did not always show a parallel course, e. g. during spontaneous regression or during treatment with radio- active phosphorus. The relative values generally showed a tendency to decrease later than the total values

SUMMA KY The chief value of determining the amount of hemoglobin in cases of anemia seems to lie in that cases of hemorrhage can thus be judged more correctly, which is especially important when a surgical operation has to lie performed, and in that the restitution

‘The total ainouiit of heinoglobiii was cle- termined by an earlier described method i Sjostrand 1948), in two cases of lieinor- rhagic anemia, and four cases of clifferelit types of chronic anemias.

Scan

d J

Clin

Lab

Inv

est D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y N

yu M

edic

al C

ente

r on

11/

22/1

4Fo

r pe

rson

al u

se o

nly.

DETERMINATION OF THE TOTAL A X O U N T OF HEMOGLOBIN IN ANEMIA A N D POLYCYTHEMIA 2 2 !

can be followed cluaiititati\rel>-. In l)ol!-- Finally the author wislic> tt 1 extend his gratitude cythelnia, cletermination of the allloullt of to the followill$ collegues. \\ ho have been kind

enough to send him cases of polycythemia for the hemoglobin can confirm an uncertain tliag- examination : Professor H. Eerglnnd. Dr. S. Ber-

nosis, possibilitate an exact judging of the lin, n r . S. I<allner, ant1 Professor J . \\-aIdenstriim. severity of the case and allow of a control :The iiivestigation has been snpportetl economically of the tendency of the disease ant1 also of by a grant from Therese ant1 Johan .-\ndersson

Memorial foundatioii. the result of administered treatment.

KEFEREKCES

Ko\vntree, L. G. &z Brown, G. E. : The volume of the blood atid plasma in health and disease. Saunders, Philadelphia, 193. (Cit. from Best. C. H. and Taylor, N. B., Physiological Basis o f Medical Practice. \Villiams and Wilkins. Baltimore. 1945.)

Sjostrancl, T. : -k t a physiol. Scantlinav. 15. 711, 1948. Thidem 18. 321. 1949.

Scan

d J

Clin

Lab

Inv

est D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y N

yu M

edic

al C

ente

r on

11/

22/1

4Fo

r pe

rson

al u

se o

nly.