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The A2 hemoglobin in hematological diseases
CLINICA
THE
CHIMICA
489
ACTA
A, HEMOGLOBIN
IN HEMATOLOGICAL
DISEASES
SUiMhIARY
Values of the A, hemoglobin were determined in 20 normal subjects patients with various hematological diseases using paper electrophoresis. values of A, l~en~oglobin were estimated in normal Slightly elevated mean values were found in patients other hematological diseases they did not differ from ficantly higher values of the A, component were found
and in 160 The mean
subjects to be 3.20 T o.gSSb. with myelofibrosis, while in the those of normal subjects. Signiin the following four nonthalas-
semic patients: in a male patient with erythroleukemia, in a woman with chronic myelosis, in a woman with myelofibrosis, and in a man with panmyelopathy. In two thalassemic patients of South European ancestry elevated values of A, hemoglobin were found repeatedly.
IXTRODUCTION
revealed In 1955, Kunkel and Walleniusls, using starch block electrophoresis, a minor component of hemoglobin, designated as the A, hemoglobin. The A, hemoglobin consists of two tl polypeptidic chains, which proved to be identical with z chains of the major component A, and of two 6 chains different from the /I chains of the major componentr7. For quantitative determination of hemoglobin A, various types of zone electrophoresis can be employed, e.g. paper electrophoresisl, starch block electrophoresis11~1a~z3~z5, cellulose acetate electrophoresis13p27, and polyacrylamide gel electrophoresis10~24. Though the results obtained varied according to the method used, most authors found that the mean values of hemoglobin A, in normal adults ranged from 2.5 to 3.57; of the total hemoglobin, with an extreme value not exceeding 57,,, Increased values of hemoglobin A, have been considered to be pathognomonic of p thalassemia minor. With the exception of @ thalassemia, a number of authors could not find increased values of the minor component*2~13~20~21~~~. An increased amount of the A, hemoglobin fraction was found only in a few cases of recurrent pernicious anemiaIs, while in other hematological disorders it was found only exceptionally: in one case of hereditary spherocytosiP and in one case of acute myeloid leukemiaz5. An increase of hemoglobin A, was also observed in patients with hemoglobin Ziirich26. * Director: Sciences.
I’rof.
J. HofzjSi,
D. SC., Corwsponding-
Member
of the Czechoslovak
Acatlcm)-
of
BRABEC
490 Decreased
amounts
of hemoglobin
A, were found in newborns9T13. This
i’t al.
low
value was observed to increase gradually and reach the adult level by the fourth and fifth month of life, as suggested by Erdem and AksoyD, or-according to Wheatherall et al.32-within the sixth and the twelfth month. A low level of the hemoglobin A, fraction in adults was observed in the following hereditary states: (a) in some forms of thalassemia, such as CI thalassemia or in certain cases of 17 thalassemia7y13>16; (b) when abnormal variants of hemoglobin A, such as hemoglobin A’, or hemoglobin Flatbush are presentZ2; (c) in th e p resence of hemoglobin Lepore in the heterozygous statesI; (d) in cases with the hereditary persistence of fetal hemoglobin33. In the group of acquired diseases, decreased levels of hemoglobin A, were reported in some cases of iron deficiency anemiaR,lR and in one case of erythroleukemia2. In the present paper, detailed results of a study of a group of patients with various blood diseases are reported. MATERIAL
AND
METHODS
Patients 20 healthy subjects (blood donors) and 160patients with various hematological diseases were examined. Diagnoses were based on clinical and laboratory examina-
tions. Groups of patients according to their diagnoses are given in Table I. Patients with an increased level of hemoglobin A, were examined repeatedly at different time intervals. Patients treated with blood transfusions did not receive any transfusions at least 3 months before the determination
of hemoglobin
A,.
\~ALUES OFHEMOGLOBIS AZ IN BL00,~DISEASES AN” IS KORMAI.SUBJECTS Gvoup
$1
Diagnosis
Polycythemia Myelofibrosis Chronic myelosis Acute myelosis Chronic lymphadenosis Lymphogranuloma Lymphoreticulosis Hereditary spherocytosis Paroxysmal nocturnal hemoglobinuria Autoimmune idiopathic hemolytic anemia Hypochromic hyposideremic anemia Panmyelopathy Hypoplastic pancytopenia Erythroleukemia Thalassemia (minor) Normal subjects
I L 3 4 2
; 9 10
II I2 13 ‘4 75 16
n = number of subjects examined R = mean value; fs = standard deviation * = significantly increased values (>R+- 3s) -+ = mean value of three examinations -I. = mean value of four examinations
Cli12.
Chim.
Ada,
28
(79701 489-494
TZ 12 14 II II IO II 77 s 12 ‘1 ‘3 T1
I L 2”
HffJ
z Y_
R
+:s
varzgr
3.5 3.X 3.5 3.2 3.4 3.2 3.4 3.2 3.4 3.3 3.1 3 .5 3.4
0.36 0.75 I.35
r.Hp.t.1 2.+-5.x* 1.74.fi*
0.72
L.L&d..f
0.75 0.67 0.56
2.0-4.4
0.p
r.g-4.2
0.49 0.5x
r.3-4.” ‘.rF+..j L..1~_3.7
F3.1+
_
6.0-’
0.5s
3.1
0.51 0.X.$ 0.66
I.%4.3 L.5-_+.2
2.7-5.7* r.9-4.2 7.6*-X.x* 5. j*-b.q* Z.IF4.3
z
z s 0 .4+ $ L ?
age, years
Name
Chronic myelosis
hiyelofibrosis
Panmyelopathy
Thalassemia (minor)
Thalassemia (minor)
S.A. 67 9
N..4. 56 0
W.J. 57 s
s.L.* 52 ?
B.M.** 22
$
Erythroleukemia
S.J. 81 $
DiLZptOSiS
HEMATOLOGICALDATAIK
* woman of Greek ancestry. ** patient of Bulgarian ancestry.
4
3
2
Patient NO.
S&X ~____
II
CLINICALAND
TABLE
years
years
22
22
52 years 53 years
23 mo. 26 mo.
60 mo. 72 mo.
mo. r5 mo.
12
3 months 3.5 mo. 4 months
Duration of disease+
7.8 7.5
7.3
IO.1
II.4
II.2
9.8 9.1
‘4.5 II.7
7.5 7.0
6.0
g%
Hb
27 26
30.5 28
34 32
32.5 29.5
43 38
29
29
24
Ht 0’ /O
A,
3.65 3.50
4.02
4.53
3.62
2.55 3.16 3.10
Erythr. 1oooinl
19 28
29 44
48 49
90 77
‘4 8
67 38
88
“ill0
Ret.
4.0 3.7
6.1
5.2
I.4 1.0
14.2 9.0
33.6 5.’
3.7 3.4 3.0
LtY‘WOcytes Iooolnl
186 enough
240 enough
2:
35 33
enough
‘67
85
i4
Thrombocytes 1000/?21
+ at the time of examination. ++ Busulphanum [r,4-bis(methylsulfonyloxy)-n-butanum].
Prednison, transfusions
Prednison, transfusions
Mylecytan, Spofa++
Prednison
Therapy
PATIENTSWITHINCREASEDVALUESOFHEMOGLOBIN
20
18
‘7
12
E~Y WV days
T,iz
6.4 6.2
6.0 5.5
5.7 5.5
5.8 5.3
7.5
8.8
7.6 8.8 8.0
$ K vl
%
u ;
HbA,
492
BRABEC et a/.
Preparation of the hemolysate Erythrocytes from blood freshly collected to heparin were washed three times with physiologic saline solution and hemolyzed in a tenfold volume of distilled water with the addition of chloroform. After centrifugation, the pure solution of hemoglobin was obtained. Electro$horesis of the hemoglobin Electrophoretic analysis of the hemolysate
was performed
on Whatman
Xo. I
paper using a discontinuous buffer system. The buffer solution used for paper was Tris-borate-EDTA buffer, pH 8.8, the electrode vessels were filled with veronalacetate buffer, pH 8.6. Separation was carried out for 1611at 1.5 mA/5 cm wide paper. After completion of the electrophoresis, the electropherograms were dried and stained using the usual technique with bromphenol blue. Zones of the hemoglobin A and A, patterns were cut out and eluted in a 2”/0 Na,CO, solution in methanol. The concentration of hemoglobin A, was estimated photometrically at il = 595 nm. RESULTS
The mean values and the range of the hemoglobin A, content in various hematological diseases and in normal adults are given in Table I. Significantly increased mean values of hemoglobin A, (@ < 0.05) were found only in patients with myelofibrosis. The mean values observed in other hematological disorders did not differ from those of normal adults. Even in the group of patients with myelofibrosis most patients had A, hemoglobin values within the normal range; a significantly higher level of hemoglobin A, was found only in one female patient and the values of five other patients approached the upper limit of the normal range. In the other diagnostic groups elevated values of hemoglobin A, were found only exceptionally. Results of the determination of hemoglobin L4,, clinical and laboratory data of patients with increased values of hemoglobin A, are given in Table II. In a patient with erythroleukemia (S.J.) markedly increased values of hemoglobin A, were found three times in a month. A female patient (S.A.) with chronic myelosis was examined twice within three months; at each of these examinations significantly higher values of hemoglobin A, were found. In a female patient (N.A.) with myelofibrosis slightly elevated values of hemoglobin A, were demonstrated twice in a year, and in a patient (W.J.) with panmyelopathy twice in four months. Increased values of hemoglobin A, were repeatedly found in two patients with thalassemia. DISCUSSIOY
In the introductory part of this paper it was pointed out that mean values as well as the range of the A, hemoglobin content depend on the method used. In this study the determination of the minor A, component was performed by paper electrophoresis. The resulting mean values of 3.2 & 0.58O/, are in agreement with the results obtained by Aksoy et al.’ who used the same technique. We can assume that increased values of reticulocytes and of the young erythrocyte population do not induce any changes in the amount of hemoglobin A,. The results of our examinations of the minor A, component in some hemolytic states,
Hb A,
IN BLOOD
493
DISEASES
where values of hemoglobin A, were found to be normal in spite of increased values of reticulocytes, also favour this assumption. Boyd et aL6 did not find any difference between the A, hemoglobin content of old and young red blood cells either. Slightly increased mean values of hemoglobin A, were found in the group of our patients with myelofibrosis. This finding, however, did not seem to be typical of myelofibrosis, as only one female patient had significantly elevated values, while the other patients showed values within the normal range, though in half of the patients they reached the upper normal limit of this range. Contrary to some authorssy18 we did not find lower values of hemoglobin A2 in hypochromic hyposideremic anemias; a possible explanation for this finding may be that our patients had light to medium degrees of anemia. Increased values of the minor component A, were found in 4 nonthalassemic of the examined patients. Strikingly, two of them had leukemia, patients, i.e. 2.5:; one had myelofibrosis (a state closely related to leukemia), and one panmyelopathy (i.e. pancytopenia with rich bone marrow) which is sometimes regarded as a preleukemic state. A number of papers in the literature have reported on various hemoglobin anomalies in leukemia, such as increased levels of fetal hemoglobin, the occurHemoglobin anomalies were most frerence of abnormal hemoglobin, etc.3~4~28~30~34. 3y4134.Our finding of a highly increased quently found especially in erythroleukemia value of hemoglobin A, in patients with erythroleukemia is at variance with Aksoy and Erdem2 who found a very low level of this minor component in their patients with the same disease. At the present time we cannot decide whether hemoglobin anomalies found mostly in leukemia (but also in some other acquired diseases) are conditioned by genetic or acquired factors. Beaven et al.& suggest that the leukemic state sometimes upsets the equilibrium of hemoglobin chain synthesis, resulting in a relative excess of non-alpha type chains. They also claim-in contrast to other authors28-that certain hemoglobin anomalies do not necessarily imply the operation of genetic factors.
11. .&KSOY AiXD s. ERDEhl, >L'akYc', 213 (1967) j22. G. 51.REAVEK,hl. J. ELLIS AND J. C. lvHITE,BYIt.J. Ham?ato/.,6 (1960) 201. G. H. BEAVEK, B. L. STEVEXS, r\‘. I)AR.CE ASD J. C. bT:HITE, l~atzc?,r, 199 (1963) A. H. BIERMAX AXD A. ZETTNER, Aww. ,J. Clin. Pathol.. s,Y (1967) 139. E. M. How, L). R. THOMAS, B. F. HORTOK AXD T. H. J. HrrshfAN, C.kz. Chim.
1297.
Acta,
16 (1967)
Uvz;. ,J. Harmatol.,
6 (1960)
is.F. E. R. y%i. \‘. RI. .4. 11. H. G.
HUEHNS,
1:.1'.FL&X,
BUTLER
E.
.L\.“AxI)
17. II.
SHOOTER,
ISGRAM ASD -4.0. T\T.STRETTOX, Xatatrf, 190 (1961) 1079. JOSEPRSOU, >I. s. AkSRI, L. SIKGER, L). k'ORK1.u AND I<.SIXGER, Blood, I\USKEL ASD c;.WALLENIUS, .SCIP1?CC, ILL (1955) ,288.
Clin. C‘hiw. Acta,
‘3 (1958) 543.
zQ (1970) 485-494
20
H. G. KUNKEL, K. CEPPELISI, \'.&~ELI.ER-EBERHARD AND J. wo~~,J.Cli>z. 1615. 21 G. K. LEE, A. HAUT, G. E. CARTWRICHTAXU ~LI.M.\X~I~TROBE,J. Lab. Clan.
22 23 24
25 26
27 2X
29 30 3I
Invest., 36(19,57) Mrd.,
72. R. C. LEE .UD T. H. J. HUISMAK, Blood, q (1964) 495. M. S. MASRI, A.M. JOSEPHSON AND K. SINGER, Blood, 13 (1958) 533. M. N~KA~~ICHI AND S. RAYMOND. Clin. Chem., g (7963) 135. H.PEARSONAND W.Mc FARLAND, U.S. Armed Forces Med. J., IO (1959) 693. K. I;. RIEDER,W. H.ZINKHAM AKD N. A. HOLTZMAN, Amev.J.Med., 39(1965) 4. R.S. ROZMAN, R.P. SACKS AND R. KATES, J.Lab.Clin.Med.,62 (1963)692. S. SHUSTER, J. R. JONES AND G. C. KILPATRICK, Bvit. &fed. J., ii (1960) 1556. K.SIR.GER, A. ~.CHERNOPP AND L.S1x~~~,Rlood,6(1951) 413. H. STOBBE AND R. SCHOLZ, Schmezz. Med. Wochschv., 96 (1966) 1269. Rlackwell Scientific Publications, D. J. WEATHERALL, Tke Thalassaemia Syndvomes,
1965, P. 117. 32 D. J. WEATHERALL,
33
et d.
BRABEC
494
J.T.
WHEELER
34 J, C. WHITE
64 (1964)
Oxford,
J. A. EDRARDS AND m'.T. A. Don-o~o~,Bvit. :llcd. j., i(1968) 679 AND J.R. KREVANS,BUU. JohnsHopkznsHosp., 109(1961) 217. AND M, ELLIS,BY~~.J. Hawnatol., h(r960) 171.
Clin.Chim. ACta, 7.8(1970) 489-494
THE
CHIMICA
489
ACTA
A, HEMOGLOBIN
IN HEMATOLOGICAL
DISEASES
SUiMhIARY
Values of the A, hemoglobin were determined in 20 normal subjects patients with various hematological diseases using paper electrophoresis. values of A, l~en~oglobin were estimated in normal Slightly elevated mean values were found in patients other hematological diseases they did not differ from ficantly higher values of the A, component were found
and in 160 The mean
subjects to be 3.20 T o.gSSb. with myelofibrosis, while in the those of normal subjects. Signiin the following four nonthalas-
semic patients: in a male patient with erythroleukemia, in a woman with chronic myelosis, in a woman with myelofibrosis, and in a man with panmyelopathy. In two thalassemic patients of South European ancestry elevated values of A, hemoglobin were found repeatedly.
IXTRODUCTION
revealed In 1955, Kunkel and Walleniusls, using starch block electrophoresis, a minor component of hemoglobin, designated as the A, hemoglobin. The A, hemoglobin consists of two tl polypeptidic chains, which proved to be identical with z chains of the major component A, and of two 6 chains different from the /I chains of the major componentr7. For quantitative determination of hemoglobin A, various types of zone electrophoresis can be employed, e.g. paper electrophoresisl, starch block electrophoresis11~1a~z3~z5, cellulose acetate electrophoresis13p27, and polyacrylamide gel electrophoresis10~24. Though the results obtained varied according to the method used, most authors found that the mean values of hemoglobin A, in normal adults ranged from 2.5 to 3.57; of the total hemoglobin, with an extreme value not exceeding 57,,, Increased values of hemoglobin A, have been considered to be pathognomonic of p thalassemia minor. With the exception of @ thalassemia, a number of authors could not find increased values of the minor component*2~13~20~21~~~. An increased amount of the A, hemoglobin fraction was found only in a few cases of recurrent pernicious anemiaIs, while in other hematological disorders it was found only exceptionally: in one case of hereditary spherocytosiP and in one case of acute myeloid leukemiaz5. An increase of hemoglobin A, was also observed in patients with hemoglobin Ziirich26. * Director: Sciences.
I’rof.
J. HofzjSi,
D. SC., Corwsponding-
Member
of the Czechoslovak
Acatlcm)-
of
BRABEC
490 Decreased
amounts
of hemoglobin
A, were found in newborns9T13. This
i’t al.
low
value was observed to increase gradually and reach the adult level by the fourth and fifth month of life, as suggested by Erdem and AksoyD, or-according to Wheatherall et al.32-within the sixth and the twelfth month. A low level of the hemoglobin A, fraction in adults was observed in the following hereditary states: (a) in some forms of thalassemia, such as CI thalassemia or in certain cases of 17 thalassemia7y13>16; (b) when abnormal variants of hemoglobin A, such as hemoglobin A’, or hemoglobin Flatbush are presentZ2; (c) in th e p resence of hemoglobin Lepore in the heterozygous statesI; (d) in cases with the hereditary persistence of fetal hemoglobin33. In the group of acquired diseases, decreased levels of hemoglobin A, were reported in some cases of iron deficiency anemiaR,lR and in one case of erythroleukemia2. In the present paper, detailed results of a study of a group of patients with various blood diseases are reported. MATERIAL
AND
METHODS
Patients 20 healthy subjects (blood donors) and 160patients with various hematological diseases were examined. Diagnoses were based on clinical and laboratory examina-
tions. Groups of patients according to their diagnoses are given in Table I. Patients with an increased level of hemoglobin A, were examined repeatedly at different time intervals. Patients treated with blood transfusions did not receive any transfusions at least 3 months before the determination
of hemoglobin
A,.
\~ALUES OFHEMOGLOBIS AZ IN BL00,~DISEASES AN” IS KORMAI.SUBJECTS Gvoup
$1
Diagnosis
Polycythemia Myelofibrosis Chronic myelosis Acute myelosis Chronic lymphadenosis Lymphogranuloma Lymphoreticulosis Hereditary spherocytosis Paroxysmal nocturnal hemoglobinuria Autoimmune idiopathic hemolytic anemia Hypochromic hyposideremic anemia Panmyelopathy Hypoplastic pancytopenia Erythroleukemia Thalassemia (minor) Normal subjects
I L 3 4 2
; 9 10
II I2 13 ‘4 75 16
n = number of subjects examined R = mean value; fs = standard deviation * = significantly increased values (>R+- 3s) -+ = mean value of three examinations -I. = mean value of four examinations
Cli12.
Chim.
Ada,
28
(79701 489-494
TZ 12 14 II II IO II 77 s 12 ‘1 ‘3 T1
I L 2”
HffJ
z Y_
R
+:s
varzgr
3.5 3.X 3.5 3.2 3.4 3.2 3.4 3.2 3.4 3.3 3.1 3 .5 3.4
0.36 0.75 I.35
r.Hp.t.1 2.+-5.x* 1.74.fi*
0.72
L.L&d..f
0.75 0.67 0.56
2.0-4.4
0.p
r.g-4.2
0.49 0.5x
r.3-4.” ‘.rF+..j L..1~_3.7
F3.1+
_
6.0-’
0.5s
3.1
0.51 0.X.$ 0.66
I.%4.3 L.5-_+.2
2.7-5.7* r.9-4.2 7.6*-X.x* 5. j*-b.q* Z.IF4.3
z
z s 0 .4+ $ L ?
age, years
Name
Chronic myelosis
hiyelofibrosis
Panmyelopathy
Thalassemia (minor)
Thalassemia (minor)
S.A. 67 9
N..4. 56 0
W.J. 57 s
s.L.* 52 ?
B.M.** 22
$
Erythroleukemia
S.J. 81 $
DiLZptOSiS
HEMATOLOGICALDATAIK
* woman of Greek ancestry. ** patient of Bulgarian ancestry.
4
3
2
Patient NO.
S&X ~____
II
CLINICALAND
TABLE
years
years
22
22
52 years 53 years
23 mo. 26 mo.
60 mo. 72 mo.
mo. r5 mo.
12
3 months 3.5 mo. 4 months
Duration of disease+
7.8 7.5
7.3
IO.1
II.4
II.2
9.8 9.1
‘4.5 II.7
7.5 7.0
6.0
g%
Hb
27 26
30.5 28
34 32
32.5 29.5
43 38
29
29
24
Ht 0’ /O
A,
3.65 3.50
4.02
4.53
3.62
2.55 3.16 3.10
Erythr. 1oooinl
19 28
29 44
48 49
90 77
‘4 8
67 38
88
“ill0
Ret.
4.0 3.7
6.1
5.2
I.4 1.0
14.2 9.0
33.6 5.’
3.7 3.4 3.0
LtY‘WOcytes Iooolnl
186 enough
240 enough
2:
35 33
enough
‘67
85
i4
Thrombocytes 1000/?21
+ at the time of examination. ++ Busulphanum [r,4-bis(methylsulfonyloxy)-n-butanum].
Prednison, transfusions
Prednison, transfusions
Mylecytan, Spofa++
Prednison
Therapy
PATIENTSWITHINCREASEDVALUESOFHEMOGLOBIN
20
18
‘7
12
E~Y WV days
T,iz
6.4 6.2
6.0 5.5
5.7 5.5
5.8 5.3
7.5
8.8
7.6 8.8 8.0
$ K vl
%
u ;
HbA,
492
BRABEC et a/.
Preparation of the hemolysate Erythrocytes from blood freshly collected to heparin were washed three times with physiologic saline solution and hemolyzed in a tenfold volume of distilled water with the addition of chloroform. After centrifugation, the pure solution of hemoglobin was obtained. Electro$horesis of the hemoglobin Electrophoretic analysis of the hemolysate
was performed
on Whatman
Xo. I
paper using a discontinuous buffer system. The buffer solution used for paper was Tris-borate-EDTA buffer, pH 8.8, the electrode vessels were filled with veronalacetate buffer, pH 8.6. Separation was carried out for 1611at 1.5 mA/5 cm wide paper. After completion of the electrophoresis, the electropherograms were dried and stained using the usual technique with bromphenol blue. Zones of the hemoglobin A and A, patterns were cut out and eluted in a 2”/0 Na,CO, solution in methanol. The concentration of hemoglobin A, was estimated photometrically at il = 595 nm. RESULTS
The mean values and the range of the hemoglobin A, content in various hematological diseases and in normal adults are given in Table I. Significantly increased mean values of hemoglobin A, (@ < 0.05) were found only in patients with myelofibrosis. The mean values observed in other hematological disorders did not differ from those of normal adults. Even in the group of patients with myelofibrosis most patients had A, hemoglobin values within the normal range; a significantly higher level of hemoglobin A, was found only in one female patient and the values of five other patients approached the upper limit of the normal range. In the other diagnostic groups elevated values of hemoglobin A, were found only exceptionally. Results of the determination of hemoglobin L4,, clinical and laboratory data of patients with increased values of hemoglobin A, are given in Table II. In a patient with erythroleukemia (S.J.) markedly increased values of hemoglobin A, were found three times in a month. A female patient (S.A.) with chronic myelosis was examined twice within three months; at each of these examinations significantly higher values of hemoglobin A, were found. In a female patient (N.A.) with myelofibrosis slightly elevated values of hemoglobin A, were demonstrated twice in a year, and in a patient (W.J.) with panmyelopathy twice in four months. Increased values of hemoglobin A, were repeatedly found in two patients with thalassemia. DISCUSSIOY
In the introductory part of this paper it was pointed out that mean values as well as the range of the A, hemoglobin content depend on the method used. In this study the determination of the minor A, component was performed by paper electrophoresis. The resulting mean values of 3.2 & 0.58O/, are in agreement with the results obtained by Aksoy et al.’ who used the same technique. We can assume that increased values of reticulocytes and of the young erythrocyte population do not induce any changes in the amount of hemoglobin A,. The results of our examinations of the minor A, component in some hemolytic states,
Hb A,
IN BLOOD
493
DISEASES
where values of hemoglobin A, were found to be normal in spite of increased values of reticulocytes, also favour this assumption. Boyd et aL6 did not find any difference between the A, hemoglobin content of old and young red blood cells either. Slightly increased mean values of hemoglobin A, were found in the group of our patients with myelofibrosis. This finding, however, did not seem to be typical of myelofibrosis, as only one female patient had significantly elevated values, while the other patients showed values within the normal range, though in half of the patients they reached the upper normal limit of this range. Contrary to some authorssy18 we did not find lower values of hemoglobin A2 in hypochromic hyposideremic anemias; a possible explanation for this finding may be that our patients had light to medium degrees of anemia. Increased values of the minor component A, were found in 4 nonthalassemic of the examined patients. Strikingly, two of them had leukemia, patients, i.e. 2.5:; one had myelofibrosis (a state closely related to leukemia), and one panmyelopathy (i.e. pancytopenia with rich bone marrow) which is sometimes regarded as a preleukemic state. A number of papers in the literature have reported on various hemoglobin anomalies in leukemia, such as increased levels of fetal hemoglobin, the occurHemoglobin anomalies were most frerence of abnormal hemoglobin, etc.3~4~28~30~34. 3y4134.Our finding of a highly increased quently found especially in erythroleukemia value of hemoglobin A, in patients with erythroleukemia is at variance with Aksoy and Erdem2 who found a very low level of this minor component in their patients with the same disease. At the present time we cannot decide whether hemoglobin anomalies found mostly in leukemia (but also in some other acquired diseases) are conditioned by genetic or acquired factors. Beaven et al.& suggest that the leukemic state sometimes upsets the equilibrium of hemoglobin chain synthesis, resulting in a relative excess of non-alpha type chains. They also claim-in contrast to other authors28-that certain hemoglobin anomalies do not necessarily imply the operation of genetic factors.
11. .&KSOY AiXD s. ERDEhl, >L'akYc', 213 (1967) j22. G. 51.REAVEK,hl. J. ELLIS AND J. C. lvHITE,BYIt.J. Ham?ato/.,6 (1960) 201. G. H. BEAVEK, B. L. STEVEXS, r\‘. I)AR.CE ASD J. C. bT:HITE, l~atzc?,r, 199 (1963) A. H. BIERMAX AXD A. ZETTNER, Aww. ,J. Clin. Pathol.. s,Y (1967) 139. E. M. How, L). R. THOMAS, B. F. HORTOK AXD T. H. J. HrrshfAN, C.kz. Chim.
1297.
Acta,
16 (1967)
Uvz;. ,J. Harmatol.,
6 (1960)
is.F. E. R. y%i. \‘. RI. .4. 11. H. G.
HUEHNS,
1:.1'.FL&X,
BUTLER
E.
.L\.“AxI)
17. II.
SHOOTER,
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