Acta Med Scand 202: 11-15, 1977

Alcohol Consumption and Hematology

MBrten Myrhed, Lena Berglund and Lars Erik BBttiger

From the Department of Clinical Alcohol and Drug Research and ?he Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden

ABSTRACT. A number of hematologlcnl variables have been Investigated and followed du- a hoepltd stay in a group of 34 nondrrhotlc male alcoholics after acute drinking bouts. The most promlnent nnd- lngs were a rise In retlculoeytes, a fail In serum Iron and a rise in WBC, especlaily with napect to the lymphocytes. HB and hematocrft valuea both fell dur- ing hoepltsllzatlon, whlle ESR and serum hnptogio- bln r w . No change WIB observed In the platekt count. It Is concluded that alcohol han marked effects on the hematological system even in subjects without serious Uver damage. The results underline the Im- portance of an adequate knowledge of the patient’s alcohol habits In the lnvestigatlon of obscure hematologic abnormalities.

Alcohol ingestion (alcohol is used here as a synonym for ethanol) has been implicated in the development of a number of hematological ab- normalities (3), including vacuoles in erythro- blasts (8, 9), megaloblastic anemia (8, 15), tran- sient hemolysis with hyperlipidemia (16, 17), a re- versible type of sideroblastic erythropoiesis (6, 7) and thrombocytopenia (4, 9). Changes in the myelopoiesis have been reported as well (1, 2, 11). Most of these studies have been performed either in vitro, in laboratory volunteers, in skid-row alcoholics or in subjects with alcohol-induced liver cirrhosis.

The purpose of the present investigation is to report on changes in a number of hematological variables during a hospital stay in alcoholdepend- ent subjects without serious liver damage.

STUDY BASE The present subject group was collected at the Depart- ment of Clinical Alcohol and Drug Research, Karolinska

Hospital. A total of 34 consecutively admitted male pa- tients, aged 2&61 years (mean 41, S.D. 10) were studied (Table I). None had or developed delirium tremens while in the hospital, and the d o r i t y were gainfully employed and apparently socially well adapted. According to the policy of the Department, all subjects were admitted vol- untarily. Nobody was suffering from hepatic complica- tions such as cirrhosis of the liver. The liver function tests are shown in Table 11. No patient had attracted particular hematologic interest earlier and all denied ingestion of un- usual beverages such as cooking fluids or rubbing alcohol. None had taken any medications known to induce hema- tological complications. The alcohol intake has been as- sessed in grams of absolute alcohol ingested per day, as described previously (12). The mean daily intake during the weeks before admission amounted to 244+ 102 g (250 5-75 cm* of hard liquor).

Blood samples were drawn on the day of admission, on the seventh day and, if the patient was still hospitalized, after three weeks. AU analyses were performed at the Department of Clinical Chemistry, Karolinska Hospital, with their routine methods. In the presentation of the separate variable the number of subjects varies. This is due to the fact that only part of the material was analysed with respect to some variables; in a few cases it is due to lost samples. The mean intrapair diRerences were ex- amined using Student’s paired I-test (13).

RESULTS As it was considered of interest to see whether or not a high alcohol intake before admission gave pronounced hematologic changes, the subjects were assessed in relation to daily consumption. This approach showed only weak correlations and consequently the results have been pooled for the whole group.

Erythropoiesis Hb values on admission and after one week’s hospi- tal stay were 148 and 141 g/l, respectively (Table 111). Hematocrit showed a mean of 43.6% on the

Acta Mcd Scand 202

12 M . Myrhed et al.

30- Age ( Y . ) n

20-30 4 3 140 I I 20 - 41-50 13 5 1-60 5 >60 I

Total 34

25-

1s-

10-

5 -

first day and 41.9% a week later. The subjects who

Table 1. Age distribution R ETlC U LOC Y TE S %.

were in-patients for 3 weeks did not show a return to the admission values. No significant differences were found in erythrocyte counts, nor in MCHC and MCV.

The greatest disparities were found with respect to reticulocytes and serum iron (Table 111). A nor- mal mean value of about 1 % for reticulocytes was observed on admission but this rose to 1.85% dur- ing the first 7 days (Fig. I ) . In the rather small group of 9 subjects followed for 3 weeks, the mean de- creased to I . 19%. There was a highly significant fall in serum iron from 27.5 to 17.7 pmol/l during the first week (Table 111). The same tendency was found among those followed for 3 weeks. It may be noted that 4 out of 22 subjects had levels 250 pmol/l on admission (Fig. 2).

Myelopoiesis From the present study it is obvious that ethanol ingestion affects the white blood picture. Thus, the WBC was 6.26 on admission and 7.20x lOa/l after 7 days in hospital (Table IV). About the same differ- ence between means was observed for those who were in-patients for 3 weeks. Although there was a rise in the number of neutrophils in both groups, it

-- 1 7 Days

Fig. 1. Changes in reticulocyte levels during hospital stay.

was not significant. This implies that the greatest differences were found for lymphocytes. Out of 22 subjects, 19 had a lower value on admission than on the seventh day, the means being 1.85 and 2 . 4 8 ~ 109/1, respectively. A similar trend was observed in the group kept off ethanol for at least 3 weeks.

Platelet count and ESR No significant differences were observed in the mean values of platelet counts (Table IV). Five out of 26 patients, however, had thrombocytopenia (70, 110, 106, 117 and I1Sx 109/1) on admission. I n all five the values became normal within the first week.

From Table IV it can be observed that ESR is lower immediately after the cessation of drinking than during the following weeks, the present means being 9 on admission and 14 mm after one week in hospital. Similar tendencies were seen among those who remained in hospital for the longer period, the levels in this group being 10 and 16 mm. respec- tively.

Haptoglobin values were strongly affected by

Table 11. Liver function tests in alcohol-dependent subjects Mean values, S.D. given within parentheses

On admission After 1 week n Reference values

S-ASAT (pkat/l) 1.53 ( 1 . 1 1 ) 0.82 (0.50)*** 28 0.204.70 S-ALAT (pkatll) O.% (0.57) 1.01 (0.61) 27 0.10-0.70

S-ALP (pkat/l) 3.84 (1.78) 3.03 ( I . l6)** 28 0.84.0 S-LD (pkat/l) 8.70 (2.33) 6.53 ( I .25)*** 28 3.5-7 .O

S-GT (pkat/l) 5.98 (8.90) 4.18 (5.56)** 25 0.1-1 .o S-bilirubin brnol/l) 9.0 (5.9) 5.9 (3.2)** 28 0-2 1

**p<O.Ol, ***p<o.001.

Alcohol consirmption and hematologp I3

50 -

45.

40.

35-

30-

25-

20-

15-

10-

S-

Table 111. Erythropoiesis in alcohol-dependent subjects

Mean values, S.D. given within parentheses

Reference On admission After 1 week n On admission After 3 weeks 11 values

Anemia is for many reasons frequently found in alcoholic patients (3). Of major causes, gas- trointestinal bleeding, extracorpuscular hemoly- sis, chiefly localized to the spleen, but also a di- rect toxic effect of alcohol on the erythropoiesis in the bone marrow may be mentioned (10). In the present study, anemia was not a common finding in the group, either on admission or during the hospi- tal stay. However, the effects of alcohol on Hb and hematocrit values could be clearly observed, as both the means decreased significantly after the cessation of drinking. These changes are probably mainly ascribable to the diuretic actions of ethanol (14), as is the effect on the ESR.

Megaloblastic anemia in alcoholics has been de- scribed by e.g. Hines (6) and Eichner and Hillman (5 ) . In the present study no definite conclusions concerning this hematologic abnormality can be drawn as the bone marrow of the subjects was not L ,

1 7 Days studied, but the high MCV values in the peripheral

148 (16) 141 (13)** 32 145 (19) 138 (11) 12 140-170 (dl) Hematocrit (%) 43.6 (3.8) 41.9 (3.7)*** 32 43.2 (4.7) 41.1 (3.2) I2 42-50 mc x 10'2/1 4.50 (0.49) 4.31 (0.60)* 30 4.57 (0.49) 4.40 (0.37) I I 4.5-5.5 MCHC (dl) 339 (19) 336 (12) 31 337 (21) 335 (10) I 1 320-360

I I 7 6 % Reticulocytes(%) 1.03 (0.64) 1.85 (0.13)** 25 0.98 (0.7) 1.19 (0.49) 9 0.2-2.0 Serum iron 27.5 (15.6) 17.7 (6.3)*** 22 24.1 (17.6) 13.5 (6.0)* 7 14-32

MCV (fl) 98 (10) 98 (11) 29 % (9) 95 (9)

(~~mol / l )

14 M . Myrhed et al.

Table IV. Myelopoiesis and some other hematologic variables in alcohol-dependent subjects Mean values, S.D. given within parentheses

Reference On admission After 1 week n On admission After 3 weeks n values

WBC x lV/l 6.26 Segmented leuco- 3.34 cytesx lV/l

Lymphacytesx 1V/l 1.85 Plateletsx IV/I 229 ESR ( d h ) 9 Haptdobin (ell) 1.24 Vitamin B,, 759 @mol/l)

Folate (nmolll) 14

(2.43) (1.84)

(0.72) (82) (5) (0.7 1) (290)

(8)

7.20 3.62

2.48 234 14 1.70 724

17

(2.08)** 32 (1.27) 22

(0.89)". 22 (86) 27 (9)** 28 (0.71)*** 25 (242) 26

(9) 25

6.95 4.01

1.95 232 10 0.91 878

15

(2.48) 8.26 (1.97) 4.55

(0.50) 2.45 (74) 227 (5) 16 (0.62) 1.41 (376) 766

(10) 15

12 4-9 1 1 1.6-6.3

1 1 0.8-4.1

12 2-10 10 0.4-1.8 13 110-660

12 7 4

9 150400

ble. However, no reduction in the size of RBC appeared during the time in hospital.

The most prominent findings concerning the erythropoiesis in the present study are in respect of reticulocytes and serum iron, which both changed significantly. This is in accordance with earlier studies reporting increased serum iron levels during the period of alcohol intake but a fall after its termi- nation (5 , 7). It is obvious that alcohol disturbs the erythropoiesis even in these rather healthy al- coholdependent subjects, but that it is soon re- stored after the cessation of alcohol intake and is followed by a reticulocytosis and a fall in serum iron.

The present study clearly shows that ethanol af- fects the while blood picture ah well. Thus, a re- duction was found with respect to total WBC, segmented leucocytes and lymphocytes. The most marked decrease appeared in lymphocytes. The re- sults are of interest, as rather few reports dealing with leucopoiesis have been published. Alcoholics have been reported to be more susceptible to pneumonia than the general population ( I I) , and as a reduced leucocyte response after an injection of endotoxin was demonstrated in that study, it was concluded that alcoholics have a diminished bone marrow reserve of leucocytes. Alcohol has also been shown to increase susceptibility to experimen- tal infections in animals and was found to produce a profound depression in the rate of leucocyte mobili- zation into traumatized skin lesion in normal people (2). However, the phagocytic ability of the leuco- cytes was unaffected by alcohol in the latter study.

There was no relationship between alcohol intake and a depressed mean platelet level on admission in

the present study. However, five subjects displayed pathologically low values on admission. They all recovered during the first week in hospital. Thrombocytopenia has frequently been observed in study populations of alcoholics and has usually been considered to be a complication of cirrhosis or attributed to inadequate dietary intake of folic acid. Figures varying from 14 % (9) to 81 % (4) have been reported. Lindenbaum and Hargrove (9) described 10 episodes of thrombocytopenia in five chronic alcoholics with delirium tremens. In all cases the platelet count rose rapidly, returning to normal within 3-7 days, and was followed by a subsequent thrombocytosis. When ethanol was administered to human volunteers, the platelet count was markedly depressed during the 3rd-5th week of alcohol inges- tion in four of nine subjects (10). At present it must be assumed that the effects of alcohol are twofold: firstly by a suppression of the production in bone marrow and secondly a shortening of the survival time (3).

There were no indications of reduced levels of vitamin BIZ and folate in the present subject group. Concomitant folate deficiency, macrocytosis and other hematological abnormalities in alcoholics have been described by some authors (6). It has been reported that some alcoholic subjects with a decreased serum folate activity have abnormally low values of serum vitamin BIZ activity but high values of serum vitamin BIZ could be observed at all levels of serum folare as well.

To sum up, the present report deals with hematological effects in a group of non-cirrhotic men with a high alcohol intake. The results indicate that significant changes are found with respect to

Acta Med Scond 202

Alcohol consumption and hematology 15

reticulocytes, serum iron, Hb, hematocrit, WBC including segmented leucocytes, lymphocytes, ESR and haptoglobin. The results underline the im- portance of an adequate knowledge of the patient's alcohol habits in the investigation of obscure hematologic abnormalities.

REFERENCES 1. Beard, J. D. & Knott, D. H.: Hemopoietic response to

experimental chronic alcoholism. Am J Med Sci 252: 518. 1966.

2. Brayton, R. G., Stokes, P. E.. Schwartz, M. S. & Louria, D. B.: Effect of alcohol and various diseases on leukocyte mobilization, phagocytosis and intracel- lular bacterial killing. N Engl J Med 262: 123, 1970.

3. BBttiger, L. E.: Alcohol and the blood. Scand J Haematol 10: 321, 1973.

4. Cowan, D. H. & Hines, J. D.: Thrombocytopenia of severe alcoholism. Ann Intern Med 74: 37, 1971.

5. Eichner, E. R. & Hillman. R. S.: The evolution of anemia in alcoholic patients. Am J Med 50: 218, 1971.

6. Hines, J. D.: Reversible megaloblastic and sideroblas- tic marrow abnormalities in alcoholic patients. Br J Haematol 16: 87, 1%9.

7. Hourihane, D. 0. B. &Weir, D. G.: Suppression of erythropoiesis by alcohol. Br Med J 1: 86, 1970.

8. Jarrold, T., Will, J. J., Davies, A. R., Duffey, P. H. & Bnunschreiber, J. L.: Bone marrow-erythroid mor- phology in alcoholic patients. Am J Clin Nutr 2 0 716, 1967.

9. Lindenbaum, J. & Hargrove, R. L.: Thrombo- cytopenia in alcoholics. Ann Intern Med 86:526, 1968.

10. Lindenbaum, J. & Lieber, D. S.: Hematologic effects of alcohol in man in the absence of nutritional deti- ciency. N En@ J Med 281: 333, 1969.

11. McFarland, W. & Libre, E. P.: Abnormal leucocyte response in alcoholism. AM Intern Med 59: 865, 1%3.

12. Myrhed, M.: Alcohol consumption in relation to factors associated with ischemic heart disease. Acta Med Scand (Suppl) 567, 1974.

13. Siegel, S.: Nonparametric statistics. McGrawhill, New York, Toronto and London 1956.

14. Wallgren, H. &Barry, H. 111: Actions of alcohol, part 1-11. Elsevier, Amsterdam, London and New York 1970.

15. Waters, A. H., Morley, A. A. & Rankin, J. G.: Effect of alcohol on hemopoiesis. Br Med J 2: 1565, 1966.

16. Westerman, M. P., Balcerzak, S. P. & Heinle, E. W.: Red cell lipids in Zieve's syndrome: Their relation to hemolysis and to red cell osmotic fiagility. J Lab Clin Med 72: 663, 1968.

17. Zieve, L.: Jaundice, hyperlipemia and hemolytic anemia: A heretofore unrecognized syndrome as- sociated with alcoholic fatty liver and cirrhosis. Ann Intern Med 48: 471, 1958.

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