유전성 Elliptocytosis에 있어서의 빈혈과 비장과의 관계

Abstract

[한글]

Splenic Role in Anemia in Hereditary Elliptocytosis

Eung Suk Ohai, M.D.

Departments of Internal Medicine and Physiology

Yonsei University College of Medicine Seoul, Korea

(Directed by Drs. P.Y.Lee, P.H.Lee and Sloan J.Wilson*)

Oval or elliptical erythrocytes can be found normally in vertebrates but in

mammalians they are normal only in camels.

Elliptocytosis in a human was first reported by Dresbach in 1904 and later its

occurrence was frimly established as a Mendelian dominant pattern by Hunter and

Adams (1929) and Cheney (1932). However, Lambrecht(1938) stated that this anomaly

in the human had already been observed by Goltz as early as 1860.

Miller and Lucas (1938) reported that the incidence of the gene in the general

population was under 0.04%. In a review of 400 cases of elliptocytosis, the

majority was found to be asymptomatic and only 12% exhibited the significant

anemia, one of the main features of this disease. The pathogenesis of this anomaly

remains obscure.

The geneses of elliptocytes and of the anemia in elliptocytosis have been studied

by many investigators during the 1930s. Stephen and Tatelbaum (1935) and

Leitner(1939) speculated that the formation of elliptocytes might be an aging

phenomenon of the erythrocytes, while others attributed to an endocrine effect

(Schartum-Hansen, 1935) or to an artefect (Vackova et al., 1937). Many authors

stressed the fact that no definite relationship existed between elliptocytes and

anemia and any association with anemia was entirely conincidental (Lieberherr,

1939; Giffin and Watkins, 1939).

However, Heilmeyer (1950) classified elliptocytosis into three categories;

nonhemolytic, hemolytic without anemia and hemolytic with anemia. The relative

frequency of each group is not yet known. The osmotic fragility of the erythrocytes

in each case varies. Therefore, it is not clear whether or not there is

autohemolysis in elliptocytosis. Moreover, the mechanism of elliptocytes formation

is obscure until some of ultrastructural defect of erythrocytes is demonstrated

(Wyandt et al., 1941; Dacie, 1954; Motulsky, 1954; Wilson, 1955; Lipton, 1955).

Recently, by improved method isotopic technic, it was found that since the

erythrocyte life span in elliptocytosis was shorter than normal, the spleen seemed

to play a part of role on the development of the associated anemia in

elliptocytosis. Thus, the role of spleen became the focus of interest.

The study presented here, therefore, is undertaken to investigater various

aspects of splenic role in the patients of elliptocytosis.

The materials consisted of 6 patients in an American family of Anglo-German

descent. Three of them were symptomatic and recorded as cases 1, 2 and 3; one of

the unaffected siblings was used a s a normal control and is recorded as case 4;

and offspring of cases 1 and 3 which were asymptomatics were recorded as cases 5, 6

and 7. The maternal family history through 5 generations included 8 persons who had

anemia, spleen trouble or gall stone. The cases 1 and 2 each had a splenectomy.

The erythrocytes in elliptocytosis were classified according to the method of

Gunther (1928) and Motulsky (1954) as follows: Type Ⅰ, normal round; Type Ⅱ,

oval; Type Ⅲ, elliptical; Type Ⅳ, rod-shaped; Type Ⅴ, microsphero-elliptical.

Fragility of the erythrocytes was determined by the conventional methods, and the

erythrocyte survival time, the organ surface radioactivity, the splenic mixing rate

of blood and the index of red cell sequestration were determined by the Cr**51

tagging technics of Ebaugh et al. (1953) and Schilling et al. (1955).

Diagnosis of hereditary elliptocytosis was easily made by the demonstration of

elliptocytes in the peripheral blood and by the family history. Cases 1 and 2 were

typed as "hemolytic group with anemia." Case 3 belonged to the "hemolytic group

without anemia." Cases 5, 6 and 7 were asymptomatic, as evidenced by lack of either

hemolysis or anemia.

The peripheral blood picture showed prodominantly type Ⅲ cells in the "hemolytic

group" and prodominantly type Ⅱ cells in the "nonhemolytic group." This strongly

indicates a definite relationship between elliptocytes and hemolysis. Splenectomy

was followed by a restoration in the normal shape of erythrocytes from the

elliptical shape. This suggests that the anemia in elliptocytosis is related to the

effect of spleen in increasing mechanical fragility. There was an increase of type

Ⅴ cells after splenectomy which is similar to that seen in other types of

hemolytic anemia.

The osmotic fragility of elliptocytes whichwas either normal or slightly

decreased was slightly increased after splenectomy. The mechanical fragility was

6.8% to 9.0% in case 1 and 7.0% to 10.0% in case 2 in comparison to a normal of

1.0% to 4.0%. There was no significant difference in the osmotic fragility of

splenic arterial and venous blood. The autohemolytic activities in 48 hours were in

normal range with and without addition of glucose.

The survival time of a normal person's erythrocytes in the patient of

elliptocytosis and of the patient's cells in a normal person showed essentially

normal time range. This result indicates that the hemolysis is neither related to

an intrinsic defect of elliptocytes nor to plasma factors.

The mean survival time of elliptocytes by autotransfusion was 26, 21 and 46 days

respectively in case 1, 2 and 3, whereas survival in cases 5, 6 and 7 was within

normal range. The index of splenic red cell sequestration was 90, 120, 70, 15, 30,

40 and 25 respectively in cases 1, 2, 3, 4, 5, 6, and 7 as compared to 30 to 60 for

normal persons. The splenic mixing rate of blood was markedly delayed in hemolytic

group. The erythrocyte survival time in cases 1 and 2 was restoring to normal after

the splenectomy. Pathologic examination of the removed spleens showed marked

enlargement (960 gm and 1020 gm in weight) and engorged sinusoids and pulps filled

with red cells, which are characteristically found in hemolytic anemia of splenic

origin.

Summary

1. A total of 6 cases of hereditary elliptocytosis in an American family of

Anglo-German descent were studied. 3 were symptomatic and 3 were asymptomatic.

2. The peripheral blood pictures showed a marked increase of the type Ⅲ cells

(elliptocytes) in the hemolytic group of the patients and of type Ⅱ cells

(ovalocytes) in the non-hemolytic group. After splenectomy the abnormal

erythrocytes were restoring to normal and subsequently the hemolysis disappeared.

Therefore, a definite relationship exists between the hemolysis of elliptocytosis

and the activity of the spleen.

3. The mechanism of hemolysis in hereditary elliptocytosis is thought to be due

to a splenic sequestration effect on deformed erythrocytes rather than to any

autohemolytic phenomenon.

[영문]

Oval or elliptical erythrocytes can be found normally in vertebrates but in mammalians they are normal only in camels.

Elliptocytosis in a human was first reported by Dresbach in 1904 and later its occurrence was frimly established as a Mendelian dominant pattern by Hunter and Adams (1929) and Cheney (1932). However, Lambrecht(1938) stated that this anomaly

in the human had already been observed by Goltz as early as 1860.

Miller and Lucas (1938) reported that the incidence of the gene in the general population was under 0.04%. In a review of 400 cases of elliptocytosis, the majority was found to be asymptomatic and only 12% exhibited the significant

anemia, one of the main features of this disease. The pathogenesis of this anomaly remains obscure.

The geneses of elliptocytes and of the anemia in elliptocytosis have been studied by many investigators during the 1930s. Stephen and Tatelbaum (1935) and Leitner(1939) speculated that the formation of elliptocytes might be an aging phenomenon of the erythrocytes, while others attributed to an endocrine effect

(Schartum-Hansen, 1935) or to an artefect (Vackova et al., 1937). Many authors stressed the fact that no definite relationship existed between elliptocytes and anemia and any association with anemia was entirely conincidental (Lieberherr, 1939; Giffin and Watkins, 1939).

However, Heilmeyer (1950) classified elliptocytosis into three categories; nonhemolytic, hemolytic without anemia and hemolytic with anemia. The relative frequency of each group is not yet known. The osmotic fragility of the erythrocytes in each case varies. Therefore, it is not clear whether or not there is

autohemolysis in elliptocytosis. Moreover, the mechanism of elliptocytes formation is obscure until some of ultrastructural defect of erythrocytes is demonstrated (Wyandt et al., 1941; Dacie, 1954; Motulsky, 1954; Wilson, 1955; Lipton, 1955).

Recently, by improved method isotopic technic, it was found that since the erythrocyte life span in elliptocytosis was shorter than normal, the spleen seemed to play a part of role on the development of the associated anemia in elliptocytosis. Thus, the role of spleen became the focus of interest.

The study presented here, therefore, is undertaken to investigater various aspects of splenic role in the patients of elliptocytosis.

The materials consisted of 6 patients in an American family of Anglo-German descent. Three of them were symptomatic and recorded as cases 1, 2 and 3; one of the unaffected siblings was used a s a normal control and is recorded as case 4; and offspring of cases 1 and 3 which were asymptomatics were recorded as cases 5, 6 and 7. The maternal family history through 5 generations included 8 persons who had anemia, spleen trouble or gall stone. The cases 1 and 2 each had a splenectomy.

The erythrocytes in elliptocytosis were classified according to the method of Gunther (1928) and Motulsky (1954) as follows: Type Ⅰ, normal round; Type Ⅱ, oval; Type Ⅲ, elliptical; Type Ⅳ, rod-shaped; Type Ⅴ, microsphero-elliptical.

Fragility of the erythrocytes was determined by the conventional methods, and the erythrocyte survival time, the organ surface radioactivity, the splenic mixing rate of blood and the index of red cell sequestration were determined by the Cr**51

tagging technics of Ebaugh et al. (1953) and Schilling et al. (1955).

Diagnosis of hereditary elliptocytosis was easily made by the demonstration of elliptocytes in the peripheral blood and by the family history. Cases 1 and 2 were typed as "hemolytic group with anemia." Case 3 belonged to the "hemolytic group without anemia." Cases 5, 6 and 7 were asymptomatic, as evidenced by lack of either hemolysis or anemia.

The peripheral blood picture showed prodominantly type Ⅲ cells in the "hemolytic group" and prodominantly type Ⅱ cells in the "nonhemolytic group." This strongly indicates a definite relationship between elliptocytes and hemolysis. Splenectomy

was followed by a restoration in the normal shape of erythrocytes from the elliptical shape. This suggests that the anemia in elliptocytosis is related to the effect of spleen in increasing mechanical fragility. There was an increase of type

Ⅴ cells after splenectomy which is similar to that seen in other types of hemolytic anemia.

The osmotic fragility of elliptocytes whichwas either normal or slightly decreased was slightly increased after splenectomy. The mechanical fragility was 6.8% to 9.0% in case 1 and 7.0% to 10.0% in case 2 in comparison to a normal of 1.0% to 4.0%. There was no significant difference in the osmotic fragility of splenic arterial and venous blood. The autohemolytic activities in 48 hours were in normal range with and without addition of glucose.

The survival time of a normal person's erythrocytes in the patient of elliptocytosis and of the patient's cells in a normal person showed essentially normal time range. This result indicates that the hemolysis is neither related to an intrinsic defect of elliptocytes nor to plasma factors.

The mean survival time of elliptocytes by autotransfusion was 26, 21 and 46 days respectively in case 1, 2 and 3, whereas survival in cases 5, 6 and 7 was within normal range. The index of splenic red cell sequestration was 90, 120, 70, 15, 30,

40 and 25 respectively in cases 1, 2, 3, 4, 5, 6, and 7 as compared to 30 to 60 for normal persons. The splenic mixing rate of blood was markedly delayed in hemolytic group. The erythrocyte survival time in cases 1 and 2 was restoring to normal after

the splenectomy. Pathologic examination of the removed spleens showed marked enlargement (960 gm and 1020 gm in weight) and engorged sinusoids and pulps filled with red cells, which are characteristically found in hemolytic anemia of splenic

origin.

Summary

1. A total of 6 cases of hereditary elliptocytosis in an American family of Anglo-German descent were studied. 3 were symptomatic and 3 were asymptomatic.

2. The peripheral blood pictures showed a marked increase of the type Ⅲ cells (elliptocytes) in the hemolytic group of the patients and of type Ⅱ cells (ovalocytes) in the non-hemolytic group. After splenectomy the abnormal erythrocytes were restoring to normal and subsequently the hemolysis disappeared.

Therefore, a definite relationship exists between the hemolysis of elliptocytosis and the activity of the spleen.

3. The mechanism of hemolysis in hereditary elliptocytosis is thought to be due to a splenic sequestration effect on deformed erythrocytes rather than to any autohemolytic phenomenon.