HEMATOLOGY
Pyknocytosis in a Neonate: An Unusual Presentation of Hereditary Elliptocytosis Ugo Carpentieri, M.D.,* Lillian
P.
Gustavson, M.D., Mary Ellen Haggard, M.D.
PYKNOCYTES
are contracted distorted with erythrocytes spiny projections that can be seen in the blood stream during the first three months of life, and occasionally for longer periods. In term infants these may range from 0.3 to 2 per cent ’of. all red cells; in premature infants, up to 5.5 per cent. A rise to 20 per cent or higher may be associated with hemc~lysis, anemia and hyper-
bilirubinemia:i
We report an infant with pyknocytosis who later presented with hereditary elliptocytosis and chronic hemolytic anemia.
Case Report A term nancy,
baby, product
was
delivered
of
uncomplicated preggravida-3 para-3, 31Birth weight: 7 ’Ib 2 ox;
to a
year-old black female. Apgar score, 7 at 1 minute Physical findings normal.
and 9
at
5 minutes.
At age six
hours, the infant appeared jaundiced lethargic. The liver was palpable 2 cm below the right costal margin. The spleen tip was at the left costal margin. Serum bilirubin was 4.8 m~°le, with 2.2 mg% as glucuronide. Blood hemoglobin level was 12.8 gm/l; hematocrit 41.7%; reticuloand
cytes 9.9%; white blood cells (WBC) 17,000 with 64% neutrophils; 7 nucleated red blood cells/100 WBC. Fifteen per
cent
of the
erythrocytes were anisopoikilo-
{Fi~. la). Spherocytosis,
pyknocytes cytosis, and polychromasia
were also present. Direct Coombs’ test, assorted cultures, and a
variety of such tests as glLicose-6-phosphate dehydrogenase (G6PD), clc>ttin~ studies, platelets, serum lipoproteins, fibrinogen, and tests of urine for reducing substance were normal or negative. Both mother and child were 0-Rh positive.
Hemoglobin electrophoresis on cord blood showed Hb A and F. The serum bilirubin progressivelyy rose to 14.4 mg% at 48 hours, and then declined under phototherapy. Because of the clinical and hematologic picture, the absence of other causes of hemolytic anemia and the presence of pyknocytes, a diagnosis of infantile pyknocytosis was made. The infant did well and was discharged at 11 day of age. The total serum bilirubin was then 5.7 mgm%; reticulocytes were 4.8%; Hb 10 gm; hct 29%. There was persisting anisopoikilocytosis, polychromasia, pyknocytosis, and spherocytosis. The child grew well with normal develc~pmental milestones. Spleen was atwaus palpable I cm below the costal margin. A bloocl smear study at six months of age showed 35 per cent elliptocytes and a few pyknocytes (Fig. Ib). At 12 months, only elliptocytes were present (Fig. Ic). Studies of osmotic fragility of the erythrocytes in both the patient and her mother, after incubation, gave normal results. Serum iron was in the normal range. Fifty per cent of the erythrocytes in the mother, and 25 per cent in one of the two brothers, showed eMiptocytosis. Prolonged intense jaundice had been noted at birth in this sibling with elliptocytosis. Hematotogic data from these individuals are shown in Table 1. The father was not available for study.
Discussion From Division
of Hematology-Oncology,
Department
Pediatrics, University of Texas Medical Branch. Correspondence to Department of Pediatrics, University of Texas Medical Branch Galveston, Texas 77550. of
*
Formation of
pyknocytes
and their
trans-
formation into irreversible crenated cells seem
76
Downloaded from cpj.sagepub.com at DALHOUSIE UNIV on June 4, 2016
Ftcr. la. smear at
and
Appearance of the erythrocytes
birth.
spherocytes
t~nisc~~oikil~3cvtnsis are
FIG. lb.
in the blood
smear
present. Pyknocytes
pyknocytes
visible.
to
be due to factors that modify the stroma or membrane of the red cells. Variation in pH and electrolytes, adenosine triphosphate availability, alteration of lipid compc~sition, abnormal proteins, viruses, chemicals and drugs have all been suggested as probable causative mechanisms.’ The main sites of destruction of pyknocytes seem to be the reticuloendothelium of the liver and spleen. Hereditary elliptocytosis, a hemolytic disorder, is due to a defect in the erythrocyte membrane and is transmitted as an autosomal dominant trait. Most affected individuals have no clinical manifestations, but in some the defect may be accompanied by mild anemia and mild chronic hemolysis with reticulocytosis and splenomegaly. The blood smear is characterized by 25 per cent life or more elliptic red blood cells. The span of elliptocytes may be normal, though shortened when hemolysis is present. The oval cells are sequestered in the spleen. Splenectomy relieves the hemolytic anemia, but obviously does not change the
of the erythrocytes in the blood Anisopoikilocvtosis is still present, rare, and quite a few ovalocytes begin
Appearance
at 6 months. are
appear.
to
TABLE 1.
Hematologic Data
on
Appearance of the erythrocytes in the blood 12 months. No pyknocytes are present and almost all the red blood cells are elliptocytes. FW . lc.’
smear at
morphologic abnormality. Elliptocytes may also be found in thalassemia, sickle cell anemia, G6PD deficiency and hereditary hemorrhagic telangiectasia.
The percentages of elliptical cells may not reach maximum levels until 4 to 5 months of age.~ In our patient these cells were not
Patient and Some
FamilT members
77
Downloaded from cpj.sagepub.com at DALHOUSIE UNIV on June 4, 2016
recognized before six months of age. It is likely that such cells were produced from the beginning, but may not have been evident initially because their small numbers were quickly destroyed in the reticuloendothelial system, or else were perhaps quickly transformed into spherocytes or pyknocytes.
Pyknocytosis in a newborn requires treatonly when complicated by anemia/or hyperbilirubinemia. Definitive diagnosis of any other form of underlying hereditary anemia may depend on adequate follow-up of the patient and hematologic evaluation ment
of his relatives.
Austin et al.1 have described infants with
elliptocytosis in whom pyknocytes were prominent during the neonatal period. They suggest that membranes of elliptocytes are particularly susceptible to the lipid environment of neonatal plasma and, therefore, are more prone to shape changes. In conclusion, infantile pyknocytosis seems to be not a distinct entity, but rather a manifestation of altered erythrocyte form that may have varied ’
causes.
In
our
infant, hered-
itary elliptocytosis seems to have been the underlying factor, as shown by later developments and the e;~istence of elliptocytosis in other members of the family.
References 1.
2.
3.
Tuffy, P., Brown, A. K., and Zuelzer, W. W.: Infantile pyknocytosis, a common erythrocyte abnormality of the first trimester. Am. J. Dis. Child. 98: 227, 1959. Williams, J. W., Beutler, E., Erslev, A. J., and
Rundles, R. W.: Hematology, New York, McGrawHill, 1972, p. 83. Wyandt, H., Bancroft, I. M., and Winship, T. O.:
Elliptic erythrocytes 68: 1043, 1941.
4.
in man. Arch. Intern. Med.
Austin,
R. F., and Desforges, J. C.: Hereditary elliptocytosis: An unusual presentation of hemolysis in the newborn associated with transient morphologic abnormalities. Pediatrics 44: 196, 1969.
78
Downloaded from cpj.sagepub.com at DALHOUSIE UNIV on June 4, 2016
Pyknocytosis in a Neonate: An Unusual Presentation of Hereditary Elliptocytosis Ugo Carpentieri, M.D.,* Lillian
P.
Gustavson, M.D., Mary Ellen Haggard, M.D.
PYKNOCYTES
are contracted distorted with erythrocytes spiny projections that can be seen in the blood stream during the first three months of life, and occasionally for longer periods. In term infants these may range from 0.3 to 2 per cent ’of. all red cells; in premature infants, up to 5.5 per cent. A rise to 20 per cent or higher may be associated with hemc~lysis, anemia and hyper-
bilirubinemia:i
We report an infant with pyknocytosis who later presented with hereditary elliptocytosis and chronic hemolytic anemia.
Case Report A term nancy,
baby, product
was
delivered
of
uncomplicated preggravida-3 para-3, 31Birth weight: 7 ’Ib 2 ox;
to a
year-old black female. Apgar score, 7 at 1 minute Physical findings normal.
and 9
at
5 minutes.
At age six
hours, the infant appeared jaundiced lethargic. The liver was palpable 2 cm below the right costal margin. The spleen tip was at the left costal margin. Serum bilirubin was 4.8 m~°le, with 2.2 mg% as glucuronide. Blood hemoglobin level was 12.8 gm/l; hematocrit 41.7%; reticuloand
cytes 9.9%; white blood cells (WBC) 17,000 with 64% neutrophils; 7 nucleated red blood cells/100 WBC. Fifteen per
cent
of the
erythrocytes were anisopoikilo-
{Fi~. la). Spherocytosis,
pyknocytes cytosis, and polychromasia
were also present. Direct Coombs’ test, assorted cultures, and a
variety of such tests as glLicose-6-phosphate dehydrogenase (G6PD), clc>ttin~ studies, platelets, serum lipoproteins, fibrinogen, and tests of urine for reducing substance were normal or negative. Both mother and child were 0-Rh positive.
Hemoglobin electrophoresis on cord blood showed Hb A and F. The serum bilirubin progressivelyy rose to 14.4 mg% at 48 hours, and then declined under phototherapy. Because of the clinical and hematologic picture, the absence of other causes of hemolytic anemia and the presence of pyknocytes, a diagnosis of infantile pyknocytosis was made. The infant did well and was discharged at 11 day of age. The total serum bilirubin was then 5.7 mgm%; reticulocytes were 4.8%; Hb 10 gm; hct 29%. There was persisting anisopoikilocytosis, polychromasia, pyknocytosis, and spherocytosis. The child grew well with normal develc~pmental milestones. Spleen was atwaus palpable I cm below the costal margin. A bloocl smear study at six months of age showed 35 per cent elliptocytes and a few pyknocytes (Fig. Ib). At 12 months, only elliptocytes were present (Fig. Ic). Studies of osmotic fragility of the erythrocytes in both the patient and her mother, after incubation, gave normal results. Serum iron was in the normal range. Fifty per cent of the erythrocytes in the mother, and 25 per cent in one of the two brothers, showed eMiptocytosis. Prolonged intense jaundice had been noted at birth in this sibling with elliptocytosis. Hematotogic data from these individuals are shown in Table 1. The father was not available for study.
Discussion From Division
of Hematology-Oncology,
Department
Pediatrics, University of Texas Medical Branch. Correspondence to Department of Pediatrics, University of Texas Medical Branch Galveston, Texas 77550. of
*
Formation of
pyknocytes
and their
trans-
formation into irreversible crenated cells seem
76
Downloaded from cpj.sagepub.com at DALHOUSIE UNIV on June 4, 2016
Ftcr. la. smear at
and
Appearance of the erythrocytes
birth.
spherocytes
t~nisc~~oikil~3cvtnsis are
FIG. lb.
in the blood
smear
present. Pyknocytes
pyknocytes
visible.
to
be due to factors that modify the stroma or membrane of the red cells. Variation in pH and electrolytes, adenosine triphosphate availability, alteration of lipid compc~sition, abnormal proteins, viruses, chemicals and drugs have all been suggested as probable causative mechanisms.’ The main sites of destruction of pyknocytes seem to be the reticuloendothelium of the liver and spleen. Hereditary elliptocytosis, a hemolytic disorder, is due to a defect in the erythrocyte membrane and is transmitted as an autosomal dominant trait. Most affected individuals have no clinical manifestations, but in some the defect may be accompanied by mild anemia and mild chronic hemolysis with reticulocytosis and splenomegaly. The blood smear is characterized by 25 per cent life or more elliptic red blood cells. The span of elliptocytes may be normal, though shortened when hemolysis is present. The oval cells are sequestered in the spleen. Splenectomy relieves the hemolytic anemia, but obviously does not change the
of the erythrocytes in the blood Anisopoikilocvtosis is still present, rare, and quite a few ovalocytes begin
Appearance
at 6 months. are
appear.
to
TABLE 1.
Hematologic Data
on
Appearance of the erythrocytes in the blood 12 months. No pyknocytes are present and almost all the red blood cells are elliptocytes. FW . lc.’
smear at
morphologic abnormality. Elliptocytes may also be found in thalassemia, sickle cell anemia, G6PD deficiency and hereditary hemorrhagic telangiectasia.
The percentages of elliptical cells may not reach maximum levels until 4 to 5 months of age.~ In our patient these cells were not
Patient and Some
FamilT members
77
Downloaded from cpj.sagepub.com at DALHOUSIE UNIV on June 4, 2016
recognized before six months of age. It is likely that such cells were produced from the beginning, but may not have been evident initially because their small numbers were quickly destroyed in the reticuloendothelial system, or else were perhaps quickly transformed into spherocytes or pyknocytes.
Pyknocytosis in a newborn requires treatonly when complicated by anemia/or hyperbilirubinemia. Definitive diagnosis of any other form of underlying hereditary anemia may depend on adequate follow-up of the patient and hematologic evaluation ment
of his relatives.
Austin et al.1 have described infants with
elliptocytosis in whom pyknocytes were prominent during the neonatal period. They suggest that membranes of elliptocytes are particularly susceptible to the lipid environment of neonatal plasma and, therefore, are more prone to shape changes. In conclusion, infantile pyknocytosis seems to be not a distinct entity, but rather a manifestation of altered erythrocyte form that may have varied ’
causes.
In
our
infant, hered-
itary elliptocytosis seems to have been the underlying factor, as shown by later developments and the e;~istence of elliptocytosis in other members of the family.
References 1.
2.
3.
Tuffy, P., Brown, A. K., and Zuelzer, W. W.: Infantile pyknocytosis, a common erythrocyte abnormality of the first trimester. Am. J. Dis. Child. 98: 227, 1959. Williams, J. W., Beutler, E., Erslev, A. J., and
Rundles, R. W.: Hematology, New York, McGrawHill, 1972, p. 83. Wyandt, H., Bancroft, I. M., and Winship, T. O.:
Elliptic erythrocytes 68: 1043, 1941.
4.
in man. Arch. Intern. Med.
Austin,
R. F., and Desforges, J. C.: Hereditary elliptocytosis: An unusual presentation of hemolysis in the newborn associated with transient morphologic abnormalities. Pediatrics 44: 196, 1969.
78
Downloaded from cpj.sagepub.com at DALHOUSIE UNIV on June 4, 2016
