A successful pregnancy in transfusion dependent homozygous β-thalassemia: A case report

Int. J. Gynaecol. Obstet., 1982,20: 319-322 International Federation of Gynaecology & Obstetrics

A SUCCESSFUL PREGNANCY IN TRANSFUSION fl-THALASSEMIA: A CASE REPORT

A.W. GOLDFARBa,

D. HOCHNERCELNIKIERb,

Hematology Servicea and the Department Jerusalem, Israel (Received (Accepted

U. BELLERb,

DEPENDENT

M. MENASHEb,

HOMOZYGOUS

I. DAGANa

and Z. PALTIb

of Obstetrics and Gynecologyb, Hadassah University Hospital, Mount Scopus,

July 8th, 1981) December 8th, 1981)

Abstract Goldjarb A W, Hochner-Celnikier D, Belier U, Menashe M, Dagan I, Palti Z (Hematology Service and the Department of Obstetrics and Gynecology, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel). A successful pregnancy in transfusion dependen t homozygous fi-thalassemia; a case report. Int J Gynaecol Obstet 20: 319-322, 1982 A rare case of successful pregnancy in a 26year-old woman with transfusion dependen t homozygous fl+-thalassemia is described. Following the delivery she became amenorrheic with no evidence of ovarian or pituitary j&lure. Transient fertility is most unusual in female patients who otherwise present with a severe clinical course of the disease.

growth and absence of sexual development [ 1,2]. The most common abnormality in these patients is dysfunction of the hypothalamic-pituitary-gonadal axis [ 21. These changes have usually been attributed to iron deposition in the involved glands, in addition to chronic hypoxia which may well be a contributory factor [3]. At present, life expectancy for homozygous P-thalassemia averages only 15-20 years [41, and rarely do these women live long enough to become pregnant. The present report describes a woman with transfusion dependent homozygous p’-thalassemia who underwent successful pregnancy. We could find only one comparable case reported in the literature [5].

Case report fl’-Thalassemia; Pregnancy; words: Homozygous; Amenorrheic; Ovarian or pituitary failure; Transient fertility; Endocrine impairment

Key

Introduction Endocrine impairment is well recorded in homozygous p-thalassemia [ 11. Most patients show severe failure of pubertal 0020-7292/82/0000-0000/$02.75 0 1982 International Federation

R.C. is a 27-year-old female, a third child to Kurdish Jewish parents. The presence of severe microcytic anemia and splenomegaly at the age of 12 months suggested the diagnosis of homozygous P-thalassemia, which was confirmed by the pathological blood smears and by hemoglobin electrophoresis, revealing increased levels of hemoglobin A, (7%) and fetal Hb (31%). The globin chain synthesis analysis was carried out according to method previously described Int J Gynaecol Obstet 20

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I

II

Iu

Iv

P

m Family 0 Normal

tree male

of

propositus

0 Normal

female

m p -Thalassemia

major

0 p -Thalassemio

intermedia

0 p -Thalassemla

minor

0 Not

fl

Fig. 1.

tested

Deceased

Family tree of propositus.

161, by ion exchange chromatography with CM-52 in urea 8M, showed synthetic ratios of P/a = 0.22, ~/CV= 0.117 and non (Y/(Y= 0.355. These ratios are indicative of p’thalassemia major. Among her siblings, there is a brother with fl-thalassemia intermedia and two others with heterozygous P-thalassemia (Fig. 1). Since infancy she required blood transfusions every 6-8 weeks to keep her hemoglobin level in a range of 7-8 g%. She developed pronounced characteristic features of the disease, which included stunted growth, typical facial changes, stick-like short arms and typical bone X-ray changes. At the age of 10 years she underwent splenectomy and for several years enjoyed a period of a marked reduction in transfusion requirement. At the age of 14 years, she developed recurrent episodes of leg ulcers. Her menarch occurred at the age of 16 years. However, no significant impairment of adrenal, pancreatic or cardiovascular function could be demonstrated. At the age of 24, she married a Syrian Jew, who did not have p-thalassemia trait, and Int J Gynaecol Obstet 20

conceived 1 year later. Her pregnancy progressed uneventfully except for blood transfusions requirement every 3 weeks until the 39th week of the pregnancy, when she was hospitalized because of pre-eclamptic toxemia with proteinuria, marked ankle edema and blood pressure of lSO/lOO mmHg. Because of the pre-eclamptic toxemia, Pitocin drip was started, following which fetal distress occurred, and a cesarian section was performed. A male infant, weighing 3600 g was delivered with an Apgar score of 9 at the first minute after delivery. Following the operation, the patient received 2 units of blood and her hemoglobin was 8 g%. She was released after 6 days in good condition. The baby was breast fed, developed normally and was found to have heterozygous p-thalassemia. Now, 2 years following the delivery. the patient is amenorrheic. although no laboratory evidence for gonadal or pituitary failure could be demonstrated, which could be attributed to iron deposition in the above glands.

Pregnancy with transfusion dependent

Discussion p-thalassemia is known to present with a great diversity of both molecular pathology [ 31. The [7] and of the clinical picture symptomathology encompasses the entire range from the most severe condition which consists of complete dependency on blood transfusions for maintenance of life, to a silent state recognisable only by sophisticated laboratory techniques. Our patient represents a clinically borderline case between p-thalassemia intermedia and p-thalassemia major. The severe clinical course of the disease, the bone changes, her complete transfusion dependency and chain synthesis analysis her hemoglobin with B-thalassemia major are compatible whereas her ability to reproduce and her marked long beneficial response to splenectomy are more characteristic of p-thalassemia intermedia [ 8,9]. Most of the cases of successful pregnancies reported in the literature [lo-131 describe females with /3-thalassemia minor or intermedia where the outcome for mother and fetus is usually satisfactory [ 14,151, although the incidence of maternal pyelonephritis, pneumonia and pulmonary embolus seem to be increased and fetal mortality is about 15% [ 161. Pregnancies associated with transfusion dependent homozygous p-thalassemia is very rare. We could find only one other by Thomas and Skalicka case, reported [ 5 ] which resembles ours. Unlike our patient this woman had received only three blood transfusions by the time she was 12 years old, and although her globin chain synthesis ratios were not reported, it would appear that the woman described was a severe case of fl-thalassemia intermedia. The patient reported here could in many ways be considered as fi-thalassemia major and as such is unique in that no other thalassemic patient, completely transfusion dependent since infancy, has been known to have undergone successful pregnancy. Since her delivery the patient is no longer living in Jerusalem

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receiving transfusions and is reportedly less regularly and frequently which may be a contributory factor in the development of her secondary amenorrhea. It is interesting to observe different patterns of the clinical expressions of the disease, among the population of the Kurdish Jews, where marriage between kin is common (Fig. 1). The different variations seem to be typical for the members of certain families. Within the community we have seen several patients with thalassemia intermedia (males and females) who were able to bear children, but none of them have a comparable severe clinical course with complete transfusion dependency. References 1 Canale VC, Steinberg P, New M, Erlandoson M: Endocrine function in thalassemia major. Ann NY Acad Sci 232: 333,1974. 2 Landau H, Spitz IM, Cividalli C, Rachmilewitz EA: Gonadotropin, thyrotropin and prolactin reserve in p-thalassemia. Clin Endocrinol 9: 163, 1978. Weatherall DJ, Clegg JB: The Thalassemia Syndromes. Blackwell Scientific Pub., Oxford, London, 1972. Pearson HA, O’Brien RT: The management of thalassemia major. Sem Hematol12: 255, 1975. Thomas RM, Skalicka: Successful pregnancy in transfusion-dependent thalassemia. Arch Dis Child 55: 575, 1980. 6 Cividalli G, Kerem H, Rachmilewitz EA: Homozygous p” and p+ thalassemia in Kurdish Jews and Arabs. Hemoglobin 1: 333, 1977. I Bank A: The thalassemia syndromes. Blood 51: 369, 1978. 8 Engelhard D, Cividalli G, Rachmilewitz EA: Splenectomy in homozygous P-thalassemia: .4 retrospective study of 30 patients. Br J Hematol 31: 391, 1975. 9 Astaldi G, Bosman C, De Santis P, Torlontano G: Spleen and thalassemia, with reference to splenectomy in thalassemia intermedia. Haematologica 62: 49, 1977. 10 Monteta E, Parlati E, Merola A, Muscianisi G: p-thalassemia e gravidanza. Minerva Ginecol 28: 562, 1976. 11 Lambert EK, Winterbleom R, Koshy U: Pregnancy in patients with hemoglobinpathies and thalassemias. J Reprod Med 19: 193,1977. 12 Perkins RP: Inherited disorders of hemoglobin synthesis and pregnancy. Am J Obstet Gynecol Ill: 130, 1971. 13 Walker EH, Wetton MJ, Beaven GH: Successful preg. nancy in a patient with thalassemia major. J Obstet Gynecol Br Commonw 76: 549, 1969. Int J Gynaecol Obstet 20

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14 Pritchard JA: Hereditary hypochromic microcytic anemia in obstetrics and gynecology. Am J Obstet Gynecol83: 1193,1962. 15 Smith MB, Whiteside MG, De Garis NC: An investigation of the complications and outcome of pregnancy in heterozygous p-thalassemia. Aust NZ J Obstet Gynecol 15: 26,1975. 16 Morrison JC, Roe PL, Stahl RL, Whybrew WD, Bucova ET, Wiser WL, Kraus AP, Fish SA: Heterozygous thalassemia and pregnancy: A 25 year experience. J Reprod Med 11: 35,1973.

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Address for reprints: Ada W. Goldfarb, M.D. Hematology Service Hadassah University Hospital, Mt Scopus Jerusalem 91240 Israel