Prolonged, pregnancy-related pure red cell aplasia; a case report

European Journal of Obstetrics & Gynecology and Reproductive Biology, 42 (1991) 233-235 0 1991 Elsevier Science Publishers B.V. All rights reserved 0028-2243/91/$03.50

EUROBS

233

01163

Prolonged, pregnancy-related

pure red cell aplasia; a case report

P. Bambery ‘, N. Varma 2, S. Varma ‘, K. Vashishta 3, S. Dash 2 and S.D. Deodhar Departments of

’

I Internal Medicine, ’ Haematology and Obstetrics and 3 Gynaecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Accepted

for publication

17 January

1991

Summary We describe the (PRCA). The course recurr over 4 years detected during this Pure red cell aplasia:

clinical course of a patient with pregnancy-related, acquired, pure red cell aplasia of PRCA was prolonged and ultimately responded only to corticosteroids. It did not of observation despite another gestation, and no other cause for PRCA could be long period.

Pregnancy

Introduction Pure Red Cell Aplasia (PRCA) is an uncommon haematological condition characterised by anaemia, reticulocytopaenia and profound erythroid hypoplasia of the marrow in the presence of normal myeloid and megakaryocytic elements in the peripheral blood and the bone marrow [l]. The condition may be cogenital or acquired. The latter variety has been associated with thymic and other neoplasia, infections, drug exposure, chemicals, haemolytic anaemia, renal failure, systemic lupus erythematosus (SLE), rheumatoid arthritis @A), nutritional deficiency, endocrine disorders, primary amyloidosis and pregnancy [2]. Only a few patients with pregnancy-related PRCA have, so far, been described [3-91. The PRCA in these patients has occurred in early [4] as well as in late pregnancy [51 and in the puerperium [6]. It has

Correspondence: P. Bambery, Medicine, Pgimer, Chandigarh

Associate Professor 160 012, India.

of Internal

also recurred in subsequent gestations 131. However, in all these patients the disorder was of short duration [2] and ended either with abortion, delivery or even spontaneously with, the gestation continuing normally to term f41. The transient nature of this condition has led to the recommendation that corticosteroid therapy need not be instituted in such patients [4]. We describe a patient who had prolonged pregnancy-related PRCA that responded only to corticosteroid therapy. The patient has now been regularly followed up for more than 48 months, and none of the disorders associated with the development of acquired PRCA have, so far, made a belated appearance [2]. Case report NK, a 35year-old mother of two living children developed severe, unexplained anaemia early in the third trimester of her third pregnancy in January 1986. She was extensively investigated and treated at another institution, but apart from

234

reticulocytopaenia no other abnormality was found. Bone marrow examination was done on three occasions and consistently revealed a cellular marrow, normoblastic or mildly megaloblastic erythropoiesis with severe erythroid hypoplasia, but normal myeloid and megakaryocytic elements. She was given several units of whole blood and packed cell transfusion along with iron, folic acid and vitamin B,, but did not show any response (Fig. 1). The pregnancy terminated in the delivery of a fresh still born male foetus in early March 1986. For the next 4 months she continued to be very severely anaemic and unresponsive to transfusions, iron and vitamins. A total of 32 units of blood had been transfused before she was referred to our institute and admitted in July 1986. She was markedly pale but had no other abnormalities on physical examination. Investigations confirmed the diagnosis of PRCA. Bone marrow examination was done here and confirmed the reports of similar tests done previ-

te&-

Retlculocy

‘I.

ously. The myeloid: erythroid ratio was 100: 1 and the erythopoiesis was normoblastic. Granulopoiesis and thromobopoiesis were normal and there were no abnormal cells. No other cause for acquired PRCA was detected. A CT scan of the thorax ruled out a thymic tumour and similarly appropriate tests eliminated SLE, RA, viral hepatitis B, haemolytic anaemia and renal failure. She had never consumed any drugs known to be associated with PRCA and had never been exposed to any similarly implicated chemicals [2]. She consumed a diet that was adequate in calories, proteins and other nutrients. There were no clinically observable signs of nutritional deficiency. As she had continued to have PRCA for more that 20 -weeks postpartum, and had not responded to conventional treatment, it was decided to start therapy with corticosteroids. The response (Fig. 1) was prompt, dramatic and sustained. The initial daily dose of 60 mg of pred-

5

7

l

OJ OJ..

-b

JANUARY

PREGNANCY

1986 DECEMBER1 STILL BORN 6 AT TERM

l

1987

)

1988

ABORTION

1

1989

1 1990

mSPONTANEOUS

XWEEKS

TRANSFUSIONS

%JKYTE xl rIL PLATELET COUNT

5 250 60

xl&L

PREDNISOLONE 1 mg 1 IRON B12 FOLATE @I//////////I Fig.

1. Comprehensive

chart

showing

7.5 290

11 280

9.7 310

88 320

7.6 305

10 350

9 324

D

progress

of anaemia and reticulocytopaenia corticosteroid therapy.

during

pregnancy,

puerperium

and

with

235

nisolone was gradually tapered to 2.5 mg on alternate days by July 1987, at which time the repeat bone marrow examination was entirely normal. The myeloid: erythroid ratio was 4: 1. Prednisolone was stopped altogether in September 1987. Since that time the patient has remained on regular follow up and has maintained a haemoglobin of 6.9-7.9 mmol/l. She is at present, completely asymptomatic and repeat tests for SLE, RA, haemolytic anaemia and other disorders have been persistently negative. Barrier contraception had been advised but was not used. She conceived again in 1988 but aborted spontaneously at 14 weeks gestation. The aborted material was normal and tests for lupus anticoagulant were negative. There were no haematologic abnormalities in this pregnancy. When last seen in July 1990, she was completely asymptomatic and her haemoglobin was 8.0 mmol/l. Discussion The diagnosis of PRCA in our patient was based on the fulfilment of the criteria suggested [1,2]. She had evidence of all of the following components of this condition: (a) Profound chronic normocytic normochromic or macrocytic normochromic anaemia with reduced reticulocytes; (b) Cellular marrow. with markedly reduced or absent nucleated red blood cells but normal granulocytic and megakaryocytic cell series; cc> Normal total and differential leucocyte count; (d) Normal platelet count and absence of haemorrhagic phenomena; (e> No extramedullary haematopoiesis. That PRCA was pregnancy-related was strongly suggested by the temporal sequence of events and by the fact that over the next 4 years no other disorder that could also be responsible for PRCA has evolved [2]. It did not redevelop in a subsequent gestation but this phenomenon is well documented [4,.5]. Pregnancy-related PRCA is an uncommon disorder, and fewer than 10 patients have been described to date. There has been no estimation of its incidence because of its rarity [2-91. The exact pathogenesis of the disturbance is un-

known, but there is speculation that it may be due to hormonal imbalances [5,9] or due to a circulating inhibitor of erythropoiesis 161. One patient with such a circulating inhibitor of erythropoiesis has been documented, and her serum added to normal marrow culture greatly reduced the activity of the red cell series. This patient, however, made a rapid spontaneous recovery [6]. We were not in a position to study the effects of our patients serum on bone marrow cultures. All previously reported patients with pregnancy-related PRCA have recovered within a few weeks or months and corticosteroids have only been used in one such patient [4]. Our patient however, continued to show severe PRCA more than 20 weeks post-partum and hence had to be treated. Whereas the usual patient with pregnancy PRCA may not need such therapy, our patient clearly exemplifies that an occasional patient will need steroids and benefit greatly from their use. Acknowledgement We are grateful to Mr. Sudershan secretarial assistance.

Kumar for

References Krantz S. Pure red cell aplasia. N Engl J Med 1974;29I: 345-350. Ammus SS, Yunis AA. Acquired pure red cell aplasia. Am J Hematol 1987;24:311-326. Picot C, Triadou P, Lacombe C, Casadevall N, Girot R. Relapsing pure red cell aplasia during pregnancy. N Engl J Med 1984;311:196. Myoshi I, Hikita T, Koi B, Kimura 1. Reversible pure red cell aplasia in pregnancy. N Engl J Med 1978;299:777. Aggio MC, Zunini C. Reversible pure red cell aplasia in pregnancy. N Engl J Med 1977;297:221-222. Seidenfeld AM, Owen J, Parchal JF, Glynn MFX. Pure red cell aplasia with an inhibitor of erythropoiesis. Can Med Assoc J 1979;121:188-190. Lehman LTG, Alcoff J. Reversible pure red cell hypoplasia in pregnancy. JAMA 1982;247:1170-1171. Skine BS, Lynch SR, Bezwoda WR, Bothwell TH, Bersterin R, Katz J. Pure red cell aplasia. S Afr Med J. 1976;50: 1353-1357. Wakabayashi Y, Takaky F. A case of pure red cell aplasia associated with pregnancy and bone marrow cells responsive to erythropoietin in vitro. Acta Haematol (Jpn) 1980;43:5 14-521.