Med J 955 - 957 The of Postgrad (1990) 66, © Fellowship Postgraduate Medicine, 1990 Postgrad Med J: first published as 10.1136/pgmj.66.781.955 on 1 November 1990. Downloaded from Thrombotic thrombocytopenic purpura with terminal pancytopenia Soo-Chin Ng' and B.A. Adam2 1Haematology Division, Department ofPathology, 2Department ofMedicine, Medical Faculty, University ofMalaya, 59100 Kuala Lumpur, Malaysia Summary: A 27 year old housewife developed thrombotic thrombocytopenic purpura during the twelfth week of pregnancy. She had partial response to initial plasma infusion and subsequent plasmapheresis. However, her clinical course was complicated by the development ofsevere pancytopenia the consequence of a hypocellular marrow. She succumbed to septicaemic shock one month after diagnosis. The development ofhypocellular marrow in thrombotic thrombocytopenicpurpura has not been reported before. Introduction Thrombotic thrombocytopenic purpura (TTP) is a 30.8 x 109/l with a slight left shift and the platelet rare disorder characterized in its form count was 10 x The direct complete by 109/1. Coomb's test was Protected by copyright. the pentad of thrombocytopenia, microangio- negative. Peripheral blood film confirmed marked pathic haemolytic anaemia (MAHA), fluctuating thrombocytopenia and a striking number of frag- neurological abnormalities, renal impairment and mented red cells and occasional nucleated red cells fever.' We report a patient with TTP in pregnancy were present. Her prothrombin time, partial who developed terminal pancytopenia secondary thromboplastin time, thrombin time and fibrin- to hypocellular marrow. ogen level were within normal limits. Bone marrow examination showed a normocellular marrow with erythroid hyperplasia and presence of normal Case report granulopoiesis and megakaryopoiesis. Urinalysis revealed microscopic haematuria. Her blood urea A 27 year old housewife gravida 3, para 4 was was elevated (18.9 mmol/l) with serum creatinine admitted to a peripheral hospital with a history of of 115 $xmol/l. Her liver functions were essentially fever for a week. She was 3 months pregnant. There normal except for elevated serum bilirubin of were no localizing symptoms or signs and she gave 50Cmol/l. Computerized axial scan of brain no history suggestive of collagen diseases. Her showed no focal lesions and cerebrospinal fluid http://pmj.bmj.com/ general condition deteriorated rapidly and 4 days (CSF) examination was normal. Cultures from later she lapsed into a coma. Her haemoglobin blood, CSF and urine showed no growth. Ultra- concentration dropped from 10 g/dl to 4 g/dl. She sound of abdomen revealed a viable fetus corre- was transferred to the University Hospital, Kuala sponding to 12 weeks' gestation. Serological tests Lumpur for further management. On examination, for dengue and arbovirus and Widal Weil Felix she was in deep coma and responded only to deep tests were negative. The diagnosis of thrombotic She was febrile with marked and a pain. pallor tinge thrombocytopenic purpura was made on the basis on September 27, 2021 by guest. ofjaundice. Her blood pressure was 120/80 mmHg. of microangiopathic haemolytic anaemia, pro- Both liver and spleen were enlarged 4 cm below the found thrombocytopenia, high fever, and evidence subcostal margins. Petechiae were noted over her of both central nervous system and renal involve- lower limbs. No fundal haemorrhage or lym- ment. phadenopathy was detected. There were no focal She was started on plasma therapy consisting of neurological signs. daily infusion of 5 units of fresh frozen plasma Her full blood count showed a haemoglobin (FFP). She made a remarkable recovery and concentration of 4.7 g/dl with a reticulocyte count regained full consciousness by the day 3 of admis- of 4%. Her white cell count was elevated at sion. However, there was persistent MAHA and thrombocytopenia and she required 2 units of packed cell transfusions on alternate days. She was Correspondence: S.C. Ng, M.R.C.P. (UK), F.R.C.P.A. started on plasmapheresis on the day 5 of admis- Accepted: 2 May 1990 sion and subsequently six more plasmaphereses 956 CLINICAL REPORTS Postgrad Med J: first published as 10.1136/pgmj.66.781.955 on 1 November 1990. Downloaded from were performed over a period of2 weeks (Figure 1). 20 , Each procedure involved an exchange of 2 litres of 20 ~ P P PP PP P plasma with the replacement fluids consisting of 10 X 5- \ I I II t units of FFP and crystalloids. There was a partial response after each procedure - she became more x 4' alert and her serum creatinine and blood urea ^ pI,I \ Death returned to normal. She also became afebrile on 8 3- \ day 14 of admission but the MAHA and throm- -40 x bocytopenia persisted. She had a spontaneous 2 2- 30 abortion on the same day. Her absolute neutrophil -20o count declined markedly and was below I x 109/1 on day 14. A bone marrow aspirate and trephine 0.5- biopsy showed hypocellular marrow with depres- sion of normal haemopoiesis. Three weeks after 1 357 14 21 2830 admissions, she became severely neutropenic Figure 1 Clinical course ofpatient. *- *, Neutrophil (<0.5 x 109/1); she was reverse isolated and count; 0- , platelet count; P, plasmapheresis. started on broad spectrum antibiotics but became febrile again and was deeply jaundiced on day 22. Staphylococcus aureus was isolated in the blood change transfusions or plasmapheresis.7'8 Our pa- culture. Her coagulation tests showed evidence of tient responded partially to plasma infusions and disseminated intravascular coagulation. Alanine plasmapheresis but unfortunately her clinical transaminase (ALT) was not raised at any time. course was complicated by the development of Despite vigorous treatment, she succumbed to severe pancytopenia, the consequence ofa hypocel- septicaemic shock 30 after admission. lular marrow. anaemia has days Hypoplastic/aplastic Protected by copyright. rarely been reported in pregnancy.9 The precise relationship between pregnancy and aplasia re- Discussion mains uncertain but it is likely to be a chance association.'0 The cause of the hypocellular mar- TTP was first described by Moschcowitz in 1925.2 row in our patient was not apparent. Non-A, In more than 90% of patients, TTP developed non-B hepatitis causing hypocellular marrow was without an apparent causal event or an underlying not likely in view of her normal ALT. Transfusion disease process.3 In a minority ofcases, the disorder associated graft-versus-host disease could follow has been associated with a variety of conditions blood product transfusions in patients with deficient including collagen diseases, antecedent respiratory cell-mediated immunity." However, the absence of infections, drugs and pregnancy. Despite a rela- skin lesions and gastrointestinal complaints and tively high incidence in women ofchild bearing age, her normal ALT made it unlikely that her bone TTP has rarely been reported during pregnancy.4'5 marrow failure was due to graft-versus-host Our patient was 12 weeks pregnant at presentation disease. Moreover, there was no suggestion that the of illness but there is no convincing evidence that patient had deficient cell-mediated immunity. One http://pmj.bmj.com/ the above associations are causal rather than may speculate that the same aetiological agent that coincidental.6 triggered off TTP also caused the hypocellular Although the aetiology and pathogenesis of the marrow. condition remain unknown, the introduction of therapy designed to remove the patient's plasma and/or to supply the patient with normal plasma has dramatically improved the of TTP. Acknowledgements prognosis on September 27, 2021 by guest. Up to 70-80% response rate has been reported for We thank Dr M.L. Ong and Dr Keith Lim for helping TTP patients treated with plasma infusions, ex- with patient care. References 1. Amorosi, E.L. & Ultmann, J.E. Thrombotic thrombo- 3. Ridolfi, R.L. & Bell, W.R. Thrombotic thrombocytopenic cytopenic purpura: report of 16 cases and review of the purpura: report of 25 cases and review of the literature. literature. Medicine 1966, 45: 139-159. Medicine 1981, 60: 413-428. 2. Moschcowitz, E. An acute febrile pleiochromic anaemia with 4. Yang, C., Nussbaum, M. & Park, H. Thrombotic throm- hyaline thrombosis of the terminal arterioles and capillaries. bocytopenic purpura in early pregnancy. Acta Haematol Ann Intern Med 1925, 31: 89-93. 1979, 62: 112-116. CLINICAL REPORTS 957 Postgrad Med J: first published as 10.1136/pgmj.66.781.955 on 1 November 1990. Downloaded from 5. Byrnes, J.J. & Khurana, M. Treatment ofthrombotic throm- 9. Fleming, A.F. Hypoplastic anaemia in pregnancy. Clin bocytopenic purpura with plasma. N Engl J Med 1977, 297: Haematol 1973, 2: 477-496. 1386-1389. 10. Blanche, P.A., Nancy, U.P. & Frederick, P.L. Classification 6. Crain, S. & Choudhury, A. Thrombotic thrombocytopenic and aetiology of the aplastic anaemias. Clin Haematol 1978, purpura, a reappraisal. JAMA 1981, 246: 1243-1246. 7: 431-457. 7. Cutter, J. Thrombotic thrombocytopenicpurpura: A ten year 11. Brubaker, D.B. Human posttransfusion graft-versus-host experience. Blood 1980, 56: 302-306. disease. Vox Sang 1983, 45: 401-420. 8. Blitzer, J.B., Granfortuna, J.M., Gottileb, A.J. et al. Throm- botic thrombocytopenic purpura: treatment with plasma- pheresis. Am J Hematol 1987, 24: 329-339. Protected by copyright. http://pmj.bmj.com/ on September 27, 2021 by guest..