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SHORT REPORT

Pulsed high-dose dexamethasone in chronic autoimmune

haemolytic anaemia of warm type

OL I VE R ME YE R,1

DO RO T H E A STAHL,2

PH I L I P P BE C KH O VE,3

D I E T E R HUH N1

AN DA B DUL GA B A R SA L A MA1

1Blutbank, Virchow-Klinikum Medizinische Fakultat der Humboldt-Universitat zu Berlin, Berlin,2Institut fur Immunologie, and 3Abt. Innere Medizin V, Ruprecht-Karls-Universitat, Heidelberg, Germany

Received 10 June 1997; accepted for publication 26 June 1997

Summary. The management of patients with autoimmune

haemolytic anaemia of warm type (AIHA) is often proble-

matic. Recently, pulsed high-dose dexamethasone (HDD) has

been shown to be effective in the treatment of autoimmune

thrombocytopenic purpura (AITP).

In this study we treated seven patients with AIHA with

HDD. The regimen recommended for treatment of refractory

AITP (40 mg dexamethasone for 4 d at the beginning of each

28d cycle) was employed in almost all cases. Prior to

dexamethasone administration, haemolysis was decompen-

sated in all seven patients. HDD was well tolerated and led to

an improvement of haemolysis in all cases.

Keywords: autoimmune haemolytic anaemia, high-dose

dexamethasone, rheumatoid arthritis, autoimmune disease.

The majority of patients with chronic autoimmune haemo-

lytic anaemia of warm type (AIHA) require, in addition tocorticosteroids as a first and base-line therapy, azathioprine

or cyclophosphamide to achieve complete remission or, at

least, satisfactory control of haemolysis. The management of

patients who do not respond to these drugs is often

frustrating (Dacie & Worlledge, 1969; Murphy & LoBuglio,

1976; Petz & Garraty, 1980; Sokol et al, 1984). A few

patients may benefit from splenectomy, high-dose intra-

venous IgG, plasmapheresis, danazol or cyclosporin A

(Engelfriet et al, 1992; Packman & Leddy, 1995), but it is

impossible to predict which therapy will be effective in which

patient.

Recently, pulsed high-dose dexamethasone (HDD) has

been shown to be effective in chronic autoimmune

thrombocytopenic purpura (AITP) that was refractory to

conventional treatment (Andersen, 1994; Caulier et al,

1995; Schiavottoet al, 1996; Bustoet al, 1996). In this study

we treated seven unselected AIHA patients with HDD.

PATIENTS AND METHODS

Seven consecutive adult patients (six female and one male

aged between 33 and 72 years) with decompensated AIHA

were included in this study. The diagnosis of AIHA was made

in accordance with established criteria, i.e. haemolytic

anaemia, detectable red blood cell (RBC) autoantibodiesand lack of other reasons for the haemolysis.

The direct antiglobulin test (DAT) was carried out by

standard technique.

Unless indicated, the patients were given six cycles of

40 mg dexamethasone (per osor by intravenous injection) for

4 consecutive days on 28 d cycles.

RESULTS

The causative autoantibodies were of the IgG classes in five

patients, and IgM in the remaining two patients. Prior to

treatment with HDD, haemolysis was decompensated in all

patients. Two patients (nos. 3 and 7) were initially criticallyill and required blood transfusions. The administration of

HDD was well tolerated and led to a reduction of RBCs

destruction in all cases. In three patients (nos. 1, 2 and 3) six

cycles of HDD led to a normalization of haemoglobin (Fig 1).

However, all three patients relapsed within a few months

after stopping of HDD. Patient 1 has been suffering from

seronegative rheumatoid arthritis for 30 years. His condition

greatly improved during treatment with HDD. He therefore

received two additional cycles of HDD and now takes 40 mg

dexamethasone once a week to remain free from rheumatic

pain (Fig 1), and his haemolysis is completely compensated.

After a relatively long-term partial remission and normal-

ization of haemoglobin levels, patients 2 and 3 gradually

British Journal of Haematology, 1997,98, 860862

860 1997 Blackwell Science Ltd

Correspondence: Professor Dr A. Salama, Blutbank, Virchow-

Klinikum, Medizinische Fakultat der Humboldt-Universitat zu

Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

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developed relapses that could be successfully compensated

with 10 mg prednisolone per day (Fig 1).

Patient 4 showed a good response to the first course of

HDD, and a second course was not given as recommended on

28 d cycles. This patient developed after 2 months a relapsethat could not be stopped either by readministration of HDD

or by therapy with high-dose prednisolone (1 g/d for 1 week),

injection of C1-esterase inhibitor (3000 units for 5 d) to

inhibit complement activation, plasma exchange, and 2-

chloro-20-deoxyadenosine (0.1 mg/kg/d for 7 d). This patient

died due to complications not related to haemolysis.

Patient 5 underwent complete remission after the second

cycle of HDD (Fig 1). Patient 6 underwent liver transplanta-

tion and did not require further treatment with HDD. The

DAT became negative in both cases.

Patient 7 is receiving chemotherapy due to non-Hodgkins

lymphoma. Her AIHA was refractory to chemotherapy,

prednisolone, intravenous high-dose IgG, and cyclosporin A.

This patient initially required two cycles of HDD to achieve

satisfactory control of the haemolysis (Fig 2). Soon blood

transfusions were no longer necessary and the patient was

discharged in good condition. The patient received a

maintenance dose of dexamethasone to prevent an acuterelapse.

DISCUSSION

The majority of patients with AIHA require long-term

therapy that, at least, includes low doses of corticosteroids

and often results in serious side-effects. Approximately 20%

of all patients with AIHA do not respond to conventional

therapies, and there is no concept for rational treatment of

such patients (Petz & Garraty, 1980; Engelfriet et al, 1992).

In this study we treated seven consecutive AIHA patients

with HDD using the regimen employed in the treatment of

refractory AITP (Andersen, 1994). Although only a few

861Short Report

1997 Blackwell Science Ltd, British Journal of Haematology 98: 860862

Fig 1. Effect of high-dose dexamethasone in six patients with autoimmune haemolytic anaemia of warm type. PRED, prednisolone; CY,

cyclophosphamide; MTX, methotrexate; AZA, azathioprine; BLT, blood transfusions; LTX, liver transplantation.

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patients were included in the present study, HDD appears to

provide an alternative to conventional AIHA treatment.

Haemolysis improved during the first cycle of HDD in all

seven patients studied, and none of the patients developed

side-effects that led to discontinuation of treatment with

HDD.

Three patients required six HDD cycles to achieve a

normalization of haemoglobin and one patient required only

two cycles. One of the former patients relapsed within 2

months, re-entered, and has maintained remission afterreceiving additional HDD cycles (Fig 1). The other two

patients developed, after 5 and 9 months respectively,

relapses that could be completely recompensated with low

doses of prednisolone (10 mg/d). Interestingly, HDD also

significantly improved the rheumatic pain of patient 1.

Patient 4 did not receive a second course at the beginning

of a 28 d cycle and relapsed despite continuous treatment

with 20mg prednisolone per day. The reason for this

patients failure could be the extreme severity of haemolysis

due to IgM autoantibody and complement activation. This

assumption is supported by the therapy course in patient 7,

who required two courses of HDD within 3 weeks because of

massive haemolysis that was also related to autoantibodies of

the IgM class. To prevent an acute relapse in this case, the

patient was maintained on low doses of dexamethasone (Fig

2). The questions of which responsive patients should be

maintained on low doses of steroids (prednisone/predniso-

lone or dexamethasone) to prevent relapses, and whether

some patients with severe AIHA may need larger amounts of

dexamethasone than the patients studied here in order to

achieve a remission, require further studies.

REFERENCES

Andersen, J.C. (1994) Response of resistant idiopathic thrombo-

cytopenic purpura to pulsed high-dose dexamethasone therapy.

New England Journal of Medicine, 330,15601564.

Busto, M.J., Llamas, P., Cabrera, R. & Fernandez, M.N. (1996)

Pulsed high-dose dexamethasone in the treatment of refractory

immune thrombocytopenia. British Journal of Haematology, 93,

738739.

Caulier, M.T., Rose, C., Roussel, M.T., Huart, C., Bauters, F. & Fenaux,

P. (1995) Pulsed high-dose dexamethasone in refractory chronicidiopathic thrombocytopenic purpura: a report on 10 cases.

British Journal of Haematology,91, 477479.

Dacie, J.V. & Worlledge, S.M. (1969) Auto-immune hemolytic

anemias.Progress in Hematology,6, 82 120.

Engelfriet C.P., Overbeeke, M.A.M. & von dem Borne, A.E.G.Kr.

(1992) Autoimmune hemolytic anemia. Seminars in Hematology,

29,312.

Murphy, S. & LoBuglio, A.F. (1976) Drug therapy of autoimmune

hemolytic anemia.Seminars in Hematology,13, 323334.

Packman, C.H. & Leddy, J.P. (1995) Acquired hemolytic anemia due

to warm-reacting autoantibodies. Williams Hematology, 5th edn

(ed. by E. Beutler, M. A. Lichtman, B. S. Coller and T. J. Kipps), pp.

677685. McGraw-Hill, New York.

Petz, L.D. & Garraty, G. (1980) Acquired Immune Hemolytic Anemias.

Churchill Livingstone, New York.Schiavotto, C., Ruggeri, M., Castaman, G. & Rodeghiero, F. (1996)

High-dose dexamethasone in adult refractory idiopathic throm-

bocytopenic purpura. British Journal of Haematology, 93, 491

492.

Sokol, R.J., Hewitt, S., Stamps, B.K. & Hitchen, P.A. (1984)

Autoimmune haemolysis in childhood and adolescence. Acta

Haematologica,72, 245257.

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1997 Blackwell Science Ltd, British Journal of Haematology 98: 860862

Fig 2.Therapy course of patient 7. PRED,

prednisolone; CY, cyclophosphamide; CSA,

cyclosporine A; BLT, blood transfusions; CHOP,

cyclophosphamide, adriamycine, vincristineand prednisolone; CHO, cyclophosphamide,

adriamycine and vincristine.