Acquired hemophilia, caused by autoantibodies against coagulation factor VIII, is usually treated with steroids, cyclophosphamide, intravenous gammaglobulins and sporadically other drugs. We describe the case of a patient in whom the common therapeutic choice was unsuccessful, but cyclosporine proved to be effective

Baele, Gaston

Derom, Eric

Petrovic, Mirko

English

Ghent University Academic Bibliography

while our patient had low IgG (1.76 g/L) and IgA(0.28 g/L). We could speculate that humoral dys-function related to rituximab therapy could havecaused loss neutralization of free viral particles byspecific antibodies, facilitating initial disseminationof the VZV but this hypothesis needs to be investi-gated further.Arancha Bermúdez, Fernando Marco, Eulogio Conde,Enrique Mazo, Marina Recio, Alberto Zubizarreta Hematology Department, Hospital UniversitarioMarqués de Valdecilla, Santander, SpainKey wordsRituximab, visceral varicella-zoster infection, lymphoma.CorrespondenceArancha Bermúdez, Servicio de Hematología, HospitalUniversitario Marqués de Valdecilla, Avda. Valdecilla s/n.39008 Santander, Spain. Phone: international +34-942-202573 – Fax: international +34-942-203450.References1. Maloney DG, Grillo-López AJ, White CA, et al. IDEC-C8 (rituximab) anti-CD20 monoclonal antibody ther-apy in patients with relapsed low-grade non-Hodgk-in’s lymphoma. Blood 1997; 90:2188-95.2. McLaughlin P, Grillo-López AJ, Link BK, et al. Ritux-imab chimeric anti-CD20 monoclonal antibody ther-apy for relapsed indolent lymphoma: half of patientsrespond to a four-dose treatment program. J ClinOncol 1998; 16:2825-33.3. Czuczman MS, Grillo-López AJ, White CA, et al. Treat-ment of patients with low-grade B-cell lymphoma withthe combination of chimeric anti-CD20 monoclonalantibody and CHOP chemotherapy. J Clin Oncol1999; 17:268-76.4. Coiffer B, Haioun C, Ketterer N, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment ofpatients with relapsing or refractory aggressive lym-phoma: a multicenter phase II study. Blood 1998; 92:1927-32.5. Schuchter ML, Wingard RJ, Piantadosi S, Burns WH,Santos GW, Saral R. Herpes zoster infection afterautologous bone marrow transplantation. Blood1989; 74:1424-7.6. David DS, Tegtmeier BR, O’Donnel MR, Paz IB,McCarty TM. Visceral varicella-zoster after bone mar-row transplantation: report of a case series and reviewof the literature. Am J Gastroenterol 1998; 93:810-3.7. Rogers SY, Irving W, Harris A, Russell NH. Visceralvaricella zoster infection after bone marrow trans-plantation without skin involvement and the use ofPCR for diagnosis. Bone Marrow Transplant 1995;15:805-7.8. Stemmer SM, Kinsman K, Tellschow S, Jones RB. Fatalnoncutaneous visceral infection with varicella-zostervirus in a patient with lymphoma after autologousbone marrow transplantation. Clin Infect Dis 1993;16:497-9.9.  Han CS, Miller W, Haake R, Weisdorf D. Varicellazoster infection after bone marrow transplantation:incidence, risk factors and complications. Bone Mar-row Transplant 1994; 13:277-83.10.  Roitt I. Essential Immunology. 9th ed. Oxford: Black-well Science Ltd; 1997.Cyclosporine treatment of acquired hemophil-ia due to factor VIII antibodiesAcquired hemophilia, caused by autoantibodiesagainst coagulation factor VIII, is usually treatedwith steroids, cyclophosphamide, intravenous gam-maglobulins and sporadically other drugs. Wedescribe the case of a patient in whom the commontherapeutic choice was unsuccessful, but cyclo-sporine proved to be effective.Sir,A 56-year old man with chronic obstructive pul-monary disease was admitted because of hemopty-sis. There was no evidence of malignancy, tuberculo-sis or autoimmune disorders. The patient did nottake any new drug before admission. Routine coag-ulation tests showed repeatedly a prolongation ofthe activated partial thromboplastin time (to 63.7sec, upper normal value 37 sec). This was due to adecrease of factor VIII:C to 0.04 IU/mL with an anti-body level against factor VIII of 40 Bethesdaunits/mL. An acquired von Willebrand syndrome wasexcluded (vWF:Ag of 2.38 IU/mL, vWF:Rco of 1.23IU/mL). Treatment during 3 months with prednisone(initially 1 mg/kg/day) and cyclophosphamide 50 mgp.o. daily, followed by i.v. gammaglobulins (0.4g/kg/day for 5 days) had no influence on the pres-ence of the antibodies. Later on a subcutaneous hem-orrhage in the left arm and bleeding in the sural mus-cles of the right leg occurred. During that periodrecombinant activated factor VII was successfullyadministered. After initiation of cyclosporin, the anti-bodies against factor VIII progressively decreased andfinally disappeared. The treatment was stopped aftereight months. The coagulation tests remained nor-mal. Spontaneously acquired antibodies against fac-tor VIII are infrequent. They peak in the third and sev-enth decades.1 Intramuscular bleeds are the mostcommon hemorrhagic manifestation. The majorcause of acquired antibodies against factor VIII,excluding hemophilia, are autoimmune disorders,scientific correspondence 895Haematologica vol. 85(8):August 2000Figure 1. Mesothelial cell with cytopathic changes sug-gestives of herpes virus infection.malignant diseases, pregnancy or drug reactions. Inabout 50% of the cases no underlying disease can beidentified. The prognosis is poor if untreated. Spon-taneous disappearance of the inhibitor has beenreported, but after a long delay. Acute bleeding peri-ods can be treated with recombinant activated fac-tor VII, as in hemophiliacs with inhibitors. Alterna-tives include large doses of factor VIII, a porcine fac-tor VIII, prothrombin complex concentrates (PCC)and activated PCC. The most frequently used treat-ments for elimination of the antibodies include oralcorticosteroids and cyclophosphamide. A high doseof i.v. gammaglobulins can also be effective.2 Thealternatives are interferon, a combination of steroids,cyclophosphamide and vincristine, or combinationchemotherapy. The effect of replacement therapy orremoving antibodies by plasmapheresis is only tran-sient.2,3 The experience with cyclosporine shows thatit might be effective in the treatment of acquiredhemophilia with a high antibody titer against factorVIII.3 Cyclosporine inhibits cell-mediated reactionsand plays a role in the induction of immune toler-ance against factor VIII. It does not affecthematopoiesis and causes fewer infectious compli-cations.4 This drug could be considered as a possibletreatment of acquired hemophilia if other modalitiesfail.Mirko Petrovic, Eric Derom, Gaston BaeleDepartment of Internal Medicine, Ghent University Hospital,Ghent, BelgiumKey words Cyclosporine, acquired hemophilia.CorrespondenceMirko Petrovic, M.D, Department of Internal Medicine,Ghent University Hospital, De Pintelaan 185, B 9000Ghent, Belgium. Phone: international +32-9-2402168 –Fax: international +32-9-2403053 – E-mail: mirko.petro-vic@rug.ac.beReferences1. Green D, Lechner K. A survey of 215 non-hemophilicpatients with inhibitors to Factor VIII. ThrombHaemost 1981; 45:200-3.2. Pirner K, Rösler W, Kalden JR, Manger B. Long-termremission after i.v. immunoglobulin therapy inacquired antihemophilic factor hemophilia with sys-temic lupus erythematosus. Z Rheumatol 1990; 49:378-81.3. Schulman S, Langevitz P, Livneh U, Mortinowitz U,Seligsohn U, Varon D. Cyclosporine therapy foracquired factor VIII inhibitor in a patient with systemiclupus erythematosus. Thromb Haemost 1996; 76:344-6.4. Pfliegler G, Boda Z, Harsfalvi J, et al. Cyclosporin treat-ment of a woman with acquired haemophilia due tofactor VIII:C inhibitor. Postgrad Med J 1989; 65:400-2.scientific correspondence896Haematologica vol. 85(8):August 2000

Cyclosporine treatment of acquired hemophilia due to factor VIII antibodies

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Cyclosporine treatment of acquired hemophilia due to factor VIII antibodies

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