2003; baxter - Supplements - Haematologica

98F. Baudo et al.of bleeding, 4 from the initial episode, 2 atrelapse and 2 during the immunosuppressivetherapy. All deaths occurred in the subgroupunrelated to pregnancy. The mortality related tobleeding is similar to that described in otherreports. 1,2,4,5 The high mortality of the cases unrelatedto pregnancy and the high percentage ofthe patients rescued suggest that other agentsalone or combined with prednisone might be areasonable choice. 2,6,9-13Pregnancy is a frequent concomitant conditionin the FVIII inhibitor syndrome. In our survey21% of the cases were associated with a pregnancy;other studies reported a lower incidence (7-11%). 2-4,6 The majority of the post-partum casesin our series were idiopathic (19/20). Theinhibitor occurred in the first pregnancy in 16out of 20 patients and did not recur in the fourwomen who had a subsequent pregnancy. Thesame observations were reported by others 7,14-16but in the survey by Solymoss the inhibitorrecurred in 3 women during pregnancies. 8 Theinhibitor was identified because of the occurrenceof bleeding in 10 women in the peripartum periodand in 10 women more than 30 days afterdelivery. In the series reported by Solymoss thebleeding occurred pre-partum in 2 women, within3 days from delivery in 3 and within 3-12months in 9. 8 In the review by Michiels bleedingoccurred during pregnancy in 1 woman, after anabortion in 1, immediately after delivery in 4,within 4 months in 8, and after a period of 4months to over 12 months in 27 women. 15 Thetime of the occurrence of bleeding is quite variable.The inhibitor is in general identified onoccasion of overt bleeding; the time of the developmentof the inhibitor in the absence of bleedingsigns cannot be determined retrospectively.The onset of bleeding in the 9 women who didnot require treatment was later (range 60-150days) than in those who required therapy (Table10). In the survey by Solymoss 3 out of 14 patientsdid not require therapy to control their bleeding. 8Mortality in post-partum patients is low. No fatalitieswere reported in our series or in that by Solymoss;4 out of 40 women (10%) died in Michiels’survey. 15Inhibitors may cross the placenta and may persistfor up to three months in the fetus, usuallywithout causing bleeding complications. 17-19 However,Ries reported a case of an intracranial hemorrhagein a neonate. 20 These data suggest thatdelivery should be managed as in hemophilia. 21In our survey information on the neonates wasnot requested.Immunosuppressive treatment with steroidsalone or in combination with other agents wasalso the preferred treatment (17/18) during thesepregnancy-related cases. The response rate washigh (94%), as too was the relapse rate (42%),but all the patients were rescued. Immunosuppressivetherapy may shorten the time to responsewithout influencing the response rate. Hauser etal. reviewed the post partum-data in the literaturecomparing immunosuppressive therapy versus notreatment. Time to response was shorter in thetreated patients but the overall response rate wasnot different. 7 Similar results were reported byMichiels. 15 These studies must be considered withcaution for a number of reasons. They are retrospective,refer to a small number of patients withheterogeneous characteristics and have no predefinedcriteria for treatment. Nevertheless steroidsmay be considered the treatment of choice. 21 Asgeneral consideration the final outcome of thepost-partum inhibitor syndrome is favorable,independently of the type of treatment. Thereforethe recognition of the syndrome is of utmostimportance.Acquired hemophilia usually occurs in generalhospitals. A prolonged aPTT should not be overlooked.In the presence of an unexplained oftensevere hemorrhage with an abnormal coagulationscreening test it is important to seek immediatespecialist advice. Because of the rarity of thedisorder, the treatment modality and the potentialrisk of severe bleeding, these patients shouldbe managed in hemophilia centers or under thesupervision of such centers. 22,23References1. Lottenberg R, Kentro TB, Kitchens CS. Acquired hemophilia.A natural history study of 16 patients with factorVIII inhibitors receiving little or no therapy. ArchIntern Med 1987;147:1077-81.2. Green D, Lechner K. A survey of 215 non-hemophilicpatients with inhibitors to Factor VIII. Thromb Haemost1981;45:200-3.3. Kessler CM, Ludlam CA. The treatment of acquired factorVIII inhibitors: worldwide experience with porcinefactor VIII concentrate. International Acquired HemophiliaStudy Group. Semin Hematol 1993;30 Suppl 1:22-7.4. Ludlam CA, Morrison AE, Kessler C. Treatment ofacquired hemophilia. Semin Hematol 1994;31 Suppl 4:16-9.5. Morrison AE, Ludlam CA. Acquired haemophilia andits treatment. Br J Haematol 1995;89:231-6.6. Bossi P, Cabane J, Ninet J, Dhote R, Hanslik T, ChosidowO, et al. Acquired hemophilia due to factor VIIIinhibitors in 34 patients. Am J Med 1998;105:400-8.7. Hauser I, Schneider B, Lechner K. Post-partum factorVIII inhibitors. A review of the literature with specialreference to the value of steroid and immunosuppressivetreatment. Thromb Haemost 1995;73:1-5.8. Solymoss S. Post partum acquired factor VIII inhibitors:results of a survey. Am J Hematol 1998;59:1-4.9. Spero JA, Lewis JH, Hasiba U. Corticosteroid therapy foracquired FVIII:C inhibitors. Br J Haematol 1991; 48:636-42.10. Green D, Rademaker AW, Briet E. A prospective, randomizedtrial of prednisone and cyclophosphamide inthe treatment of patients with factor VIII autoantibodies.Thromb Haemost 1993;70:753-7.11. Herbst KD, Rapaport SI, Kenoyer DG, Stanton W, FeinsteinDI. Syndrome of an acquired inhibitor of factorVIII responsive to cyclophosphamide and prednisone.Ann Intern Med 1981;95:575-8.12. Lian EC, Larcada AF, Chiu AY. Combination immunosuppressivetherapy after factor VIII infusion foracquired factor VIII inhibitor. Ann Intern Med 1989;110:774-8.13. Shaffer LG, Phillips MD. Successful treatment ofacquired hemophilia with oral immunosuppressive therapy.Ann Intern Med 1997;127:206-9.14. Neidhardt B, Bartels O, Hahn B. Postpartum hemo-haematologica vol. 88(supplement n. 12):september 2003