Tesis

Proporsi dan karakteristik inhibitor faktor VIII serta perubahan inhibitor faktor VIII titer rendah pada anak penyandang hemofilia A = Proportion, Characteristic of FVIII Inhibitor and Observation in Low Titer FVIII Inhibitor in Child with Hemophilia A.

Latar belakang: Inhibitor faktor VIII (FVIII) merupakan komplikasi utama dari penggunaan FVIII eksogen yang merupakan terapi utama hemofilia A. Pemeriksaan inhibitor FVIII diperlukan untuk deteksi dini, penyesuaian terapi dan pencegahan komplikasi hemofilia A tetapi pemeriksaannya belum dilakukan rutin di Indonesia sehingga perlu dilakukan penelitian untuk mengetahui proporsi, karakteristik dan faktor risiko inhibitor FVIII untuk menentukan kebijakan dalam tata laksana hemofilia A selanjutnya. Selain itu inhibitor titer rendah pada sebagian pasien hemofilia A masih menimbulkan pertanyaan mengenai kepentingan klinis dari terdeteksinya inhibitor tersebut. Oleh karena itu perlu dilakukan penelitian untuk mengetahui makna klinisnya. Tujuan: Mengetahui proporsi, karakteristik dan faktor yang memengaruhi terbentuknya inhibitor serta perubahan inhibitor titer rendah pada anak penyandang hemofilia A di RSCM. Metode: Penelitian potong lintang pada penyandang hemofilia A anak di RSCM serta longitudinal pada subjek dengan inhibitor titer rendah. Subjek dengan inhibitor titer rendah dilakukan pengukuran ulang inhibitor dalam waktu 6 bulan. Pemeriksaan inhibitor menggunakan metode Nijmegen Bethesda asay. Inhibitor persisten bila masih terdeteksi dalam 6 bulan dan transien bila tidak terdeteksi dalam 6 bulan. Faktor risiko yang dinilai yaitu jenis hemofilia, usia saat terdiagnosis, usia saat pertama menggunakan FVIII eksogen, riwayat keluarga dengan inhibitor, golongan darah, exposures days, annual bleeding rate, annual joint bleeding rate, target joint, jenis dosis, riwayat pembedahan atau perdarahan mayor. Hasil: Terdapat 100 subjek yang ikut serta dalam penelitian ini, terdiri dari 76 subjek dengan hemofilia A berat, 16 subjek hemofilia A sedang dan 8 subjek hemofilia A ringan. Prevalens inhibitor pada penelitian ini sebesar 13% terdiri dari 8% inhibitor titer tinggi dan 5% inhibitor titer rendah. Faktor risiko yang berpengaruh terhadap kejadian inhibitor adalah riwayat keluarga dengan inhibitor yaitu dengan nilai risiko relatif (RR) 3,259 p= 0,022 (IK 95% 1,185– 8,693). 5 subjek dengan inhibitor titer rendah 2 diantaranya merupakan inhibitor persisten dan salah satunya menjadi inhibitor persisten tinggi. Kesimpulan: Faktor risiko yang berpengaruh terhadap kejadian inhibitor adalah riwayat keluarga dengan inhibitor. Progresifitas inhibitor titer rendah dapat terjadi sehingga pemeriksaan inhibitor perlu dilakukan minimal sekali dalam 6 bulan.
Kata kunci: hemofilia A, inhibitor FVIII, anak


Background: Inhibitor FVIII was complication of replacement therapy in hemofilia A. Inhibitor FVIII was needed for early detection, therapy adjustment and prevention for complication in hemophilia A therapy. Routine inhibitor testing is challenging in Indonesia due to limited resources, making it impossible to do early detection of FVIII inhibitor status in hemophilia A patient. Research needs to be carried out to determine the proportion, characteristics and risk factors of inhibitors to determine policies for further management of hemophilia. In addition, low titer inhibitors in some hemophilia A patients still raise questions regarding the clinical importance of detecting these inhibitors. Therefore, research needs to be carried out to determine its clinical meaning. Objective: To determine the proportions, characteristics and factors that influence the formation of inhibitors and changes in low titer inhibitors in children with hemophilia A at RSCM. Method: Cross-sectional research conducted at RCSM on children with hemophilia A and longitudinal study for subject with low titer inhibitor FVIII. Subject with low titer inhibitor FVIII were had Inhibitor measurements twice within 6 months interval. FVIII inhibitor titer was determined using the Nijmegen-Bethesda assay. Inhibitors were considered persistent if they were still detected in measurements taken 6 months apart, while they were considered transient if no inhibitors were detected in the second measurement. Risk factors assessed were type of hemophilia, age at diagnosis, age at first use of exogenous FVIII, family history of inhibitors, blood type, exposure days, annual bleeding rate, annual joint bleeding rate, target joint, type of dose, history of surgery or major bleeding. Results: There were 100 subjects included in this study, consisting of 76 subjects with severe hemophilia A, 16 subjects with moderate hemophilia A and 8 subjects with mild hemophilia A. The prevalence of inhibitors in this study was 13% consisting of 8% high titer inhibitors and 5% low titer inhibitors. The risk factor that influences the incidence of inhibitors is a family history of inhibitors with relative risk (RR) 3,259 p= 0,022 (95% CI 1,185 – 8,693). 5 subjects with low titer inhibitors, 2 of them were persistent inhibitors and one of them was a high persistent inhibitor. Conclusion: Risk factor of FVIII inhibitors was family history of inhibitors. Low titer inhibitor FVIII can be progress to be high titer so inhibitor tests need to be carried out at least once every 6 months.
Keywords: hemophilia A, inhibitor, pediatric