Clinical Manifestations, Treatment Characteristics, and Clinical Outcomes in Patients with Immune Thrombotic Thrombocytopenic Purpura (iTTP) in a Real-World Setting: An Interim Analysis of the Turkish iTTP Registry
Sema Karakuş1, Şule Mine Bakanay2, Sevgi Kalayoğlu Beşişik3, Ahmet Emre Eşkazan4, Orhan Ayyıldız5, Emel Gürkan6, Ozan Salim7, Volkan Karakuş8, Nil Güler9, Muzaffer Keklik10, Osman İlhami Özcebe11, Fahir Özkalemkaş12, Vildan Özkocaman12, Umut Yılmaz4, Senem Dadin3, Mehmet Ali Uçar6, Mehmet Sönmez13, Abdullah Karakuş5, Ünal Ataş7, Lütfullah Zahit Koç8, Eren Gündüz14, Sibel Kabukçu Hacıoğlu9, Başak Ünver Koluman9, Gülsüm Özet2, Tekin Güney15, Kemal Fidan10, Tülay Karaağaç Akyol11, Cevat İlteriş Kıkılı3, Fatih Demirkan16, İrfan Yavaşoğlu17, Simten Dağdaş15, Merve Kestane13, Havva Üsküdar Teke14, Selami Koçak Toprak18, Aylin Karataş16, Münci Yağcı19, Düzgün Özatlı20, Zübeyde Nur Özkurt19, Osman İlhan21, Muhlis Cem Ar41Başkent University Faculty of Medicine, Department of Hematology, Ankara, Türkiye2Ankara Yıldırım Beyazıt University Faculty of Medicine, Bilkent City Hospital, Clinic of Hematology, Ankara, Türkiye
3İstanbul University, İstanbul Faculty of Medicine, Department of Hematology, İstanbul, Türkiye
4İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Hematology, İstanbul, Türkiye
5Dicle University Faculty of Medicine, Department of Hematology, Diyarbakır, Türkiye
6Çukurova University Faculty of Medicine, Department of Hematology, Adana, Türkiye
7Akdeniz University Faculty of Medicine, Department of Hematology, Antalya, Türkiye
8University of Health Sciences Türkiye, Antalya Training and Research Hospital, Clinic of Hematology, Antalya, Türkiye
9Pamukkale University Faculty of Medicine, Department of Hematology, Denizli, Türkiye
10Erciyes University Faculty of Medicine, Department of Hematology, Kayseri, Türkiye
11Hacettepe University Faculty of Medicine, Department of Hematology, Ankara, Türkiye
12Bursa Uludağ University Faculty of Medicine, Department of Hematology, Bursa, Türkiye
13Karadeniz Technical University Faculty of Medicine, Department of Hematology, Trabzon, Türkiye
14Eskişehir Osmangazi University Faculty of Medicine, Department of Hematology, Eskişehir, Türkiye
15University of Health Sciences, Bilkent City Hospital, Clinic of Hematology, Ankara, Türkiye
16Dokuz Eylül University Faculty of Medicine, Department of Hematology, İzmir, Türkiye
17Aydın Adnan Menderes University Faculty of Medicine, Department of Hematology, Aydın, Türkiye
18Ankara University Faculty of Medicine, Department of Hematology, Ankara, Türkiye
19Gazi University Faculty of Medicine, Department of Hematology, Ankara, Türkiye
20Ondokuz Mayıs University Faculty of Medicine, Department of Hematology, Samsun, Türkiye
21Lokman Hekim University Faculty of Medicine, Department of Hematology, Ankara, Türkiye
Objective: This study aimed to investigate the clinical manifestations, treatment patterns, and clinical outcomes of patients with immune thrombotic thrombocytopenic purpura (iTTP) across Türkiye via an interim analysis of the Turkish iTTP Registry.
Materials and Methods: A total of 215 patients with iTTP (median age at diagnosis: 41 years; 58.6% female) diagnosed between 2001 and 2023 were retrospectively analyzed in the interim analysis of a prospective non-interventional observational multicenter iTTP registry study (ClinicalTrials.gov Identifier: NCT05950750) conducted at 19 tertiary hematology centers. Data on patient demographics, disease characteristics at initial admission, treatment characteristics and responses, exacerbations/relapses, and survival outcome were obtained from electronic case report forms.
Results: Infection (15.0%), new drug initiation (9.7%), and pregnancy/ postpartum period (6.3%) within 3 weeks before diagnosis were the most prevalent potential triggers. Patients presented most commonly with systemic/constitutional (fatigue: 68.8%; fever: 18.1%) and neurological (headache: 40.0%; vertigo: 32.1%) symptoms, followed by hemorrhagic, gastrointestinal, renal, and cardiovascular manifestations. Based on PLASMIC risk scoring, 77.8% of patients were initially at high risk for TTP. The initial treatment was begun within the first 48 hours of hospital admission for 64.1% of patients (36.2% on the day of admission). Treatment was mainly based on therapeutic plasma exchange (92.1%) and steroids (63.7%), while rituximab was used in 15.8% of patients. The clinical response rate was 79.9% and clinical remission was achieved by 68.2% of patients. Regarding a thrombospondin type 1 motif member (ADAMTS13) 13 levels, partial and complete responses were achieved by 17.7% and 14.6%, respectively. During a median of 30 months (range: 0.1-262.4 months) of follow-up, 35 patients experienced exacerbations/relapses. Mortality occurred in 11 (5.5%) patients and was found to be diseaserelated in 6 cases (3.0%).
Conclusion: This interim analysis of the nationwide Turkish iTTP Registry study provides valuable data on real-world clinical practices in the diagnosis and management of iTTP at different hematology clinics across the country.
İmmün Trombotik Trombositopenik Purpura (iTTP) Hastalarının Klinik Bulguları, Tedavi Özellikleri ve Klinik Sonuçlarının Gerçek Yaşam Değerlendirmesi: Türk iTTP Kayıt Çalışması Ara Analizi
Sema Karakuş1, Şule Mine Bakanay2, Sevgi Kalayoğlu Beşişik3, Ahmet Emre Eşkazan4, Orhan Ayyıldız5, Emel Gürkan6, Ozan Salim7, Volkan Karakuş8, Nil Güler9, Muzaffer Keklik10, Osman İlhami Özcebe11, Fahir Özkalemkaş12, Vildan Özkocaman12, Umut Yılmaz4, Senem Dadin3, Mehmet Ali Uçar6, Mehmet Sönmez13, Abdullah Karakuş5, Ünal Ataş7, Lütfullah Zahit Koç8, Eren Gündüz14, Sibel Kabukçu Hacıoğlu9, Başak Ünver Koluman9, Gülsüm Özet2, Tekin Güney15, Kemal Fidan10, Tülay Karaağaç Akyol11, Cevat İlteriş Kıkılı3, Fatih Demirkan16, İrfan Yavaşoğlu17, Simten Dağdaş15, Merve Kestane13, Havva Üsküdar Teke14, Selami Koçak Toprak18, Aylin Karataş16, Münci Yağcı19, Düzgün Özatlı20, Zübeyde Nur Özkurt19, Osman İlhan21, Muhlis Cem Ar41Başkent University Faculty of Medicine, Department of Hematology, Ankara, Türkiye2Ankara Yıldırım Beyazıt University Faculty of Medicine, Bilkent City Hospital, Clinic of Hematology, Ankara, Türkiye
3İstanbul University, İstanbul Faculty of Medicine, Department of Hematology, İstanbul, Türkiye
4İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Department of Hematology, İstanbul, Türkiye
5Dicle University Faculty of Medicine, Department of Hematology, Diyarbakır, Türkiye
6Çukurova University Faculty of Medicine, Department of Hematology, Adana, Türkiye
7Akdeniz University Faculty of Medicine, Department of Hematology, Antalya, Türkiye
8University of Health Sciences Türkiye, Antalya Training and Research Hospital, Clinic of Hematology, Antalya, Türkiye
9Pamukkale University Faculty of Medicine, Department of Hematology, Denizli, Türkiye
10Erciyes University Faculty of Medicine, Department of Hematology, Kayseri, Türkiye
11Hacettepe University Faculty of Medicine, Department of Hematology, Ankara, Türkiye
12Bursa Uludağ University Faculty of Medicine, Department of Hematology, Bursa, Türkiye
13Karadeniz Technical University Faculty of Medicine, Department of Hematology, Trabzon, Türkiye
14Eskişehir Osmangazi University Faculty of Medicine, Department of Hematology, Eskişehir, Türkiye
15University of Health Sciences, Bilkent City Hospital, Clinic of Hematology, Ankara, Türkiye
16Dokuz Eylül University Faculty of Medicine, Department of Hematology, İzmir, Türkiye
17Aydın Adnan Menderes University Faculty of Medicine, Department of Hematology, Aydın, Türkiye
18Ankara University Faculty of Medicine, Department of Hematology, Ankara, Türkiye
19Gazi University Faculty of Medicine, Department of Hematology, Ankara, Türkiye
20Ondokuz Mayıs University Faculty of Medicine, Department of Hematology, Samsun, Türkiye
21Lokman Hekim University Faculty of Medicine, Department of Hematology, Ankara, Türkiye
Amaç: Bu çalışma, Türkiye genelinde immün trombotik trombositopenik purpura (iTTP) hastalarının klinik bulgularını, tedavi modellerini ve klinik sonuçlarını Türk iTTP kayıt sisteminin ara analizine dayanarak araştırmayı amaçlamıştır.
Gereç ve Yöntem: Bu retrospektif, girişimsel olmayan, gözlemsel çok merkezli iTTP kayıt çalışmasının (ClinicalTrials.gov Identifier: NCT05950750) ara analizine 19 üçüncü basamak hematoloji merkezinden 2001-2023 yılları arasında tanı almış toplam 215 iTTP hastası (ortanca tanı yaşı 41, %58,6’sı kadın) dahil edilmiştir. Hastaların demografik özellikleri, ilk başvurudaki tanı özellikleri, aldıkları tedaviler ve tedavi yanıtları, hastalık alevlenme ve nüks oranları ve sağkalım sonuçları her merkez tarafından elektronik olgu rapor formuna kaydedilmiştir.
Bulgular: Tanıdan önceki 3 hafta içerisinde enfeksiyon (%15), yeni ilaç başlanması (%9,7) ve gebelik/postpartum durum (%6,3) en sık gözlenen potansiyel uyarıcı faktörler olarak bulunmuştur. Hastaların en sık sistemik/konstitüsyonel (bitkinlik %68,8; ateş %18,1) ve nörolojik (baş ağrısı %40, vertigo %32,1) semptomlarla geldiği, bunları kanama, gastrointestinal, renal ve kardiyovasküler semptomların takip ettiği gözlenmiştir. Başlangıç PLASMIC risk skorlamasına göre hastaların %77,8’i TTP için yüksek risk kategorisinde idi. Hastaların %64,1’ine (%36,2’sine ilk 24 saat içerisinde) başvuru sonrası ilk 48 saat içerisinde tedavi başlanmıştı. Başlangıç tedavisi plazma değişimi (%92,1) ve steroid (%63,7), yanısıra rituksimab (%15,8) da kullanılmıştı. Hastaların %79,9’unda klinik yanıt, %68,2’sinde ise klinik remisyon sağlanmıştır. ADAMTS13 yanıtı değerlendirildiğinde, sırasıyla %17,7 ve %14,6 hastada kısmi ve tam remisyon elde edilmişti. Ortanca 30 ( 0,1- 262,4 ) aylık takipte 35 (%16,3) hastada alevlenme/relaps saptanırken toplam 11 (%5,5) hasta kaybedildi ve ölümlerin 6 (%3)’ünün hastalık ilişkili olduğu tespit edildi.
Sonuç: Bu ulusal iTTP kayıt çalışmasının ara analizi Türkiye’deki farklı hematoloji merkezlerinden iTTP tanı ve tedavisine ait çok değerli gerçek-yaşam verisini sağlaması açısından önemlidir.
Manuscript Language: English
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