Konjenital trombosit fonksiyon bozukluğu tanısıyla izlenen olgularımızın mutasyon analizi ve klinik olarak değerlendirilmesi
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Dosyalar
Tarih
2013
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Yayıncı
Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Glanzman trombastenisi ve Bernard Soulier Sendromu (BSS), nadir görülen konjenital trombosit fonksiyon bozukluğu hastalıklarıdır. BSS, makrotrombositopeni ve uzamış kanama zamanı ile karakterizedir. BSS, trombosit yüzeyinde hasarlı damar duvarına yapışmadan sorumlu GpIb/V/IX kompleksinin yokluğu veya disfonksiyonundan kaynaklanır. GT ise trombositlerin yüzeyinde GpIIb/IIIa reseptörünün yokluğu veya disfonksiyonundan kaynaklanan ve trombosit agregasyonunu bozan otozomal resesif kalıtımlı bir hastalıktır Bu tez çalışmasının amacı, Meram Tıp Fakültesi Çocuk hematoloji bölümünde konjenital trombosit fonksiyon bozukluğu (GT ve BSS) tanısıyla takip edilen olguların klinik ve laboratuar bulgularının ayrıntılı değerlendirilmesi, genetik mutasyon tipinin araştırılması ve mutasyon tipi ile klinik bulgular arasındaki ilişkinin incelenmesidir. Yöntem: Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi Çocuk Hematoloji Onkoloji bilim dalında takip edilen GT tanılı 20 olgu ve BSS tanılı 7 olgu çalışmaya dâhil edildi. Olguların dosya kayıtları geriye dönük olarak incelendi, klinik ve laboratuar bulguları ayrıntılı olarak dökümante edildi. Hastaların yaşı, cinsi, tanı alma yaşı, tanıdaki trombosit değerleri, akım sitometri bulguları (CD42ab, CD41, CD61), trombosit fonksiyon testi sonuçları, kanama fenotipleri ve mutasyon tipleri kaydedildi. Ayrıca GT ve BSS olgularını mutasyon analizi yapılarak, klinik gidişat ile olan ilişkisi araştırıldı. Olgularının kanama skorlaması, güncel bir kanama skorlama sistemine göre yapıldı. Bulgular: BSS ve GT hastalarında en sık görülen kanama şekillerinin mukokutanöz kanamalar (burun kanaması, diş eti kanaması, cilde ait kanamalar, menoraji, vb) olduğu görüldü. Olgulardan hiçbirinde kanamaya bağlı ölüm tespit edilmedi. Genetik olarak BSS olgularda 3 farklı mutasyon tanımlanmış olup, olguların altısında GP1BB geninde, birinde GP1BA geninde homozigot mutasyon tespit edildi. Bu mutasyonlar yeni tanımlanan mutasyonlar idi. Glanzman trombastenili olgularında glikoprotein IIB gen değişimleri incelendi ve 6 olguda değişim tespit edildi. Bu mutasyonlardan 5'i yeni tanımlanan mutasyon idi. Klinik bulgular ile genotip arasında gerek GT gerekse BSS hastalarında anlamlı bir korelasyon saptanmadı. Sonuç: Mukokutanöz kanamalar, trombosit fonksiyon bozukluklarında başlıca hastaneye başvuru sebebidir. Glanzman trombastenili olgularda tespit edilen 6 mutasyondan 5 tanesi, ve BSS' li olgularda gösterilen 3 farklı mutasyon tipi, literatürde daha önce tanımlanmamış mutasyonlardır. Bu mutasyonlarla klinik seyir arasındaki ilişkinin tanımlanabilmesi için daha kapsamlı çalışmalara ihtiyaç vardır.
Glanzman Thrombastenia (GT) and Bernard Soluier syndrome (BSS) are rare congenital platelet dysfunction disorders. BSS is characterized by macrothrombocytopenia and prolonged bleeding time. BSS is arised from dysfunction or absence of GpIb/V/IX which is responsible for platelet adhesion to damaged surface of blood vessels. GT is an autosomal recessive disease disrupting platelet aggregation, which is arised from absence or dysfunction of GpIIb/IIIa surface receptor on platelets. The purpose of this study is detailed evaluation of clinic and laboratory findings of patients with congenital thrombocyte dysfunction, is investigation of genetic mutation type and investigation of relationship between mutation type and clinical findings, in our pediatric haematology department of Meram Medical Faculty. Methods: Seven patients diagnosed with BSS and 20 patients with GT are included in the study, followed by pediatric haematology oncology department of NEÜ Meram Medical Faculty. The file records of the patients were retrospectively reviewed and clinical and larobatory findings were detailed documented. The patient's age, sex, diagnose age, platelet count at diagnosis, flow sytometry data (CD42ab, CD41, CD61), platelet function tests, bleeding phenotype and mutations were recorded. The relationship mutation with clinical outcome was examined, which is made the mutation analysis of GT and BSS patients. Bleeding scales of patients were obtained by using a currently scoring system. Results: It was seen that mucocutaneous bleedings are the most common form of bleeding in patients with BSS and GT ( epistaxis, gum bleeding, cutaneous bleeding, menorrhagia, etc.). None of the cases of death due to bleeding was detected. Three different mutations were determined in BSS cases, homozygous mutations were detected in GP1BB gene in six of all cases, GP1BA gene in one. These mutations were newly identified mutations. Glycoprotein IIB gene changes were examined and detected in 6 cases with GT. Five of all mutations were newly identified mutations. There is no significant correlation between clinical findings and genotype in both GT and BSS patients. Discussion: Mucocutaneous bleedings are the major reason to refer to hospital in platelet dysfunctions. Five of the 6 mutations identified in GT cases, and three different mutations identified in BSS are not previously identified in literature. More extensive studies are needed to identify correlation between clinical outcome and these mutations.
Glanzman Thrombastenia (GT) and Bernard Soluier syndrome (BSS) are rare congenital platelet dysfunction disorders. BSS is characterized by macrothrombocytopenia and prolonged bleeding time. BSS is arised from dysfunction or absence of GpIb/V/IX which is responsible for platelet adhesion to damaged surface of blood vessels. GT is an autosomal recessive disease disrupting platelet aggregation, which is arised from absence or dysfunction of GpIIb/IIIa surface receptor on platelets. The purpose of this study is detailed evaluation of clinic and laboratory findings of patients with congenital thrombocyte dysfunction, is investigation of genetic mutation type and investigation of relationship between mutation type and clinical findings, in our pediatric haematology department of Meram Medical Faculty. Methods: Seven patients diagnosed with BSS and 20 patients with GT are included in the study, followed by pediatric haematology oncology department of NEÜ Meram Medical Faculty. The file records of the patients were retrospectively reviewed and clinical and larobatory findings were detailed documented. The patient's age, sex, diagnose age, platelet count at diagnosis, flow sytometry data (CD42ab, CD41, CD61), platelet function tests, bleeding phenotype and mutations were recorded. The relationship mutation with clinical outcome was examined, which is made the mutation analysis of GT and BSS patients. Bleeding scales of patients were obtained by using a currently scoring system. Results: It was seen that mucocutaneous bleedings are the most common form of bleeding in patients with BSS and GT ( epistaxis, gum bleeding, cutaneous bleeding, menorrhagia, etc.). None of the cases of death due to bleeding was detected. Three different mutations were determined in BSS cases, homozygous mutations were detected in GP1BB gene in six of all cases, GP1BA gene in one. These mutations were newly identified mutations. Glycoprotein IIB gene changes were examined and detected in 6 cases with GT. Five of all mutations were newly identified mutations. There is no significant correlation between clinical findings and genotype in both GT and BSS patients. Discussion: Mucocutaneous bleedings are the major reason to refer to hospital in platelet dysfunctions. Five of the 6 mutations identified in GT cases, and three different mutations identified in BSS are not previously identified in literature. More extensive studies are needed to identify correlation between clinical outcome and these mutations.
Açıklama
Anahtar Kelimeler
Trombosit fonksiyon bozukluğu, Thrombocyte dysfunction, Mutasyon, Mutation, Kanama, Bleeding
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Tokgöz, H. (2013). Konjenital trombosit fonksiyon bozukluğu tanısıyla izlenen olgularımızın mutasyon analizi ve klinik olarak değerlendirilmesi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Dahili Tıp Bilimleri Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Konya.
