E-ISSN: 1308-5263
Thrombolysis with Systemic Recombinant Tissue Plasminogen Activator in Children: A Multicenter Retrospective Study [Turk J Hematol]
Turk J Hematol. 2021; 38(4): 294-305 | DOI: 10.4274/tjh.galenos.2021.2021.0038  

Thrombolysis with Systemic Recombinant Tissue Plasminogen Activator in Children: A Multicenter Retrospective Study

Emine Zengin1, Nazan Sarper1, Arzu Yazal Erdem2, Işık Odaman Al3, Melike Sezgin Evim4, Neşe Yaralı2, Burcu Belen5, Arzu Akçay6, Ayşen Yıldırım7, Tuba Hilkay Karapınar3, Adalet Meral Güneş4, Sema Aylan Gelen1, Hale Ören8, Lale Olcay5, Birol Baytan4, Hüseyin Gülen7, Gülyüz Öztürk6, Mehmet Fatih Orhan9, Yeşim Oymak3, Sibel Akpınar10, Özlem Tüfekçi8, Meryem Albayrak11, Burçak Tatlı Güneş12, Aylin Canpolat13, Namık Özbek2
1Kocaeli University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Kocaeli, Turkey
2University of Health Sciences Turkey, Ankara City Hospital, Department of Pediatrics, Division of Pediatric Hematology, Ankara, Turkey
3University of Health Sciences Turkey, Dr. Behçet Uz Pediatrics and Pediatric Surgery Training and Research Hospital, İzmir, Turkey
4Uludağ University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Bursa, Turkey
5Başkent University Ankara Hospital, Clinic of Pediatrics, Division of Pediatric Hematology, Ankara, Turkey
6Acıbadem Mehmet Ali Aydınlar University Acıbadem Hospital, Clinic of Pediatric Hematology, İstanbul, Turkey
7Celal Bayar University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Manisa, Turkey
8Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, İzmir, Turkey
9Sakarya University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Sakarya, Turkey
10University of Health Sciences Turkey, Kanuni Sultan Süleyman Training and Research Hospital, Clinic of Pediatrics, Division of Pediatric Hematology, İstanbul, Turkey
11Kırıkkale University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Kırıkkale, Turkey
12University of Health Sciences Turkey, Tepecik Training and Research Hospital, Department of Pediatrics, Division of Pediatric Hematology, İzmir, Turkey
13İstanbul Medeniyet University Göztepe Training and Research Hospital, Clinic of Pediatrics, Division of Pediatric Hematology, İstanbul, Turkey

Objective: This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA).
Materials and Methods: Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h.
Results: Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p>0.05).
Conclusion: Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.

Keywords: Rekombinant doku plazminojen aktivatörü, Tromboliz, Çocukluk trombozu


Çocuklarda Sistemik Rekombinant Doku Plazminojen Aktivatörü ile Tromboliz: Çok Merkezli Bir Retrospektif Çalışma

Emine Zengin1, Nazan Sarper1, Arzu Yazal Erdem2, Işık Odaman Al3, Melike Sezgin Evim4, Neşe Yaralı2, Burcu Belen5, Arzu Akçay6, Ayşen Yıldırım7, Tuba Hilkay Karapınar3, Adalet Meral Güneş4, Sema Aylan Gelen1, Hale Ören8, Lale Olcay5, Birol Baytan4, Hüseyin Gülen7, Gülyüz Öztürk6, Mehmet Fatih Orhan9, Yeşim Oymak3, Sibel Akpınar10, Özlem Tüfekçi8, Meryem Albayrak11, Burçak Tatlı Güneş12, Aylin Canpolat13, Namık Özbek2
1Kocaeli University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Kocaeli, Turkey
2University of Health Sciences Turkey, Ankara City Hospital, Department of Pediatrics, Division of Pediatric Hematology, Ankara, Turkey
3University of Health Sciences Turkey, Dr. Behçet Uz Pediatrics and Pediatric Surgery Training and Research Hospital, İzmir, Turkey
4Uludağ University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Bursa, Turkey
5Başkent University Ankara Hospital, Clinic of Pediatrics, Division of Pediatric Hematology, Ankara, Turkey
6Acıbadem Mehmet Ali Aydınlar University Acıbadem Hospital, Clinic of Pediatric Hematology, İstanbul, Turkey
7Celal Bayar University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Manisa, Turkey
8Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, İzmir, Turkey
9Sakarya University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Sakarya, Turkey
10University of Health Sciences Turkey, Kanuni Sultan Süleyman Training and Research Hospital, Clinic of Pediatrics, Division of Pediatric Hematology, İstanbul, Turkey
11Kırıkkale University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology, Kırıkkale, Turkey
12University of Health Sciences Turkey, Tepecik Training and Research Hospital, Department of Pediatrics, Division of Pediatric Hematology, İzmir, Turkey
13İstanbul Medeniyet University Göztepe Training and Research Hospital, Clinic of Pediatrics, Division of Pediatric Hematology, İstanbul, Turkey

Amaç: Geriye dönük çok merkezli bir çalışma düzenleyerek, çocuk hematoloji uzmanlarının sistemik rekombinant doku plazminojen aktivatörü (rtPA) kullanımı ile ilgili deneyimlerinin ortaya konması amaçlandı
Gereç ve Yöntem: Türkiye’deki 13 pediatrik hematoloji merkezinden geriye dönük veriler toplandı. rtPA tedavisinin dozu ve süresi, eşzamanlı antikoagülan tedavi, tam pıhtı erimesi (TPE), kısmi pıhtı erimesi (KPE) ve kanama komplikasyonları değerlendirildi. Düşük doz (DD) rtPA tedavisi 0,01-0,06 mg/kg/saat ve yüksek doz (YD) 0,1-0,5 mg/kg/saat olarak tanımlandı.
Bulgular: 2005-2019 yılları arasında ortanca yaşı 5 yıl (1 gün-17,75 yıl) olan 54 hastanın 55 trombotik epizodu değerlendirildi. Hastaların tanıları; intrakardiyak tromboz (n=16), derin ven trombozu (DVT) (n=15), inme dışı arteriyel tromboz (n=14), pulmoner tromboemboli (PE) (n=6) ve inme (n=4) idi. Trombüs saptanmasından rtPA başlangıcına kadar geçen süre medyan 12 saat (2 sa-504 sa) idi ve inme, inme olmayan arteriyel tromboz ve intrakardiyak tromboza kıyasla DVT ve PE için anlamlı olarak daha uzundu (p=0,024). Atakların %63,6’sında rtPA tedavisinden önce heparin başlandı. Atakların 22’sine DD ve 33’üne YD rtPA uygulandı. DD ve YD rtPA ataklarının sırasıyla %90’ında ve %36’sında eş zamanlı antikoagülasyon kullanıldı (p=0,0001). DD ve YD rtPA infüzyonlarının medyan toplam süresi sırasıyla 30 sa (2 sa- 120 sa) ve 18 sa (2 sa-120 sa) idi (p=0,044). Ölümcül olmayan majör ve minör kanama oranları DD için sırasıyla %12,5, %16,7 ve YD rtPA için %3,2, %25,8 idi. rtPA infüzyonlarının sonunda, atakların sırasıyla %32,7’sinde TPE ve %49’unda KPE elde edildi. Tromboliz için en başarılı bölge intrakardiyak trombozdu. YD’ye karşı DD rtPA uygulaması, TPE/ KPE veya kanama ile korele değildi (p>0,05).
Sonuç: Yüksek riskli trombozlu çocuklarda sistemik trombolitik tedavi, deneyimli hematologlar tarafından rekanalizasyon ve kanamanın yakın takibi altında doğru endikasyon ve doğru zamanda kullanıldığında etkin bir şekilde hayat ve organ kurtarabilir.

Anahtar Kelimeler: Recombinant tissue plasminogen activator, Thrombolysis, Childhood thrombosis


Emine Zengin, Nazan Sarper, Arzu Yazal Erdem, Işık Odaman Al, Melike Sezgin Evim, Neşe Yaralı, Burcu Belen, Arzu Akçay, Ayşen Yıldırım, Tuba Hilkay Karapınar, Adalet Meral Güneş, Sema Aylan Gelen, Hale Ören, Lale Olcay, Birol Baytan, Hüseyin Gülen, Gülyüz Öztürk, Mehmet Fatih Orhan, Yeşim Oymak, Sibel Akpınar, Özlem Tüfekçi, Meryem Albayrak, Burçak Tatlı Güneş, Aylin Canpolat, Namık Özbek. Thrombolysis with Systemic Recombinant Tissue Plasminogen Activator in Children: A Multicenter Retrospective Study. Turk J Hematol. 2021; 38(4): 294-305

Corresponding Author: Emine Zengin, Türkiye


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