THE ADMINISTRATION OF GRANULOCYTE COLONY-STIMULATING FACTOR TO HEALTHY DONORS FOR ALLOGENEIC PERIPHERAL BLOOD PROGENITOR CELL COLLECTİON MAY INDUCE THE TISSUE FACTOR DEPENDENT PATHWAY

Year 2001, Volume: 54 Issue: 3, 211 - 220, 30.09.2001

Pervin Topçuoğlu

Abstract

The hypercoagulable state caused by the use of rhG-CSF has been cited in several case reports. Since tissue factor (TF) is the main initlator of the coagulation protease cascade, we examined whether or not rhG-CSF had an inductive effect on the TF-dependent pathway. We reasured plasma TF antigen (TF Ag) and TF
procoagulant activity (TF PCA), TF expression on peripheral biood monocytes and neutrophils and plasma coagulation factor activities in 18 healthy donors (8F/10M; aged 17-52) receiving 10yg/kg/day rhG-CSF for five days in the aim of peripheral blood progenitor cell mobilization. Blood samples were collected before starting G-CSF and on the first day of stem'celi apheresis. There were significant Increases in TF Ag (p<0.05) and TF PCA (p>0.06) levels. Flow cytometric evaluation revealed a significant increase in TF expression on CD33 (4) celis (p-0.04). Mean plasma FVİİİ activity and vWWF activity also increased significantiy. Thrombin time was slightiy prolonged (p-0.06) due to significant increases in plasma D-dimer levels (p<0.05). in addition, while FIX activity remained stable, there were marked decreases in mean plasma FX and Fil activities and a slight decrease in FV activity that resulted in significant prolongation of prothrombin time. The administration of rhG-CSF in healthy stem cell donors increased the mean TF Ag and TF PCA in plasma and TF expression on celis, decreased extrinsic pathway factor activity, increased D-dimer levels and endothelial markers and prolonged PT. in conclusion, the administration of rhG-CSF led to a 'prothrombotic state” via stimulation of TF and increased endothelia| markers such as F Vili and vWF. in light of these findings, the use of rhG-CSF for stem cell mobilization should be undertaken cautiousiy in healthy donors with underiying thrombotic risk factors.

Keywords

Coagulation , G-CSF , Healthy Donor , Tissue Factor

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ALLOJENEİK PERİFERİK KÖK HÜCRE TOPLANAN SAĞLIKLI VERİCİLERDE GRANÜLOSİT KOLONİ STİMÜLE EDİCİ FAKTÖR KULLANIMI DOKU FAKTÖRÜ BAĞIMLI YOLU UYARA-: BİLİR

Abstract

Granülosit koloni stimule edici faktör (rhG-CSF) kullanımının neden olduğu hiperkoagulabiliteden değişik vaka sunularında söz edilmektedir. Doku faktörünün (DF) koagulasyon-proteaz kaskadının esas başlatıcısı olduğundan dolayı, rhG-CSF'nin DF bağımlı yol üzerine uyarıcı bir etkisi olup olmadığı çalışıldı. Periferik kan kök hücre mobilizasyonu amacı ile 10yg/kg/gün rhGCSF 3 gün süre ile kullanan 18 sağlıklı (8K/T0E, yaş 17-52) vericide, plazma DF antijen (DF:Ag) DF prokoagulan aktivite
(DF:PKA), periferik kandaki monosit ve nötrofillerde DF:Ag ekspresyonu ve plazma koagulasyon faktör aktivite düzeyleri çalışıldı. Kan örnekleri G-CSF başlamadan önce ve kök hücre aferezinin ilk günü toplandı. DF:Ag (p<0,05) ve DF:PKA'da (p-0,06) önemli artış vardı. Akım sitometrik değerlendirme CD33 (4) hücrelerde DF ekspresyonunda anlamlı bir artış ortaya kondu (p-0,04). Beraberinde plasma FVİlI ve WWE aktivitesi de anlamlı olarak arttı. Trombin zamanı, plazma D-Dimer seviyesindeki anlamlı artış (p<0,05) nedeni ile hafif uzadı (p-0,06). Ek olarak FIX aktivitesi sabit kalırken, ortalama plazma FX ve Fil aktivitelerinde ise belirgin azalma ve protrombin zamanında (PTZ) anlamlı uzamaya neden olan FVİI aktivitesinde hafif bir azalma vardı. Sağlıklı kök hücre vericilerinde rhG-CSF kullanımı ortalama plazma DF:Ag ve DF:PKA ve hücrelerde DF ekspresyonunu arttırdı, ekstrensek yol faktör aktivitesini azalttı D-Dimer düzeyleri ve endotelyal belirleyicileri arttırdı ve PTZ'yi uzattı. Sonuç olarak rhG-CSF kullanımı DF uyarımı ve, FVİİ ve vWEF gibi endotelyal belirleyicileri arttırarak bir 'protrombotik durum”a neden olmaktadır. Bu bulguların ışığında kök hücre mobilizasyonu için rhGCSF kullanırken sağlıklı vericilerde altta yatabilecek trombotik risk faktörleri dikkate alınmalıdır. Biz G-CSF kullanımından önce sağlıklı vericilerin altta yatan trombotik risk faktörleri yönünden değerlendirilmelerini öneriyoruz.

Keywords

Koagulasyon , G-CSF , Sağlıklı Verici , Doku Faktörü

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Project Number

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Thanks

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