Kronik karaciğer hastalıklarında serumdaki doğal antikoagulanların düzeyindeki değişiklikler ve portal tromboz ile ilişkileri

Alterations in serum levels of the natural anticoagulants in chronic liver diseases and their relations to portal thrombosis

Özet

Karaciğerden sentezlenen doğal antikoagulan faktörler olan Protein C (PC), Protein S (PS) ve Antitrombin III (ATIII)'ün akut ve kronik karaciğer hastalıklarında serum düzeylerinin azaldığı bildirilmiştir. Kongenital veya akkiz eksiklikleri tekrarlayıcı tromboembolik olaylarla ilişkili olan bu faktörlerin karaciğer sirozundaki (KS) serum aktivite değişikliklerini ve bunun karaciğer sirozunda komplikasyon olarak karşımıza çıkan portal sistem trombozu ile ilişkisini değerlendirdik. Çalışmaya 49 KS (E 31, K 18; yaş ort. 55.9; Child A 12, B 22, C 15), 17 Kronik aktif hepatit (KAH) (E 7, K 10; yaş ort. 53.4) ve 18 kontrol (K) (E 8, K 10 ; yaş ort. 51.3) alındı. PC, total PS, ATIII aktiviteleri nefelometrik yöntemle ölçüldü. KS, KAH ve K gruplarında sırasıyla PC % 45.0 ± 28.4, % 54.2 ± 22.7, % 92.0 ± 17.8 (p 0.05), PS aktivitesi tromboz olanlarda % 75.2 ± 23.7, olmayanlarda % 73.2 ± 32.4 (p > 0.05) ve ATIII aktiviteleri tromboz olanlarda % 52.1 ± 23.0, olmayanlarda % 43.8 ± 19. 6(p>0, 05) olup tromboz oluşumu ile PC, PS, ATIII aktiviteleri arasında ilişki saptanamadı. KS ve KAH'te PC, PS ve ATIII aktivitelerinde belirgin azalma olmaktadır. KS'daki azalmanın sentez fonksiyonundaki ilerleyici bozulmaya bağlı olduğu düşünülmekte iken KAH'teki azalmanın nedenini açıklamak için ileri çalışmalar gereklidir. KS'da sıklıkla rastladığımız trombotik olaylar ile bu antikoagulan faktörlerin eksikliği arasında ilişki saptanmamıştır.

Abstract

Protein C (PC), Protein S (PS) and Antithrombin III (ATIII), which are synthesized in the liver are natural anticoagulant factors. Deficiency of these substances has been found in some acute and chronic liver diseases. Congenital or acquired deficiency of these factors has been associated with recurrent thromboembolic events. The aim of this study was to determine the serum levels of these substances in chronic liver disease and whether there is any correlation between PC, PS, ATIII and portal thrombosis. Serum PC, total PS and ATIII activity was measured in 49 patients with liver cirrhosis (LC) (31male, 18 female; mean age 55.9; 12 Child A, 22 Child B ,15 Child C patients), 17 patientschronic active hepatitis (CAH) ( 7 male, 10 female; mean age 53.4) and 18 control subjects (C) (8male, 10 female; mean age 51.3) by nephelometric method. Serum activities in LC, CAH and C groups were as follows: PC: 45.0 ±28.4%, 54.2 ±22.7 % and, 92.0 ±17.8 % respectively (p<0.001); PS: 74.5 ±31.5 %, 74.9 ± 31.9 % and 111.5 ± 29 %, respectively (p <0.001); ATIII: 47.0 ± 24.3 %, 84.2 ± 20.9 %, and 126.8 ± 21.1% respectively (p <0.001). ATIII decreased progressively from Child A to Child C (p < 0. 001) while PC and PS activities did not differ among these groups. There was a negative correlation between PS, ATIII and prothrombin time and a positive correlation between PC, PS, ATIII and prothrombin activity. In patients with potal thrombosis, serum PC activity was 56.7 ± 37.0 %, while it was 41.8±27.0 % in patients without portal thrombosis (p > 0.05). PS activity was 75.2 ± 23.7 % in patients with portal thrombosis and 73.2+32.4 % in patients without thrombosis (p > 0.05). ATIII activities were 52.1 ± 23, 0 %, and 43.8 ±19.6% in patients with thrombosis and patients without thrombosis, respectively (p > 0.05). There were no significant association between activities of PC, PS and ATIII and presence of portal thrombosis. In summary PC, PS, and ATIII were found to be low in patients with liver cirrhosis and chronic active hepatitis. Low levels in patients with cirrhosis may be due to progressive synthetic dys-function but the cause of low levels in CAH is unclear. There was no correlation between portal thrombosis and deficiency of anticoagulant factors.