Hipotiroidik hastalarda tedavi öncesi ve tedavi sonrası trombin ile aktive edilebilen fibrinoliz inhibitör antijen düzeyi
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Date
2008
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Trakya Üniversitesi
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info:eu-repo/semantics/openAccess
Abstract
Hipotiroidi, toplumda yaygın olarak görülen bir tiroit hastalığıdır. Hipotiroidinin, kardiyovasküler hastalıklara eğilim yarattığı ve düşük tiroit hormon seviyeleriyle kardiyovasküler hastalıkların seyri arasında ilişki olduğu bilinmektedir. Bu bilgiler ışığında hipotiroidinin hemostaz mekanizmaları üzerine etkileri güncel olarak araştırılmakta olan bir konudur. Yapılan araştırmalarda ılımlı hipotiroidi olgularında (Tiroit stimülan hormon< 50UIu/ml) fibrinolitik aktivitede azalma, şiddetli hipotiroidi olgularında (Tiroit stimülan hormon>50 UIu/ml) ise fibrinolitik aktivitede artış olduğu gösterilmiştir. Son yıllarda insan plazmasından izole edilmiş bir molekül olan trombin tarafından aktive edilebilen fibrinoliz inhibitörü; fibrin polimerlerinden lizin ve arjinin kalıntılarını uzaklaştırarak plazminojenin fibrin ile etkileşimini engellemekte, fibrin yıkımının yavaşlamasına neden olmaktadır. Bu çalışmada, hipotiroidinin trombin ile aktive edilebilen fibrinoliz inhibitör antijen konsantrasyonu ve trombin ile aktive edilebilen fibrinoliz inhibitör aktivitesinin yanı sıra, doku plazminojen aktivatör ve plazminojen aktivatör inhibitör-1 düzeylerine etkisinin incelenmesi amaçlanmıştırÇalışmaya aşikar hipotiroidili 31 olgu ile yaş ve cinsiyet açısından eşleştirilmiş 25 sağlıklı olgu alındı. Hipotiroidili hasta grubuna kan örneklerinin alınmasından sonra L-tiroksin tedavisi başlandı. Tedavi başlanan hastalar 8 haftalık aralar ile tiroit fonksiyon testleri ile değerlendirildi. Ötiroit durumun sağlanmasından sonra kan örnekleri tekrarlandı. Enzim bağlı immun assay yöntemiyle trombin ile aktive edilebilen fibrinoliz inhibitör antijen konsantrasyonu, doku plazminojen aktivatör ve plazminojen aktivatör inhibitör-1 düzeyleri, kromojenik metodla trombin ile aktive edilebilen fibrinoliz inhibitör aktivite düzeyleri çalışıldıHipotiroidi grubunda sağlıklı kontrollerle karşılaştırıldığında trombin ile aktive edilebilen fibrinoliz inhibitör antijen konsantrasyonu (%1.63±0.42, %1.32±0.36, p=0.006) ve trombin ile aktive edilebilen fibrinoliz inhibitör aktivite düzeyleri (14.20±4.12 µgr/ml, 11.6±3.49 µgr/ml, p=0.0016) yüksek olarak saptandı. Grupların doku plazminojen aktivatör ve plazminojen aktivatör inhibitör-1 düzeylerinde anlamlı farklılık tespit edilmedi. Hipotiroidi grubunun serbest tiroksin ve tiroit stimülan hormon düzeyleri ile trombin ile aktive edilebilen fibrinoliz inhibitör antijen konsantrasyonları arasında ilişki olduğu gösterildi (r=-0.373, p=0.039; r=0.748, p<0.001, sırasıyla). Regresyon analizinde tiroit stimülan hormon düzeyinin trombin ile aktive edilebilen fibrinoliz inhibitör antijen düzeyine etkili olduğu saptandı (p<0.001, ß=0.671, %95 güvenirlik aralığı 0.008-0.017). L-tiroksin tedavisi sonrasında incelenen trombin ile aktive edilebilen fibrinoliz inhibitör antijen konsantrasyonları (%1.63±0.42, %1.34±0.33, p<0.05) ve trombin ile aktive edilebilen fibrinoliz inhibitör aktivite düzeylerinin (14.2±4.1 µgr/ml, 12.0±2.77 µgr/ml, p<0.05) anlamlı şekilde azaldığı, doku plazminojen aktivatör ve plazminojen aktivatör inhibitör-1 düzeylerinin ise değişmediği görüldüBu sonuçlar, hipotiroidili olgularda hipofibrinolitik durumun varlığını ve ötiroidizmin sağlanmasının artmış kardiyovasküler hastalık riskinin azaltılmasındaki önemini göstermektedir.Anahtar kelimeler: Hipotiroidizm, Fibrinoliz, Trombin ile aktive edilebilen fibrinoliz inhibitör
Hypothyroidism is a common thyroid disorder in the community. It is well known that hypothyroidism causes tendency for cardiovascular diseases and there is a close relationship between low thyroid hormone levels and the course of cardiovascular disorders. In this regard the effects of hypothyroidism on hemostasis mechanisms are topics of ongoing research. Several studies indicated a decreased versus increased fibrinolytic activity in patients with mild (Thyroid-stimulating hormone<50 IU/mL) and overt (Thyroid stimulating hormone>50 IU/mL) hypothyroidism. It was recently shown that thrombin-activatable fibrinolysis inhibitor, a novel molecule isolated from human plasma, inhibits fibrinolysis and also fibrin-plasminogen interaction by removal of lysine and arginine residues from fibrin monomers. The aim of this study was to determine the effects of overt hypothyroidism on thrombin-activatable fibrinolysis inhibitor antigen levels, thrombin-activatable fibrinolysis inhibitor activity and also tissue plasminogen activator and plasminogen activator inhibitor-1 levelsThirty one overt hypothyroid patients and age-sex matched 25 healthy controls were enrolled in the study. Patients were treated with L-thyroxine following collection of bloodsamples. Thyroid function tests were measured at 8 weeks intervals. Thyroid functions were reevaluated following attainment of euthyroid status. Thrombin-activatable fibrinolysis inhibitor antigen, tissue plasminogen activator, plasminogen activator inhibitor-1 levels and thrombin-activatable fibrinolysis inhibitor activity were measured with enzyme-linked immunosorbent assay and chromogenic assay, respectivelyThrombin-activatable fibrinolysis inhibitor antigen concentration (%1.63±0.42, %1.32±0.36, p=0.006) and thrombin-activatable fibrinolysis inhibitor activity (14.2±4.12 ?g/mL, 11.6±3.49 ?g/mL, p=0.0016) levels were elevated in hypothyroid patient compared to controls. Tissue plasminogen activator and plasminogen activator inhibitor-1 levels were not significantly different between groups. In hypothroid patients thrombin-activatable fibrinolysis inhibitor antigen concentrations were correlated with T4 (r=-0.373, p=0.039) and thyroid stimulating hormone levels (r=0.748, p<0.001). Regression analysis showed that thyroid stimulating hormone levels were predictors of thrombin-activatable fibrinolysis inhibitor antigen concentrations (p<0.001, ß=0.671, %95 CI: 0.008-0.017). We observed that following L-thyroxin treatment thrombin-activatable fibrinolysis inhibitor antigen concentrations (%1.63±0.42, %1.34±0.33, p<0.05) and thrombin-activatable fibrinolysis inhibitor activity levels (14.2±4.1 ?g/mL, 12.0±2.77 ?g/mL, p<0.05) were significantly decreased, but tissue plasminogen activator and plasminogen activator inhibitor-1 levels remained unchangedThis results point out that fibrinolytic activity was decreased in hypothyroid patients and therefore attainment of euthroid status is important in ameliorating increased risk of cardiovascular disease.Key words: Hypothyroidism, Fibrinolysis, Thrombin Activatable Fibrinolysis Inhibitor
Hypothyroidism is a common thyroid disorder in the community. It is well known that hypothyroidism causes tendency for cardiovascular diseases and there is a close relationship between low thyroid hormone levels and the course of cardiovascular disorders. In this regard the effects of hypothyroidism on hemostasis mechanisms are topics of ongoing research. Several studies indicated a decreased versus increased fibrinolytic activity in patients with mild (Thyroid-stimulating hormone<50 IU/mL) and overt (Thyroid stimulating hormone>50 IU/mL) hypothyroidism. It was recently shown that thrombin-activatable fibrinolysis inhibitor, a novel molecule isolated from human plasma, inhibits fibrinolysis and also fibrin-plasminogen interaction by removal of lysine and arginine residues from fibrin monomers. The aim of this study was to determine the effects of overt hypothyroidism on thrombin-activatable fibrinolysis inhibitor antigen levels, thrombin-activatable fibrinolysis inhibitor activity and also tissue plasminogen activator and plasminogen activator inhibitor-1 levelsThirty one overt hypothyroid patients and age-sex matched 25 healthy controls were enrolled in the study. Patients were treated with L-thyroxine following collection of bloodsamples. Thyroid function tests were measured at 8 weeks intervals. Thyroid functions were reevaluated following attainment of euthyroid status. Thrombin-activatable fibrinolysis inhibitor antigen, tissue plasminogen activator, plasminogen activator inhibitor-1 levels and thrombin-activatable fibrinolysis inhibitor activity were measured with enzyme-linked immunosorbent assay and chromogenic assay, respectivelyThrombin-activatable fibrinolysis inhibitor antigen concentration (%1.63±0.42, %1.32±0.36, p=0.006) and thrombin-activatable fibrinolysis inhibitor activity (14.2±4.12 ?g/mL, 11.6±3.49 ?g/mL, p=0.0016) levels were elevated in hypothyroid patient compared to controls. Tissue plasminogen activator and plasminogen activator inhibitor-1 levels were not significantly different between groups. In hypothroid patients thrombin-activatable fibrinolysis inhibitor antigen concentrations were correlated with T4 (r=-0.373, p=0.039) and thyroid stimulating hormone levels (r=0.748, p<0.001). Regression analysis showed that thyroid stimulating hormone levels were predictors of thrombin-activatable fibrinolysis inhibitor antigen concentrations (p<0.001, ß=0.671, %95 CI: 0.008-0.017). We observed that following L-thyroxin treatment thrombin-activatable fibrinolysis inhibitor antigen concentrations (%1.63±0.42, %1.34±0.33, p<0.05) and thrombin-activatable fibrinolysis inhibitor activity levels (14.2±4.1 ?g/mL, 12.0±2.77 ?g/mL, p<0.05) were significantly decreased, but tissue plasminogen activator and plasminogen activator inhibitor-1 levels remained unchangedThis results point out that fibrinolytic activity was decreased in hypothyroid patients and therefore attainment of euthroid status is important in ameliorating increased risk of cardiovascular disease.Key words: Hypothyroidism, Fibrinolysis, Thrombin Activatable Fibrinolysis Inhibitor
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Tıpta Uzmanlık
Keywords
Endokrinoloji ve Metabolizma Hastalıkları, Endocrinology and Metabolic Diseases
