Hiperlipidemik olgularda plazma antitrombin III, protein C ve plazminojen aktiviteleri
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Date
1998
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Uludağ Üniversitesi
Abstract
Bu çalışma, hiperlipideminin ateroskleroz gelişimindeki primer rolünün yamsıra, sekonder olarak koagülasyona eğilimi arttırarak da aterogeneze katkıda bulunup bulunmadığını araştırmak amacıyla planlandı. Fibrinojen, trombinin etkisiyle fibrin ipliklerini oluşturarak pıhtılaşmada merkezi rol oynayan bir glikoproteindir. Antitrombin III, trombin ve aktif pıhtılaşma faktörleriyle (faktör IXa, Xa, XIa, XIIa) inaktif kompleksler oluşturan doğal bir antikoagülandır. Protein C de faktör Va ve Villa' yi inhibe ederek antikoagülan etki gösterir. Plazminojen ise, pıhtı eritilmesini sağlayan fibrinolitik sistemin başlıca elemanıdır. Çalışma üçü farklı tip hiperlipidemik (hipertrigliseridemik, hiperkolesterolemik, karışık tip hiperlipidemik) ve biri kontrol grubu olmak üzere dört grupta gerçekleştirildi. Her grupta 15 erkek ve 15 kadından oluşan 30 olgu vardı. Tüm gruplarda serum ürik asit, glukoz, üre, kreatinin, trigliserid, total kolesterol miktar belirtimi enzimatik yöntemlerle yapıldı. Lipoprotein elektroforezi fraksiyonları, sellüloz asetat kullanılarak belirlendi. Apo Al ve B, nefelometrik olarak, Lp (a) ise, ELISA yöntemiyle ölçüldü. Plazmada fibrinojen düzeyi Clauss yöntemiyle, antitrombin III, protein C ve plazminojen aktiviteleri ise, kromojenik substrat kullanılarak spektrofotometrik olarak saptandı.Fibrinogen düzeyi, hiçbir deney grubunda kontrol grubuna göre istatistiksel olarak anlamlı fark göstermedi. Plazminojen aktivitesi (%), kontrol grubuna (99.8+12) göre, hipertrigliseridemik grupta (103+16.1) ve kanşık tip hiperlipidemi grubunda (106+11.9) daha yüksek bulunurken, hiperkolesterolemik grupta (98.4±12.2) kontrol grubuna oldukça yakın bir değer elde edildi. Protein C aktivitesi (%), tüm deney gruplarında kontrol grubuna (100+14.8) göre daha yüksekti ve en yüksek değer, kanşık tip hiperlipidemi grubunda (121+12.6) saptandı. Antitrombin III aktivitesi (%), tüm hiperlipidemik gruplarda normolipidemik gruba göre daha düşüktü. Kontrol grubu ortalama değeri 100+12.5 iken, en düşük değer (90.2+16.8) kanşık tip hiperlipidemi grubunda bulundu. Çalışmanın sonunda hiperlipideminin koagülasyon sistemi üzerinde etkili olduğu düşünüldü. Deney gruplannda görülen protein C aktivitesi yüksekliğinin, hiperlipideminin indüklediği hiperkoagülasyon durumuna kompansatuar olarak geliştiği sonucuna vanldı. Antikoagülan aktivitede majör rol oynayan antitrombin IH'ün deney gruplannda düşük bulunması, bu gruplarda koagülan aktivitenin daha da artmış olabileceğini düşündürdü. Buradan hiperlipidemilerde antitrombin III aktivitesi düşüklüğünün, ateroskleroz riskini arttıran bir faktör olabileceği kanısına vanldı. Bu açıdan çalışmamızda ateroskleroz gelişiminde en fazla risk altında bulunan olgu grubunun kanşık tip hiperlipidemi grubu olduğu sonucuna vanldı. Elde edilen bilgiler ışığında; ateroskleroz riski taşıyan hiperlipidemik olgulann izlenmesinde antikoagülan parametrelerin de değerlendirilmesi ve gerekli görülen olgularda erken dönemde antikoagülan tedaviye başlanması, yararlı olabilir kanısına varıldı.
It is well known that hyperlipidemia plays a major role in atherosclerosis. In this study, whether hyperlipidemia has a secondary role in atherogenesis by increasing the tendency to coagulation was investigated. Fibrinogen is a glycoprotein that plays a major role in coagulation by forming fibrin strands by the action of thrombin. Antithrombin III is a natural anticoagulant, forming inactive complexes with thrombin and active coagulation factors (factor IXa, Xa, XIa, Xlla). Protein C also shows anticoagulant effect by inhibiting factor Va and Villa. Plasminogen is a major element in fibrinolytic system that provides fibrin degradation. The work was carried out in three experimental groups (hypertriglyceridemic, hypercholesterolemic, mixed type hyperlipidemic) and one control group. There were 30 cases, consisting of 15 men and 15 women in each group. In all groups, serum uric acid, glucose, urea, creatinine, triglyceride, total cholesterol levels were measured by enzymatic methods. Electrophoretic fractions of lipoproteins were determined by using cellulose acetate. Apo AI and B were measured nephelometrically and lipoprotein (a) by ELISA. Plasma fibrinogen levels were measured by Clauss method. Plasma antithrombin III, protein C and plasminogen activities were determined spectrophotometrically by using a chromogenic substrate.Fibrinogen levels were not significantly different in any of the experimental groups compared to the control group. While plasminogen activities (%) of hypertriglyceridemic group (103+16.1) and mixed type hyperlipidemic group (106±11.9) were sinificantly higher than that of the control group (99.8±12), the value of hypercholesterolemic group (98.4+12.2) was quite close to that of the controls. Protein C activities of all experimental groups were higher than that of the controls (100±14.8) and the highest value was in the mixed type hyperlipidemic group (121+12.6). Antithrombin III activities of all hyperlipidemic groups were lower than that of the control group. While the mean antithrombin III activity of the control group was 100+12.5, the lowest value (90.2±16.8) was in the mixed type hyperlipidemic group. The results of the study suggest that hyperlipidemia has some influence on coagulation. It can be concluded that the high protein C activities in experimental groups were compansatory to the hypercoagulation induced by hyperlipidemia. Since antithrombin III plays a major role in anticoagulant activity, low antithrombin III activities in experimental groups suggest that coagulant activity might be more pronounced in these groups. Consequently, low antithrombin III activity in hyperlipidemic cases can be thought as a risk factor for atherosclerosis. Accordingly, mixed type hyperlipidemia group has the greatest risk for atherosclerosis in this study. In conclusion, it may be beneficial to evaluate the anticoagulant parameters in monitoring hyperlipidemic cases that are under risk for atherosclerosis and to start early anticoagulant therapy in desired cases.
It is well known that hyperlipidemia plays a major role in atherosclerosis. In this study, whether hyperlipidemia has a secondary role in atherogenesis by increasing the tendency to coagulation was investigated. Fibrinogen is a glycoprotein that plays a major role in coagulation by forming fibrin strands by the action of thrombin. Antithrombin III is a natural anticoagulant, forming inactive complexes with thrombin and active coagulation factors (factor IXa, Xa, XIa, Xlla). Protein C also shows anticoagulant effect by inhibiting factor Va and Villa. Plasminogen is a major element in fibrinolytic system that provides fibrin degradation. The work was carried out in three experimental groups (hypertriglyceridemic, hypercholesterolemic, mixed type hyperlipidemic) and one control group. There were 30 cases, consisting of 15 men and 15 women in each group. In all groups, serum uric acid, glucose, urea, creatinine, triglyceride, total cholesterol levels were measured by enzymatic methods. Electrophoretic fractions of lipoproteins were determined by using cellulose acetate. Apo AI and B were measured nephelometrically and lipoprotein (a) by ELISA. Plasma fibrinogen levels were measured by Clauss method. Plasma antithrombin III, protein C and plasminogen activities were determined spectrophotometrically by using a chromogenic substrate.Fibrinogen levels were not significantly different in any of the experimental groups compared to the control group. While plasminogen activities (%) of hypertriglyceridemic group (103+16.1) and mixed type hyperlipidemic group (106±11.9) were sinificantly higher than that of the control group (99.8±12), the value of hypercholesterolemic group (98.4+12.2) was quite close to that of the controls. Protein C activities of all experimental groups were higher than that of the controls (100±14.8) and the highest value was in the mixed type hyperlipidemic group (121+12.6). Antithrombin III activities of all hyperlipidemic groups were lower than that of the control group. While the mean antithrombin III activity of the control group was 100+12.5, the lowest value (90.2±16.8) was in the mixed type hyperlipidemic group. The results of the study suggest that hyperlipidemia has some influence on coagulation. It can be concluded that the high protein C activities in experimental groups were compansatory to the hypercoagulation induced by hyperlipidemia. Since antithrombin III plays a major role in anticoagulant activity, low antithrombin III activities in experimental groups suggest that coagulant activity might be more pronounced in these groups. Consequently, low antithrombin III activity in hyperlipidemic cases can be thought as a risk factor for atherosclerosis. Accordingly, mixed type hyperlipidemia group has the greatest risk for atherosclerosis in this study. In conclusion, it may be beneficial to evaluate the anticoagulant parameters in monitoring hyperlipidemic cases that are under risk for atherosclerosis and to start early anticoagulant therapy in desired cases.
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Keywords
Hiperlipidemi, Koagülasyon, Antitrombin III, Protein C, Plazminojen, Hyperlipidemia, Coagulation, Antithrombin III, Plasminogen
Citation
Cangül, H. (1998). Hiperlipidemik olgularda plazma antitrombin III, protein C ve plazminojen aktiviteleri. Yayınlanmamış doktora tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.