만성신부전환자에서 혈장 단백 C 및 S 의 임상적 의의

이귀순(Kwi Soon Lee),하성규(Sung Kyu Ha),박종훈(Chong Hoon Park),서정건(Jung Kun Seo),이호영(Ho Yung Lee),한대석(Dae Suk Han),송경순(Kyung Soon Song) 대한내과학회 1997 대한내과학회지 Vol.53 No.2

N/A Objectives: Patients with chronic renal failure have increased hemorrhagic tendency due to an uremic platelet dysfunction and complications from anticoagulants used in hemodialysis. They are also prone to have thrombotic complications in the cerebral vessels, coronary arteries and A-V fistula, due to hypercoagulability from changes in various factors. Recently, deficiencies in plasma protein C and S, which are physiological anticoagulants, have been reported to cause thrombosis. In chronic renal failure, plasma protein C and S activities are known to be decreased. Methods: In the present study, activities and antigen concentrations of plasma protein C and S, as well as AT-III activities were investigated in three groups; the normal control group, the predialysis group of chronic renal failure patients treated conservatively, and the hemodialysis group. The findings were analyzed for their relationship to hypercoagulability. Results: 1) The activities of plasma protein C, S and antithrombin-III were significantly lower in the predialysis chronic renal failure group as compared to the control. Antithrombin-III concentrations in the hemodialysis group assayed immediately prior to dialysis were significantly lower than those of the control group. But, protein C antigen concentrations in the hemodialysis group assayed immediately prior to dialysis were significantly higher than those of the control group. There was no significant difference between these groups in plasma protein C activities, and plasma protein S activities and antigen concentrations. 2) In the hemodialysis group, antithrombin-III activities, antigen concentration and activities of plasma protein C were significantly higher than after dialysis as compared to those before the dialysis. 3) There were no significant difference in plasma protein C, S and antithrombin-III activities and plasma protein C and S antigen concentrations in hemodialysis patients between with and without thrombosis at arterio-venous fistula site. However, plasma protein C and antithrombin-III activities were significantly lower in those with thrombosis as compared to those of the normal control group. There were no significant difference in plasma protein C and S activities and antigen concentrations in those without thrombosis as compared to those of the normal control group. 4) There were no significant diffrences in plasma protein C, protein S and antithrombin-III activities and antigen concentrations in dialysis patients with and without recombinant erythropoietin treatment. 5) There were no significant correlations between serum creatinine and creatinine clearance, and plasma antithrombin-III, protein C and protein S activities and antigen concentrations in predialysis group. Conclusion : These results suggest that the decrease in plasma antithrombin-III, protein C and S could be the factors causing hypercoagulability in chronic renal failure patients, and the decreased activities of these factors may return to normal by dialysis. In the hemodialysis group, there were no significant diffrences in plasma protein C and S and antithrombin-III activities and antigen concentrations between the group which showed clinical thrombosis and the group which did not. However, in those who had thrombosis, plasma protein C and antithrombin-III activities are significantly lower than the control group. Administration of recombinant human erythropoietin does not appear to affect the activities of plasma protein C and S and antithrombin-III. In predialysis chronic renal failure patients, there was no significant relationship between renal function and plasma protein C and S and antithrombin-III.

패혈증 유발 파종성 혈관내 응고 환자에서 AntithrombinⅢ 보충의 임상적 효과 분석

박주연,정선미,오명현,김재송,손은선 한국병원약사회 2019 병원약사회지 Vol.36 No.2

Background : A recent research study published in Japan showed the clinical effects of ATⅢ supplementation therapy in patients with sepsis-induced disseminated intravascular coagulation (DIC). The study found that in-hospital mortality decreased only in the group with ATⅢ activation of 43% or less (HR: 0.603, P=0.045). Based on that study, it would be needed to verify a domestic application standard, starting a supplementation therapy at 70% or less of ATⅢ activity. Hence, this study conducted a retrospective analysis of clinical effects according to ATⅢ activation and suggested the need for a new application standard. Methods : Data collected from the electronic medical record were divided into two groups based on 43% ATⅢ activation and the data were analyzed for differences in prothrombin time (PT) and platelet improvement, PT and platelet variation, and 28-day mortality. Results : In 76 sepsis-induced DIC patients who were injected with ATⅢ from January 2015 to December 2017, 35 patients (46.05%) had an ATⅢ activation of 43% or less and 41 (53.95%) were over 43 percent. The number of patients who had PT improvement after ATⅢ supplementation therapy was 16 (45.7%) in the 43% or less ATIII group and 12 (29.3%) in the 43% group (P=0.138). Three patients (8.6%) had platelet improvement in the 43% or less group and three (7.3%) had platelet improvement in the 43% ATIII group (P=1.000). The PT variation was -4.94±7.65 and -3.38±4.89 in the 43% or less and 43% ATIII groups, respectively (P=0.286). The platelet variation was 11.47±30.7 and 6.31±31.86 in the 43% or less and 43% ATIII groups, respectively (P=0.478). The 28-day mortality was 48.6% in the 43% or less ATIII group and 41.5% in the 43% group (P=0.534). Conclusions : As a result of comparing patients exceeding 43% ATⅢ activation with those below 43%, the frequency of PT improvement and the mean of PT variation showed that the patients with 43% ATⅢ activation or less had a tendency toward improvement on a numerical basis. Accordingly, large-scale, multi-center studies are needed to generate a new domestic application standard for ATⅢ supplementation therapy.

뇌동맥류성 지주막하출혈 환자에서의 혈중 Antithrombin Ⅲ와 뇌척수액내 섬유소/섬유소원 분해산물

허용도,임만빈,손은익,김동원,이정교,김인홍,전동석 대한신경외과학회 1990 Journal of Korean neurosurgical society Vol.19 No.7

본원 신경외과에 입원한 뇌동맥류성 지주막하를 출혈환자 29례를 대상으로 혈중 antithrombin Ⅲ를 측정하고 뇌척수내 섬유소/섬유소원 분해 산물들을 측정하여 뇌혈관 연축 증상의 발현과의 관계를 조사한 바 혈중 antithrombin Ⅲ의 측정치는 대조군과 실험군 및 연축군과 비연축군간에 차이가 없었다. 따라서 뇌혈관 연축 증상의 발현 여부는 개개인의 혈중 antithrombin Ⅲ의 차이에 의하지 않는다는 것을 알았다. 뇌척수액의 섬유소/섬유소원 분해 산물들의 측정치는 대조군보다 실험군에서 높았으며 비록 통계학적 유의성은 없었으나 연축군에서 비연축군보다 높았고 또한 섬유소/섬유소원 분해 산물들이 40㎍/㎖였던 예들에서는 38%의 환자들이 뇌혈관 연축증상을 보인 반면 10㎍/㎖ 혹은 그 이하인 예들에서는 22%에서만 뇌혈관 연축 증상을 보였으므로 plasmin 혹은 섬유소/섬유소원 분해 산물들과 뇌혈관 연축 증상의 발현과 관계있지 않나 추측된다. 또한 향후에는 뇌척수액내에서 antithrombin Ⅲ를 측정하여 뇌혈관 연축 증상을 보이는 환자들에게서 낮게 측정되거나 혹은 경시적 변동에서 조기에 뇌척수액에서 감소하는 것이 확인된다면 뇌혈관 연축 발생의 기전을 밝히는데 도움이 될 것으로 사료된다. It is known that antithrombin Ⅲ is a potent vasodilator and plasmin is a vasoconstrictor, and some patients with a subarachnoid hemorrhage(SAH) develop clinical vasospasm and some patients do not Under the hypothesis that the development of clinical vasospasm might depend on the difference of the blood level of antithrombin Ⅲ in each patient with a SAH and that the plasmin might have a role in the development of clinical vasospasm, we repeatedly checked the levels of blood antithombin Ⅲ with a single radial immunodiffusion method and CSF fibrinogen degredation products(FDP : indirect indicator of plasmin activity) with a latex-test(ThromboWellcotest®) during the period between 1-4,5-11 and 12-24 days after a SAH in 29 patients. 10 patients with diseases except those with a SAH were selected as a control group. First, we analyzed the difference of the average levels of blood antithrombin Ⅲ and CSF FDP between aneurysmal SAH patients and control patients and then, between patients with clinical vasospasm(8 cases) and patients without clinical vasospasm(21 cases). Secondly, we also analyzed the difference of these data between patients with clinical vasospasm and patients without clinical vasospasm according to the sampling day after a SAH. As a result, there was no statistical difference between the average blood level of antithrombin Ⅲ in control and m SAH patients(29.06±3.04 vs. 25.61± 6.95, respectively), and in patients with clinical vasospasm and in patients without clinical vasospasm(26.59±7.65 vs. 23.67±7.40,respectively). The average CSF levels of FDP is higher in SAH patients than in control patients(18.16±14.36 vs. 1.00±3.16, respectively: p<0.01). It is also higher in patients with clinical vasospasm than in patients without clinical vasospasm. However, there is no statistical significance(28.75±9.91 vs. 21.75±12.07, respectively: p>0.05). In the analysis of the average CSF levels of the FDP according to the sampling day after a SAH, even though the average level is higher in patients with clinical vasospasm than in patients without clinical vasospasm(l-4 days : 31.43±14.64 vs. 27.33±1624, 5-11 days : 23.75±17.68 vs. 18.10±16.32, 12-24 days : 32.50±13.89 vs. 18.82±16.54, respectively), a statistical significant difference was noticed only in levels which were checked between 12 and 24 days after a SAH(p<0.05). This study concludes that the blood level of antithrombin Ⅲ shows no difference between the control and SAH patients, and patients with clinical vasospasm and patients without clinical vasospasm. Although it suggests a causal relationship between the FDP itself or plasmin in CSF and the development of clinical vasospasm, it does not justfy any valid conclusion.

토끼에서 안티트롬빈 Ⅲ 투여가 전신 슈발츠만 반응에 미치는 영향

지정희 大韓血液學會 1995 大韓血液學會誌 Vol.30 No.3

재발성 정맥혈전증을 유발한 Antithrombin III와 Protein C 복합 결핍증 1예

엄민섭,박연희,설재일,채수엽,유문빈,강기훈,이병수,채은하,박정식,정용환,안승혜,이효진 대한내과학회 2002 대한내과학회지 Vol.62 No.5

Primary venous thrombosis caused by deficiency or qualitative abnormality of antithrombin III, protein C and protein S is usually inherited as an autosomal dominant trait. Usually, deep vein thrombosis or pulmonary thromboembolism is developed by such abnormalities, however, mesenteric vein thrombosis is rarely reported. A 27-year-old man with previous history of deep vein thrombosis underwent segmental resection of jejunum due to mesenteric vein thrombosis complicated by necrosis of jejunum. Postoperative investigation disclosed combined deficiency of antithrombin III and protein C. His son also showed deficiency of antithrombin III. Postoperatively, he is on life-long warfarin therapy without experiencing recurrence of venous thrombosis.(Korean J Med 62:570-574, 2002) Antithrombin III, protein C, protein S 결핍증에 의한 원발성 정맥 혈전증은 상염색체 우성으로 유전되는 질환이다. 심부 정맥 혈전증이나 폐 색전증 등이 이러한 원인질환에 의해 발생할 수 있으며 장간막 정맥혈전증은 비교적 드물게 보고되었다. 본 증례는 과거력상 하지 심부 정맥 혈전증으로 혈전 제거술을 시행 받았던 27세 젊은 남자에서 재발한 장간막 정맥 혈전증의 증례이다. 환자는 장간막 정맥 혈전증에 의한 소장 괴사로 응급 장 절제술을 시행 받았다. 수술 후 혈전증의 원인을 찾기 위해 시행한 검사에서 antithrombin III와 protein C가 결핍되어 있었고 환자의 아들에서도 antithrombin III가 결핍되어 있었다. 이 환자는 혈전증이 재발된 상태였고 장괴사로 인한 응급수술이 필요했던 생명이 위험할 정도의 합병증을 동반한 상태였으므로, 수술 후 warfarin 요법을 시행 중이며 현재까지 약 1년 이상 정맥 혈전증의 재발은 관찰되지 않았다. 감사의 글Antithrombin 유전자의 염기서열분석 검사를 해주신 서울대학교 박선양 교수께 감사드립니다.

Changes in Plasma Levels of Natural Anticoagulants in Disseminated Intravascular Coagulation: High Prognostic Value of Antithrombin and Protein C in Patients with Underlying Sepsis or Severe Infection

최규태,홍기호,김지은,김현경 대한진단검사의학회 2014 Annals of Laboratory Medicine Vol.34 No.2

Background: Dysfunctional natural anticoagulant systems enhance intravascular fibrin for- mation in disseminated intravascular coagulation (DIC), and plasma levels of natural anti- coagulants can be used in the diagnosis and prognosis of DIC. Herein, the diagnostic value of 4 natural anticoagulants was assessed, and the prognostic value of antithrombin and protein C were validated in a large population. Methods: Part 1 study included 126 patients with clinically suspected DIC and estimated plasma levels of 4 candidate anticoagulant proteins: antithrombin, protein C, protein S, and protein Z. Part 2 comprised 1,846 patients, in whom plasma antithrombin and protein C levels were compared with other well-known DIC markers according to the underlying dis- eases. The 28-day mortality rate was used to assess prognostic outcome. Results: Antithrombin and protein C showed higher areas under the ROC curve than pro- tein S and protein Z. In part 2 of the study, antithrombin and protein C levels significantly correlated with DIC score, suggesting that these factors are good indicators of DIC severity. Antithrombin and protein C showed significant prognostic power in Kaplan–Meier analyses. In patients with sepsis/severe infection, antithrombin and protein C showed higher hazard ratios than D-dimer. Platelet count showed the highest hazard ratio in patients with hemato- logic malignancy. In patients with liver disease, the hazard ratio for antithrombin levels was significantly high. Conclusions: Decreased plasma anticoagulant levels reflect florid consumption of the phys- iologic defense system against DIC-induced hypercoagulation. Plasma antithrombin and protein C levels are powerful prognostic markers of DIC, especially in patients with sepsis/ severe infection.

Studies on Therapeutic Effects and Pathological Features of an Antithrombin Preparation in Septic Disseminated Intravascular Coagulation Patients

Yuichiro Sakamoto,Satoshi Inoue,Takashi Iwamura,Tomoko Yamashita,Atsushi Nakashima,Yoichi Nishimura,Hiroyuki Koami,Hisashi Imahase,Akiko Goto,Kosuke Chris Yamada,Kunihiro Mashiko,Hiroyuki Yokota 연세대학교의과대학 2013 Yonsei medical journal Vol.54 No.3

Purpose: Few reports have been made on the therapeutic effects as well as pathological features of an antithrombin preparation in patients diagnosed with septic disseminated intravascular coagulation (DIC) by the diagnostic criteria for acute DIC. Materials and Methods: A total of 88 sepsis patients who had received inpatient hospital care during the period from January 2000 through December 2008 were divided into two groups, an antithrombin group and a non-antithrombin group, to study the outcomes. Furthermore, the relationship between sepsis-related factors and DIC in 44 patients was studied. Results: The antithrombin group contained 34 patients, and the non-antithrombin group contained 54 patients. The outcomes were significantly better in the antithrombin group. The levels of protein C were low in DIC patients. Conclusion: Our results suggest that early administration of antithrombin might improve outcomes of septic DIC patients in the diagnostic criteria for Japanese Association for Acute Medicine acute DIC.

항트롬빈Ⅲ(Antithrombin Ⅲ) 결핍증 환자의 울체피부염에서 발생한 지방피부경변증 1예

이정덕,배은영,유충의,조상현 대한피부과학회 2003 대한피부과학회지 Vol.41 No.5

Antithrombin is one of the main endogenous anticoagulants. Antithrombin deficiency may result from hereditary or acquired factors. Inherited antithrombin deficiency is an uncommon autosomal disorder associated with a tendency to venous thromboembolism. Stasis dermatitis occurs as a result of venous stasis caused by venous incompetence or deep vein thrombosis. Furthermore, lipodermatosclerosis that refers to the skin induration and hyperpigmentation of the legs, often occurs in patients who have venous insufficiency. We report a case of stasis dermatitis, complicated by lipodermatosclerosis on both legs of a patient with hereditary antithrombin Ⅲ deficiency. (Korean J Dermatol 2003;41(5) : 645-648)

반복자연유산 환자에서 Antithrombin III 결핍증에 대한 연구

남윤성,차광렬,김남근,강명서,오도연,Nam, Yoon-Sung,Cha, Kwang-Yul,Kim, Nam-Keun,Kang, Myung-Seo,Oh, Do-Yeon 대한생식의학회 2001 Clinical and Experimental Reproductive Medicine Vol.28 No.4

Objective : To analyze the antithrombin II deficiency in patients with recurrent spontaneous abortion. Material and Method: The blood samples were tested by chromogenic assay to evaluate the activity of antithrombin III. Results: There was only one case of antithrombin III deficiency. This patient experienced one neonatal death after delivery and one FDIU (fetal death in utero). And also this patient showed a lupus anticoagulant and the prolongation of PTT. Conclusions: Women with recurrent miscarriage who have no obvious identified cause should consider hematologic screening. Antithrombin III deficiency could be a cause of recurrent spontaneous abortion. But the incidence is very rare in Korean patients.

선천성 Antithrombin III 결핍증에서 발생한 폐색전증 1 예

박형관,박창민,고경행,임명수,김유일,황준화,임성철,김영철,박경옥,Park, Hyeong-Kwan,Park, Chang-Min,Ko, Kyoung-Haeng,Rim, Myung-Soo,Kim, Yu-Il,Hwang, Jun-Hwa,Lim, Sung-Chul,Kim, Young-Chul,Park, Kyung-Ok 대한결핵및호흡기학회 1999 Tuberculosis and Respiratory Diseases Vol.47 No.3

저자들은 갑작스런 흉통을 주소로 내원한 젊은 남자에서 AT III 결핍증에 의한 폐색전증을 진단하고 세 자녀 모두에서도 AT III 결핍이 확인됨으로써 폐색전증을 동반한 선천성, 가족성 AT III 결핍증을 경험하였기에 문헌고찰과 함께 보고한다. We report a case of congenital and familial antithrombin III deficiency developing massive pulmonary thromboembolism. A 44-year-old man was admitted to our hospital because of sudden chest pain and severe dyspnea. Five years ago, he was operated due to a mesenteric vein thrombosis of unknown cause. On admission, radioisotopic venogram showed deep vein thrombosis and lung scintigram showed multiple segmental perfusion defects. His plasma antithrombin III level was 10.5 mg/dL which was less than 50% of normal and those of a son and two daughters were also decreased. After treatment with tissue plasminogen activator, heparin and coumadin, his symptom and lung scintigram were significantly improved. As far as we reviewed, there were very rare reports with congenital antithrombin III deficiency presenting as pulmonary thromboembolism in Korea.