BACKGROUND Antithrombin Ⅲ(AT3)deficiency,an autosomal dominant disease,increases the likelihood of an individual developing venous thromboembolism(VTE).Longterm anticoagulation treatment is required for those sufferi...BACKGROUND Antithrombin Ⅲ(AT3)deficiency,an autosomal dominant disease,increases the likelihood of an individual developing venous thromboembolism(VTE).Longterm anticoagulation treatment is required for those suffering from AT3 deficiency.CASE SUMMARY A man aged 23,who had a history of deep venous thrombosis(DVT),experienced recurrent pain and swelling in his right lower extremity for three days following withdrawal of Rivaroxaban.He was diagnosed with DVT and antithrombin Ⅲ deficiency as genetic testing revealed a single nucleotide variant in SERPINC1(c.667T>C,p.S223P).The patient was advised to accept long-term anticoagulant therapy.CONCLUSION Inherited AT3 deficiency due to SERPINC1 mutations results in recurrent VTE.Patients may benefit from long-term anticoagulant therapy.展开更多
AIM： To examine whether antithrombin （AT） could prevent hepatic ischemia/reperfusion （I/R）-induced hepatic metastasis by inhibiting tumor necrosis factor （TNF）-α-induced expression of E-selectin in rats. METH...AIM： To examine whether antithrombin （AT） could prevent hepatic ischemia/reperfusion （I/R）-induced hepatic metastasis by inhibiting tumor necrosis factor （TNF）-α-induced expression of E-selectin in rats. METHODS： Hepatic I/R was induced in rats and mice by clamping the left branches of the portal vein and the hepatic artery. Cancer cells were injected intrasplenically. The number of metastatic nodules was counted on day 7 after I/R. TNF-α and E-selectin mRNA in hepatic tissue, serum fibrinogen degradation products and hepatic tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2, were measured. RESULTS： AT inhibited increases in hepatic metastasis of tumor cells and hepatic tissue mRNA levels of TNF-α and E-selectin in animals subjected to hepatic I/R. Argatroban, a thrombin inhibitor, did not suppress any of these changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities. I/R-induced increases of hepatic tissue levels of 6-keto-PGF1α were significantly enhanced by AT. Pretreatment with indomethacin completely reversed the effects of AT. Administration of OP-2507, a stable PGI2 analog, showed effects similar to those of AT in this model. Hepatic metastasis in congenital AT-deficient mice subjected to hepatic I/R was significantly increased compared to that observed in wild-type mice. Administration of AT significantly reduced the number of hepatic metastases in congenital AT-deficient mice. CONCLUSION： AT might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting TNF-α-induced expression of E-selectin through an increase in the endothelial production of PGI2. These findings also raise the possibility that AT might prevent hepatic metastasis of tumor cells if administered during the resection of liver tumors.展开更多
Antithrombin(AT) is a natural anticoagulant with antiinflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT maydecr...Antithrombin(AT) is a natural anticoagulant with antiinflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT maydecrease blood loss during eschar excision, reducing blood transfusion requirements. There are no human randomized, placebo-controlled studies, which have tested the true benefit of this agent in these conditions. Two main forms of AT are either plasma-derived AT(ph AT) and recombinant AT(rh AT). Major ovine studies in burn and smoke inhalation injury have utilized rh AT. There have been no studies which have either translated the basic rh AT research in burn trauma, or determined the tolerance and pharmacokinetics of rh AT concentrate infusions in burn patients. Advantages of rh AT infusions are no risk of blood borne diseases and lower cost. However, the majority of human burn patient studies have been conducted utilizing ph AT. Recent Japanese clinical trials have started using ph AT in abdominal sepsis successfully. This review examines the properties of both ph AT and rh AT, and analyzes studies in which they have been utilized. We believe that it is time to embark on a randomized placebo-controlled multi-center trial to establish the role of AT in both civilian and military patients with burn trauma.展开更多
AIM:To investigate the effects of antithrombin Ⅲ(AT Ⅲ) injection via the portal vein in acute liver failure.METHODS:Thirty rats were intraperitoneally challenged with lipopolysaccharide(LPS) and D-galactosamine(GalN...AIM:To investigate the effects of antithrombin Ⅲ(AT Ⅲ) injection via the portal vein in acute liver failure.METHODS:Thirty rats were intraperitoneally challenged with lipopolysaccharide(LPS) and D-galactosamine(GalN) and divided into three groups:a control group;a group injected with AT Ⅲ via the tail vein;and a group injected with AT Ⅲ via the portal vein.AT Ⅲ(50 U/kg body weight) was administrated 1 h after challenge with LPS and GalN.Serum levels of inflammatory cytokines and fibrin degradation products,hepatic fibrin deposition,and hepatic mRNA expression of hypoxiarelated genes were analyzed.RESULTS:Serum levels of alanine aminotransferase,tumor necrosis factor-α and interleukin-6 decreased significantly following portal vein AT Ⅲ injection compared with tail vein injection,and control rats.Portal vein AT Ⅲ injection reduced liver cell destruction and decreased hepatic fibrin deposition.This treatment also significantly reduced hepatic mRNA expression of lactate dehydrogenase and heme oxygenase-1.CONCLUSION:A clinically acceptable dose of AT Ⅲ injection into the portal vein suppressed liver damage,probably through its enhanced anticoagulant and antiinflammatory activities.展开更多
This study sought to elucidate the genetic correlation of cerebral venous sinus thrombosis caused by a hereditary antithrombin deficiency in a Chinese family, at the genetic and protein levels. A nonsense mutation fro...This study sought to elucidate the genetic correlation of cerebral venous sinus thrombosis caused by a hereditary antithrombin deficiency in a Chinese family, at the genetic and protein levels. A nonsense mutation from C to T on locus 6431 in exon 3B of the antithrombin gene was observed, leading to an arginine （CGA） to stop codon （TGA） change in the protein. This is the first report of this mutation in China. Ineffective heparin therapy in the propositus patient is associated with a lack of heparin binding sites after antithrombin gene mutation. Characteristic low intracranial pressure in the acute phase might be specific to this patient with cerebral venous sinus thrombosis.展开更多
AIM： To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease （IBD） and to characterize bhe anti-inflammatory action of antithrombin Ⅲ （ATⅢ） on...AIM： To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease （IBD） and to characterize bhe anti-inflammatory action of antithrombin Ⅲ （ATⅢ） on leukocyte kinetics and liver damage. METHODS： Hepatic and intestinal microcirculation was investigated by intravital videomicroscopy. Standardized models of experimental chronic liver cirrhosis and bowel inflammation were employed. Animals were divided into four groups （n = 6/group）： controls, animals with cirrhosis, animals with cirrhosis and IBD, animals with cirrhosis and IBD treated with ATIII. RESULTS： Cirrhosis facilitated leukocyte rolling and sticking in hepatic sinusoids （1.91±0.28 sticker/μm vs 0.5±0.5 sticker/μm in controls, P〈0.05）. The effect enhanced in animals with cirrhosis and IBD （5.4±1.65 sticker/μm）, but reversed after ATIII application （3.97±1.04 sticker/μm, P〈0.05）. Mucosal blood flow showed no differences in cirrhotic animals and controls （5.3±0.31 nL/min vs5.4±0.25 nL/min） and was attenuated in animals wibh cirrhosis and IBD significantly （3.49±0.6 nL/min）. This effect was normalized in the treatment group （5.13±0.4 nL/min, P〈0.05）. Enzyme values rose during development of cirrhosis and bowel inflammation, and reduced after ATIII application （P〈0.05）. CONCLUSION： Liver cirrhosis in the presence of IBD leads to a significant reduction in mucosal blood flow and an increase in hepatic leukocyte adherence with consecutive liver injury, which can be prevented by administration of ATⅢ.展开更多
The combined use of batifiban, a synthetic platelet GP II b/IIIa receptor antagonist, and an- tithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation （NSTE） acute corona...The combined use of batifiban, a synthetic platelet GP II b/IIIa receptor antagonist, and an- tithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation （NSTE） acute coronary syndrome （ACS） and those scheduled for percutaneous coronary intervention. To observe whether antithrombin agents affect the pharmacokinetic and pharmacodynamic properties of batifiban in combination therapy and optimize clinical administration dosage of batifiban, an open-label and parallel study was conducted. Thirty healthy subjects were randomly divided into three groups, which were sequentially treated with batifiban alone, or oral coadministration of clopidogrel, aspirin and UFH, or batifiban coadministered with these antithrombin agents. Blood samples were collected at pre-specified time points. The evaluation index included the inhibition of platelet aggregation and pharmacokinetic parameters. The pharmacokinetic parameters of batifiban and batifiban coadministered with antithrombin agents showed no significant differences. The mean inhibition rate of platelet aggre- gation （%） suggested that neither batifiban alone nor antithrombin agents alone could provide such po- tent inhibition rate （〉80%） to obtain the best clinical efficacy, but they had a synergistic effect on plate- let inhibition. No serious adverse effects were observed. The results in these healthy subjects suggest that batifiban coadministrated with antithrombin agents could achieve optimum clinical treatment effect for patients with NSTE ACS, and also those scheduled for percutaneous coronary intervention.展开更多
A new approach for the separation of antithrombin III with high performance affinity chromatography (HPAC) was described. A novel monodisperse, non-porous, cross-linked poly (glycidyl methacrylate) beads (PGMA) were u...A new approach for the separation of antithrombin III with high performance affinity chromatography (HPAC) was described. A novel monodisperse, non-porous, cross-linked poly (glycidyl methacrylate) beads (PGMA) were used as the affinity support. With the water-soluble carbodiimide, heparin was linked covalently to amino-PGMA-beads, which was prepared by amination of PGMA. The adsorbent obtained exhibits high binding activity to antithrombin III (ATIII), good resolution and excellent mechanical properties and can be used under high flow rate.展开更多
Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd ...Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd day, and 70 % of the activity at the 7th day. FⅧ:c showed no obvious change after 24 h, until the 3rd day. It lost 40 %-60 % of the activity after 36 h and was reduced to the 30 % of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor Ⅷ of bank stored blood can be used to replenish antithrombin Ⅲ, while bank stored blood in one day can be used to replenish FⅧ.展开更多
Recurrent thrombotic occlusions are one major problem in patients with thrombosis of the inferior vena cava. Due to this, we report a new surgical strategy for the construction of aorto-caval (mesenteric-caval) fistul...Recurrent thrombotic occlusions are one major problem in patients with thrombosis of the inferior vena cava. Due to this, we report a new surgical strategy for the construction of aorto-caval (mesenteric-caval) fistula in a patient with homozygous Antithrombin III (ATIII)-Deficiency. The patient survived postoperatively and only surgical complications grade I and II (Clavien-Dindo classification) were reported after short-term and one year follow-up. After one year, the CT-angiography did not show any caval thrombosis or stenosis and no restriction or occlusion of the fistula. Thus, the mesenteric-caval fistula could be safely performed and resulted in a satisfactory patency.展开更多
基金Supported by the National Natural Science Foundation of China,No.81670433 and No.81970398the Project of Zhejiang Medical Young Talents(2017)+1 种基金Zhejiang Medical and Health Science and Technology Project,No.2020RC014the Natural Science Foundation of Zhejiang Province,No.LR22H020002.
文摘BACKGROUND Antithrombin Ⅲ(AT3)deficiency,an autosomal dominant disease,increases the likelihood of an individual developing venous thromboembolism(VTE).Longterm anticoagulation treatment is required for those suffering from AT3 deficiency.CASE SUMMARY A man aged 23,who had a history of deep venous thrombosis(DVT),experienced recurrent pain and swelling in his right lower extremity for three days following withdrawal of Rivaroxaban.He was diagnosed with DVT and antithrombin Ⅲ deficiency as genetic testing revealed a single nucleotide variant in SERPINC1(c.667T>C,p.S223P).The patient was advised to accept long-term anticoagulant therapy.CONCLUSION Inherited AT3 deficiency due to SERPINC1 mutations results in recurrent VTE.Patients may benefit from long-term anticoagulant therapy.
文摘AIM： To examine whether antithrombin （AT） could prevent hepatic ischemia/reperfusion （I/R）-induced hepatic metastasis by inhibiting tumor necrosis factor （TNF）-α-induced expression of E-selectin in rats. METHODS： Hepatic I/R was induced in rats and mice by clamping the left branches of the portal vein and the hepatic artery. Cancer cells were injected intrasplenically. The number of metastatic nodules was counted on day 7 after I/R. TNF-α and E-selectin mRNA in hepatic tissue, serum fibrinogen degradation products and hepatic tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2, were measured. RESULTS： AT inhibited increases in hepatic metastasis of tumor cells and hepatic tissue mRNA levels of TNF-α and E-selectin in animals subjected to hepatic I/R. Argatroban, a thrombin inhibitor, did not suppress any of these changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities. I/R-induced increases of hepatic tissue levels of 6-keto-PGF1α were significantly enhanced by AT. Pretreatment with indomethacin completely reversed the effects of AT. Administration of OP-2507, a stable PGI2 analog, showed effects similar to those of AT in this model. Hepatic metastasis in congenital AT-deficient mice subjected to hepatic I/R was significantly increased compared to that observed in wild-type mice. Administration of AT significantly reduced the number of hepatic metastases in congenital AT-deficient mice. CONCLUSION： AT might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting TNF-α-induced expression of E-selectin through an increase in the endothelial production of PGI2. These findings also raise the possibility that AT might prevent hepatic metastasis of tumor cells if administered during the resection of liver tumors.
文摘Antithrombin(AT) is a natural anticoagulant with antiinflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT maydecrease blood loss during eschar excision, reducing blood transfusion requirements. There are no human randomized, placebo-controlled studies, which have tested the true benefit of this agent in these conditions. Two main forms of AT are either plasma-derived AT(ph AT) and recombinant AT(rh AT). Major ovine studies in burn and smoke inhalation injury have utilized rh AT. There have been no studies which have either translated the basic rh AT research in burn trauma, or determined the tolerance and pharmacokinetics of rh AT concentrate infusions in burn patients. Advantages of rh AT infusions are no risk of blood borne diseases and lower cost. However, the majority of human burn patient studies have been conducted utilizing ph AT. Recent Japanese clinical trials have started using ph AT in abdominal sepsis successfully. This review examines the properties of both ph AT and rh AT, and analyzes studies in which they have been utilized. We believe that it is time to embark on a randomized placebo-controlled multi-center trial to establish the role of AT in both civilian and military patients with burn trauma.
文摘AIM:To investigate the effects of antithrombin Ⅲ(AT Ⅲ) injection via the portal vein in acute liver failure.METHODS:Thirty rats were intraperitoneally challenged with lipopolysaccharide(LPS) and D-galactosamine(GalN) and divided into three groups:a control group;a group injected with AT Ⅲ via the tail vein;and a group injected with AT Ⅲ via the portal vein.AT Ⅲ(50 U/kg body weight) was administrated 1 h after challenge with LPS and GalN.Serum levels of inflammatory cytokines and fibrin degradation products,hepatic fibrin deposition,and hepatic mRNA expression of hypoxiarelated genes were analyzed.RESULTS:Serum levels of alanine aminotransferase,tumor necrosis factor-α and interleukin-6 decreased significantly following portal vein AT Ⅲ injection compared with tail vein injection,and control rats.Portal vein AT Ⅲ injection reduced liver cell destruction and decreased hepatic fibrin deposition.This treatment also significantly reduced hepatic mRNA expression of lactate dehydrogenase and heme oxygenase-1.CONCLUSION:A clinically acceptable dose of AT Ⅲ injection into the portal vein suppressed liver damage,probably through its enhanced anticoagulant and antiinflammatory activities.
基金the National Natural Science Foundation of China, No. 81041019the National High-Technology Research and Development Program of China (863 Program), No.2006AA02Z436
文摘This study sought to elucidate the genetic correlation of cerebral venous sinus thrombosis caused by a hereditary antithrombin deficiency in a Chinese family, at the genetic and protein levels. A nonsense mutation from C to T on locus 6431 in exon 3B of the antithrombin gene was observed, leading to an arginine （CGA） to stop codon （TGA） change in the protein. This is the first report of this mutation in China. Ineffective heparin therapy in the propositus patient is associated with a lack of heparin binding sites after antithrombin gene mutation. Characteristic low intracranial pressure in the acute phase might be specific to this patient with cerebral venous sinus thrombosis.
文摘AIM： To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease （IBD） and to characterize bhe anti-inflammatory action of antithrombin Ⅲ （ATⅢ） on leukocyte kinetics and liver damage. METHODS： Hepatic and intestinal microcirculation was investigated by intravital videomicroscopy. Standardized models of experimental chronic liver cirrhosis and bowel inflammation were employed. Animals were divided into four groups （n = 6/group）： controls, animals with cirrhosis, animals with cirrhosis and IBD, animals with cirrhosis and IBD treated with ATIII. RESULTS： Cirrhosis facilitated leukocyte rolling and sticking in hepatic sinusoids （1.91±0.28 sticker/μm vs 0.5±0.5 sticker/μm in controls, P〈0.05）. The effect enhanced in animals with cirrhosis and IBD （5.4±1.65 sticker/μm）, but reversed after ATIII application （3.97±1.04 sticker/μm, P〈0.05）. Mucosal blood flow showed no differences in cirrhotic animals and controls （5.3±0.31 nL/min vs5.4±0.25 nL/min） and was attenuated in animals wibh cirrhosis and IBD significantly （3.49±0.6 nL/min）. This effect was normalized in the treatment group （5.13±0.4 nL/min, P〈0.05）. Enzyme values rose during development of cirrhosis and bowel inflammation, and reduced after ATIII application （P〈0.05）. CONCLUSION： Liver cirrhosis in the presence of IBD leads to a significant reduction in mucosal blood flow and an increase in hepatic leukocyte adherence with consecutive liver injury, which can be prevented by administration of ATⅢ.
基金supported by National Science & Technology Specific Projects in the 12th Five-Year Plan of China (No.2011ZX09302-002-01)
文摘The combined use of batifiban, a synthetic platelet GP II b/IIIa receptor antagonist, and an- tithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation （NSTE） acute coronary syndrome （ACS） and those scheduled for percutaneous coronary intervention. To observe whether antithrombin agents affect the pharmacokinetic and pharmacodynamic properties of batifiban in combination therapy and optimize clinical administration dosage of batifiban, an open-label and parallel study was conducted. Thirty healthy subjects were randomly divided into three groups, which were sequentially treated with batifiban alone, or oral coadministration of clopidogrel, aspirin and UFH, or batifiban coadministered with these antithrombin agents. Blood samples were collected at pre-specified time points. The evaluation index included the inhibition of platelet aggregation and pharmacokinetic parameters. The pharmacokinetic parameters of batifiban and batifiban coadministered with antithrombin agents showed no significant differences. The mean inhibition rate of platelet aggre- gation （%） suggested that neither batifiban alone nor antithrombin agents alone could provide such po- tent inhibition rate （〉80%） to obtain the best clinical efficacy, but they had a synergistic effect on plate- let inhibition. No serious adverse effects were observed. The results in these healthy subjects suggest that batifiban coadministrated with antithrombin agents could achieve optimum clinical treatment effect for patients with NSTE ACS, and also those scheduled for percutaneous coronary intervention.
文摘A new approach for the separation of antithrombin III with high performance affinity chromatography (HPAC) was described. A novel monodisperse, non-porous, cross-linked poly (glycidyl methacrylate) beads (PGMA) were used as the affinity support. With the water-soluble carbodiimide, heparin was linked covalently to amino-PGMA-beads, which was prepared by amination of PGMA. The adsorbent obtained exhibits high binding activity to antithrombin III (ATIII), good resolution and excellent mechanical properties and can be used under high flow rate.
文摘Coagulation factor Ⅷ and antithrombin Ⅲ activity were detected in 15 health donors. It was found that antithrombin Ⅲ activity decreased obviously 12 h after blood drawing. It lost 56 % of the activity at the 3rd day, and 70 % of the activity at the 7th day. FⅧ:c showed no obvious change after 24 h, until the 3rd day. It lost 40 %-60 % of the activity after 36 h and was reduced to the 30 % of the original activity at the 5th day. Our results suggested that at the 3rd day coagulation factor Ⅷ of bank stored blood can be used to replenish antithrombin Ⅲ, while bank stored blood in one day can be used to replenish FⅧ.
文摘Recurrent thrombotic occlusions are one major problem in patients with thrombosis of the inferior vena cava. Due to this, we report a new surgical strategy for the construction of aorto-caval (mesenteric-caval) fistula in a patient with homozygous Antithrombin III (ATIII)-Deficiency. The patient survived postoperatively and only surgical complications grade I and II (Clavien-Dindo classification) were reported after short-term and one year follow-up. After one year, the CT-angiography did not show any caval thrombosis or stenosis and no restriction or occlusion of the fistula. Thus, the mesenteric-caval fistula could be safely performed and resulted in a satisfactory patency.
