OBJECTIVES: To observe the changes of the formation time of venous thrombus in rats, and to provide new ideas and methods for the estimation on thrombus formation time of the forensic cases died from thrombosis. METHODS: Totally 80 rats were randomly divided into 10 groups （0 h, 3 h, 6 h, 12 h, 1 d, 3 d, 1 week, 2 weeks, 3 weeks and 4 weeks after operation）. A vein thrombosis model was established by the "narrow" method. The processes of thrombosis, organization, recanalization and the features of change on hemosiderin and calcium salt were observed by HE stain, Perls stain and Von Kossa stain. The expression changes of CD61, α-SMA and CD34 were observed by immunohistochemical staining technique. RESULTS: Platelets adhered to the exposed blood vessel intima 3 h after operation, and platelet trabeculae were formed by the repeated accumulation of platelets 1 d after operation. The thrombus organization formed through the fibroblasts from vessel wall that grew into the interior of the thrombus 3 d after operation. Endothelial cells covered the surface of thrombus and then the new blood vessels were reformed, and the vessels were reconstructed. The expression of CD61 upregulated at the stages of the thrombus formation （3 h） and thrombus reformation （4 weeks）, and reached the peak 1 d after thrombus formation. The release of hemosiderin and the initial expression of α-SMA were detected 3 d later. Calcium deposit and expression of CD34 were observed 1 week later. CONCLUSIONS The hemosiderin, calcium salt, CD61, α-SMA and CD34 show time-dependent changing characteristics, which is expected to provide a reference for the estimation on thrombus formation time of the forensic cases died from thrombosis.
Animals ; Antigens, CD34/analysis* ; Hemosiderin/metabolism* ; Rats ; Venous Thrombosis/pathology*

OBJECTIVETo investigate the relationship between endothelial protein C receptor(EPCR) gene 6936A/G polymorphism and deep vein thrombosis (DVT).

METHODSThe study group included 65 DVT patients and 71 normal controls. Plasma sEPCR was measured by ELISA. Genomic DNA was extracted by using Genomic Purification Kit. A 315bp EPCR product was amplified by a standard PCR reaction, and the bands were confirmed by direct sequencing after purification.

RESULTS(1) sEPCR levels in healthy controls with 6936AG genotype were significantly higher than that in those with 6936AA genotype \[(0.97 ± 0.32) ng/L vs (0.61 ± 0.24) ng/L, P < 0.01)\], and so did in DVT patients \[(0.87 ± 0.21) ng/L vs (0.50 ± 0.18) ng/L, P < 0.01\]. (2) The sEPCR levels of DVT patients \[(0.68 ± 0.32) ng/L\] were significantly higher than that of healthy controls \[(0.54 ± 0.22) ng/L\](P < 0.05). (3) The distribution of 6936A/G genotype was higher in DVT patients than in healthy controls (P < 0.05). (4) Subjects with 6936A/G had an increased risk of thrombosis (OR = 2.75, 95%CI = 1.04 - 7.30) (P < 0.05).

CONCLUSIONSEPCR gene 6936A/G polymorphism is associated with increased plasma sEPCR levels. The sEPCR levels in DVT patients were significantly higher than that in healthy controls. The subject with 6936AG likely had an increased risk of thrombosis.

Case-Control Studies ; Humans ; Polymorphism, Genetic ; Protein C ; metabolism ; Thrombosis ; Venous Thrombosis ; genetics

Malignant tumor is one of the important acquired risk factors of venous thromboembolism (VTE). As the transmembrane receptor of coagulation factor Ⅶ and activated coagulation factor Ⅶa
Humans ; Neoplasms/complications* ; Risk Factors ; Thromboplastin/metabolism* ; Thrombosis ; Venous Thromboembolism/physiopathology*

Plasminogen is a key proenzyme in the fibrinolytic and thrombolytic systems. Congenital deficiency of plasminogen and molecular abnormality of plasminogen (dysplasminogenemia) have been reported in association with the thrombotic tendency in human. In dysplasminogenemia, the level of immunoreactive plasminogen is normal, although the functional activity is reduced. Human plasminogen gene spans about 52.5 kb of DNA and consists of 19 exons. Three types of mutations (Ala601Thr, Val355Phe, and Asp676Asn) have been described in dysplasminogenemia. In this study, we measured the plasminogen activity in patients with deep vein thrombosis and analyzed the DNA sequence to detect three point mutations (Ala601Thr, Val355Phe and Asp676Asn) in patients with hypo/dysplasminogenemia. Dysplasminogenemia was identified in 3 (8.3%) of unrelated 36 patients with deep vein thrombosis and the Ala601Thr mutation was detected in all three patients with dysplasminogenemia. In conclusion, dysplasminogenemia is not rare in deep vein thrombosis, which suggests a risk factor for the thrombosis in Korean population.
Adult ; Aged ; Alanine/metabolism* ; Female ; Human ; Korea ; Male ; Middle Aged ; Plasminogen/genetics* ; Plasminogen/metabolism ; Point Mutation* ; Risk Factors ; Sequence Analysis, DNA ; Threonine/metabolism* ; Venous Thrombosis/blood ; Venous Thrombosis/genetics*

Acute mesenteric venous thrombosis (MVT) is an uncommon form of intestinal ischemia with high mortality and usually occurs in the setting of preexisting comorbidities including thrombophilia and abdominal inflammatory conditions. Hyperhomocysteinemia has been known to be a risk factor for thromboembolism, often located on an unusual site. Considering that homocysteine metabolism is determined genetically to a high degree, a mutant of methylenetetrahydrofolate reductase (MTHFR) C677T causes hyperhomocysteinemia, leading to thrombophilia. Until now, there have been few reports of MVT associated with MTHFR gene mutation. We, herein, report a case of small bowel infarction associated with MVT by MTHFR gene mutation in an adult without any other risk factors of thrombophilia.
Adult ; Comorbidity ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Infarction* ; Ischemia ; Mesenteric Veins ; Metabolism ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Mortality ; Risk Factors ; Thromboembolism ; Thrombophilia ; Thrombosis ; Venous Thrombosis*

PURPOSE: Hyperhomocysteinemia has been identified as an independent risk factor in arterial and venous thrombosis. Mutations in genes encoding methylenetetrahydrofolate reductase (MTHFR), involved in the metabolism of homocysteine, may account for reduced enzyme activity and elevated plasma homocysteine levels. In this study, we investigated the interrelation of MTHFR C677T genotype and level of homocysteine in patients with arterial and venous thrombosis. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 146 patients who were diagnosed as having arterial and venous thrombosis. We excluded patients diagnosed with atrial fibrillation. We examined routinely the plasma concentration of total homocysteine level and MTHFR C677T polymorphism for evaluation of thrombotic tendency in all patients. Screening processes of MTHFR C677T polymorphism were performed by real-time polymerase chain reaction. RESULTS: Investigated groups consisted of thrombotic arterial occlusion in 48 patients and venous occlusion in 63 patients. The distribution of the three genotypes was as follows: homozygous normal (CC) genotype in 29 (26.1%), heterozygous (CT) genotype in 57 (51.4%), and homozygous mutant (TT) genotype in 25 (22.5%) patients. There were no significant differences among individuals between each genotype group for baseline characteristics. Plasma concentration of homocysteine in patients with the TT genotype was significantly increased compared to the CC genotype (P<0.05). CONCLUSION: We observed a significant interaction between TT genotypes and homocysteine levels in our results. The results might reflect the complex interaction between candidate genes and external factors responsible for thrombosis.
Atrial Fibrillation ; Genotype ; Homocysteine* ; Humans ; Hyperhomocysteinemia ; Mass Screening ; Medical Records ; Metabolism ; Methylenetetrahydrofolate Reductase (NADPH2)* ; Plasma* ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Risk Factors ; Thrombosis ; Venous Thrombosis

Thrombophilia that is common among Caucasians is caused by genetic polymorphisms of coagulation factor V Leiden (R506Q) and prothrombin G20210A. Unlike that in Caucasians, thrombophilia that is common in the Japanese and Chinese involve dysfunction of the activated protein C (APC) anticoagulant system caused by abnormal protein S and protein C molecules. Approximately 50% of Japanese and Chinese individuals who develop venous thrombosis have reduced activities of protein S. The abnormal sites causing the protein S molecule abnormalities are distributed throughout the protein S gene, PROS1. One of the most common abnormalities is protein S Tokushima (K155E), which accounts for about 30% of the protein S molecule abnormalities in the Japanese. Whether APC dysfunction occurs in other Asian countries is an important aspect of mapping thrombophilia among Asians. International surveys using an accurate assay system are needed to determine this.
Asian Continental Ancestry Group ; Blood Coagulation ; Blood Proteins/genetics/metabolism ; Humans ; Protein C/genetics/*metabolism ; Protein S/chemistry/genetics/metabolism ; Thrombophilia/epidemiology/*etiology ; Venous Thrombosis/etiology/genetics

OBJECTIVETo analyze the relation of plasma D-dimer levels and incidence of deep venous thrombosis after spinal surgery.

METHODSThe clinical data of 63 patients underwent spinal surgery from October 2009 to October 2010 were retrospective analyzed. There were 40 males and 23 females with an average age of 48 years old(21 to 76) in operation. Operation levels of 15 cases were in cervical vertebrae, 4 cases were in thoracic vertebrae,and 44 cases were in lumbar vertebrae. Thirty patients with spinal fracture were caused by trauma and 33 patients without trauma, 11 patients combined with nerve injury. The patients were divided into two groups according to plasma D-dimer levels, more than or equal to 500 microg/L was D-dimer positive group and less than 500 microg/L was D-dimer negative group. Venous blood of all patients early morning with empty stomach were testd on admission, and at 2 h, 1 d, 2 d, 3 d, 4 d, 6 d, 8 d, 10 d, 15 d after operation,respectively.

RESULTSThere was no statistically significant differences in sex, operative segments, implants, operative posture, age, bleed volume, body weight, peroperative D-dimer levels between two groups. After operation, plasma D-dimer of 19 patients were more than or equal to 500 microg/L, with persistent or progressive increasing. Two cases occurred deep venous thrombosis in D-dimer positive group, they respectively were found at 3 days and 8 days after operation. Both of them underwent posterior decompression and internal fixation. However,no deep venous thrombosis was found in D-dimer negative group.

CONCLUSIONPostoperative D-dimer assay can effective predict deep venous thrombosis occurrence. D-dimer level more than or equal to 500 microg/L will be considered as a risk factor for deep venous thrombosis after spinal surgery.

Adult ; Aged ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Spine ; surgery ; Ultrasonography ; Venous Thrombosis ; blood ; diagnostic imaging ; surgery ; Young Adult

To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg.kg(-1).(-1)) was administered (i.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gene expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. It was suggested that the anticoagulant effects on vein grafts of human TFPI gene transfection are better than those of aspirin.
Administration, Oral ; Anticoagulants/*metabolism ; Aspirin/*administration & dosage ; Aspirin/metabolism ; Coronary Artery Bypass ; Disease Models, Animal ; Lipoproteins/*metabolism ; Plasmids/metabolism ; Tissue Transplantation/*methods ; Transfection ; Ultrasonography, Doppler/methods ; Veins/*transplantation ; Venous Thrombosis/metabolism

Central venous catheterization (CVC)-related venous thrombosis is a common but serious clinical complication, thus prevention and treatment on this problem should be extensively investigated. In this research, we aimed to investigate the incidence rate of CVC-related venous thrombosis in senile patients and give a further discussion on the related risk factors and predictors. A total of 324 hospitalized senile male patients subjected to CVC were selected. Retrospective investigation and analysis were conducted on age, underlying diseases, clinical medications, catheterization position and side, catheter retention time, and incidence of CVC-related venous thrombosis complications. Basic laboratory test results during catheterization and thrombogenesis were also collected and analyzed. Among the 324 patients, 20 cases (6.17%) of CVC-related venous thrombosis were diagnoseds. The incidence rate of CVC-related venous thrombosis in subclavian vein catheterization was significantly lower than that in femoral vein catheterization (P<0.01) and that in internal jugular vein catheterization (P<0.05). No statistically significant difference was found between femoral vein catheterization and internal jugular vein catheterization (P<0.05). Previous venous thrombosis history (P<0.01), high lactate dehydrogenase level (P<0.01), low high-density lipoprotein (HDL) level (P<0.05), and low albumin level (P<0.05) were found as risk factors or predictors of CVC-related venous thrombosis in senile male patients. Subclavian vein catheterization was the most appropriate choice among senile patients to decrease the incidence of CVC-related venous thrombosis. Previous venous thrombosis history, high lactate dehydrogenase level, low HDL level, and low albumin level were important risk factors in predicting CVC-related venous thrombosis.
Aged ; Aged, 80 and over ; Biomarkers ; metabolism ; Central Venous Catheters ; adverse effects ; Femoral Vein ; pathology ; Humans ; Incidence ; Jugular Veins ; pathology ; Male ; Retrospective Studies ; Risk Factors ; Subclavian Vein ; pathology ; Venous Thrombosis ; epidemiology ; etiology