OBJECTIVE: To investigate the factors affecting ferric chloride (FeCl₃) - induced carotid artery thrombosis model experiment. METHODS: After the common carotid artery was damaged by FeCl₃, the injured vessels were dissected for fixation, embedding, frozen section, and then processed HE staining. The carotid thrombus area ratio was calculated. We examined the effect of FeCl₃ concentration (5%, 10% and 15%), reaction time (2, 4 and 6 min), and recipient mouse age (4-5, 6-8 and 10 weeks) on the formation and stability of arterial thrombosis model. The model was injected through the post-glomus venous plexus of mouse eyeball with 0.075 μg/g and 0.1 μg/g R300 to verify the accuracy of the FeCl₃-induced model on thrombus formation by adjusting the platelet number. RESULTS: HE staining showed that thrombus formation induced by 10% and 15% FeCl₃ was more stable, dense and larger than 5% FeCl₃-induced thrombosis. 10% FeCl₃ induced the formation of dense and large thrombosis after 4 and 6 minutes of vascular endothelium injury, while the thrombosis induced for 2 minutes were looser and smaller in area. Mouse age can not affect thrombus formation and stability, because there were no significant differences in the formation of dense thrombus and thrombus area induced by 10% FeCl₃ among three different age groups of mice. CONCLUSION Many factors affect the formation and stability of arterial thrombosis model induced by FeCl₃. This optimal experimental conditions for construction of a stable carotid artery thrombosis model are 10% FeCl₃, 4 minutes for injury, and 6-8 week old mice.
Animals ; Mice ; Ferric Compounds/adverse effects* ; Chlorides ; Disease Models, Animal ; Carotid Artery Thrombosis/chemically induced* ; Male

OBJECTIVE: To investigate the effects of Tongxinluo (TXL) on thromboangiitis obliterans (TAO) and the underlying mechanisms. METHODS: Ninety male C57/BL6J mice were randomly divided into 6 groups according to a random number table: the sham group, TAO model group, Compound Danshen Tablet (CDT) group, and the high-, medium-, and low-dose TXL groups. All mice except the sham group were injected with sodium laurate (0.1 mL, 5 mg/mL) in the femoral artery to establish TAO mouse model. After modeling, mice in the sham and TAO model groups were intragastrically administered 0.5% (w/v) sodium carboxymethylcellulose, mice in the CDT group were intragastrically administered 0.52 g/kg CDT, and mice in the TXL-H, TXL-M, and TXL-L groups were intragastrically administered 1.5, 0.75, and 0.38 g/kg TXL, respectively. After 4 weeks of gavage, the recovery of blood flow in the lower limbs of mice was detected by Laser Doppler Imaging. The pathological changes and thrombosis of the femoral artery were observed by morphological examination. The expressions of tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in the femoral artery wall were detected by HE staining. Levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), endothelin-1 (ET-1), interleukin (IL)-1β and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). Levels of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) were detected by a fully automated biochemical analyzer. RESULTS: TXL promoted the restoration of blood flow in the lower limbs, reduced the area of thrombosis in the femoral artery, and alleviated the pathological changes in the femoral artery wall. Moreover, the levels of TXB2, ET-1, IL-6, IL-1β, TNF-α and iNOS were significantly lower in the TXL groups compared with the model group (P<0.05 or P<0.01), while the level of 6-keto-PGF1α was significantly higher (P<0.01). In addition, APTT, PT, and TT were significantly prolonged in TXL groups compared with the model group (P<0.05 or P<0.01), and FIB levels were significantly decreased compared with the model group (P<0.01). CONCLUSIONS TXL had a protective effect on TAO mice, and the mechanism may involve inhibition of thrombosis and inflammatory responses. TXL may be a potential drug for the treatment of TAO.
Mice ; Male ; Animals ; Thromboangiitis Obliterans/chemically induced* ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Thrombosis

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Objective The benefit of short-term dual antiplatelet therapy (DAPT) following second-generation drug-eluting stents implantation has not been systematically evaluated. To bridge the knowledge gap, we did a meta-analysis to assess the efficacy of ≤6 months versus ≥12 months DAPT among patients with second-generation drug-eluting stents.Methods We searched online databases and identified randomized controlled trials that assess the clinical impact of short-term DAPT (≤6 months) published before March 3, 2016. The efficacy endpoints included the incidence of all-cause death, myocardial infarction, cerebrovascular accidents, and definite or probable stent thrombosis. Safety endpoint defined as major bleeding was also evaluated and discussed.Results We included 5 trials that randomized 9473 participants (49.8%, short-term DAPT duration vs. 50.2%, standard duration). A total of 9445 (99.7%) patients reported the efficacy endpoints, and the safety endpoint was available from 4 studies (n=8457). There was no significant difference in efficacy endpoints between short-term and standard DAPT duration (≥12 months) [risk ratio (RR) 0.96; 95% confidence intervals (CI), 0.80-1.15]. Short-term DAPT duration did not significantly increase the individual risk of all-cause death, myocardial infarction, cerebrovascular accidents, or definite or probable stent thrombosis. Although short-term DAPT obviously reduced risk of major bleeding compared with standard DAPT (RR 0.53; 95% CI, 0.29-0.96), significant publication bias was found when accessing the safety endpoint of the 4 studies (Egger's test, P=0.009).Conclusions The efficacy of short-term DAPT was comparable with that of standard duration DAPT. DAPT less than 6 months may be appropriate for patients receiving second-generation drug-eluting stents implantation.
Drug-Eluting Stents ; Humans ; Myocardial Infarction ; chemically induced ; Platelet Aggregation Inhibitors ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Stroke ; chemically induced ; Thrombosis ; chemically induced ; Time Factors

Acute Disease ; Anaphylaxis ; drug therapy ; Epinephrine ; administration & dosage ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnosis ; etiology ; Thrombosis ; chemically induced ; complications

4-Hydroxycoumarins ; toxicity ; Blood Coagulation Disorders ; chemically induced ; Humans ; Thrombosis ; chemically induced

From July 2013 to February 2015, 4 infant patients with complex congenital heart disease, who underwent open heart surgery in Xiangya Hospital of Central South University, were diagnosed as heparin-induced thrombocytopenia (HIT). After comprehensive treatments, such as intensive monitoring of the platelet count, close observation of thromboembolic skin lesions and close monitoring of argatroban therapy, 3 patients were cured and 1 died. HIT is rare but serious in patients who received heparin therapy. The incidence of mortality and thrombosis is very high. Early identification and diagnosis of high-risk groups can improve the prognosis.
Anticoagulants ; adverse effects ; Cardiac Surgical Procedures ; Heparin ; adverse effects ; Humans ; Incidence ; Infant ; Pipecolic Acids ; therapeutic use ; Platelet Count ; Prognosis ; Thrombocytopenia ; chemically induced ; Thrombosis

AIM: The fruits of Lagenaria siceraria (Molina) Standl. (Cucurbitaceae), a commonly used vegetable, are reported to possess various medicinal properties. In previous studies, the fibrinolytic potential of an ethanolic extract of fruits of Lagenaria siceraria was investigated in comparison with kaempferol isolated from it. The aim of the present study was to explore its mechanistic antithrombotic potential and antiplatelet activity using a wide dose range in different in vitro and in vivo models, and to quantify the total phenolic, flavonoid, and kaempferol contents using a colorimetric method. METHOD: The antithrombotic potential was investigated using tail bleeding time in mice, a plasma recalcification assay, and pulmonary thromboembolism in mice. The antiplatelet activity was studied using an in vitro model to investigate IC50 value. RESULTS: A significant amount of total phenols, flavonoids, and kaempferol was quantified in L. siceraria ethanolic extract. An ethanolic extract of the fruits of L. siceraria showed a significant increase in tail bleeding time and plasma recalcification time, significant protection against ADP induced pulmonary thromboembolism in mice, and also inhibited the platelet aggregation induced by ADP in vitro. The study suggested that the fruits of L. siceraria exhibit significant antithrombotic potential due to inhibition of ADP-mediated platelet aggregation and the involvement of various non-cellular chemical mediators of blood. CONCLUSION This finding may be helpful in treating the serious consequences of the thrombus formed in blood vessels which include atherothrombotic diseases, such as myocardial or cerebral infarction. So, further investigation should be done for revealing exact mechanism of action behind these types of activities.
Adenosine Diphosphate ; Animals ; Calcium ; blood ; Cucurbitaceae ; chemistry ; Female ; Fibrinolytic Agents ; analysis ; pharmacology ; therapeutic use ; Fruit ; Goats ; Kaempferols ; analysis ; pharmacology ; therapeutic use ; Male ; Mice ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; analysis ; pharmacology ; therapeutic use ; Polyphenols ; analysis ; pharmacology ; therapeutic use ; Pulmonary Embolism ; blood ; chemically induced ; drug therapy ; Rats, Wistar ; Thrombosis ; prevention & control

OBJECTIVEThe effect of tranexamic acid (TA) on patients receiving total knee arthroplasty (TKA) has been reported in many small clinical trials. But single trials are not sufficient enough to clarify the effectiveness and safety of TA. So, we carried out a meta-analysis of randomized controlled trials to investigate the efficacy and safety of the intravenous use of TA in TKA.

METHODSLiteratures were retrieved in Cochrane Library, OVID, PubMed, EMBASE, CNKI and Wanfang Data. All the related literatures were checked by two independent investigators and only the high quality randomized controlled trials were enrolled. Relevant data were analyzed using RevMan 5.1 to compare the difference of blood loss, transfusion and complications between TA group and control group.

RESULTSThere were 353 related literatures and only 22 randomized controlled trials met the inclusion criteria. The use of TA in TKA significantly reduced total blood loss by a mean of 435.41 ml (95% CI 300.62-570.21, P less than 0.01), post-operative blood loss by a mean of 406.69 ml (95% CI 333.16-480.22, P less than 0.01). TA also significantly lowered the transfusion rate (risk difference 0.30, 95% CI 0.21-0.39, P less than 0.01) and transfusion volume (mean difference 0.95 unit, 95% CI 0.53-1.37, P less than 0.01). The risks between TA group and control group in developing deep vein thrombosis and pulmonary embolism were not statistically significant.

CONCLUSIONTA is beneficial for patients undergoing TKA, which can significantly reduce total blood loss, postoperative blood loss, transfusion rate, and transfusion volume. Meanwhile TA is recommended to reduce deep vein thrombosis and pulmonary embolism following TKA.

Antifibrinolytic Agents ; therapeutic use ; Arthroplasty, Replacement, Knee ; Blood Loss, Surgical ; prevention & control ; Blood Transfusion ; Humans ; Postoperative Hemorrhage ; prevention & control ; Pulmonary Embolism ; chemically induced ; Randomized Controlled Trials as Topic ; Tranexamic Acid ; adverse effects ; therapeutic use ; Venous Thrombosis ; chemically induced

BACKGROUNDStent thrombosis is one of severe complications after sirolimus-eluting stent implantation. Rapamycin (sirolimus) promotes arterial thrombosis in in vivo studies. However, the underlying molecular and transcriptional mechanisms of this adverse effect have not been thoroughly investigated. This study was designed to examine the effects of rapamycin on the expression of the gene, Kruppel-like factor 2 (KLF2), and its transcriptional targets in mice.

METHODSMice were randomly divided into four groups: the control group (intraperitoneal injection with 2.5% of dimethyl sulfoxide (DMSO) only), rapamycin group (intraperitoneal injection with 2 mg/kg of rapamycin only), Ad-LacZ + rapamycin group (carotid arterial incubation with Ad-LacZ plus intraperitoneal injection with 2 mg/kg of rapamycin 10 days later), and Ad-KLF2 + rapamycin group (carotid arterial incubation with Ad-KLF2 plus intraperitoneal injection with 2 mg/kg rapamycin 10 days later). The carotid arterial thrombosis formation was induced by FeCl3 and the time of arterial thrombosis was determined. Finally, the RNA and protein of carotid arteries were extracted for KLF2, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), endothelial nitric oxide synthase (eNOS), thrombomodulin (TM) mRNA and protein analysis.

RESULTSCompared with controls, treatment with rapamycin inhibited KLF2, eNOS and TM mRNA and protein expression, and enhanced TF and PAI-1 mRNA and protein expression, and shortened time to thrombotic occlusion from (1282 ± 347) seconds to (715 ± 120) seconds (P < 0.01) in vivo. Overexpression of KLF2 strongly reversed rapamycin-induced effects on KLF2, eNOS, TM, TF and PAI-1 expression. KLF2 overexpression increased the time to thrombotic occlusion to control levels in vivo.

CONCLUSIONSRapamycin induced an inhibition of KLF2 expression and an imbalance of anti- and pro-thrombotic gene expression, which promoted arterial thrombosis in vivo. Overexpression of KLF2 increased KLF2 expression and reversed time to thrombosis in vivo.

Animals ; Carotid Arteries ; metabolism ; Drug-Eluting Stents ; adverse effects ; Kruppel-Like Transcription Factors ; analysis ; genetics ; physiology ; Mice ; Mice, Inbred C57BL ; Nitric Oxide Synthase Type III ; physiology ; Plasminogen Activator Inhibitor 1 ; physiology ; Sirolimus ; pharmacology ; Thrombomodulin ; physiology ; Thrombosis ; chemically induced