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Thromboembolism (TE) is a common and serious complication of nephrotic syndrome (NS). NS is associated with hypercoagulability, which may be induced by changes in coagulation, anticoagulant, and fibrinolytic factors. Moreover, accumulating evidence supports the hypothesis that the complex interactions between genetic and acquired risk factors in TE should be considered and that genetic susceptibility should not be ignored. Extracellular vesicles (EVs) also play unique roles. Further research on EVs may provide new insights into the discovery and treatment of TE associated with NS. The occurrence of NS accompanied by TE may be associated with various risk factors. Preventive anticoagulant therapy can not only reduce the risk of TE in patients but also aggravate the risk of bleeding. Heparin and vitamin K antagonists (VKAs), traditional anticoagulant drugs, have been extensively applied in the prevention and treatment of thromboembolic diseases, and emerging direct oral anticoagulants (DOACs) also provide an alternative choice. Owing to the particularity of NS, the safe application of DOACs still needs to be addressed. This review aimed to comprehensively describe the pathophysiology of TE in NS, as well as analyze the associated risk factors, the opportunity for preventive anticoagulation, and current anticoagulant information. [ABSTRACT FROM AUTHOR]

Abstract Background: Snake venom phospholipases A2 (svPLA2) are biologically active toxins, capable of triggering and modulating a wide range of biological functions. Among the svPLA2s, crotoxin (CTX) has been in the spotlight of bioprospecting research due to its role in modulating immune response and hemostasis. In the present study, novel anticoagulant mechanisms of CTX, and the modulation of inflammation-induced coagulation were investigated. Methods: CTX anticoagulant activity was evaluated using platelet poor plasma (PPP) and whole blood (WB), and also using isolated coagulation factors and complexes. The toxin modulation of procoagulant and pro-inflammatory effects was evaluated using the expression of tissue factor (TF) and cytokines in lipopolysaccharide (LPS)-treated peripheral blood mononuclear cells (PBMC) and in WB. Results: The results showed that CTX impaired clot formation in both PPP and WB, and was responsible for the inhibition of both intrinsic (TF/factor VIIa) and extrinsic (factor IXa/factor VIIIa) tenase complexes, but not for factor Xa and thrombin alone. In addition, the PLA2 mitigated the prothrombinase complex by modulating the coagulation phospholipid role in the complex. In regards to the inflammation-coagulation cross talk, the toxin was capable of reducing the production of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, and was followed by decreased levels of TF and procoagulant activity from LPS-treated PBMC either isolated or in WB. Conclusion: The results obtained in the present study recognize the toxin as a novel medicinal candidate to be applied in inflammatory diseases with coagulation disorders.

The aim of this work was to extract, isolate, and purify polysaccharides from the heads of Hypomesus olidus and to evaluate their anticoagulant activities and anticoagulant mechanisms. Response surface methodology was used to optimize the extraction conditions for ultrasonic‐assisted extraction of polysaccharides from the heads of Hypomesus olidus. The optimal extraction conditions consisted of ultrasonic power of 275 W, ultrasonic time of 50 min, and solid–liquid ratio of 5 ml/g, giving the yield of crude polysaccharides (GYT) of 7.73 ± 0.042%. Three polysaccharide fractions, GYT‐1, GYT‐2, and GYT‐3 were purified from GYT by using DEAE‐cellulose‐52 column and Sephadex G‐100 column for anticoagulant activities. The results showed that two doses (2 and 4 mg/ml) of GYT‐1 and GYT‐3 could significantly prolong (p <.01) in partial thromboplastin time (APTT) (2.19 and 2.37 times, 2.22 and 2.44 times, respectively) and thrombin time (TT) (2.39 and 2.46 times, 2.44 and 2.80 times, respectively) compared with normal control. In particular, GYT‐3 had stronger anticoagulant activity than GYT‐1, and it was composed of arabinose, fructose, glucose, and lactose with molar ratios of 0.595:1: 2.026:0.273. However, GYT‐2 had no anticoagulant activity (p >.05). In addition, anticoagulation mechanism of polysaccharides from the heads of Hypomesus olidus (GYT‐3) was evaluated. The results showed that the anticoagulant activity of GYT‐3 was based on their binding with antithrombin AT‐III. And the inhibitory effects of GYT‐3 on factor IIa and Xa were related to the concentration of AT‐III in plasma. This study may provide a new and promising anticoagulant drug. [ABSTRACT FROM AUTHOR]

Abstract: DSS1 and DSS2 are two oversulfated dermatan sulfate derivatives with sulfur contents of 7.8% and 11.5%, respectively. DSS1 and DSS2 both enhanced the rate at which antithrombin (AT) inactivates thrombin according to a concentration dependent manner. The analysis of the experimental data, using our previously described kinetic model [Biomaterials 1997, 18, 203] (i) suggested that both DSS1 and DSS2 catalyzed the thrombin–AT reaction according to a mechanism in which the oversulfated derivative quickly formed with AT a complex, which was more reactive towards thrombin than the free inhibitor and (ii) allowed us to determine the dissociation constants of the polysaccharide–inhibitor complexes, which were (1.15±0.74)×10−7 and (7.17±0.65)×10−9 M, and the catalyzed reaction rate constants, which were (2.29±0.15)×108 and (8.71±0.08)×108 M−1 min−1, for DSS1 and DSS2, respectively. These data suggested that the oversulfation confers an affinity for AT to dermatan sulfate and that the higher the sulfur content the higher the affinity for AT. They also suggested that the reactivities of the polysaccharide–AT complexes formed towards the protease increased with the sulfur content. [Copyright &y& Elsevier]

Background: Snake venom phospholipases A 2 (svPLA 2 ) are biologically active toxins, capable of triggering and modulating a wide range of biological functions. Among the svPLA 2 s, crotoxin (CTX) has been in the spotlight of bioprospecting research due to its role in modulating immune response and hemostasis. In the present study, novel anticoagulant mechanisms of CTX, and the modulation of inflammation-induced coagulation were investigated., Methods: CTX anticoagulant activity was evaluated using platelet poor plasma (PPP) and whole blood (WB), and also using isolated coagulation factors and complexes. The toxin modulation of procoagulant and pro-inflammatory effects was evaluated using the expression of tissue factor (TF) and cytokines in lipopolysaccharide (LPS)-treated peripheral blood mononuclear cells (PBMC) and in WB., Results: The results showed that CTX impaired clot formation in both PPP and WB, and was responsible for the inhibition of both intrinsic (TF/factor VIIa) and extrinsic (factor IXa/factor VIIIa) tenase complexes, but not for factor Xa and thrombin alone. In addition, the PLA 2 mitigated the prothrombinase complex by modulating the coagulation phospholipid role in the complex. In regards to the inflammation-coagulation cross talk, the toxin was capable of reducing the production of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, and was followed by decreased levels of TF and procoagulant activity from LPS-treated PBMC either isolated or in WB., Conclusion: The results obtained in the present study recognize the toxin as a novel medicinal candidate to be applied in inflammatory diseases with coagulation disorders., Competing Interests: Competing interests: The authors declare that they have no competing interests.

The aim of this work was to extract, isolate, and purify polysaccharides from the heads of Hypomesus olidus and to evaluate their anticoagulant activities and anticoagulant mechanisms. Response surface methodology was used to optimize the extraction conditions for ultrasonic-assisted extraction of polysaccharides from the heads of Hypomesus olidus . The optimal extraction conditions consisted of ultrasonic power of 275 W, ultrasonic time of 50 min, and solid-liquid ratio of 5 ml/g, giving the yield of crude polysaccharides (GYT) of 7.73 ± 0.042%. Three polysaccharide fractions, GYT-1, GYT-2, and GYT-3 were purified from GYT by using DEAE-cellulose-52 column and Sephadex G-100 column for anticoagulant activities. The results showed that two doses (2 and 4 mg/ml) of GYT-1 and GYT-3 could significantly prolong ( p  < .01) in partial thromboplastin time (APTT) (2.19 and 2.37 times, 2.22 and 2.44 times, respectively) and thrombin time (TT) (2.39 and 2.46 times, 2.44 and 2.80 times, respectively) compared with normal control. In particular, GYT-3 had stronger anticoagulant activity than GYT-1, and it was composed of arabinose, fructose, glucose, and lactose with molar ratios of 0.595:1: 2.026:0.273. However, GYT-2 had no anticoagulant activity ( p  > .05). In addition, anticoagulation mechanism of polysaccharides from the heads of Hypomesus olidus (GYT-3) was evaluated. The results showed that the anticoagulant activity of GYT-3 was based on their binding with antithrombin AT-III. And the inhibitory effects of GYT-3 on factor IIa and Xa were related to the concentration of AT-III in plasma. This study may provide a new and promising anticoagulant drug., Competing Interests: All authors declare no conflicts of interest., (© 2019 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.)