Coagulation Dysfunction in Patients with Liver Cirrhosis and Splenomegaly and Its Countermeasures: A Retrospective Study of 1522 Patients

Lv, Yunfu; Liu, Ning; Li, Yejuan; Wu, Junzhen; Zheng, Jiaxuan; Li, Xinqiu; Zeng, Min

doi:10.1155/2023/5560560

Cited by 3 publications

(4 citation statements)

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“…Papain was evaluated via in vitro study using PT and PTT assays, which can be used to study the extrinsic and intrinsic coagulation cascade. PT assays primarily involve procedures that initiate the extrinsic coagulation factor (factor VII) and common (factors II, V, and X) pathways, as well as fibrinogen [43], whereas the aPTT assay involves procedures that initiate intrinsic coagulation system, comprising factors VIII, IX, XI, and XII [44]. In this study, we found that papain is able to prolong PT and aPTT even at a concentration of 8 U/mL Prolongation of PT can be due to a deficiency in any of the factors involved in the extrinsic and common pathways of blood coagulation or the presence of papain.…”

Section: Discussionmentioning

confidence: 99%

Unveiling the Potent Fibrino(geno)lytic, Anticoagulant, and Antithrombotic Effects of Papain, a Cysteine Protease from Carica papaya Latex Using κ-Carrageenan Rat Tail Thrombosis Model

Yang,

Zahan,

Yoon

et al. 2023

IJMS

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While fibrinolytic enzymes and thrombolytic agents offer assistance in treating cardiovascular diseases, the existing options are associated with a range of adverse effects. In our previous research, we successfully identified ficin, a naturally occurring cysteine protease that possesses unique fibrin and fibrinogenolytic enzymes, making it suitable for both preventing and treating cardiovascular disorders linked to thrombosis. Papain is a prominent cysteine protease derived from the latex of Carica papaya. The potential role of papain in preventing fibrino(geno)lytic, anticoagulant, and antithrombotic activities has not yet been investigated. Therefore, we examined how papain influences fibrinogen and the process of blood coagulation. Papain is highly stable at pH 4–11 and 37–60 °C via azocasein assay. In addition, SDS gel separation electrophoresis, zymography, and fibrin plate assays were used to determine fibrinogen and fibrinolysis activity. Papain has a molecular weight of around 37 kDa, and is highly effective in degrading fibrin, with a molecular weight of over 75 kDa. Furthermore, papain-based hemostatic performance was confirmed in blood coagulation tests, a blood clot lysis assay, and a κ-carrageenan rat tail thrombosis model, highlighting its strong efficacy in blood coagulation. Papain shows dose-dependent blood clot lysis activity, cleaves fibrinogen chains of Aα, Bβ, and γ-bands, and significantly extends prothrombin time (PT) and activated partial thromboplastin time (aPTT). Moreover, the mean length of the infarcted regions in the tails of Sprague–Dawley rats with κ-carrageenan was shorter in rats administered 10 U/kg of papain than in streptokinase-treated rats. Thus, papain, a cysteine protease, has distinct fibrin and fibrinogenolytic properties, suggesting its potential for preventing or treating cardiovascular issues and thrombosis-related diseases.

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Section: Discussionmentioning

confidence: 99%

Unveiling the Potent Fibrino(geno)lytic, Anticoagulant, and Antithrombotic Effects of Papain, a Cysteine Protease from Carica papaya Latex Using κ-Carrageenan Rat Tail Thrombosis Model

Yang,

Zahan,

Yoon

et al. 2023

IJMS

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“…In MASLD patients, there is also an alteration of the levels of antithrombin and von Willebrand factor (vWF) [66,67], whose altered activation of the latter leads to the dysregulated formation of a platelet plug [66]. The severity of alteration in hemostasis was more pronounced in patients with advanced liver disease such as MASH or cirrhosis [68,69], in which more advanced hepatocellular damage is present [59]. Hepatocellular damage of a significant degree could result in a compromised production of various coagulation factors, including fibrinogen; thrombin; and factors V, VII, IX, and X.…”

Section: Coagulation Dysfunctionsmentioning

confidence: 99%

“…Hepatocellular damage of a significant degree could result in a compromised production of various coagulation factors, including fibrinogen; thrombin; and factors V, VII, IX, and X. These factors are predominantly synthesized in the liver [68,69]. As a result, this gives rise to an increased vulnerability to both thrombotic and hemorrhagic events [68,69].…”

Section: Coagulation Dysfunctionsmentioning

confidence: 99%

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Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

Pezzino,

Luca,

Castorina

et al. 2024

Life

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The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.

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Portosystemic shunt for variceal esophagogastric bleeding and risk of early re-bleeding. Rationale for involuntary intervention: A single-center observational controlled study

Khoronko,

Kosovtsev,

Korobka

et al. 2024

Kuban. nauсh. med. vestnik

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Background. Variceal esophageal-gastric bleeding is considered to be a life-threatening complication of portal hypertension in patients with cirrhosis. In some cases, only portosystemic shunt can serve as a life-saving intervention for the patient.Aim. To justify the forced expediency of transjugular intrahepatic portosystemic shunt (TIPS) in case of ineffective drug and endoscopic hemostasis or a high risk of early recurrence of variceal bleeding.Methods. A single-center observational controlled study was conducted to analyze the results of shunt procedure in 62 patients during the period of 2017–2023. The patients were divided into 2 groups: the main group (n = 32) with patients who underwent “early” shunt procedure in a “salvage” variant (n = 10) with continued bleeding and in a “pre-emptive” variant (n = 22) with a high risk of early recurrence of hemorrhage, and the control group (n = 30) with patients who underwent planned shunt procedure. The value of the portosystemic pressure gradient was calculated by subtracting the value of the pressure in the inferior vena cava recorded at the initial stage of the operation from the value of the initial pressure in the portal vein, measured by direct manometry. The authors compared the dynamics of the portosystemic pressure gradient in the study groups at similar stages of the intervention — initial, after embolization of the veins of portal blood flow to the varix, after shunt stenting. The study involved the analysis of mortality rates (6-week, one-year, for the entire observation period) and complications. Statistica-for-Windows 12.0 (StatSoft®, USA) and Excel (Microsoft, USA) were used to calculate descriptive statistics.Results. Patients of both groups achieved normalization of pressure in the portal vein system and, accordingly, the portosystemic pressure gradient as a result of shunt surgery. Effective portal decompression was confirmed by their significant reduction. In the portal vein, the pressure decreased from 33.84 ± 2.70 to 20.53 ± 1.27 mmHg (t = 4.46; p < 0.001) in the main group and from 32.80 ± 3.07 to 20.10 ± 1.60 mmHg (t = 3.67; p < 0.001) in the control group. The dynamics of the portosystemic pressure gradient showed a significant decrease from 26.16 ± 2.69 to 10.06 ± 0.88 mm Hg (t = 5.69; p < 0.001) in the main group, and from 24.83 ± 2.73 to 9.67 ± 1.21 mm Hg (t = 5.08; p < 0.001) in the control group. Together with embolization of the vessels of the hepatofugal inflow of portal blood to the varices, this led to a stable and long-term cessation of variceal bleeding. When comparing the results of shunt procedure in the study groups, no significant differences were found in terms of differentiated mortality rates and complications in both the early and long-term periods. In the main group, the 6-week and one-year mortality rates accounted for 6.3% (n = 2) and 15.6% (n = 5), in the control group — 6.7% (n = 2) and 13.3% (n = 4), respectively (p = 0.917). Mortality in the main group comprised 25.0% (n = 8) over 58 months, in the control group — 23.3% (n = 7) over 60 months (p = 0.886).Conclusion. The transjugular shunt provides a significant reduction in the portosystemic pressure gradient. “Salvage” and “pre-emptive” shunt options can prevent death and early recurrence of bleeding. Their effectiveness increases due to endovascular blockage of vessels that ensures the overflow of esophagogastric varices with portal blood.

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Coagulation Dysfunction in Patients with Liver Cirrhosis and Splenomegaly and Its Countermeasures: A Retrospective Study of 1522 Patients

Cited by 3 publications

References 42 publications

Unveiling the Potent Fibrino(geno)lytic, Anticoagulant, and Antithrombotic Effects of Papain, a Cysteine Protease from Carica papaya Latex Using κ-Carrageenan Rat Tail Thrombosis Model

Unveiling the Potent Fibrino(geno)lytic, Anticoagulant, and Antithrombotic Effects of Papain, a Cysteine Protease from Carica papaya Latex Using κ-Carrageenan Rat Tail Thrombosis Model

Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

Portosystemic shunt for variceal esophagogastric bleeding and risk of early re-bleeding. Rationale for involuntary intervention: A single-center observational controlled study

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