Efficacy of recombinant human soluble thrombomodulin in preventing walled-off necrosis in severe acute pancreatitis patients

Eguchi, Takaaki; Tsuji, Yoshihisa; Yamashita, Hiroshi; Fukuchi, Takumi; Kanamori, Atsushi; Matsumoto, Keīichi; Hasegawa, Takashi; Kitada, Ryuki; Tsujimae, Masahiro; Iwatsubo, Taro; Koyama, Soichiro; Ubukata, Satoshi; Fujita, Mikio; Okada, Akihiko

doi:10.1016/j.pan.2015.08.002

Cited by 18 publications

(26 citation statements)

References 54 publications

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“…Treatment with heparin has been also found to be effective in the prevention of pancreatitis-evoked encephalopathy [17]. Moreover, treatment with recombinant human soluble thrombomodulin seems to be useful in preventing walled-off necrosis in patients with severe acute pancreatitis [18]. …”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

Warzecha

Sendur

Ceranowicz

et al. 2017

IJMS

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Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

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Section: Introductionmentioning

confidence: 99%

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

Warzecha

Sendur

Ceranowicz

et al. 2017

IJMS

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“…Eguchi et al [197] performed a retrospective analysis of 54 adult patients with SAP diagnosed according to Japanese severity scoring system, treated in a single center (Osaka Saiseikai Nakatsu Hospital, Osaka, Japan), of whom 24 developed DIC and were therefore treated with recombinant human soluble thrombomodulin (rTM). The study included patients in whom treatment started within the first 48 h from the onset of pain.…”

Section: Therapeutic Effects Of Anticoagulants In Acute Pancreatitismentioning

confidence: 99%

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Dumnicka

Maduzia

Ceranowicz

et al. 2017

IJMS

154

113

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Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

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“…We administered TM-α, the world's first recombinant form of human thrombomodulin, which acts on coagulation and inflammation to regulate the anticoagulant cascade. Since TM-α therapy significantly improved DIC and alleviated bleeding symptoms as compared with heparin therapy in a Japanese phase III clinical trial of DIC patients, TMα has been widely used to treat patients with DIC in Japan [9,10,18,19]. In the present case, PVT disappeared following TM-α therapy in accordance with the dosage and route of administration for DIC, while there is no reported evidence about the treatment of portal vein thrombosis with TM-α this time.…”

Section: Discussionmentioning

confidence: 61%

Acute Portal Vein Thrombosis Treated with Recombinant Human Soluble Thrombomodulin Combined with Antithrombin III

Nakayama¹,

Matsumoto²

2020

Case Reports in Medicine

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Portal vein thrombosis is a major complication associated with liver cirrhosis. In cirrhotic patients, a decrease in procoagulant and anticoagulant factors and an unstable balance between them is observed, and a relative decrease in the activation of anticoagulant drivers is one of the main causes of portal vein thrombosis (PVT). Herein, we report a case of acute portal thrombosis associated with liver cirrhosis and treated with a recombinant form of soluble thrombomodulin (thrombomodulin alpha, TM-α) in combination with antithrombin III. TM-α was administered in accordance with the dosage and route of administration for disseminated intravascular coagulation therapy and resulted in dissolution of PVT with a gradual decrease in D-dimer levels. No adverse events were observed during the course of treatment. In the future, in addition to conventional anticoagulation therapy using heparin or antivitamin K drugs, novel therapies targeting protein C activation using a recombinant form of soluble thrombomodulin may play an important role in the treatment of acute PVT.

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Efficacy of recombinant human soluble thrombomodulin in preventing walled-off necrosis in severe acute pancreatitis patients

Abstract: Treatment of SAP patients treated by rTM may prevent progression from pancreatic necrosis/ischemia to WON.

Cited by 18 publications

References 54 publications

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Acute Portal Vein Thrombosis Treated with Recombinant Human Soluble Thrombomodulin Combined with Antithrombin III

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