Nafamostat mesilate reduces blood-foreign surface reactions similar to biocompatible materials

Usui, Akihiko; Hiroura, Manabu; Kawamura, Mitsuo; Hibi, M; Yoshida, Katsuhiko; Murakami, Fumihiko; Tomita, Yasuhiro; Ooshima, Hideki; Murase, M

doi:10.1016/0003-4975(96)00634-0

Cited by 15 publications

(5 citation statements)

References 12 publications

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“…One report found no difference in XIIa during CPB between the noncoated group and the Duraflo group (18). In our study, however, XIIa increased during CPB in the noncoated group whereas it did not increase in the Duraflo group.…”

Section: Discussioncontrasting

confidence: 91%

Effects of Duraflo II Heparin‐Coated Cardiopulmonary Bypass Circuits on the Coagulation System, Endothelial Damage, and Cytokine Release in Patients with Cardiac Operation Employing Aprotinin and Steroids

et al. 1999

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The effects of Duraflo II heparin coated cardiopulmonary bypass circuits, low-dose aprotinin, and steroids on the coagulation system, endothelial damage, and cytokine release were evaluated by comparing those treated with low-dose aprotinin and steroids. Twenty-four adult patients undergoing coronary artery bypass grafting, aortic valve replacement, or valve repair surgery were randomly assigned to 2 groups: either heparin-coated (Duraflo group, n = 12) or noncoated equipment (noncoated group, n = 12) groups. In the Duraflo group, the cardiopulmonary reservoir was also coated with heparin. There were no significant differences in age at the time of operation, aortic cross-clamp time, cardiopulmonary bypass time, and rectal temperature during cardiopulmonary bypass. Standard systemic heparinization was performed. Methylpredonisolone and low-dose aprotinin were given in both groups of patients. Serum XIIa factor, TAT, and IL-6 were significantly higher in the control group than in the Duraflo group during cardiopulmonary bypass (p < 0.01). Serum IL-8 was significantly higher in the control group than in the Duraflo group at 24 h after cardiopulmonary bypass (p < 0.05). No significant difference was found in serum thrombomodulin and TNF-alpha; both were within normal during the study period. These results indicate that the use of Duraflo II heparin coated equipment and a heparin-coated cardiopulmonary reservoir suppressed excess coagulation and inflammatory reaction induced by cardiopulmonary bypass.

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Section: Discussioncontrasting

confidence: 91%

Effects of Duraflo II Heparin‐Coated Cardiopulmonary Bypass Circuits on the Coagulation System, Endothelial Damage, and Cytokine Release in Patients with Cardiac Operation Employing Aprotinin and Steroids

et al. 1999

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“…It is generally known that NM not only inhibits activation of the coagulation factors, but also inhibits platelet aggregation in the ECC at that concentration. [12][13][14][15] We also attempted to examine whether NM actually disaggregates aggregated platelets, and found that NM disaggregated ADP-stimulated platelets obtained from HD patients. It is interesting that NM significantly inhibited platelet aggregation and disaggregated aggregated platelets at approximately the same concentrations of HD (10 g/ml, or 1.9 ϫ 10 -5 M); moreover, this disaggregatory effect was achieved at concentrations lower than the therapeutic concentration used for HD.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, NM has been used in the clinical settings of pancreatitis, disseminated intravascular coagulation, and extracorporeal circulation (ECC), such as during hemodialysis therapy (HD), plasmapheresis, and cardiopulmonary bypass. [5][6][7][8][9][10][11][12][13][14][15] A recent study reported that amidinonaphthol derivatives such as NM not only inhibit platelet aggregation, but also disaggregate aggregated platelets after stimulation of healthy donor plateletrich plasma (PRP). 16 However, neither this effect nor the fact that NM has a disaggregatory effect on aggregated platelets was discussed in the context of clinical application.…”

mentioning

confidence: 99%

Effects of Nafamostat Mesilate on ADP-Induced Platelet Aggregation and Disaggregation in Hemodialysis Patients

Miyata

Shirakawa²,

Acharya³

et al. 2006

ASAIO Journal

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Nafamostat mesilate (NM), a synthetic protease inhibitor, is the most commonly used anticoagulant in the setting of extracorporeal circulation (ECC) in patients with bleeding tendency. It inhibits both platelet aggregation and activation of coagulation factors. Although it has been reported that NM disaggregates aggregated platelets, little is known about such an effect in the setting of hemodialysis therapy (HD). We examined the effects of NM on adenosine 5'-diphosphate (ADP)-induced platelet aggregation and disaggregation using platelet-rich plasma obtained from 6 HD patients. The platelet aggregation was stimulated by 3 microM ADP and change of aggregation was monitored by an aggregometer. NM adjusted to the final concentrations of 0.1 (1.9 x 10(-7)), 1.0 (1.9 x 10(-6)), 10, (1.9 x 10(-5)), and 100 (1.9 x 10(-4)) microg/ml (M) or veronal-buffered saline (VBS) as control was added before or after to the stimulation of ADP. NM not only inhibited platelet aggregation, but also disaggregated already aggregated platelets at concentrations of 1.0 microg/mln or higher. Moreover, NM almost completely disaggregated at 100 microg/ml. This NM concentration of 1.0 microg/ml was lower than the therapeutic concentration in ECC of HD (i.e., 10 M(-5)). Both inhibitory and disaggregatory effects of NM expressed a dose-related dependency. Our results suggest that NM can exert both aggregation inhibitory and disaggregatory effects on platelets of HD patients within the therapeutic concentration.

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“…,Fibrinolysis is important in the hemorrhagic diathesis associated with cardiopulmonary bypass [7]. Heparin and its fractions have been known to pos-ses~profibrinolytic potential.…”

Section: Discussionmentioning

confidence: 99%

Argatroban as a Potential Anticoagulant in Cardiopulmonary Bypass-Studies in a Dog Model

Sakai,

Ohteki,

Narita

et al. 1999

Cardiovascular Surgery

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Argatroban is a selective thrombin inhibitor synthesized in Japan. Argatroban, which has a high affinity for thrombin, and markedly inhibits thrombin-induced reactions, has been used in patients with artherosclerosis obliterans. The efficiency of argatroban, instead of heparin, as an anticoagulant in dog models of cardiopulmonary bypass was explored. In the first study, argatroban was administered as a bolus plus infusion for 1 h during cardiopulmonary bypass at doses of 1.0 mg + 10 μg/kg per min, 2.0 mg + 10 μg/kg per min and 3.0 mg + 10 μg/kg per min ( n = 2 per group). Activated clotting time and arterial gas analyses were performed beforehand and 10 min thereafter. In the second study, there were four groups. In the first group ( n = 5) no coated extracorporeal circuit was used and heparin (2 mg/kg) was used as an anticoagulant. In the second group ( n = 5). a coated extracorporeal circuit was used and heparin was used (2 mg/kg) as an anticoagulant. In the third group ( n = 3), no coated extracorporeal circuit was used and argatroban (2.0 mg + 10μg/kg per min) was used as an anticoagulant. In the fourth group ( n = 5), a coated extracorporeal circuit was used and argatroban was used (2.0 mg + 10 μg/kg per min) as an anticoagulant. All animals were perfused for 120 min at 40 ml/kg per minute. Platelet count, activated clotting time, thrombin—antithrombin III complex, antithrombin III. fibrinogen, fibrinogen degradation products and C3a were measured to evaluate platelet, coagulofibrinolytic and the complement system. Activated clotting time values and the effect of argatroban during cardiopulmonary bypass indicated a dose-dependent response. The next highest dosing group (2.0 mg + 10 μg/kg per minute) had activated clotting time values of 250–300 seconds during cardiopulmonary bypass and fell after reaching near-normal levels within 60 minutes. No clots were noted in the extracorporeal circuit. The argatroban group showed lower levels in their coagulofibrinolytic system compared with the heparin group. The platelet count remained at a high level in the argatroban group. It is concluded that the combination of heparinized cardiopulmonary bypass circuits, and the use of argatroban as an anticoagulant, is safe and reduces the activation of coagulation and fibrinolytic systems and preserves platelet count.

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Nafamostat mesilate reduces blood-foreign surface reactions similar to biocompatible materials

Cited by 15 publications

References 12 publications

Effects of Duraflo II Heparin‐Coated Cardiopulmonary Bypass Circuits on the Coagulation System, Endothelial Damage, and Cytokine Release in Patients with Cardiac Operation Employing Aprotinin and Steroids

Effects of Duraflo II Heparin‐Coated Cardiopulmonary Bypass Circuits on the Coagulation System, Endothelial Damage, and Cytokine Release in Patients with Cardiac Operation Employing Aprotinin and Steroids

Effects of Nafamostat Mesilate on ADP-Induced Platelet Aggregation and Disaggregation in Hemodialysis Patients

Argatroban as a Potential Anticoagulant in Cardiopulmonary Bypass-Studies in a Dog Model

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