Comparison of gabexate mesilate and nafamostat mesilate for disseminated intravascular coagulation associated with hematological malignancies

Abstract

We evaluated clinical outcomes of disseminated intravascular coagulation (DIC) in patients with hematological malignancies treated with synthetic protease inhibitors (SPIs) and compared the effects of gabexate mesilate (FOY) and nafamostat mesilate (FUT). We retrospectively examined 127 patients [acute myeloid leukemia (n = 48), acute lymphoblastic leukemia (n = 25), and non-Hodgkin lymphoma (n = 54)] with DIC, who were diagnosed according to Japanese Ministry of Health, Labour and Welfare criteria and treated with SPIs [FOY (n = 55) and FUT (n = 72)] at our hospital from 2006 to 2015. The DIC resolution rates on days 7 and 14 were 42.6% and 62.4%, respectively. No significant differences were observed in DIC resolution rates between the FUT and FOY groups [40.3% vs. 45.5% (day 7), P = 0.586; 56.3% vs. 69.8% (day 14), P = 0.179, respectively]. Multivariate analysis revealed that response to chemotherapy was the only independent predictor of DIC resolution on days 7 and 14 (ORR 2.81, 95% CI 1.32-5.98, P = 0.007; ORR 2.51, 95% CI 1.12-5.65, P = 0.026). Resolution of DIC was correlated with improvement of background hematological malignancies, and no significant differences were observed between the two SPIs.

Comparison of Danaparoid Sodium and Synthetic Protease Inhibitors for the Treatment of Disseminated Intravascular Coagulation Associated with Hematological Malignancies: A Retrospective Analysis

“…There are some differences in the recommendations regarding the use anticoagulants for DIC, and a consensus has not been reached in the guidelines, which could be attributed to the scarcity of randomized controlled studies and clinical results of observational studies. Table 5 summarizes prior studies on the use of anticoagulants for the treatment of DIC in patients with hematological malignancies [9, 12, 15, 18-25]. DIC resolution rates on day 7 have been reported to be 40–60%, which is consistent with our results.…”

“…In this study, we retrospectively collected the clinical data of 188 consecutive adult patients with hematological malignancy-related DIC who were treated with danaparoid or SPIs. In principle, as first-line treatment of DIC, SPIs were used at the Jichi Medical University [12], and danaparoid was administered at the Saitama Medical Center according to institute policy from April 2006 to December 2015. Patients who were initially treated with recombinant human soluble thrombomodulin, UFH, or LMWH were excluded from the analysis.…”

“…The clinical efficacy of SPIs for DIC is comparable with that of UFH, and SPIs are known to reduce the bleeding tendency in patients [2]. Regarding SPIs, we recently reported that there was no significant difference in the efficacy of FOY and FUT regarding DIC [12].…”

Diversity of disseminated intravascular coagulation and selection of appropriate treatments

“… Synthetic protease inhibitor Synthetic protease inhibitors exert antithrombin activity in an AT-independent manner. Representative drugs are nafamostat and gabexate [ 14 ]. These drugs show few side effects of bleeding, and are thus indicated when heparins are difficult to use due to concerns about side effects of bleeding.…”

ACE2: THE DOORWAY TO SARS-CoV-2

“…Another protease inhibitor with a broad-spectrum serine protease inhibitor function, nafamostat mesylate (NM) blocks SARS-CoV-2 infection of human lung cells with a markedly higher efficiency than camostat mesylate [97]. NM is approved in Japan and South Korea for the treatment of pancreatitis, disseminated intravascular coagulation, and systemic inflammatory response syndrome via suppression of thrombin, plasmin, kallikrein, trypsin, and Cl esterase in the complement system, as well as factors VIIa, Xa, and XIIa in the coagulation cascade [98][99][100][101].…”