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

Abstract

Background: Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan. Objectives: To compare the clinical results of the treatment of DIC with danaparoid or SPIs. Methods: We retrospectively examined 188 patients with hematological malignancy-related DIC. Results: DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21–4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15–13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278). Conclusions: Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.

Disseminated intravascular coagulation: epidemiology, biomarkers, and management

“…The anti‐Xa agent fondaparinux has not been evaluated in DIC patients, while the anti‐Xa agent danaparoid sodium, which is available in Japan, and synthetic protease inhibitors have been suggested by the Japanese Society of Thrombosis and Haemostasis for anticoagulant treatment during DIC 88 . A recent retrospective Japanese study compared the effect of danaparoid sodium and synthetic protease inhibitors in patients with haematological malignancy complicated by DIC, but no difference in DIC resolution was found between the two agents in the multivariate analysis 89 . As no randomised controlled trials (RCTs) have evaluated the effect on mortality or resolution of DIC, these anticoagulant agents need further investigation.…”

Rationale for the Role of Heparin and Related GAG Antithrombotics in COVID-19 Infection

“…Many hospitalized patients already present with serious complications that require urgent therapeutic intervention. Despite the advice of the ISTH, 180 but in keeping with data from COVID-19 patients treated with UFU or LMWH, 72 data from in-vitro studies and experience in the treatment of acute HIT 181,182 and ICU patients, [161][162][163][164][165]167 therapeutic infusions of danaparoid would appear to be the best approach for all COVID-19 patients, unless there is a high risk of bleeding (exacerbation). It is not clear from publications what the optimal dose and administration route of sulodexide should be.…”

“…However, as well as evidence of a unique immune modulating activity in patients with HIT, 159,160 therapeutic dosing with danaparoid has been used successfully to treat acutely ill patients 161,162 and problems similar to those that complicate COVID-19, e.g. DIC 163 –165 (including a hyperfibrinolytic variant 166 ), HIT, 167 patients with renal 168 –170 and varying degrees of hepatic failure in patients with cirrhosis, or hepatoma complicated by portal vein thrombosis 113,171,172 and patients with autoimmune diseases (such as PNH 173,174 and SLE/APL syndromes 175,176 ) and also to prevent chemotherapy-induced TMA 177,178 that like viral associated TMA also appears to be complement mediated. 179 Encouragingly, for many drugs in the past extrapolation from even in-vitro experimental data has yielded successes for many clinical problems.…”

Targeting Biological Polyanions in Blood: Strategies toward the Design of Therapeutics

“…Heparinoids are a group of heparin-like glycosaminoglycans which includes compounds produced naturally such as chondroitin sulfate, heparan sulfate, and dermatan sulfate or a mixture of heparinoids such as danaparoid. Danaparoid, a low molecular weight heparinoid, has been shown to be effective in treatment of heparin induced thrombocytopenia (HIT), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). , Fondaparinux is a synthetic methoxy-derivate of the active pentassacharide sequence of natural heparin and has a molecular weight of 1728 Da. Fondaparinux has demonstrated to be an attractive anticoagulant candidate due to its specific inhibition of FXa via irreversible high affinity binding to antithrombin (AT; K d = 36 ± 11 nM), and ability to manage HIT with low thrombotic risk. − Though the synthetic route of fondaparinux is complex, consisting of 50 steps, risk of contamination and batch-to-batch variation is eliminated compared to natural heparins.…”

“…Danaparoid, a low molecular weight heparinoid, has been shown to be effective in treatment of heparin induced thrombocytopenia (HIT), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). 18,19 Fondaparinux is a synthetic methoxy-derivate of the active pentassacharide sequence of natural heparin and has a molecular weight of 1728 Da. Fondaparinux has demonstrated to be an attractive anticoagulant candidate due to its specific inhibition of FXa via irreversible high affinity binding to antithrombin (AT; K d = 36 ± 11 nM), 20 and ability to manage HIT with low thrombotic risk.…”