Recombinant human thrombomodulin in the treatment of acute myeloid leukemia patients complicated by disseminated intravascular coagulation: retrospective analysis of outcomes between patients treated with heparin and recombinant human thrombomodulin therapy

Takezako, Naoki; Sekiguchi, Naohiro; Nagata, Akihisa; Homma, Chiho; Takezako, Yayoi; Noto, Satoshi; Natori, Kazuhiko; Miwa, Akiyoshi

doi:10.1016/j.thromres.2015.03.029

Cited by 17 publications

(9 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DIC resolution rates on day 7 have been reported to be 40–60%, which is consistent with our results. The cumulative incidence of bleeding-related mortality tended to be lower in the SPI group than in the danaparoid group (3.3 vs. 6.6%); however, these incidences were lower than those in previous studies about UFH and LMWH (6.1–12.5%) [15, 22-23, 25]. In addition, most previous studies were retrospective studies in patients with different backgrounds, and therefore prospective studies are needed to evaluate the use of anticoagulants, including danaparoid and SPIs, for the treatment of DIC.…”

Section: Discussioncontrasting

confidence: 54%

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

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 54%

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

et al. 2019

View full text Add to dashboard Cite

show abstract

“…OS in AML patients with DIC is significantly worse than that in AML patients without DIC. [ 29 ] Thus, in addition to controlling AML, successful treatment of DIC itself is indispensable for better clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…[ 22 , 30 , 31 ] In the setting of hematologic malignancies, Takezako et al revealed that OS was superior in AML patients treated with rTM when compared with heparin. [ 29 ] Aota et al reported that there were no significant differences in the DIC resolution rates and mortality between the rTM (n = 21) and GM (n = 206) groups. [ 22 ] In the present study, rTM treatment could contribute to improved OS in non-APL AML patients compared with GM treatment.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of disseminated intravascular coagulation by recombinant human soluble thrombomodulin in patients with acute myeloid leukemia

et al. 2018

View full text Add to dashboard Cite

Disseminated intravascular coagulation (DIC) is a life-threatening condition that frequently occurs in patients with hematologic malignancies. Currently, recombinant human soluble thrombomodulin (rTM) is a therapeutic DIC drug that is manufactured and sold in Japan only. We evaluated the efficacy of rTM compared to that of gabexate mesilate (GM), which was previously used routinely for treating DIC in Japan, in patients with acute myeloid leukemia (AML). This retrospective study enrolled 43 AML patients, including 17 with acute promyelocytic leukemia (APL), that was complicated with DIC. DIC resolution rates in non-APL AML and rTM-treated APL patients were 68.4% and 81.8%, respectively. In non-APL AML patients, the duration of rTM administration was significantly shorter than that of GM (7 vs 11 days), suggesting that rTM could improve DIC earlier than GM, although rTM was used in patients with more severe DIC. Moreover, treatment with rTM significantly improved DIC score, fibrinogen, fibrin/fibrinogen degradation product (FDP), and prothrombin time (PT) ratio. Conversely, treatment with GM only improved the DIC score and FDP. In APL patients, the duration of rTM administration was also significantly shorter than that of GM. No severe side effects associated with the progression of bleeding were observed during rTM administration. These findings suggest that rTM is safe, and its anti-DIC effects are more prompt than GM for treating AML patients with DIC.

show abstract

“…This novel agent seems to mediate fewer hemorrhagic side-effects than low-molecularweight heparin and improves overall survival. [20][21][22] Daily rTM from admission, however, failed to prevent severe epistaxis in the present young patient. Combination therapy using nafamostat mesilate or heparin and TXA may be dramatically effective for severe bleeding in patients with DIC and enhanced fibrinolysis.…”

Section: Discussionmentioning

confidence: 50%

“…Recombinant thrombomodulin is generally recommended in DIC associated with adult AML. This novel agent seems to mediate fewer hemorrhagic side‐effects than low‐molecular‐weight heparin and improves overall survival . Daily rTM from admission, however, failed to prevent severe epistaxis in the present young patient.…”

Section: Discussionmentioning

confidence: 67%

Hemostatic function in hyperfibrinolytic disseminated intravascular coagulation

Ishihara

Nogami

Onishi

et al. 2019

Pediatrics International

View full text Add to dashboard Cite

Background Global hemostatic mechanism(s) in patients with disseminated intravascular coagulation (DIC) are poorly understood. There are few diagnostic criteria of DIC based on overall or global hemostatic mechanisms. Methods We have assessed in detailed the dynamic global hemostatic changes using thrombin and plasmin generation assay (T/P‐GA), clot fibrinolytic waveform analysis (CFWA) and not‐activated rotational thromboelastometry (NATEM), in a young girl with DIC associated with acute myeloid leukemia (AML). The ratios of endogenous thrombin potential (T‐EP) and plasmin lag time (P‐LT) relative to normal plasma was sourced from pooled normal plasma from healthy volunteers on T/P‐GA. Results The inverse P‐LT ratio prior to tranexamic acid (TXA) treatment was greater than the T‐EP ratio (1.1–2.8 and 0.83–1.2, respectively). Significant reduction in inverse P‐LT ratio (0.084–1.3) was observed after TXA treatment. The interval from clotting to the initiation of fibrinolysis (fibrinolysis lag time: FLT) in CFWA was significantly shorter than the control at onset (74.2–91.6 s vs 109 s), indicating enhanced fibrinolysis. Data from an adult with acute promyelocytic leukemia‐associated DIC also supportively showed a high inverse P‐LT ratio (2.1) and shortened FLT (83.7 s). The clotting time in patient whole blood using NATEM‐mode during an episode of severe epistaxis markedly shortened beyond control, but returned to normal after the addition of an anti‐tissue factor (TF) monoclonal antibody. Conclusion The release of intravascular TF contributed to sustained activation of coagulation and subsequent fibrinolytic activity in this patient with AML‐associated DIC, and T/P‐GA could provide better quantitative data than conventional assays in these circumstances.

show abstract

Recombinant human thrombomodulin in the treatment of acute myeloid leukemia patients complicated by disseminated intravascular coagulation: retrospective analysis of outcomes between patients treated with heparin and recombinant human thrombomodulin therapy

Cited by 17 publications

References 34 publications

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

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

Successful treatment of disseminated intravascular coagulation by recombinant human soluble thrombomodulin in patients with acute myeloid leukemia

Hemostatic function in hyperfibrinolytic disseminated intravascular coagulation

Contact Info

Product

Resources

About