Disseminated Intravascular Coagulation: Evaluation of Therapeutic Approaches

Heene, D. L.

doi:10.1055/s-0028-1087122

Cited by 18 publications

(5 citation statements)

References 85 publications

(143 reference statements)

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“…However, additional anti-coagulant treatments may be required in many cases because of life-threatening abnormal coagulation states. Unfractionated heparin (UFH) has been widely used as an anticoagulant therapy in DIC in the absence of better alternatives, although it has not been shown to offer any survival benefit in controlled trials [24][25][26]. On the other hand, in a multicenter double-blind trial that compared LMWH with UFH, LMWH (dalteparin sodium) significantly reduced organ failure (p b 0.05), reduced bleeding symptoms (p b 0.1), and had a higher safety rate than UFH (p b 0.05) [27].…”

Section: Discussionmentioning

confidence: 99%

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

Sekiguchi

Nagata

et al. 2015

Thrombosis Research

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Section: Discussionmentioning

confidence: 99%

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

Sekiguchi

Nagata

et al. 2015

Thrombosis Research

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“…This study was not a placebo‐controlled trial, because of ethical constraints in Japan, where six anticoagulants, including unfractionated heparin, low molecular weight heparin (LMWH) and heparinoid have been approved for DIC treatment. We used low‐dose unfractionated heparin as a comparator, because heparin is typically used in anticoagulant therapy for DIC [1,6,9,21]. Although no randomized trial has proven the efficacy of heparin, three clinical trials on sepsis using natural anticoagulants suggested that the mortality rate was lower among patients who received low‐dose heparin for prevention of deep vein thrombosis than among those who did not receive heparin [22–24].…”

Section: Discussionmentioning

confidence: 99%

“…Heparin has been widely used for anticoagulant therapy in DIC in the absence of better alternatives, although it has not been shown to offer any survival benefit in controlled trials [1,6,9,10]. Also, the safety of heparin in patients with DIC complicated by profuse bleeding symptoms is the subject of debate.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of recombinant human soluble thrombomodulin (ART‐123) in disseminated intravascular coagulation: results of a phase III, randomized, double‐blind clinical trial

Saito¹,

Maruyama²,

Shimazaki³

et al. 2007

Journal of Thrombosis and Haemostasis

559

498

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Summary. Background: Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. Objectives: We conducted a multicenter, double‐blind, randomized, parallel‐group trial to compare the efficacy and safety of recombinant human soluble thrombomodulin (ART‐123) to those of low‐dose heparin for the treatment of disseminated intravascular coagulation (DIC) associated with hematologic malignancy or infection. Methods: DIC patients (n = 234) were assigned to receive ART‐123 (0.06 mg kg−1 for 30 min, once daily) or heparin sodium (8 U kg−1 h−1 for 24 h) for 6 days, using a double‐dummy method. The primary efficacy endpoint was DIC resolution rate. The secondary endpoints included clinical course of bleeding symptoms and mortality rate at 28 days. Results: DIC was resolved in 66.1% of the ART‐123 group, as compared with 49.9% of the heparin group [difference 16.2%; 95% confidence interval (CI) 3.3–29.1]. Patients in the ART‐123 group also showed more marked improvement in clinical course of bleeding symptoms (P = 0.0271). The incidence of bleeding‐related adverse events up to 7 days after the start of infusion was lower in the ART‐123 group than in the heparin group (43.1% vs. 56.5%, P = 0.0487). Conclusions: When compared with heparin therapy, ART‐123 therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients.

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“…A remarkable use of heparin [39], and one closely related to its actions on hemostatic mechanisms, is its use for treatment of disseminated intravascular coagulation (DIC). DIC is a secondary event in numerous diseases and clinical conditions occurring as an acute syndrome or as a chronic, compensated process.…”

Section: Heparin and The Hemostatic Balancementioning

confidence: 99%

“…Heparin is not always effective in the treatment of DIC [69], due to (i) lack of effect with inadequate dose or increased resistance to heparin; (ii) heparin given too late (irreversible organ changes); (iii) mechanism for deposition of microthrombi independent of thrombin; (iv) a severe hemostatic defect present which is increased by heparin. Regarding (i), "it seems difficult to accurately predict the dosage required to manage an individual patient with acute DIC" [39]. This can be due to the underlying disease causing a marked reduction in antithrombin III, release of platelet factor 4, etc.…”

Section: Heparin and The Hemostatic Balancementioning

confidence: 99%

Pharmacodynamics and Clinical Effectiveness of Heparin

Jaques¹,

Mahadoo²

2008

Semin Thromb Hemost

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It has been generally assumed that the clinical use of heparin is simply an extension of the initial laboratory use to prevent blood coagulation in test tubes and cannulae. Here the effects of mixing heparin with blood appear to be the same in vivo and in vitro. Evidence was obtained early that this was an oversimplification of the situation and the large amount of data that has now accumulated calls for a reevaluation of this basic assumption in a number of aspects which bear on the clinical use of this important drug. DISSIMILARITY BETWEEN IN VIVO and IN VITRO EFFECTS OF HEPARINThe most clear-cut demonstration that the effects of heparin in vivo are not the same as those when this drag is added to blood in vitro is the appearance of enzymes in the general circulation which were not present in significant amounts before injection of the drug-e.g., lipoprotein lipase [70] and diamine oxidase [15], also known as histaminase. This dissimilarity was early indicated for the effect of heparin on thrombosis when compared with coagulation tests in vitro. Solandt and Best [103], in the initial paper to report the use of heparin in an extracorporeal circulation, measured the effectiveness of heparin in preventing platelet thrombi in glass chambers inserted in arteriovenous shunts in dogs. Immediately after the injection of heparin, the clotting time reached infinity (the blood became incoagulable), as was the case when a comparable amount of heparin was added to the blood outside the body. However, formation of thrombi was not prevented until 20-60 minutes after the injection. When the clotting time had again become measurable 2-7 hours later, thrombus formation did not occur. It was not for yet another hour (when the clotting time was essentially normal) that accumulation of platelets and formation of thrombi occurred again in the shunt. Hence, the anticoagulant effect and the prevention of thrombus formation appeared to be two distinct properties of heparin.

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Disseminated Intravascular Coagulation: Evaluation of Therapeutic Approaches

Cited by 18 publications

References 85 publications

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

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

Efficacy and safety of recombinant human soluble thrombomodulin (ART‐123) in disseminated intravascular coagulation: results of a phase III, randomized, double‐blind clinical trial

Pharmacodynamics and Clinical Effectiveness of Heparin

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