Comparison of Hemorrhagic Effect of Heparin and Human Activated Protein C with Use of Thrombostat 4000

Katsuura, Yasuhiro; Tanabe, Hirofumi; Kiyoki, Mamoru; Funatsu, Asami

doi:10.1159/000217208

Cited by 3 publications

(3 citation statements)

References 19 publications

(27 reference statements)

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“…This agrees with other experimental studies in rats, other animals, and humans [16,18,[26][27][28] . In this experiment, there was no signifi cant alteration of BT in the enoxaparin groups compared with controls.…”

Section: Discussionsupporting

confidence: 93%

Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis

Carelli¹,

Maffei²,

Mattar³

et al. 2005

Pathophysiol Haemos Thromb

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Synergism between low-molecular-weight heparin and low doses of unfractionated heparin (UH) enhancing anti-factor Xa activity and the release of tissue factor pathway inhibitor was observed. The aim of this study was to verify whether this association is effective in preventing experimental venous thrombosis. Seventy rats were allocated into 7 groups: the control group treated with distilled water, the H₃₅₀ group treated with UH 350 IU/kg, the E₂ group treated with enoxaparin 2 mg/kg, the H₁₇₅ group treated with UH 175 IU/kg, the E₁ group treated with enoxaparin 1 mg/kg, the H₁₇₅ + E₁ group treated with UH 175 IU/kg plus enoxaparin 1 mg/kg, and the H₁₀₀ + E_0.5 group treated with UH 100 IU/kg plus enoxaparin 0.5 mg/kg. Forty minutes after subcutaneous injection, thrombosis was induced in vena cava. Three hours later, if present, thrombi were withdrawn and weighed. Bleeding time, activated partial thromboplastin time, thrombin time (TT), and anti-factor Xa were measured at the beginning and end of the experiment. Forty-eight other animals were treated, but without inducing thrombus, and tests were performed 40 min after injection. Thrombus developed in 90.9% of control animals, 20% of the H₃₅₀ group, 22.2% of the E₂ group, 10% of the H₁₇₅ + E₁ group, and 30% of the H₁₀₀ + E_0.5 group; there was a difference between group C and the other groups. Only in the H₃₅₀ and H₁₇₅ + E₁ groups were TT and activated partial thromboplastin time prolonged in relation to control at the end of the experiment. Forty minutes after injection, TT was prolonged in the H₃₅₀ and H₁₇₅ + E₁ groups. In conclusion, combinations of low doses of low-molecular-weight heparin and low doses of UH were as effective as high doses of each one used alone in preventing thrombus development in rat vena cava.

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Section: Discussionsupporting

confidence: 93%

Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis

Carelli¹,

Maffei²,

Mattar³

et al. 2005

Pathophysiol Haemos Thromb

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“…APC mediates the coagulation inhibition without the requirement of the host thrombin–thrombomodulin system. Such a benefit of APC is already represented by its efficacy in treating animal models of thrombus formation ( Gruber & Griffin, 1992) or DIC ( Katsuura et al , 1994 , 1996) . In this study, we showed that infused APC controlled the hypercoagulation in a protein C null individual ( Fig 1A).…”

Section: Resultsmentioning

confidence: 99%

A case of purpura fulminans is caused by homozygous Δ8857 mutation (protein C‐Nagoya) and successfully treated with activated protein C concentrate

Nakayama

Matsushita

Hidano³

et al. 2000

Br J Haematol

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Summary. We report a Japanese patient who developed purpura fulminans and disseminated intravascular coagulation (DIC) shortly after birth. The patient was diagnosed to be homozygous for protein C deficiency and was treated with an activated protein C (APC) concentrate. Intravenous infusions of APC markedly improved the necrotic skin lesions and the anticoagulation by APC enabled successful DIC control. The identified mutation (D8857) results in impaired intracellular transport and protein maturation and would be the cause of the complete protein C deficiency. This is the seventh case of the mutation that has been exclusively reported in Japan, but is the first report of a homozygous case. Our findings propose new therapeutic and diagnostic tools for the management of this fatal thrombotic disease.

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“…[47] In in vivo animal studies, little or no prolongation of bleeding time was detected in association with activated protein C administration. [43,46,47,50,51] Effects on Coagulation Markers in Patients with Sepsis Change over time and percentage change from baseline in plasma D-dimer levels (normal range 0.0 to 0.39 mg/L) were measured in patients who participated in the two randomised, double-blind, placebo-controlled trials of drotrecogin alfa (activated) [section 3]. [20,22] D-dimer levels indicate coagulation has occurred in conjunction with fibrinolysis activation, forming fibrin breakdown products.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Drotrecogin Alfa (Activated)

Lyseng‐Williamson¹,

Perry²

2002

Drugs

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Drotrecogin alfa (activated), recombinant human activated protein C, inhibits coagulation and inflammation and promotes fibrinolysis in patients with severe sepsis. 850 patients with severe sepsis treated with intravenous drotrecogin alfa (activated) 24 microg/kg/h for 96 hours had a significantly greater reduction in 28-day all-cause mortality (24.7%) than 840 placebo recipients (30.8%) in a randomised, double-blind, placebo-controlled study. The drug was associated with a 19.4% reduction in the relative risk of death at 28 days compared with placebo. Baseline characteristics of and pre-existing conditions in patients with sepsis appeared to have no effect on the efficacy of drotrecogin alfa (activated). A significantly greater reduction in median percentage change from baseline plasma D-dimer levels (a coagulation marker) was seen with drotrecogin alfa (activated) treatment than with placebo on study days 1 to 7 in patients with severe sepsis. On study days 1, 4, 5, 6 and 7, a significantly greater median reduction in interleukin-6 levels (an inflammation marker) from baseline was seen with drotrecogin alfa (activated) treatment than placebo. Drotrecogin alfa (activated) was associated with an increased incidence of serious bleeding events during the infusion period [2.4% vs 1.0% with placebo; p = 0.024] and the 28-day study period (3.5 vs 2.0%; p = 0.06) of the efficacy trial. This increase was primarily related to procedure-related events; there were no significant differences between the treatment groups in nonprocedure-related serious bleeding events. The most frequent site of bleeding was the gastrointestinal tract. With the exception of bleeding events, there were no clinically significant differences between treatment groups in the efficacy trial in the incidence of adverse events. Of the 210 deaths in patients with severe sepsis treated with drotrecogin alfa (activated) 24 microg/kg/h in the efficacy trial, four deaths due to haemorrhage and one due to cerebral oedema were possibly related to the study drug.

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Comparison of Hemorrhagic Effect of Heparin and Human Activated Protein C with Use of Thrombostat 4000

Cited by 3 publications

References 19 publications

Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis

Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis

A case of purpura fulminans is caused by homozygous Δ8857 mutation (protein C‐Nagoya) and successfully treated with activated protein C concentrate

Drotrecogin Alfa (Activated)

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