Inhibition of low molecular weight heparin by protamine chloride in vivo

Harenberg, Job; Gnasso, Agostino; Vries, J. X. de; Zimmermann, Rainer; Augustin, J.

doi:10.1016/0049-3848(85)90003-9

Cited by 51 publications

(33 citation statements)

References 23 publications

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“…This dissocia tion has already been described [ 12] and was very recently confirmed in dogs by a work conducted during our study [13]. Moreover, in man, the neutralization has been tested with protamine chloride [14], In spite of the small number of patients studied in our work, the difference noted in vivo is in good correlation with in vitro findings. The throm bin time and anti-lla activity were corrected under conditions comparable to unfraction ated heparin.…”

Section: Discussionsupporting

confidence: 77%

Partial Reversal of Low Molecular Weight Heparin (PK 10169) Anti-Xa Activity by Protamine Sulfate: In vitro and in vivo Study during Cardiac Surgery with Extracorporeal Circulation

Massonnet-Castel¹,

Pelissier²,

Bara³

et al. 1986

Pathophysiol Haemos Thromb

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Neutralization of a low molecular weight (LMW) heparin fraction by protamine sulfate was evaluated in vitro and in vivo. Anti-Xa and anti-IIa activities were measured by amidolytic and coagulation methods (activated partial thromboplastin time, APTT). Fifteen patients (4 males and 11 females) underwent surgery with extracorporeal circulation. In vitro, anti-Xa and anti-IIa activities and APTT of unfractionated heparin were neutralized with a protamine/heparin (P/H) gravimetric ratio of 1.6, 1.33 and about 2, respectively. Anti-IIa activity and APTT induced by PK 10169 were completely corrected at a P/H ratio of 1 and 2, respectively, while anti-Xa activity was incompletely neutralized at a ratio of 5. In vivo, in 9 patients who did not receive intravenous protamine sulfate, a good correlation was found between doses of PK 10169 infused, anti-IIa plasma level and blood loss. In 3 patients who were treated prophylactically with protamine, bleeding was normal or only slightly increased. In 3 patients who received protamine because of hemorrhage, mean anti-Xa and anti-IIa were 2.3 and 0.54 U before and 1.32–0.06 U after neutralization. Bleeding was stopped by a second dose of protamine in 1 patient, but blood loss was abnormal in the other patients. However, a correlation between bleeding and anti-Xa or anti-IIa activities was not clearly evident.

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Section: Discussionsupporting

confidence: 77%

Partial Reversal of Low Molecular Weight Heparin (PK 10169) Anti-Xa Activity by Protamine Sulfate: In vitro and in vivo Study during Cardiac Surgery with Extracorporeal Circulation

Massonnet-Castel¹,

Pelissier²,

Bara³

et al. 1986

Pathophysiol Haemos Thromb

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“…Indeed, the present model has been pre viously reported to be particularly sensitive not only to platelet-active compounds but also to drugs inhibiting blood coagulation [18,19], It is noteworthy that this effect of protamine sulphate was also observed in another model of bleeding in the rabbit (not shown) therefore suggesting that is was not due to an interfer ence in this particular model. There has been some uncertainty regarding the dose of prot amine sulphate required to counteract the bleeding caused by heparin [9,10,20]. Hepa rin-induced bleeding enhancement was inhib ited by protamine sulphate at doses which completely abrogated its antithrombotic effi cacy in a venous thrombosis model as well as Discussion its anticoagulant activity (APTT and anti-fac tor Xa activity) measured ex vivo.…”

Section: A P T T and Anti-factor Xa Activity In Ratsmentioning

confidence: 99%

Protamine Sulphate Inhibits Pentasaccharide (SR 80027)-Induced Bleeding without Affecting Its Antithrombotic and Anti-Factor Xa Activity in the Rat

Bernat¹,

Herbert²

1996

Pathophysiol Haemos Thromb

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The neutralization of a potent anti-factor Xa pentasaccharide (SR 80027) and heparin-induced bleeding enhancement by protamine sulphate was studied in vivo. Bleeding time, as measured by transection of the tail of anaesthetized rats, increased after the administration of standard heparin and SR 80027. Doses of 0.6 and 2.5 mg/kg of heparin and SR 80027, respectively, were required to enhance blood loss to the same extent (6-fold increase). Protamine sulphate (10 mg/kg, i.v.) reduced blood loss induced by both compounds but also neutralized the anti-factor Xa activity as well as the antithrombotic activity of standard heparin measured in a venous thrombosis model. However, protamine sulphate did not affect the anti-factor Xa activity or the antithrombotic activity of SR 80027. These data suggest that protamine sulphate may be an effective antidote for the bleeding side-effects of SR 80027 but they also indicate that the bleeding tendency associated with this type of compounds cannot be attributed to their anti-factor Xa activity.

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“…Several investigators have reported that protamine antagonizes the LMWH inhibition of factor Xa by 40-80%. 13,[29][30][31] The apparently complete reversal of LMWHinduced anti-Xa activity that we measured after protamine could be due to the lesser level of anticoagulation produced in these sheep ( sion nor thromboxane release after protamine reversal of heparin anticoagulation. Thus, complement activation and leukosequestration may be sensitive indicators of polyanion-polycation complex formation but may not be involved in triggering thromboxane production during the heparin-protamine reaction.…”

Section: Discussionmentioning

confidence: 92%

“…Suffolk sheep weighing [25][26][27][28][29][30][31][32][33][34][35] kg were anesthetized by mask with 1-2% halothane (Halocarbon Laboratories, Hackensack, N.J.) in pure oxygen and surgically instrumented using sterile techniques. The right femoral artery was cannulated with a polyvinyl chloride catheter advanced to the midthoracic aorta to sample blood and monitor systemic blood pressure (Psa).…”

Section: Animal Preparationmentioning

confidence: 99%

Neutralization of low molecular weight heparin by polybrene prevents thromboxane release and severe pulmonary hypertension in awake sheep.

et al. 1990

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Protamine reversal of heparin anticoagulation in patients is occasionally associated with life-threatening acute pulmonary hypertension. In a sheep model, we evaluated the effect on this adverse cardiopulmonary reaction of modifying the type of heparin (low molecular weight heparin compared with unfractionated heparin) and the type of heparin antagonist (polybrene compared with protamine). Protamine reversal of low molecular weight heparin (LMWI) and polybrene reversal of unfractionated heparin induced more than a 10-fold increase of plasma thromboxane B2 levels, a threefold increase of pulmonary vascular resistance and pulmonary artery pressure, and a 25% decrease of Pao2. A similar adverse reaction followed protamine reversal of conventional unfractionated heparin. However, with polybrene (1 mg/lkg) reversal of LMWH (1 mg/kg), we measured neither pulmonary hypertension (pulmonary artery pressure was 22.6±3.6 mm Hg at 1 minute after polybrene reversal of LMWH compared with 47.9±4.2 mm Hg after protamine reversal of unfractionated heparin, p

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Inhibition of low molecular weight heparin by protamine chloride in vivo

Cited by 51 publications

References 23 publications

Partial Reversal of Low Molecular Weight Heparin (PK 10169) Anti-Xa Activity by Protamine Sulfate: In vitro and in vivo Study during Cardiac Surgery with Extracorporeal Circulation

Partial Reversal of Low Molecular Weight Heparin (PK 10169) Anti-Xa Activity by Protamine Sulfate: In vitro and in vivo Study during Cardiac Surgery with Extracorporeal Circulation

Protamine Sulphate Inhibits Pentasaccharide (SR 80027)-Induced Bleeding without Affecting Its Antithrombotic and Anti-Factor Xa Activity in the Rat

Neutralization of low molecular weight heparin by polybrene prevents thromboxane release and severe pulmonary hypertension in awake sheep.

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