Comparative effects of heparin and PK 10169, a low molecular weight fraction, in a canine model of arterial thrombosis

Mestre, Michel; Clairefond, P; Mardiguian, J; Trillou, M; Fur, G. Le; Uzan, A.

doi:10.1016/0049-3848(85)90137-9

Cited by 26 publications

(14 citation statements)

References 5 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.…”

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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“…Considerable variation in anti-Xa activities has been documented and some uncertainty remains about the efficacy of enoxaparin in some breeds of dog 55,152,153. Dalteparin does appear efficacious in dogs for venous and arterial thromboprophylaxis 154,155. The level of anti-Xa activity that confers thromboprophylaxis remains uncertain, but, given the variation in phar-Summary of studies investigating the use of antithrombotic drugs in dogs with immune-mediated hemolytic anemia (IMHA)…”

mentioning

confidence: 99%

ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs

Swann

Garden

Fellman

et al. 2019

Veterinary Internal Medicne

187

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Immune‐mediated hemolytic anemia (IMHA) causes severe anemia in dogs and is associated with considerable morbidity and mortality. Treatment with various immunosuppressive and antithrombotic drugs has been described anecdotally and in previous studies, but little consensus exists among veterinarians as to the optimal regimen to employ and maintain after diagnosis of the disease. To address this inconsistency and provide evidence‐based guidelines for treatment of IMHA in dogs, we identified and extracted data from studies published in the veterinary literature. We developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria, explanation of treatment regimens, and validity of statistical methods. In combination with our clinical experience and comparable guidelines for humans afflicted with autoimmune hemolytic anemia, we used the conclusions of this process to make a set of clinical recommendations regarding treatment of IMHA in dogs, which we refined subsequently by conducting several iterations of Delphi review. Additionally, we considered emerging treatments for IMHA in dogs and highlighted areas deserving of future research. Comments were solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted for publication. The resulting document is intended to provide clinical guidelines for management of IMHA in dogs. These guidelines should be implemented pragmatically, with consideration of animal, owner, and veterinary factors that may vary among cases.

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“…Carter et al [6] have shown that several LMWH fractions, includ ing PK 10169, were able to prevent venous thrombosis in an animal model using venous stasis and injection of a thrombogcnic mix ture. More recently, Mestre et al [13] have demonstrated that PK 10169 could be also a potential antithrombotic agent in a model of coronary artery thrombosis. Our results are also in agreement with those previously re ported, although the physicochemical hetero geneity of LMWH fractions limits the com parability of the results achieved in the re spective clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Heparin Fraction PK10169: A New Therapeutic Means for Anticoagulant Therapy?

Huet¹,

Gouault-Heilmann²

1986

Pathophysiol Haemos Thromb

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To test the efficacy and safety of low molecular weight heparin (LMWH) fractions in thromboembolic diseases, 2 pilot studies were performed. The aim of the first was to test the antithrombotic efficacy of the LMWH PK 10169 (Pharmuka Laboratories) in 9 patients (group I) with acute pulmonary embolism documented by pulmonary angiography and scintiscan. The second study was intended to test the safety of the same LMWH fraction in a group (group II) of 30 patients at high risk of bleeding but also requiring antithrombotic therapy. In the 2 groups, the antithrombotic efficacy of PK 10169 was found to be excellent: no recurrence of pulmonary embolism was noted in group I and no thrombotic event occurred in group II. Neither side effects nor major bleeding complications occurred in either group. However, 1 patient in group II had a moderate bleeding in relation to a transient overdosage, and 3 others exhibited minor bleeding which did not necessitate dosage adjustment. In these studies, PK 10169, at the dosage used, proved an effective antithrombotic therapy with few side effects even in a group of patients considered to be at high risk of bleeding.

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Comparative effects of heparin and PK 10169, a low molecular weight fraction, in a canine model of arterial thrombosis

Cited by 26 publications

References 5 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

ACVIM consensus statement on the treatment of immune‐mediated hemolytic anemia in dogs

Low Molecular Weight Heparin Fraction PK10169: A New Therapeutic Means for Anticoagulant Therapy?

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