scholarly journals Protamine Sulfate Neutralization Profile of Various Dosages of Bovine, Ovine and Porcine UFHs and Their Depolymerized Derivatives in Non-Human Primates

2021 ◽  
Vol 27 ◽  
pp. 107602962110055
Author(s):  
Ahmed Kouta ◽  
Walter Jeske ◽  
Lee Cera ◽  
Azarfrooz Farshid ◽  
Richard Duff ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Intestinal Mucosa ◽  
Mammalian Species ◽  
Low Molecular Weight ◽  
Effective Inhibitor ◽  
Low Molecular Weight Heparins ◽  
Primate Model ◽  
Protamine Sulphate ◽  
Mucosal Tissues ◽  
Human Primate

Introduction: Currently used unfractionated heparins (UFHs) and low molecular weight heparins (LMWHs) are derived from porcine intestinal mucosa. However, heparins have also been manufactured from tissues of other mammalian species such as cow (Bovine) and sheep (Ovine). Protamine sulphate (PS) is an effective inhibitor of heparin and is used clinically to neutralize both LMWH and UFH. In this study, we determined the PS neutralization profile of these agents in non-human primate model using anti-Xa and anti-IIa methods. Material and Methods: UFHs obtained from bovine, ovine and porcine mucosal tissues and their respective depolymerized LMWHs were administered at both, gravimetric (0.5 mg/kg) and potency adjusted (100 U/kg) dosages regimen intravenously to individual groups of primates in cross over studies. PS was administered at a fixed dosage and the relative neutralization of these anticoagulants was measured utilizing amidolytic anti-Xa and anti-IIa methods. Results: These studies have demonstrated that, the equi-gravimetric dosages of BMH, PMH and OMH have comparable PS neutralization profiles. At potency adjusted dosages, all UFHs were completely neutralized by PS. Although comparable, the LMWHs were not fully neutralized by PS in both the anti-Xa and anti-IIa assays. PS was more efficient in neutralizing the anti-IIa effects of LMWHs. Conclusion: Heparins of diverse origins showed comparable neutralization profiles by PS in the amidolytic anti-Xa and anti-IIa assays.

Generic Low Molecular Weight Heparins May Not Have the Same Safety –Efficacy Profile As the Branded Low Molecular Weight Heparins in Acute Coronary Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2308-2308
Author(s):  
Debra Hoppensteadt ◽  
Walter Jeske ◽  
Jeanine M. Walenga ◽  
Bruce E Lewis ◽  
Jawed Fareed
Keyword(s):  
Molecular Weight ◽  
Acute Coronary Syndrome ◽  
Animal Studies ◽  
Conflicts Of Interest ◽  
Pharmacokinetic Parameters ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Primate Model ◽  
Coronary Syndrome ◽  
Molecular Weight Distributions

Abstract Abstract 2308 Low molecular weight heparins such as enoxaparin and dalteparin are widely used for the management of Acute Coronary Syndrome (ACS). Recently, several generic versions of enoxaparin and dalteparin have been approved in various countries for all of the branded product's indications. However, no data on their clinical equivalence in ACS is available. Since generic versions of enoxaparin and dalteparin are manufactured by different processes and may use starting material from different sources, these drugs may differ in their pharmacological profile in simulated ACS settings. To compare the pharmacodynamic effects, a branded version of enoxaparin was compared with three generic versions in a primate model at a dosage of 1 mg/kg IV. Such pharmacokinetic parameters as TFPI release, TAFI modulation, vWF release, and TF mediated platelet activation were measured. Anticoagulant effects of these drugs were also measured after IV administration using iSTAT ACT and aPTT. Simulated catheter related thrombosis studies were carried out to differentiate each agent in contact, intrinsic and extrinsic clotting systems. The generic versions of enoxaparin namely, Cutenox (Gland Pharma), Fibrinox (Sandoz AG) and Versa (EuroPharma) exhibited product based pharmacodynamic differences compared with the branded product and the results are provided in the following table. Each of the generic products exhibited its own specific pharmacologic profile despite comparable molecular weight distributions and anti-Xa potencies. Significant differences were noted in the anticoagulant effects of each of these agents as compared with the branded products. Some differences were also noted in HIT antibody mediated aggregation studies. The differences between the branded and generic versions of LMWHs may be due to the higher dosages used and the IV administration which leads to higher circulating levels of these agents. These observations suggest the need for additional animal studies and clinical trials to validate the use of generic versions of LMWHs in such critical indications as ACS and related syndromes. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Nursing Skill and Responsibility in Administration of Low Molecular Weight Heparin by Prefilled Syringe

2021 ◽  
pp. 85-92
Author(s):  
Vaishali Tembhare ◽  
Gaurav Mujbaile ◽  
Seema Singh ◽  
Achita Sawarkar ◽  
Maduri Shambharkar ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Blood Test ◽  
Low Molecular Weight Heparin ◽  
Occult Blood ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Protamine Sulphate ◽  
Subcutaneous Tissues ◽  
Skin Discoloration ◽  
Medicine Administration

Abstract: Low-molecular-weight heparins (LMWHs) have proven to be effective in the prevention and treatment of thrombotic disorders, as well as   substitute for unfractionated heparin (UFH). LMWHs are a diverse collection of medicines with different biochemical and pharmacological characteristics, despite the fact that they all have antithrombotic actions. Medicine is administered into the subcutaneous tissues with these injections. Small amounts of injections are delivered by the subcutaneous approach, which involves inserting a small thin needle beneath the skin and slowly injecting the medicine. Low molecular weight heparins make up dalteparin and enoxaparin, two anticoagulants. The rights of medicine administration must be followed by nurses. For patients on LMWH medication, the most essential blood test is prothrombin time. Following administration, look for any signs of bleeding, such as occult blood in the stool, malena, bleeding gums, and skin discoloration/hematoma. The antidote for low molecular weight heparin is protamine sulphate. It is effective at counteracting the effects of LMWH. 100 units of LMWH are neutralised by 1 mg of protamine sulphate.If it's been more than 8 hours since you've given LMWH, provide 0.5 mg protamin per 100 units of LMWH.

A simulated post-angioplasty low molecular weight heparin schedule in a non-human primate model

1993 ◽  
Vol 70 (4) ◽  
pp. 295-306
Author(s):  
Peter Bacher ◽  
Omer Iqbal ◽  
Blazej Lojewski ◽  
Jeanine M. Walenga ◽  
Fred Leya ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Primate Model ◽  
Human Primate

A Perspective on Low Molecular Weight Heparins in the Management of Thrombosis

1993 ◽  
Vol 13 (S 01) ◽  
pp. S5-S11 ◽  
Author(s):  
Debra Hoppensteadt ◽  
Jeanine Walenga ◽  
A Ahsan ◽  
O Iqbal ◽  
W Jeske ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Mechanism Of Action ◽  
Manufacturing Process ◽  
Laboratory Tests ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Pharmacological Management

SummaryThe introduction of low molecular weight heparins has added a new dimension to the pharmacological management of thrombotic disorders. Because of different chemical and pharmacological characteristics, due to the manufacturing process, each LMWH should be considered as a distinct entitity and only be used for its given indication. A list of commercially available LMWHs is included. The mechanism of action of the LMWHs and their use in various disorders are discussed. Available laboratory tests for monitoring LMWHs are presented and their limitations pointed out.

Neutralisation of Heparan Sulphate and Low Molecular Weight Heparin by Protamine

1985 ◽  
Vol 53 (01) ◽  
pp. 086-089 ◽  
Author(s):  
A R Hubbard ◽  
C A Jennings
Keyword(s):  
Molecular Weight ◽  
Plasma Proteins ◽  
Low Molecular Weight Heparin ◽  
Heparan Sulphate ◽  
Activated Partial Thromboplastin Time ◽  
Weight Basis ◽  
Low Molecular Weight ◽  
Protamine Sulphate ◽  
At Iii ◽  
Reference Preparation

SummaryThe neutralisation by protamine sulphate (PS) of heparan sulphate (HS), a low molecular weight heparin (LMWH), and a reference preparation of unfractionated heparin (UH), was studied by activated partial thromboplastin time (APTT) and anti-Xa clotting assays. UH was most easily neutralised in the APTT assay by PS (on a weight for weight basis), followed by LMWH and HS. The neutralisation of APTT activity by PS closely followed the loss of activity in the anti-Xa clotting assay, when plasma was used as the source of At III. When the anti-Xa clotting assay was carried out using purified At III in place of plasma, HS and LMWH were neutralised by much lower amounts of PS and resembled UH neutralisation more closely. Resistance of HS anti-Xa activity to PS neutralisation decreased with increasing plasma dilution. The presence of bovine albumin with purified At III concentrate increased the resistance of HS to PS neutralisation. It is concluded that PS binding to UH, HS and LMWH is probably related more to their degree of sulphation than molecular weight and that non-specific interactions between PS and plasma proteins inhibit the binding of PS to HS and LMWH.

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