The Use of a Heparin Removal Device: A Valid Alternative to Protamine

Hendrikx, Marc; Leunens, Veerle; Vandezande, E; Wallyn, A; Flameng, W.

doi:10.1177/039139889702000308

Cited by 7 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animal experiments have demonstrated the efficiency of the device without any adverse effects. [8][9][10][11] No blood component damage was observed, there were no significant changes in haematocrit level, leucocyte profiles or platelets, 9 and haemodynamics remained stable. The optimal regimen is nevertheless not clearly defined.…”

Section: Discussionmentioning

confidence: 88%

Assembly of the Heparin Removal Device for patients with suspected adverse reaction to protamine sulphate

Jegger¹,

Tevaearai²,

Horisberger³

et al. 2000

Perfusion

View full text Add to dashboard Cite

Protamine sulphate is routinely used after cardiopulmonary bypass (CPB) to restore the patient's baseline coagulatory state. However, adverse reactions are encountered, and alternative means to neutralize heparin are, therefore, necessary. The Heparin Removal Device (HRD) constitutes an extracorporeal circuit that allows ex vivo deheparinization by mean of a polycationic ligand that binds heparin molecules. This paper presents the setup of the HRD circuit. It is illustrated by the report of a 68-year-old man with a known severe crustacean allergy. The patient (78 kg, 170 cm) was admitted for elective coronary artery bypass graft surgery. It was decided that the HRD would be used as a precaution in order to avoid the risks of using protamine sulphate. The CPB time and aortic crossclamp time were 70 and 40 min, respectively. At the end of CPB, the device was inserted and processing started. Activated coagulation time values were monitored over a 130 min period and diminished from 480 to 300 s after 45 min, 220 s after 90 min, and settled at 150 s. Haemostasis was acceptable and processing stopped. The operation was terminated and the patient transferred to the intensive care unit. Clinical evolution was excellent, with minimal postoperative bleeding. The HRD presents an alternative to protamine sulphate when this drug is contraindicated for a certain patient population who might have a suspected, known or emergency adverse reaction.

show abstract

Section: Discussionmentioning

confidence: 88%

Assembly of the Heparin Removal Device for patients with suspected adverse reaction to protamine sulphate

Jegger¹,

Tevaearai²,

Horisberger³

et al. 2000

Perfusion

View full text Add to dashboard Cite

show abstract

“…Although intravenous administration of protamine alone could produce systemic hypotension, myocardial depression, and an increase in vascular permeability ( , ), it has been demonstrated clinically that the combined use of protamine and heparin actually triggers the activation of complement system that subsequently elicits more toxic responses ( , ). The quest for a better protamine alternative is therefore in profound scrutiny in recent years ( − ).…”

Section: Introductionmentioning

confidence: 99%

PEG-Modified Protamine with Improved Pharmacological/Pharmaceutical Properties as a Potential Protamine Substitute: Synthesis and in Vitro Evaluation

et al. 2004

View full text Add to dashboard Cite

Cardiopulmonary bypass (CPB) procedures are frequently associated with massive inflammatory responses, resulting in a high rate of morbidity and mortality in routine cardiac operations. One recognized attribute of these deleterious responses is the synergic effect of heparin and protamine, which elicit the activation of the complement system in vivo. To circumvent such toxic effects following protamine reversal of heparin anticoagulation in the CPB procedures, we proposed that poly(ethylene glycol) (PEG)-modified protamine could retain the heparin-neutralization ability and yet diminish the induced complement activation by the formed heparin-protamine complexes (HPC), thereby providing highly improved pharmacological properties. PEGylation of protamine was carried out by utilizing N-hydroxysuccinimidyl (NHS) conjugation chemistry. Size exclusion chromatography (SEC), reverse-phase high performance liquid chromatography (RP-HPLC), and matrix-assisted laser desorption mass spectrometry (MALDI-MS) were used to assess the conjugation stiochiometry, the purity of the conjugates, and the site of PEG modification, respectively. The heparin-neutralizing activity was determined by using heparin affinity chromatography and various biological assays including the plasma-activated partial thromboplastin time (aPTT), anti-Xa, and anti-IIa methods. The potency in inducing complement activation was examined in vitro using the CH50 hemolytic assay. The PEG-modified protamine was successfully synthesized with a PEG/protamine stiochiometry of 1:1. Only one conjugation site for PEG that was located at the N-terminal end of protamine was obtained. In the biological evaluations, the PEG-modified protamine displayed a full retention of the heparin-neutralizing ability of protamine and a significantly reduced activity in complement activation following its complexation with heparin. Results from studies of the particle size and zeta potential indicated that the PEG-modified protamine formed substantially smaller aggregates with heparin, rendering them less effective in triggering the size-dependent complement responses. As with protamine, PEG-modified protamine exhibited an enhanced aqueous solubility, therefore attaining significantly improved pharmaceutical properties. These preliminary results suggested that the PEG-modified protamine conjugate might serve as a potential protamine substitute with improved therapeutic and pharmaceutical properties in heparin reversal.

show abstract

“…Other approaches to suppress complement activation use heparin-coated (34) or heparin removal devices (35). The disadvantage of these efforts is that these devices only inhibit activation on biomaterials and have no effect on complement activation caused by gas surfaces or reperfusion of previously ischemic tissues.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Heparin/Protamine Complex-Induced Complement Activation by Compstatin in Baboons

Soulika

Khan

Hattori

et al. 2000

Clinical Immunology

View full text Add to dashboard Cite

The Use of a Heparin Removal Device: A Valid Alternative to Protamine

Cited by 7 publications

References 27 publications

Assembly of the Heparin Removal Device for patients with suspected adverse reaction to protamine sulphate

Assembly of the Heparin Removal Device for patients with suspected adverse reaction to protamine sulphate

PEG-Modified Protamine with Improved Pharmacological/Pharmaceutical Properties as a Potential Protamine Substitute: Synthesis and in Vitro Evaluation

Inhibition of Heparin/Protamine Complex-Induced Complement Activation by Compstatin in Baboons

Contact Info

Product

Resources

About