Interaction Of Protamine Sulfate With Thrombin

Cobel-Geard, R; Penner, John A.; Hassouna, Houria I.

doi:10.1055/s-0038-1652083

Cited by 6 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A higher protamine to heparin ratio of 3:1 significantly affected the R time in the study by Khan et al 14 . Effects of protamine that may reduce thrombin generation 16,17 include reduction in FV and FVII activation 18 and FVIII activity 19 . However, in our study there was no evidence that protamine added an additional anticoagulant effect, as the R time and K time remained unchanged or in some patients the R time reduced.…”

Section: Discussioncontrasting

confidence: 58%

The heparin‐von Willebrand factor interaction and conventional tests of haemostasis – the challenges in predicting bleeding in cardiopulmonary bypass

et al. 2020

View full text Add to dashboard Cite

Summary Bleeding is a significant complication of cardiopulmonary bypass (CPB), despite routine anticoagulation monitoring. This is likely to be multifactorial. In this prospective, single‐centre cohort study of 30 patients undergoing CPB surgery, our aim was to characterise the changes in von Willebrand factor (VWF) function, platelet interaction and the global coagulation changes during and after CPB surgery and to determine whether bleeding can be predicted. Samples were taken at six time points before, during and after CPB surgery. We observed a significant rise in VWF antigen (VWF:Ag) throughout surgery, which continued postoperatively. The absolute VWF collagen‐binding assays (VWF:CB) and VWF ristocetin cofactor (VWF:RCo) rose significantly but the VWF:CB/VWF:Ag and VWF:Ag/VWF:RCo fell significantly (P = 0·0015 and P = 0·0143), suggesting loss of large multimers. We detected a non‐significant trend to loss of VWF:RCo after heparinisation and a significant recovery after protamine reversal which could reflect a direct heparin effect. There was a significant increase in the R and K times with a fall in alpha angle and maximum amplitude after heparin administration, using heparinase‐thromboelastography (TEG). The parameters both significantly improved following protamine (P = 0·007 and P = 0·0054). The activated clotting time (ACT) and heparin anti‐Xa level correlated poorly; neither predicted clinically significant bleeding. None of these parameters had a relationship with intraoperative blood loss or requirement for blood product replacement.

show abstract

Section: Discussioncontrasting

confidence: 58%

The heparin‐von Willebrand factor interaction and conventional tests of haemostasis – the challenges in predicting bleeding in cardiopulmonary bypass

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Several previous studies have demonstrated an anticoagulant effect of protamine [4][5][6][10][11][12] . For example, Mochizuki et al showed that protamine to heparin ratios >1.3:1 in vitro prolong the ACT and reduce ADP-induced platelet aggregation 5 .…”

Section: Protamine Concentration (Mg/ml) R Time (Min)mentioning

confidence: 99%

“…The mechanism involved in the anticoagulant effect of protamine has not been fully elucidated, but appears to involve several processes 10,11 . Protamine is known to precipitate fibrinogen and fibrin monomer 10 , and also reversibly inhibits thrombin, and the inactivation of thrombin by antithrombin III 11 .…”

Section: Protamine Concentration (Mg/ml) R Time (Min)mentioning

confidence: 99%

The Effect of Excess Protamine on Thrombelastography in Vitro

Gibbs

Weightman

Sheminant

et al. 2006

Anaesth Intensive Care

View full text Add to dashboard Cite

The aim of the current study was to assess the direct effect of protamine on conventional thrombelastography in vitro. Protamine was added to blood samples collected from 25 adult cardiac surgical patients prior to the induction of anaesthesia and after separation from cardiopulmonary bypass. The final protamine concentrations were 0 (control), 0.05 mg/ml, 0.1 mg/ml and 0.2 mg/ml (i.e. sufficient to reverse heparin 0, 5, 10 and 20 IU/ml respectively, assuming a 1:1 reversal ratio). In the pre-induction samples, protamine was associated with increases in r time and reductions in maximum amplitude (P<0.01). After bypass, the control samples demonstrated a heparin effect as expected, which was corrected by the addition of protamine 0.05 mg/ml. However, the higher concentrations of protamine were again associated with increases in r time and reductions in maximum amplitude (P<0.01). The results indicate that protamine has a direct anticoagulant effect on conventional thrombelastography in vitro. This effect occurs whether protamine is present alone, or whether protamine is present in excess after neutralization of heparin. Unless this effect is taken into account, excess protamine may confound the interpretation of conventional thrombelastography in cardiac surgical patients.

show abstract

“…This may be due to direct interactions of protamine with clotting factors, particularly thrombin. 40 In addition to confirming the ability of rPF4 to reverse heparin anticoagulation without apparent adverse side effects, these data highlight another potential limitation of protamine, specifically a narrow therapeutic window.…”

Section: Use Of Rpf4 In Animal and Ex Vivo Human Studiesmentioning

confidence: 62%

Recombinant Platelet Factor 4 for Heparin Neutralization

Mixon¹,

Dehmer²

2004

Semin Thromb Hemost

View full text Add to dashboard Cite

Protamine sulfate has been used for many years to reverse the effects of unfractionated heparin, but it can cause hemodynamic changes and other serious side effects. Platelet factor 4 (PF4) is a naturally occurring protein synthesized in megakaryocytes and eventually stored in the alpha granules of platelets for later release. Although the complete physiologic role of PF4 is unknown, it is highly effective for the neutralization of heparin anticoagulation. Several preliminary animal studies and trials using blood obtained from cardiopulmonary bypass circuits suggested recombinant PF4 (rPF4) would be an effective alternative to protamine. In the first open-label, phase 1 human study, patients received rPF4 in doses of 0.5, 1.0, 2.5, or 5.0 mg/kg over 3 minutes to reverse heparin anticoagulation after diagnostic cardiac catheterization. There were no important hemodynamic changes and the rPF4 was highly effective in neutralizing heparin. Serial measurements of rPF4 levels showed a monophasic elimination pattern with a serum half-life of 25.5 +/- 13.5 minutes that was independent of dose administered. A randomized and blinded trial comparing rPF4 to protamine confirmed the safety and effectiveness of rPF4. Although rPF4 was initially being evaluated as a clinical alternative to protamine, it is not currently being developed for general clinical use.

show abstract

Interaction Of Protamine Sulfate With Thrombin

Cited by 6 publications

References 0 publications

The heparin‐von Willebrand factor interaction and conventional tests of haemostasis – the challenges in predicting bleeding in cardiopulmonary bypass

The heparin‐von Willebrand factor interaction and conventional tests of haemostasis – the challenges in predicting bleeding in cardiopulmonary bypass

The Effect of Excess Protamine on Thrombelastography in Vitro

Recombinant Platelet Factor 4 for Heparin Neutralization

Contact Info

Product

Resources

About