PMID- 9768770
OWN - NLM
STAT- MEDLINE
DCOM- 19981026
LR  - 20190704
IS  - 0003-2999 (Print)
IS  - 0003-2999 (Linking)
VI  - 87
IP  - 4
DP  - 1998 Oct
TI  - Protamine reversal of heparin affects platelet aggregation and activated clotting 
      time after cardiopulmonary bypass.
PG  - 781-5
AB  - Bleeding after cardiopulmonary bypass (CPB) is related to multiple factors. 
      Excess protamine weakens clot structure and decreases platelet function; 
      therefore, an increased activated clotting time (ACT) after protamine reversal of 
      heparin may be misinterpreted as residual heparin anticoagulation. We evaluated 
      the effects of protamine, recombinant platelet factor 4 (rPF4), and 
      hexadimethrine on ACT in blood obtained after CPB. In addition, we examined the 
      effect of protamine on in vitro platelet aggregation. Incremental doses of 
      protamine, rPF4, and hexadimethrine were added to heparinized blood from CPB, and 
      ACTs were performed. Incremental concentrations of protamine were added to 
      heparinized platelet-rich plasma, and aggregometry was induced by adenosine 
      diphosphate (ADP) and collagen. The mean heparin concentration at the end of CPB 
      was 3.3 U/mL. Protamine to heparin ratios >1.3:1 produced a significant 
      prolongation of the ACT that was not seen with rPF4 and was observed only with 
      5:1 hexadimethrine to heparin ratios. ADP-induced platelet aggregation was 
      reduced with protamine administration > or =1.3:1. Excessive protamine reversal 
      of heparin prolongs ACT and alters ADP-induced platelet aggregation in a 
      dose-dependent manner in vitro. Additional protamine administered to treat a 
      prolonged ACT may further increase clotting time, reduce platelet aggregation, 
      and potentially contribute to excess bleeding after CPB. IMPLICATIONS: We found 
      that excess protamine prolonged the activated clotting time and altered platelet 
      function after cardiopulmonary bypass, whereas heparin antagonists, such as 
      recombinant platelet factor 4 and hexadimethrine, exhibited a wider therapeutic 
      range without adversely affecting the activated clotting time. Approaches to 
      avoid excess protamine or use of alternative heparin antagonists after 
      cardiopulmonary bypass may be beneficial.
FAU - Mochizuki, T
AU  - Mochizuki T
AD  - Department of Anesthesiology, Emory University School of Medicine, The Emory 
      Clinic, Atlanta, Georgia, USA.
FAU - Olson, P J
AU  - Olson PJ
FAU - Szlam, F
AU  - Szlam F
FAU - Ramsay, J G
AU  - Ramsay JG
FAU - Levy, J H
AU  - Levy JH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Anesth Analg
JT  - Anesthesia and analgesia
JID - 1310650
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin Antagonists)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Protamines)
RN  - 0 (Recombinant Proteins)
RN  - 37270-94-3 (Platelet Factor 4)
RN  - 4C905MSK4W (Hexadimethrine Bromide)
RN  - 61D2G4IYVH (Adenosine Diphosphate)
RN  - 9005-49-6 (Heparin)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Adenosine Diphosphate/pharmacology
MH  - Anticoagulants/*pharmacology
MH  - *Cardiopulmonary Bypass
MH  - Collagen/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Heparin/*pharmacology
MH  - Heparin Antagonists/*pharmacology
MH  - Hexadimethrine Bromide/pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Platelet Aggregation/*drug effects
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Platelet Factor 4/pharmacology
MH  - Protamines/*pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - *Whole Blood Coagulation Time
EDAT- 1998/10/13 00:00
MHDA- 1998/10/13 00:01
CRDT- 1998/10/13 00:00
PHST- 1998/10/13 00:00 [pubmed]
PHST- 1998/10/13 00:01 [medline]
PHST- 1998/10/13 00:00 [entrez]
AID - 10.1097/00000539-199810000-00008 [doi]
PST - ppublish
SO  - Anesth Analg. 1998 Oct;87(4):781-5. doi: 10.1097/00000539-199810000-00008.