PMID- 1537108
OWN - NLM
STAT- MEDLINE
DCOM- 19920327
LR  - 20190623
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 85
IP  - 3
DP  - 1992 Mar
TI  - Platelet factor 4 efficiently reverses heparin anticoagulation in the rat without 
      adverse effects of heparin-protamine complexes.
PG  - 1102-9
AB  - BACKGROUND: It has been observed that the reversal of heparin anticoagulation in 
      humans by protamine sulfate (PS) results in various adverse reactions including 
      leukopenia, thrombocytopenia, activation of complement, increased vascular 
      permeability, systemic hypotension, pulmonary vasoconstriction, and pulmonary 
      edema. The purpose of this study was to compare the efficacy and effects of 
      native platelet factor 4 (PF4) and recombinant platelet factor 4 (rPF4) with 
      those of PS in heparin neutralization in vivo, using a rat model. METHODS AND 
      RESULTS: Sprague-Dawley rats were anesthetized with sodium pentobarbital, and the 
      right femoral vein and carotid artery were cannulated. For determination of 
      activated partial thromboplastin time, platelet count, white blood cell count, 
      and complement titer, arterial blood samples were taken before and immediately 
      after heparin (10 units/100 g) infusion and at several time points after the 
      infusion of the neutralizing agent (PS, 0.1 mg/100 g; PF4, 0.5 mg/100 g). In 
      separate groups of animals, mean arterial blood pressure was monitored throughout 
      identical protocols and the lungs were prepared for histological examination. The 
      anticoagulant activity of heparin was effectively reversed by all of the 
      neutralizing agents (PS, PF4, and rPF4). Platelet count (48% of initial), white 
      blood cell count (52% of initial), complement titer (60% of initial), and mean 
      arterial pressure (20% decrease) decreased significantly in heparinized animals 
      receiving PS but not in those receiving PF4 or rPF4. Lung interstitium appeared 
      normal when heparin was followed by PF4; however, interstitial edema and 
      hemorrhage were observed with heparin-PS. CONCLUSIONS: These results suggest that 
      PF4 efficiently reverses heparin anticoagulation in the rat without the adverse 
      effects of heparin-protamine complexes. Therefore, rPF4 may be an appropriate 
      substitute for PS in patients undergoing cardiovascular surgery and other 
      procedures that require heparin anticoagulation.
FAU - Cook, J J
AU  - Cook JJ
AD  - Department of Physiology, Temple University School of Medicine, Philadelphia, PA 
      19140.
FAU - Niewiarowski, S
AU  - Niewiarowski S
FAU - Yan, Z
AU  - Yan Z
FAU - Schaffer, L
AU  - Schaffer L
FAU - Lu, W
AU  - Lu W
FAU - Stewart, G J
AU  - Stewart GJ
FAU - Mosser, D M
AU  - Mosser DM
FAU - Myers, J A
AU  - Myers JA
FAU - Maione, T E
AU  - Maione TE
LA  - eng
GR  - HL-19055/HL/NHLBI NIH HHS/United States
GR  - HL-36579/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Heparin Antagonists)
RN  - 0 (Protamines)
RN  - 0 (Recombinant Proteins)
RN  - 37270-94-3 (Platelet Factor 4)
SB  - IM
MH  - Animals
MH  - Blood Coagulation/*drug effects
MH  - Female
MH  - Hemorrhage/chemically induced
MH  - Heparin Antagonists/*pharmacology
MH  - Humans
MH  - Lung Diseases/chemically induced
MH  - Platelet Factor 4/*pharmacology
MH  - Protamines/*adverse effects
MH  - Pulmonary Edema/chemically induced
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Recombinant Proteins/pharmacology
EDAT- 1992/03/01 00:00
MHDA- 1992/03/01 00:01
CRDT- 1992/03/01 00:00
PHST- 1992/03/01 00:00 [pubmed]
PHST- 1992/03/01 00:01 [medline]
PHST- 1992/03/01 00:00 [entrez]
AID - 10.1161/01.cir.85.3.1102 [doi]
PST - ppublish
SO  - Circulation. 1992 Mar;85(3):1102-9. doi: 10.1161/01.cir.85.3.1102.