PMID- 8091389
OWN - NLM
STAT- MEDLINE
DCOM- 19941018
LR  - 20151119
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 71
IP  - 5
DP  - 1994 May
TI  - Evaluation of recombinant platelet factor 4 and protamine sulfate for heparin 
      neutralization: clotting and clearance studies in rat.
PG  - 609-14
AB  - Recombinant platelet factor 4 (rPF4) efficiently neutralized heparin 
      anticoagulant activity in rats without the adverse effect of protamine sulfate 
      (PS) (Circulation 1992; 85: 1102). This study confirmed that rPF4 and PS 
      neutralized heparin in rats. In vitro addition of excess PS but not rPF4 to 
      plasma prolonged the activated partial thromboplastin time. Injection of rPF4 or 
      PS 2 min following injection of 3H-heparin augmented loss of radioactivity from 
      the circulation over the first 2 min but did not affect the half life of 
      3H-heparin for the next 58 min. PS was coupled to 
      4-(p-Azidosalicylamido)butylamine (ASBA), radioiodinated and purified by means of 
      heparin-agarose chromatography. Heparin prevented the rapid loss of 125I-rPF4 
      from the circulation within the first 2 min but modestly increased loss of 
      radioiodinated derivatized PS. Heparin extended the half-life of derivatized 
      radioiodinated PS (measured between 2 and 60 min after injection) while modestly 
      shortening that of 125I-rPF4. Both radioiodinated heparin binding proteins 
      accumulated predominantly in liver and kidney. A greater percentage of 
      radioactivity was found in these organs with rPF4 than with PS but more PS was 
      found in urine. A larger percentage of radioiodinated derivatized PS than 
      125I-rPF4 was undetected. These results indicate that rPF4 and PS affect the 
      kinetics of heparin clearance similarly but that organ deposition of the two 
      agents may differ and offer an explanation of different physiological effects 
      seen previously.
FAU - Korutla, L N
AU  - Korutla LN
AD  - Department of Physiology, Temple University School of Medicine, Philadelphia, PA 
      19140.
FAU - Stewart, G J
AU  - Stewart GJ
FAU - Lasz, E C
AU  - Lasz EC
FAU - Maione, T E
AU  - Maione TE
FAU - Niewiarowski, S
AU  - Niewiarowski S
LA  - eng
GR  - HL 47456/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Heparin Antagonists)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Protamines)
RN  - 0 (Recombinant Proteins)
RN  - 37270-94-3 (Platelet Factor 4)
SB  - IM
MH  - Animals
MH  - Blood Coagulation Tests
MH  - Evaluation Studies as Topic
MH  - Female
MH  - Heparin Antagonists/*pharmacology
MH  - Iodine Radioisotopes
MH  - Metabolic Clearance Rate
MH  - Platelet Factor 4/pharmacokinetics/*pharmacology
MH  - Protamines/pharmacokinetics/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/pharmacokinetics/pharmacology
EDAT- 1994/05/01 00:00
MHDA- 1994/05/01 00:01
CRDT- 1994/05/01 00:00
PHST- 1994/05/01 00:00 [pubmed]
PHST- 1994/05/01 00:01 [medline]
PHST- 1994/05/01 00:00 [entrez]
PST - ppublish
SO  - Thromb Haemost. 1994 May;71(5):609-14.