PMID- 1665467
OWN - NLM
STAT- MEDLINE
DCOM- 19920409
LR  - 20180216
IS  - 0301-0147 (Print)
IS  - 0301-0147 (Linking)
VI  - 21
IP  - 4
DP  - 1991
TI  - Determination of the levels of unfractionated and low-molecular-weight heparins 
      in plasma: their effect on thrombin-mediated feedback reactions in vivo. 
      Preliminary results after subcutaneous injection.
PG  - 258-72
AB  - We define a standard independent unit (SIU) of heparin as that amount that, in 
      plasma containing 1 mumol of ATIII, raises the (pseudo-)first-order breakdown 
      constant of factor Xa by 1 min-1. These units measure all material with a high 
      affinity for ATIII (HAM); only material above the critical chain length of 17 
      monosaccharide units (above critical chain length material; ACLM) catalyzes the 
      inactivation of thrombin. An SIU of ACLM is therefore analogously defined as the 
      amount that, in plasma containing 1 mumol of ATIII, will raise the 
      (pseudo-)first-order breakdown constant of thrombin by 1 min-1. Of any given 
      heparin preparation one can determine the specific HAM and ACLM activities in 
      terms of SIU/mg. On the basis of the factor Xa and thrombin breakdown constants 
      found in a plasma sample one can then determine the levels of HAM and ACLM. 
      Preliminary experiments were carried out in plasma samples obtained after 
      subcutaneous injection of unfractionated heparin (UFH) and of two types of 
      low-molecular-weight heparin (LMWH). About three times more of UFH activity than 
      of LMWH activity has to be injected to obtain the same levels of ACLM in the 
      plasma. Only with the LMWHs significant amounts of BCLM are found, which rises 
      higher and persists longer than the ACLM. We determined the course of thrombin 
      generation in platelet-rich plasma (PRP) and in platelet-poor plasma (PPP), as 
      well as in the PPP factor Xa generation curve and the course of prothrombin 
      conversion. The observed inhibitions correlated much better with the levels of 
      ACLM than with those of below critical chain length material. The difference 
      between UFH and LMWHs can therefore not be explained in terms of antithrombin and 
      anti-factor-Xa activity. The essential difference between UFH and LMWH appears in 
      the feedback effect of thrombin in PRP, where thrombin generation is both 
      inhibited and retarded by LMWH, while it is only retarded but hardly inhibited by 
      UFH.
FAU - Hemker, H C
AU  - Hemker HC
AD  - Department of Biochemistry, Rijksuniversiteit Limburg, Maastricht, The 
      Netherlands.
FAU - Beguin, S
AU  - Beguin S
FAU - Bendetowicz, A V
AU  - Bendetowicz AV
FAU - Wielders, S
AU  - Wielders S
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Haemostasis
JT  - Haemostasis
JID - 0371574
RN  - 0 (Factor Xa Inhibitors)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9001-26-7 (Prothrombin)
RN  - 9035-58-9 (Thromboplastin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Adult
MH  - Enzyme Activation
MH  - Factor Xa Inhibitors
MH  - Feedback/drug effects
MH  - Heparin, Low-Molecular-Weight/*blood/pharmacokinetics/pharmacology
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Pilot Projects
MH  - Prothrombin/metabolism
MH  - Thrombin/*metabolism
MH  - Thromboplastin/metabolism
MH  - Weights and Measures
EDAT- 1991/01/01 00:00
MHDA- 1991/01/01 00:01
CRDT- 1991/01/01 00:00
PHST- 1991/01/01 00:00 [pubmed]
PHST- 1991/01/01 00:01 [medline]
PHST- 1991/01/01 00:00 [entrez]
AID - 10.1159/000216235 [doi]
PST - ppublish
SO  - Haemostasis. 1991;21(4):258-72. doi: 10.1159/000216235.