PMID- 8738586
OWN - NLM
STAT- MEDLINE
DCOM- 19961204
LR  - 20180216
IS  - 0301-0147 (Print)
IS  - 0301-0147 (Linking)
VI  - 26
IP  - 3
DP  - 1996 May-Jun
TI  - Can the haemorrhagic component of heparin be identified? Or an attempt at clean 
      thinking on a dirty drug.
PG  - 117-26
AB  - Heparin consists of different classes of molecules. We distinguish 
      below-critical-chain length heparin (BCLM, MW < 5,400), with only anti-factor Xa 
      activity and above-critical-chain length material (ACLM, MW > 5,400) with both 
      antithrombin and anti-factor Xa activity. In this article we introduce a division 
      within the ACLM fraction, between extra large material (MW > 8,000) and ACLM-low 
      (MW 5,400-8,000). Extra large material is abundantly present in unfractionated 
      heparin but is rare in low-molecular-weight (LMW) heparins. We noted that 
      injection of an LMW heparin causes 5- to 10-fold higher plasma levels of ACLM 
      than injection of a clinically equivalent dose of unfractionated heparin (UFH) 
      and proportionally higher inhibitions of the clotting system. So with LMW heparin 
      one can afford higher levels of anticoagulation than with UFH at a lower risk of 
      bleeding. We surmise that this is caused by the virtual absence of the 
      (haemorrhagic) extra-large-molecular-weight fraction from LMW heparins. A 
      laboratory artefact, i.e. the absence of Ca2+ in the anti-factor Xa tests, makes 
      that heparin mixtures that lack extra large heparin molecules show a (spuriously) 
      high ratio of anti-factor Xa activity over anti-thrombin activity. So the 
      correlation between a high aXa/alla ratio and a favourable ratio of 
      antithrombotic effect over bleeding is not necessarily caused by the presence of 
      BCLM. In fact BCLM is a poor anticoagulant; in mixtures of ACLM and BCLM, ACLM 
      causes by far the larger part of the anticoagulant effect. We surmise that the 
      LMW fraction of ACLM is the active anticoagulant component in any heparin 
      preparation and, isolated, would make a proper third-generation heparin.
FAU - Hemker, H C
AU  - Hemker HC
FAU - Beguin, S
AU  - Beguin S
FAU - Kakkar, V V
AU  - Kakkar VV
LA  - eng
PT  - Editorial
PT  - Review
PL  - Switzerland
TA  - Haemostasis
JT  - Haemostasis
JID - 0371574
RN  - 0 (Anticoagulants)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Anticoagulants/*adverse effects/isolation & purification
MH  - Fibrinolytic Agents/*adverse effects/isolation & purification
MH  - Hemorrhage/*chemically induced
MH  - Heparin/*adverse effects/isolation & purification
MH  - Heparin, Low-Molecular-Weight/adverse effects
MH  - Humans
MH  - Molecular Weight
RF  - 50
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
AID - 10.1159/000217197 [doi]
PST - ppublish
SO  - Haemostasis. 1996 May-Jun;26(3):117-26. doi: 10.1159/000217197.