Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a familial study of AT III, a type III antithrombin III variant which was identified in the propositus by gene analysis as Pro 41 Leu heterozygous mutation. None of the four members of the family who presented with defective heparin cofactor (hep-cofactor) activity, and therefore probably carried the mutation, had experienced deep venous thrombosis. The abnormal AT III was purified from the propositus' plasma, taking advantage of the difference in NaCl concentrations required to elute variant and normal AT III from heparin-Sepharose. The antithrombin and anti-Xa activities of the purified variant AT III were comparable to those observed for normal AT III, but hep-cofactor activity was strikingly reduced. The enhancement by heparin of thrombin and F Xa inhibition by normal and variant AT III was compared in the absence of NaCl and in the presence of normal NaCl concentrations. The difference between the degrees of inhibition by normal and variant AT III was maximal at physiological ionic strength (i.e. at a concentration of 0.15 M). The quantification of heparin AT III interaction with both normal and variant purified proteins in a double reciprocal plot yielded similar dissociation constants but a 9-fold decrease in the maximal pseudo-first order constant. This suggests that Pro 41 is more involved in the molecular changes induced by heparin than in the primary binding of the activator.
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PMID:Clinical and biochemical characterization of antithrombin III Franconville, a variant with Pro 41 Leu mutation. 237 10

Low-Molecular-Weight Heparin (LMWH) fractions are prepared from standard unfractionated heparin (UFH) and are thus similar to it in many aspects. The major advantages of LMWH are improved efficacy and safety, longer half-life and reduced need for laboratory monitoring. In addition, the dangers of UFH administered by continuous infusion in the hospital setting are often not fully appreciated and the necessary monitoring and dosage adjustment poorly carried out resulting in inadequate doses being given. LMWHs are the drug of choice in many clinical situations. Four LMWHs are now licensed in the UK for prophylaxis of venous thrombo-embolism during or after surgery (Certoparin, Dalteparin [Fragmin], Enoxaparin [Lovenox/Clexane] and Tinzaparin [Inno-hep]; a fifth is licensed but not currently available in the UK. Dalteparin, Enoxaparin and Tinzaparin are licensed for the treatment of Deep Vein Thrombosis (DVT), and Tinzaparin additionally for the treatment of Pulmonary Embolism (PE), but so far none is licensed for use in pregnancy or paediatrics.
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PMID:Current Clinical Practice: Low-Molecular-Weight Heparins in The Prophylaxis and Treatment of Thrombo-Embolic Disease. 2742 41