PMID- 9421696
OWN - NLM
STAT- MEDLINE
DCOM- 19980127
LR  - 20181113
IS  - 0012-6667 (Print)
IS  - 0012-6667 (Linking)
VI  - 54
IP  - 6
DP  - 1997 Dec
TI  - Danaparoid. A review of its pharmacology and clinical use in the management of 
      heparin-induced thrombocytopenia.
PG  - 903-24
AB  - Danaparoid, a low molecular weight heparinoid consisting of a mixture of heparan, 
      dermatan and chondroitin sulfates, has well established antithrombotic activity. 
      The drug has a high antifactor Xa to antifactor IIa (thrombin) activity ratio, a 
      low tendency to cause bleeding and minimal effects on the fibrinolytic system. 
      Danaparoid has a low cross-reactivity rate with heparin-associated antiplatelet 
      antibodies (0 to 20%; mean approximately 10%). This represents a significant 
      advantage over low molecular weight heparins (LMWHs) as a potential replacement 
      agent for unfractionated heparin (UFH) in patients with immune-mediated (type II) 
      heparin-induced thrombocytopenia (HIT). In a worldwide compassionate-use 
      programme involving a total of 667 patients with HIT to date, 93% of danaparoid 
      treatment courses were considered to be successful. Thrombocytopenia resolved in 
      91% of episodes. In a multicentre randomised comparative trial of danaparoid and 
      dextran in patients with HIT plus thrombosis (HITT), significantly more 
      danaparoid than dextran recipients had resolution of thromboses, and an effective 
      clinical response was achieved in significantly more danaparoid recipients. 
      Results of a retrospective case-controlled study of danaparoid and ancrod in 
      patients with HITT showed significantly fewer new or progressive thromboses with 
      danaparoid. In the compassionate-use programme, danaparoid was associated with a 
      mortality rate of 10.4% during treatment (up to 3.5 years) and 7.8% during the 
      follow-up period (3 months). 14 of 114 deaths during the follow-up period were 
      considered to be related to danaparoid therapy. A mortality rate of 23.5% was 
      reported in patients accepted for but not treated with, danaparoid. Mortality 
      rates with danaparoid, ancrod and dextran in the comparative studies were similar 
      (7, 11 and 12%, respectively). Severe bleeding was reported in 3.1% of patients 
      in the compassionate-use programme, persistent or recurrent thrombocytopenia in 
      2.6% and new thromboembolic events/extension of existing thrombosis in 1.7%. The 
      incidence of bleeding was similar with danaparoid and dextran in a comparative 
      trial. Although in vitro cross-reactivity does not always translate into clinical 
      cross-reactivity, testing is currently recommended, when possible, before 
      initiation of danaparoid therapy. Thus, danaparoid appears to be an effective and 
      well tolerated replacement agent for UFH in many patients with HIT who require 
      further anticoagulation. The drug has low cross-reactivity with HIT-associated 
      antibodies. Further comparative trials are needed to confirm these promising 
      findings.
FAU - Wilde, M I
AU  - Wilde MI
AD  - Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
FAU - Markham, A
AU  - Markham A
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - Drugs
JT  - Drugs
JID - 7600076
RN  - 0 (Drug Combinations)
RN  - 0 (Heparinoids)
RN  - 24967-94-0 (Dermatan Sulfate)
RN  - 9005-49-6 (Heparin)
RN  - 9007-28-7 (Chondroitin Sulfates)
RN  - 9050-30-0 (Heparitin Sulfate)
RN  - BI6GY4U9CW (danaparoid)
SB  - IM
EIN - Drugs 1998 Apr;55(4):517
MH  - Blood Coagulation/drug effects
MH  - Chondroitin Sulfates/adverse effects/pharmacokinetics/*pharmacology/*therapeutic 
      use
MH  - Dermatan Sulfate/adverse effects/pharmacokinetics/*pharmacology/*therapeutic use
MH  - Drug Combinations
MH  - Heparin/adverse effects
MH  - Heparinoids/adverse effects/pharmacokinetics/pharmacology/therapeutic use
MH  - Heparitin Sulfate/adverse effects/pharmacokinetics/*pharmacology/*therapeutic use
MH  - Humans
MH  - Thrombocytopenia/chemically induced/*drug therapy/physiopathology
RF  - 116
EDAT- 1998/01/09 00:00
MHDA- 1998/01/09 00:01
CRDT- 1998/01/09 00:00
PHST- 1998/01/09 00:00 [pubmed]
PHST- 1998/01/09 00:01 [medline]
PHST- 1998/01/09 00:00 [entrez]
AID - 10.2165/00003495-199754060-00008 [doi]
PST - ppublish
SO  - Drugs. 1997 Dec;54(6):903-24. doi: 10.2165/00003495-199754060-00008.