Summary
Eczematous lesions, resulting from type IV sensitizations are well-known and relatively
frequent cutaneous adverse effects of s.c. heparin therapy. If anticoagulation is
further required intravenous heparin, heparinoids or lepirudin may be used as a substitute.
However, these alternatives are not optimal in terms of practicability and/or safety-profiles.
As molecular weight of different heparin preparations has repetitively been implied
to determine the frequency of sensitization, we hypothesized, that due to its low
molecular weight the pentasaccharide fondaparinux may provide a practicable and safe
anticoagulant therapy in patients with delayed type hypersensitivity reactions (DTH)
to heparin and other oligosaccharides. To test this concept, patients referred for
diagnosis of cutaneous reactions after s.c. anticoagulant treatment underwent a series
of in vivo skin allergyand challenge-tests with unfractionated heparin, a series of low molecular
weight heparins (nadroparin, dalteparin, tinzaparin, enoxaparin and certoparin), the
heparinoid danaparoid and the synthetic pentasaccharide fondaparinux. In total, data
from twelve patients was evaluated. In accordance with previously published data,
we report a high crossreactivity among heparins and heparinoids. In contrast – and
in support of our initial hypothesis – sensitization towards the synthetic pentasaccharide
fondaparinux was rarely observed. Plotting the cumulative incidence against the determined
molecular weight of the individual anticoagulant preparations, shows that molecular
weight generally is a key determinant of sensitization towards heparins and other
oligosaccharides (r2=0.842, p=0.009). Hence, fondaparinux may be used as a therapeutic alternative in
patients with cutaneous DTH relations towards heparin and other polysaccharides.
Keywords
Heparins / glycosaminoglycans - clinical trials - heparins / LMWH - immunity (auto-)