Hypersensitivity reactions
UFH may induce all types of DHRs, mostly type IV and type II
(188). Cutaneous NIHRs to subcutaneous
heparin occur at the injection site as itchy erythematous or eczematous
plaques usually on the 7th-10th day
of treatment; although they can appear on the 1-3thday in case of antecedent sensitization
(189). Risk factors for NIHRs to heparin
are obesity, female gender, old age, pregnancy, and repeated exposures
(190,191). If the treatment is continued regardless of a local reaction,
the patient may develop generalized eczema or exanthem (192,193).
Patients with a NIHR to UFH or LMWH at injection site usually tolerate
intravenous administration of UFH (189). Cross-reactivity among LMWHs
has been reported in NIHRs (194).
However, fondaparinux is generally well-tolerated in patients who react
to LMWHs (191). Heparin may induce DRESS
(195) and SJS
(196).
Immune-mediated heparin-induced thrombocytopenia (HIT) is induced by IgG
antibodies against complex of heparin and platelet-factor 4 tetramers
(197). HIT manifests as a more than 50%
decrease in the platelet count in 5 to 10 days after the onset of
treatment (198). The risk of HIT is
increased exclusively with UFH (199). Treatment includes the
discontinuation of heparin and the introduction of an alternative
anticoagulant such as argatroban, fondaparinux, danaparoid, or
bivalirudin (198).
The IgE-mediated reactions to heparin manifesting as urticaria,
angioedema, and anaphylaxis are rare
(194,200,201). Positive STs with UFH and
LMWHs have been reported (194,200,201,202). Cross-reactivity in IHRs has
been reported between UFH and LMWH and among LMWHs
(202).
For IHRs with heparins, diagnostic approach primarily consists of SPTs
and IDTs (17). The results of BAT with
UFH and LMWH are controversial (201,203,204). Heparin itself may cause a
release of histamine, leading to a false positive ST. Further serial
dilutions of heparin (1:100, 1:1.000, 1:10.000) might be needed (201).
IDTs and PTs with the culprit and alternative heparin are performed in
NIHRs (205). PTs, with tape stripping,
are less sensitive but may be positive
(188).
DPT is considered when the diagnosis is obscure, tissue pathology is
unavailable, or an alternative anticoagulant needs to be determined
(206). Subcutaneous DPTs with UFC and
LMWHs are performed with increasing doses reaching up to a daily dose on
the first day, then are evaluated on three consecutive days and day 7 in
case of NIHRs. Intravenous DPTs with UFC may also be necessary to prove
tolerance for emergency situations both for IHRs and NIHRs
(188,189).
A standard protocol for UFH desensitization has not been established yet
and published as case reports (207,208).