Abstract
Heparin induced thrombocytopenia (HIT) is a serious adverse drug reaction caused by
transient antibodies against platelet factor 4 (PF4)/heparin complexes, resulting
in platelet activation and potentially fatal arterial and/or venous thrombosis. Most
cases of HIT respond to cessation of heparin and administration of an alternative
non-heparin anticoagulant, but there are cases of persisting HIT, defined as thrombocytopenia
due to platelet activation/consumption for greater than seven days despite standard
therapy. These patients remain at high risk for thrombotic events, which may result
in limb-loss and mortality. Intravenous immunoglobulin (IVIg) has been proposed as
an adjunct therapy for these refractory cases based on its ability to saturate FcγRIIa
receptors on platelets, thus preventing HIT antibody binding and platelet activation.
We describe 2 cases of persisting HIT (strongly positive antigen and functional assays,
and persisting thrombocytopenia >7 days) with rapid clinical response to IVIg. We
performed in-vitro experiments to support IVIg response. Healthy donor platelets (1 × 10e6)
were treated with PF4 (3.75 μg/mL) for 20 min followed by 1-hour incubation with patients’
sera. Platelet activation with and without addition of IVIg (levels equivalent to
those reached in a patient after treatment with 2 gm/Kg) was evaluated in the PF4-dependent
P-selectin expression assay (PEA). A significantly decreased platelet activation was
demonstrated after the addition of IVIg to both patient samples, which correlated
well with the rapid clinical response that each patient experienced. Thus, our study
supports the use of IVIg as an adjunct therapy for persisting HIT.
Keywords
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Article info
Publication history
Published online: June 26, 2018
Accepted:
June 21,
2018
Received:
June 11,
2018
Identification
Copyright
© 2018 Elsevier Ltd. All rights reserved.
