Abnormal clot microstructure formed in blood containing HIT-like antibodies. Issue 193 (September 2020) - Thomas, Bethan R.
Abstract: Introduction: Thrombosis is a severe and frequent complication of heparin-induced thrombocytopenia (HIT). However, there is currently no knowledge of the effects of HIT-like antibodies on the resulting microstructure of the formed clot, despite such information being linked to thrombotic events. We evaluate the effect of the addition of pathogenic HIT-like antibodies to blood on the resulting microstructure of the formed clot. Materials and methods: Pathogenic HIT-like antibodies (KKO) and control antibodies (RTO) were added to samples of whole blood containing Unfractionated Heparin and Platelet Factor 4. The formed clot microstructure was investigated by rheological measurements (fractal dimension; d f ) and scanning electron microscopy (SEM), and platelet activation was measured by flow cytometry. Results and conclusions: Our results revealed striking effects of KKO on clot microstructure. A significant difference in d f was found between samples containing KKO ( d f = 1.80) versus RTO ( d f = 1.74; p < 0.0001). This increase in d f was often associated with an increase in activated platelets. SEM images of the clots formed with KKO showed a network consisting of a highly branched and compact arrangement of thin fibrin fibres, typically found in thrombotic disease. This is the first study to identify significant changes in clot microstructure formed in blood containing HIT-like antibodies. These observed alterations in clot microstructure can be potentially exploited as a much-needed biomarker for the detection, management and monitoring of HIT-associated thrombosis. Highlights: The diagnosis of thrombosis in patients receiving heparin remains wholly inadequate. We identify abnormal microstructure in blood clots containing HIT-like antibodies. A structural biomarker, the fractal dimension, was significantly elevated in these clots. This has potential application in the detection of thrombosis associated with HIT.