The paradoxical behaviour of heparin as an effective anticoagulant and a promoter of severe fatal rare blood clots involving autoantibodies needs to be understood for prevention purposes. This review explains the rationale behind this behaviour of heparin in such rare cases of blood clot, which is usually followed by its characteristic thrombocytopenia—a phenomenon known as heparin-induced thrombocytopenia (HIT).
Peer-reviewed scientific literature relating to heparin-induced thrombocytopenia was deconstructed and reconstructed to expose the inductive factors behind the involvement of heparin in severe blood clot and inducement of thrombocytopenia.
Studies show that defective B cells of class B-1 cells and marginal zone B are the key players of HIT, as they fail to confer the autoantibodies they express with the needed protein to distinguish between self and non-self. These corrupt autoantibodies bind to the heparin-PF4 complex, which was identified as one of the autoantigens that induces the expression of the IgG autoantibodies. The molar ratio of heparin to PF4 is a determinant of the immunogenicity and avidity of the autoantibody IgG, which desist from binding to them, but the autoantibodies from the defective B cells move towards these autoantigens to initiate HIT. Defective anticoagulant secreting cells and pre-existing risk factors of blood clots, such as birth hormone pills and SARS-Cov-2, may also contribute to HIT in people who develop some of these defective B cells.
The moderate formation of heparin-PF4 complex is likely an unrecognized part of the healthy mechanism our body uses to trigger IgG autoantibodies and deploy them as a first line of defence during an inflammation. However, due to anomalies in some B-1 cells and marginal zone B cells, this healthy mechanism could result in the inducement of thrombocytopenia.