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D-Dimer: D-dimers are a degradation product of fibrinogen, a mesh of fibrils that stabilises platelet plugs. They represent two D-domains of fibrinogen joined together, and a cleavage point in fibrinogen releases them into the wild. #FOAMed #medtwitter
In an otherwise & #39;healthy person& #39; an excess of D-dimer likely represents an ongoing thrombotic disease process such as DVT. However it is going to be high in any disease where there is increased turnover of clot - even if a clinically relevant clot itself never materialises
There are a huge number of diseases where the coag cascade is highly active even if it is degraded before achieving a fully occlusive thrombus. Pregnancy is one such, DIC of course, and inflammation of any kind.
Inflammation and coagulopathy have profound crossover - for example thrombin has multple effects not just on complement directly but endothelial permeability, cell adhesion etc all summarised in this beautiful diagram https://www.genome.jp/kegg-bin/show_pathway?hsa04610">https://www.genome.jp/kegg-bin/...
Indeed one action of neutrophils is to chuck out nets of DNA that interlock with fibrin, trap pathogens and stop them disseminating - NETosis. There is a mollusc that literally throws out immunoglobulins attached to fibrinogen.
Kallikrein can also directly evoke complement activation. The mannose binding lectose pathway and the thrombin pathway both converge on PAR4 which is a G protein that activates platelets. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372068/">https://www.ncbi.nlm.nih.gov/pmc/artic...
https://academic.oup.com/ehjcvp/article/2/3/175/2197072">https://academic.oup.com/ehjcvp/ar...
https://onlinelibrary.wiley.com/doi/full/10.1111/ijlh.12665">https://onlinelibrary.wiley.com/doi/full/...
https://www.sciencedirect.com/science/article/pii/S0049384819303263">https://www.sciencedirect.com/science/a...
so whilst D-dimer is indeed entirely non specific, it is very much not a surprise that it carries a mortality burden, or even that haemorrhage evokes a SIRS response.
