Functional biology of human culprit thrombi in ST-segment elevation myocardial infarction: innate immunity and neutrophil extracellular traps

Leukocytes can affect a coronary thrombus through the activity of released products and their incorporation into clot material. This narrative Review examines how innate immune cells and their extracellular products support coagulation, affect clot dissolution and relate to reperfusion in ST-segment elevation myocardial infarction (STEMI). We prioritize studies of human culprit thrombi and culprit-site samples, integrating functional experiments with cellular profiling, histology and clinical observations. Two distinct experimental systems illustrate this contribution. Tissue factor-bearing neutrophil extracellular trap preparations generated ex vivo from culprit-site neutrophils support coagulation, while recombinant DNase augments tissue plasminogen activator-mediated ex-vivo lysis of recovered coronary thrombi in a separate system. Local plasma priming and platelet–neutrophil interactions help explain how procoagulant extracellular material can be generated. Histology shows where intact cells, remnants and extracellular structures coexist, whereas cellular profiling characterizes the cells captured from this heterogeneous material. Clinical studies relate selected tissue features and local DNA-related measurements to embolization, impaired reperfusion, microvascular obstruction and subsequent events; the associations differ by analyte, sampling site and endpoint. Distinguishing cellular state, extracellular structure, demonstrated function and clinical phenotype allows these findings to inform one another without assigning a function to a staining signal alone. The therapeutic questions follow from the biology: can further release be suppressed, can retained material be dismantled, and does changing a defined clot function improve the relevant myocardial or patient outcome?