Background: While plaque rupture is a pivotol causative event for myocardial infarction (MI) the amplitude of the haemostatic response may also be a key determining factor in whether the vessel becomes occluded. Elevated levels of some individual coagulation factors are seen in patients who have suffered an early MI but the reactions that occur in blood between these proteins are complex, involving multiple control mechanisms, meaning that it is difficult to predict the importance of changes on the extent and rate of thrombin and hence clot formation.

Aims: To investigate how small variations in multiple plasma coagulation proteins interact to control thrombin generation.

Methods: A mathematical representation of the coagulation cascade was used to predict system wide coagulation responses using profiles of coagulation factors measured in 162 donors who had suffered an MI< 50 years and 186 age/sex matched controls. Machine learning techniques were used to stratify donors and investigate patterns between data and model predictions.

Results: Differential response patterns were identified not only between healthy donors and premature MI patients, but also between males and females. The modelling highlights key points of control within the coagulation cascade and allows the identification of coagulation proteins that control the differential response seen between subsets of donors. In males the key proteins that contribute to the differences seen between case and controls are TF, FVIII, FIX and the inhibitor TFPI whereas in females FII, FVIII and FIX control the outcome.

Conclusions: We have identified key changes in procoagulant profiles that propagate through the coagulation cascade to produce shifts in thrombin generation. These changes are found to vary by gender and suggest that donor stratification, enhancing our understanding of therapeutic efficacy, may be possible.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/system-wide-investigation-into-coagulation-profile-of-premature-myocardial-infarction-subjects/