A Nov. 2022 proteomics study in Scientific Reports looked at protein differences in people with POTS.
Proteomics studies are neat because they don’t examine a specific pathway or focus on a hypothesis. Instead, the researchers will sample a wide swath of different metabolites in the blood. This gives an unbiased look at what is going on.
The POTS proteomics study included 65 people with POTS and 65 age-matched healthy controls. The average age was 30, and >80% of the participants were women.
The results showed 30 significantly different proteomic biomarkers in the POTS group.
Breaking down the results:
Platelet-related proteins were increased. These proteins included receptors for von Willebrand factor as well as platelet adhesion proteins and platelet assembly proteins.
A couple of proteins related to inhibiting platelet aggregation were downregulated, which could also contribute to an increase in aggregation.
Two proteins involved in regulating cardiac contractility were upregulated in the POTS group. Additionally, a protein (thrombospondin-4) involved in cardiac muscle contractility was downregulated.
Inflammation and immune response proteins were also found to be altered. The beta-2-microglobulin protein is part of the MHC I complex-cell surface proteins that display proteins to alert the immune system that something is wrong in a cell.
Myosins are muscle cells. In the POTS group, there was an upregulation in skeletal muscle myosin as well as in another type of myosin found in vascular smooth muscles (muscles surrounding blood vessels).
To summarize: clotting, the immune system, cardiac muscles, and vascular muscles… POTS could be a disorder from inflammation, a hyperactive adrenergic system, or an autoimmune response. 
References:
Johansson, Madeleine, et al. “Plasma Proteomic Profiling in Postural Orthostatic Tachycardia Syndrome (POTS) Reveals New Disease Pathways.” Scientific Reports, vol. 12, Nov. 2022, p. 20051. PubMed Central, https://doi.org/10.1038/s41598-022-24729-x.