An observation that the SII did not perform well in PV patients with prior thrombosis history could be explained by the fact that these patients receive cytoreductive treatment and different potent cardioprotective medications for CVRF control and secondary prevention (i.e., angiotensin-converting enzyme inhibitors (ACE-is), statins, sodium–glucose cotransporter-2 (SGLT2) inhibitors, anticoagulants, etc.), which could modulate their thrombotic risk over time. The gene discussed is ACE; the disease is acquired polycythemia vera.