Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterized by the absence of glycosylphosphatidylinositol (GPI)-anchored proteins due to mutations in the PIG-A gene. This deficiency leads to intravascular hemolysis, bone marrow failure, and an increased risk of thrombotic events. This study investigates the relationship between phosphatidylinositol (PI) and phosphatidylcholine (PC) in hematopoietic cells of PNH patients and their association with clinical outcomes, specifically platelet counts and thrombotic risk. We analyzed blood samples from 22 PNH patients and 14 healthy controls, quantifying lipid content using high-performance liquid chromatography. Our results reveal a significant increase in the PI/PC molar ratio in PNH patients, reflecting decreased levels of PC in cellular membranes, which correlates with thrombocytopenia. These findings suggest that phospholipid imbalances are linked to both the functional deficiencies of hematopoietic cells and the heightened thrombotic tendency seen in PNH. Ultimately, this study underscores the potential for targeted therapies aimed at addressing lipid metabolism in managing PNH and mitigating thrombotic risks. Future investigations could explore the clinical implications of dietary or pharmacological interventions designed to restore lipid balance in these patients.