Post-prandial analysis of fluctuations in the platelet count and platelet function in patients with the familial chylomicronemia syndrome

Abstract

BackgroundThe familial chylomicronemia syndrome (FCS) is an ultra rare disease caused by lipoprotein lipase (LPL) deficiency associated with potentially lethal acute pancreatitis risk. Thrombocytopenia (platelet count < 150,000 × 109/L) has been reported in patients with FCS, treated or not with volanesorsen, a second generation APOC3 anti-sense oligonucleotide. Chylomicrons are the lipoproteins delivering fat after a meal and FCS thus has a post-prandial origin. Platelet count and function have not been studied post-prandially in FCS.ObjectiveTo evaluate post-prandial fluctuations in the platelet count (PLC) and functional defects of hemostasis in FCS.MethodsPLC, functional defects in hemostasis and hematologic variables were measured up-to 5 h after a meal in 6 homozygotes for FCS causing gene variants (HoLPL), 6 heterozygotes for LPL loss-of-function variants (HeLPL) and 7 normolipidemic controls.ResultsHourly post-prandial PLC was significantly lower in HoLPL than in controls (P < 0.009). Compared to the other groups, the PLC tended to decrease rapidly (in the first hour) post-meal in HoLPL (P = 0.03) and remained lower than baseline 5-h post-meal (P = 0.02) whereas it tended to slightly increase in normolipidemic controls (P = 0.02). Platelet function was not affected by the prandial status. In HoLPL, post-prandial fluctuations in the PLC positively correlated with the lymphocyte count (P = 0.005) and negatively with neutrophil/lymphocyte ratio (NLR).ConclusionThe PLC decreases post-prandially in FCS (HoLPL), is not associated with changes in functional defects of hemostasis and correlates with the NLR, a marker of acute pancreatitis severity.