EP1843 - LBA_ECE_1388 - Resistant hypertriglyceridaemia associated with low-molecular-weight heparin in heterozygous LPL variant carriers
Bildiriler > Özet Bildiri
Yazarlar: Murat Tozman, Adam D McIntyre, Robert Hegele, Ilgin Simsir, Gökçen ÜNAL KOCABAŞ
European Journal of Endocrinology, , , Uluslararası, Özet Bildiri, Wos, cilt 195
DOI: 10.1093/ejendo/lvag096.1860
Özet
Abstract Introduction and Objective Biallelic pathogenic variants in the apolipoprotein (APO) C2, APOA5l, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), lipase maturation factor 1 (LMF1), and lipoprotein lipase (LPL) genes cause familial chylomicronemia syndrome (FCS). Although heterozygous carriers typically exhibit a milder phenotype, severe hypertriglyceridemia (HTG) may develop in the presence of secondary triggers. Low-molecular-weight heparin (LMWH) can increase the release of LPL from the endothelium, potentially leading to an initial transient reduction in triglyceride (TG) levels; however, with continued use, rapid clearance of circulating LPL and limited resynthesis capacity may result in depletion of the functional LPL pool. In this report, we present a possible association between enoxaparin use and resistant HTG in a patient carrying a heterozygous pathogenic LPL variant. Case Presentation A 49-year-old man presented with a TG level of 5502 mg/dL (63.3 mmol/L), without a history of alcohol consumption. His medical history was notable for myocardial infarction 14 years earlier, 11 episodes of pancreatitis, and portal and splenic vein thrombosis following a severe pancreatitis episode six months prior, as well as pancreatitis-related secondary diabetes mellitus. Glycemic control was stable, with a hemoglobin A1c level of 6.4% at presentation. Genetic analysis identified a heterozygous pathogenic variant in the LPL gene, c.347G>C (p.Arg116Pro). Although the patient's sister carried the same heterozygous variant, her TG levels had been reported to be no higher than 500 mg/dL (5.6 mmol/L). Despite treatment with fenofibrate, rosuvastatin, nicotinic acid, orlistat, and intravenous insulin infusion, the TG level remained elevated at 4770 mg/dL (53.9 mmol/L), without a meaningful reduction. After treatment reassessment, LMWH was discontinued due to its potential contributory role, and rivaroxaban was initiated. Following this modification, the TG level decreased to 1516 mg/dL (17.1 mmol/L). Discussion and Conclusion The marked interindividual variability in phenotypic severity among heterozygous LPL variant carriers suggests a substantial contribution of secondary modifiers. In our patient, persistently elevated TG levels despite intensive lipid-lowering therapy and adequate glycemic control suggested an ongoing precipitating factor. The substantial decline in TG levels following discontinuation of LMWH suggests that anticoagulant therapy may have had a clinically relevant impact in the setting of genetically limited LPL activity. This observation underscores the importance of carefully reviewing not only metabolic determinants but also concomitant pharmacologic treatments in patients with severe and refractory HTG. In individuals with an underlying genetic predisposition, LMWH use should be assessed on an individual basis for its potential contributory role.