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Introduction: Severe hypertriglyceridemia (HTG > 1,000 mg/dL) is a metabolic emergency that can precipitate pancreatitis and multiorgan failure. Intravenous (IV) insulin is first-line therapy, but its effectiveness depends on functional lipoprotein lipase (LPL). Optimal rescue therapy when insulin fails remains plasmapheresis, though its implementation requires prompt assessment and activation of many moving parts. Description: A 44-year-old female with a history of hypertension, gestational diabetes in six pregnancies, and three spontaneous abortions, presented to the emergency department for a 3-week history of pleuritic chest pain. Initial laboratories showed triglycerides (TG) > 4,000 mg/dL, glucose 452 mg/dL, corrected calcium of 5.6 mg/dL, and normal lipase. She was admitted to the ICU for aggressive isotonic fluids and weight-based IV insulin infusion. Euglycemia was achieved within 12 h, yet TG remained > 4,000 mg/dL after 24 h, suggestive of insulin-resistant HTG. With the lab capped at “>4,000 mg/dL,” her true TG level could have been substantially higher. Given persistent extreme TGs and concern for impending organ damage, therapeutic plasmapheresis was initiated. Two apheresis sessions over 24 h reduced TG to 615 mg/dL. Fenofibrate and omega-3 ethyl esters were started, and insulin was titrated. The patient was discharged by day 5 with TG of 349 mg/dL, on a low-fat diet, oral lipid-lowering therapy, and adhered to close follow-up. Discussion: This case highlights three key teaching points: 1. Insulin resistance can blunt lipid-clearing effects of IV insulin, necessitating early alternative therapy. 2. Pseudohypocalcemia may occur in extreme HTG because high lipid levels artifactually lower total calcium measurements. 3. Early plasmapheresis yields a rapid, durable triglyceride reduction, even absent frank pancreatitis, and may prevent end-organ injury. Implementation requires rapid coordination with the blood bank to secure apheresis equipment, calcium-containing replacement fluid (albumin or plasma), and trained personnel. The American Society for Apheresis assigns plasmapheresis a Category II recommendation for HTG-induced pancreatitis. Our experience underscores the importance of aligning these “moving parts” promptly, especially in resource-limited settings or off hours.