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Bloodletting to Treat Severe Hypertriglyceridemia

Background: Plasmapheresis is necessary to treat some cases of severe hypertriglyceridemia. Objective: To describe successful treatment of severe hypertriglyceridemia in a patient for whom plasmapheresis was not possible. Case Report: A 39-year-old man came to the emergency department with nausea, vomiting, malaise, headache, and slowly deteriorating alertness. He had diabetes mellitus of an unknown type and a history of cholelithiasis and cholecystitis. He had been prescribed daily doses of sitagliptin, 100 mg; dapagliflozin, 10 mg; and pantoprazole, 40 mg, but he was taking these drugs intermittently. Two days earlier, he saw an outpatient physician for nausea, vomiting, unwanted weight loss, and headaches that had been increasing for several months. At that time, he had very high levels of triglycerides (203.4 mmol/L [18000 mg/dL]) and cholesterol (37.01 mmol/L [1429 mg/dL]), as well as elevated hemoglobin A1c (13.9%). Physical examination in the emergency department revealed a score of 7 on the Glasgow Coma Scale, Kussmaul breathing, and a body mass index of 29.7 kg/m2. Shortly after the patient arrived, his Glasgow score decreased to 4 and he was intubated. Computed tomography angiography revealed no pathologic findings, and lumbar puncture results were unremarkable. Intravenous fluids and vasopressor support were initiated for hypovolemic shock. The patient was admitted to our intensive care unit with severe ketoacidosis (arterial blood pH, 7.154; PaO 2, 129 mm Hg; PaCO 2, 27 mm Hg; bicarbonate, 9.1 mmol/L; base excess, 18 mmol/L; glucose, 17.09 mmol/L [308 mg/dL]; lactate, 1.6 mmol/L; and ketone and glucose positivity on urine testing) and hyperviscosity syndrome due to extremely high levels of triglycerides (163.14 mmol/L [14437 mg/dL]) and cholesterol (30.8 mmol/L [1189 mg/dL]). In addition, he had elevated pancreatic enzyme levels (P-amylase, 3.40 kat/L; lipase, 9.29 kat/L), pseudohyponatremia (serum sodium, 127 mmol/L), and hypokalemia (potassium, 2.9 mmol/L), with a C-peptide level of 0.33 nmol/L (1.0 ng/mL) (normal range, 0.36 to 1.46 nmol/L [1.1 to 4.4 ng/mL]) and an elevated creatinine level (127.3 mol/L [1.44 mg/dL]). His serum was visibly lipemic (Figure). Figure. Blood samples drawn during the patient's admission to the intensive care unit, after they rested for 135 minutes. We started treatment with intravenous infusions of insulin, 40% glucose, heparin, and piperacillintazobactam. We initiated extracorporeal plasmapheresis with physiologic saline and albumin as replacement fluid after priming with 1000 IU of heparin and adding another 1000 IU as a bolus. However, a few minutes later, the filter (Plasmaflo OP-08W [Asahi Kasei Kuraray Medical]) clogged, and we had to stop plasmapheresis. We reattempted plasmapheresis using 2000 IU of heparin to prime the filter, with another heparin bolus of 2000 IU, but the filter clogged again. We then withdrew 1 L of whole blood and replaced it with 2 units of red cell concentrates and 3 units of fresh frozen plasma. Repeated laboratory testing showed decreased levels of triglycerides (107.96 mmol/L [9554 mg/dL]) and cholesterol (27.48 mmol/L [1061 mg/dL]). We withdrew another liter of whole blood and replaced it with physiologic saline. Repeated studies showed that the patient's triglyceride level decreased to 80.67 mmol/L (7139 mg/dL) and his cholesterol level to 22.2 mmol/L (858 mg/dL). With continued heparin and insulin therapy, his triglyceride level dropped to 60.38 mmol/L (5343 mg/dL). On the second day, we started omega-3 fatty acids and fenofibrate via nasogastric tube. In addition, our third attempt at plasmapheresisusing a heparin bolus of 2000 IU and a centrifugal device (Spectra Optia [Terumo BCT])was successful, lowering the patient's triglyceride level to 10.36 mmol/L (917 mg/dL) and his cholesterol level to 17.4 mmol/L (672 mg/dL). We extubated the patient on day 5, and he was free of residual neurologic symptoms. Additional studies on day 10 revealed that our patient had normal values for glucagon (104 ng/L (normal, <209 ng/L) and C-peptide (0.63 nmol/L [1.9 g/L]) and no antibodies that indicated autoimmune diabetes in adults. Outpatient genetic testing with screening for familial hypertriglyceridemia found only normal variants of APOA5, APOC2, GPIHBP1, and LMF1. However, the evaluation found a rare variant of unknown significance in exon 26 of APOB and a functional polymorphism in exon 2 of LPL that is present in 3% of Europeans (1). Discussion: Clinicians should keep in mind that prompt initiation of insulin therapy combined with fibrate and omega-3 fatty acids is first-line therapy for hypertriglyceridemia in patients with diabetic ketoacidosis. In severe cases of hypertriglyceridemia, plasmapheresis also may lower triglyceride levels and thus prevent pancreatitis (2). If plasmapheresis cannot be done due to extreme hyperviscosity, our experience demonstrates that conventional bloodletting with replacement may be an effective alternative. To our knowledge, this is the first report to describe this procedure. We hypothesize that our patient's extreme hypertriglyceridemia with hyperviscosity syndrome was caused by a combination of insulin resistance, obesity, inappropriate diet, and insufficiently treated diabetes mellitus. This cascade of events may have started with ketoacidosis, possibly triggered by the patient's dapagliflozin therapy (3,4). Our patient's illness also may have been affected by his functional LPL polymorphism, which has been associated with low high-density lipoprotein cholesterol and high serum triglyceride levels, or by his APOB variant producing altered apolipoprotein B.