Role of therapeutic plasma exchange in the treatment of severe hypertriglyceridemia: an experience

Abstract

Hypertriglyceridemia of obesity, the metabolic syndrome, and type II diabetes mellitus are highly prevalent in Saudi Arabia. Severe hypertriglyceridemia is a rare but well known cause of acute pancreatitis. In treatment pancreatic rest, lifestyle changes, and lipid-lowering medications are essential, but the response is slow. Recently the role of therapeutic plasma exchange (TPE) has been stressed for fast and effective management in addition to insulin and heparin infusion. TPE for hypertriglyceridemic pancreatitis resulted in drastic improvements in clinical and laboratory findings and patient outcomes as suggested in our cases. However, this procedure is limited due to its high cost and availability only in specialized hospitals.

Introduction

Severe hypertriglyceridemia (SHTG) is known to cause acute pancreatitis accounting for up to 10% of all pancreatitis episodes. ¹ It is generally believed that SHTG and serum triglyceride (TG) levels higher than 11.3 mmol/L, trigger acute pancreatitis and its serious complications. Such high levels of serum TG have been accounted as the third most common cause of acute pancreatitis after ethanol use and gallstones. This threshold, however, is arbitrary and the level above which acute pancreatitis might occur is actually unknown. Such patients need a fast and effective treatment to reduce TG levels in order to minimize the chance of acute pancreatitis and prevent other cardiovascular complications. Current data suggest that the use of therapeutic plasma exchange (TPE) (plasmapheresis) is a more effective option to lower TG levels rapidly over short period of time other than infusions of insulin and heparin.^2,3 Usually, one to three sessions are effective in lowering TG levels along with a reduction in the severity of signs and symptoms of pancreatitis. It should be performed as early as possible, at 24–48 h intervals, until TG levels have been lowered to 5.65 mmol/L. ⁴ We also found a significant rapid reduction in TG levels and improvement in organ failure using TPE as a therapeutic tool in patients with type II diabetes mellitus who presented with abdominal pain and SHTG. TPE was carried out using the femoral line dialysis catheter, MCS (Heamonetics, Braintree, MA, USA) 1:1 plasma exchange using 5% albumin. We also explored the utility of TPE in primary prophylaxis. Thus we report two cases in order to better understand the role of TPE in such populations.

Case 1

A 47-year-old, Sudanese obese man with a known case of type II diabetes mellitus presented to emergency room with severe epigastric pain (pain scale score of 7), nausea, vomiting for 1 day, and who was afebrile. He had a history of recurrent attacks of pancreatitis. On general examination the patient was alert, conscious, well-oriented with a Glasgow Coma Scale (GCS) score of 15. At the time of admission the patient’s blood pressure was 138/89 mmHg, pulse 84 bpm, respiratory rate 20/min, and body mass index (BMI) 33 kg/m². The abdominal examination revealed epigastric tenderness and guarding. There was no past history of smoking or alcohol use. Relevant past drug history included sitagliptin/metformin, omega-3 fatty acids, and olmesartan. Abdomenal ultrasound revealed an enlarged fatty liver and bulky hypoechoic pancreas suggestive of acute pancreatitis. Further biochemical investigation strongly indicated acute pancreatitis induced by SHTG (Table 1).

Table 1.

Case 1, Laboratory investigation before and after therapeutic plasma exchange.

Test	Initial result	First session therapeutic plasma exchange	Discharge day	Reference range
HBA1c	9.9%	–	–	< 6.0%
Cholesterol	2.8	3.2	4.3	< 5.17 mmol/L
Triglycerides *	42.95	4.96	4.12	< 1.69 mmol/L
Low-density lipoprotein $	TI	0.92	2.44	< 2.58 mmol/L
High-density lipoprotein	1.05	0.26	0.34	> 1.03 mmol/L
Amylase	148	117	44	20–100 U/L
Lipase	415	245	99	< 60 U/L
Creatinine	53	47	51	55–110 µmol/L
Sodium	135	139	141	135–147 mmol/L
Potassium	4.2	3.8	4.0	3.5–5.0 mmol/L
Calcium	2.11	1.92	2.21	2.10–2.55 mmol/L
Hemoglobin	14.5	14.5	12.3	132–172 g/L
White blood cell count	14.2	14.1	7.3	4–11 × 10^9/l

*

The measuring range for assayed serum triglyceride is 10 mmol/L. Further dilution (1:5) was made in instrument automatically by default.

$

Interference due to high triglycerides level above 22.6 mmol/L.

Due to clinical condition and a very high TG level (42.95 mmol/L) on admission, the patient underwent TPE along with stat gemfibrozil and omega-3 fatty acids. The total plasma volume exchanged at the TPE session was 2517 ml. TG levels dropped by 88.5% to 4.96 mmol/L after the TPE session. The patient’s condition improved gradually, the abdominal pain subsided, and he started feeding orally, which was well tolerated. The patient was started on insulin glargine injection (Lantus ®) 10 units at bed time and insulin glulisine (Apidra®) 4 units three times a day. The patient was discharged on the third day without any complications. The treatment was continued and TG levels decreased to 4.12 mmol/L. No follow up was made by the patient.

Case 2

A 37-year-old Lebanese obese man with a significant past history of hypertriglyceridemia during the last 10 years came to hospital for elective TPE to prevent acute pancreatitis due to high TG levels. He was being treated on gemfibrozil tablets. The last episode of acute pancreatitis had been treated conservatively 3 weeks before with fenofibrate due to the nonavailability of TPE in the primary care setup. He also had type II diabetes mellitus and hypertension. There was a family history of hypertriglyceridemia and diabetes mellitus.

On general examination the patient was alert, conscious, with a well-oriented GCS scale of 15. At the time of admission the patient’s blood pressure was 130/70 mmHg, pulse 77 bpm, respiratory rate 18/min, and BMI 35 kg/m². The abdominal examination was unremarkable. The patient is a heavy smoker (20 cigarettes or more per day), although no past history of alcohol use was revealed. Relevant past drug history included metformin, omega-3 fatty acids, fenofibrate, and ramipril. No radiological investigation was carried out. Laboratory investigation strongly indicated SHTG, which is an indication of the need for TPE to prevent recurrent acute pancreatitis (Table 2).

Table 2.

Case 2, Laboratory investigation before and after therapeutic plasma exchange.

Test	Initial result	First session therapeutic plasma exchange	Second session therapeutic plasma exchange	Follow-up day 15	Reference range
HBA1c	7.2%	–	–		< 6.0%
Cholesterol	5.40	2.80	2.33	3.80	< 5.17 mmol/L
Triglycerides *	19.83	6.68	7.14	3.85	< 1.69 mmol/L
Low-density lipoprotein $	0.91	0.74	0.45	2.27	< 2.58 mmol/L
High-density lipoprotein	0.30	0.17	0.62	0.36	> 1.03 mmol/L
Amylase	39	–	–	–	20–100 U/L
Lipase	28	–	–	–	0–60 U/L
Creatinine	86	63	82	79	55–110 µmol/L
Sodium	136	138	140	138	135–147 mmol/L
Potassium	4.1	3.8	4.0	3.9	3.5–5.0 mmol/L
Calcium	2.39	2.34	2.34	2.13	2.10–2.55 mmol/L
Hemoglobin	16.9	15.7	16.7	14.8	132–172 g/L
White blood cell count	10.6	10.4	12.3	9.8	4–11 × 10^9/l

*

The measuring range for assayed serum triglyceride is 10 mmol/L. Further dilution (1:5) was made in instrument automatically by default.

$

Interference due to high triglycerides level above 22.6 mmol/L.

TPE was carried out to achieve the target of TG levels lower than 5.65 mmol/L. After one session, the TG level dropped by 66.3% from 19.83 mmol/L to 6.68 mmol/L. Therefore the second session of TPE was performed after an interval of 24 h. After the second session no significant change in TG levels was noted, 7.14 mmol/L. The total plasma volume exchanged at the first session was 2409 ml and 1946 ml at the second session. No complications were noted during or after the procedure. The patient was discharged and continued on oral medication for lipid management using gemfibrozil 600 mg tablets twice daily and omega-3 fatty acids 1 g capsule once a day. The patient was followed up on day 15 and had a serum TG level further reduced by 46% to 3.85 mmol/L.

Discussion

Causes of hypertriglyceridemia-induced pancreatitis (HTIP) can be familial or due to secondary factors such as untreated/poorly controlled diabetes mellitus, obesity, alcohol abuse, pregnancy, or medications. Both of our cases had exacerbated SHTG (serum TG concentrations above 11.3 mmol/L) due to uncontrolled diabetes mellitus (HBA1c 9.9% and 7.2%. in case 1 and case 2, respectively). In uncontrolled diabetes mellitus, insulin deficiency leads to lipolysis and inhibition of lipoprotein lipase in peripheral tissues that leads to elevated TG levels.

In addition to conservative management, such as decreased oral intake, intravenous hydration, and pain management, infusions of insulin and heparin have been used to lower TG levels in HTIP. ⁵ All such treatment modalities are insufficient to obtain a rapid response. TPE provides faster reduction of serum TG levels to prevent disease complications. Recent systematic review of the use of apheresis showed a significant average reduction of serum TG levels by 85.4%. ² According to the American Society of Apheresis and the American Medical Association Council on Scientific Affairs, hypertriglyceridemia is a class III indication for TPE. ³ Treatment is based on removing 2–3 L of plasma via filtration and replacing the volume with 5% human albumin with or without fresh frozen plasma. A single treatment often takes about 2 h. Such a rapid reduction in serum TG was seen in our cases; in case 1, a reduction of serum TG by 88.5% from 42.95 mmol/L to 4.96 mmol/L and in case 2, reduction of serum TG by 46% from 19.83 mmol/L to 3.85 mmol/L. The reduction of serum TG is comparable to results achieved by Gavva and colleagues and Seda and colleagues, 84% and 77%, respectively.^6,7 Recently Joglekar and colleagues reported a mean reduction of TG levels to 70% with a mean length of hospital stay of 7.3 days. ⁴ We found the average hospital stay was 3 days in our cases with the mean reduction in TG levels up to 67%. This length of hospital stay might increase for patients with complications, such as sepsis at the time of admission as presented in case 2 by Joglekar and colleagues. The patient presented to us had no such complication.

The idea of using as TPE as primary prophylaxis in our case 2 was also found to be successful as a marked reduction in serum TG and serum total cholesterol levels was observed after TPE sessions and on follow-up day 15 (Table 2). We intend to demonstrate the applicability of this technique, similar to Francisco and colleagues, as primary prophylaxis in the presence of extremely high serum TG levels. ⁸ Although TPE is limited due to its high cost and requirement for a specialized center, it is still advisable as prophylaxis for SHTG. This is due to the advantage of preventing serious complications associated with SHTG and safety experience claimed and published by different authors.^4,6–8 Further, the use of TPE as prophylaxis is beneficial as the time of intervention using TPE might be at critical point. Better results in terms of mortality and morbidity have been achieved in patients as soon as they receive TPE.^9,10 Patients undergoing repetitive TPE to prevent recurring pancreatitis have a lower risk of pancreatitis, resulting in fewer hospitalizations and reduced health costs.^8,11 Therefore, it is necessary to maintain regular, long-term TPE sessions (e.g. one session every 4 weeks). We were able to follow up patients at day 15 and found TG levels lower than 5.65 mmol/L.

In both cases we found TPE to be a successful and safe alternative for the treatment of severe hypertriglyceridemia. No complications were noted. The most common complications of TPE previously reported were urticaria, paresthesias, rigors, headaches, hypotension, muscle cramps, and catheter-related problems. ¹² Such complications can easily be avoided by sterile technique, continuous observation, and proper monitoring of patients provided by highly trained medical personnel.