Therapeutic apheresis--state of the art in the year 2005

Therapeutic apheresis is an extracorporeal blood purification method for the treatment of diseases in which pathological proteins or cells have to be eliminated. Selective plasma processing is more efficient in pathogen removal than unselective plasma exchange and does not require a substitution fluid like albumin. This overview presents the various selective devices for the treatment of plasma (plasmapheresis) and blood cells (leukocyte apheresis). Prospective randomized trials were performed for the treatment of age-related macular degeneration (Rheopheresis), sudden hearing loss (heparin-induced lipoprotein precipitation [HELP]), rheumatoid arthritis (Prosorba), dilative cardiomyopathy (Ig-Therasorb, Immunosorba), acute-on-chronic liver failure (molecular adsorbent recirculating system [MARS]), and ulcerative colitis (Cellsorba). Prospective non-randomized controlled trials were carried out treating hypercholesterolemia (Liposorber) and crossmatch-positive recipients before kidney transplantation (Immunosorba). Uncontrolled studies were done for ABO-incompatibility in living donor kidney transplantation (KT) (Glycosorb), acute humoral rejection after KT (Immunosorba) and acute liver failure (Prometheus). According to the 2002 International Apheresis Registry covering 11428 sessions in 811 patients, 79% of the patients showed an improvement of their condition by apheresis and only a few sessions were fraught with adverse effects (AE). The major AE were blood access difficulties (3.1%) and hypotension (1.6%). In summary, therapeutic apheresis is a safe and effective procedure for the treatment of diseases refractory to drug therapy.     

RheoNet Registry Analysis of Rheopheresis for Microcirculatory Disorders With a Focus on Age-Related Macular Degeneration

The purpose of establishing the RheoNet registry was to evaluate the safety and efficacy of rheopheresis, a specific method of therapeutic apheresis used to treat microcirculatory disorders. Apheresis centers providing rheopheresis therapy and physicians caring for the underlying disease were asked to participate in the registry, and the registry data were analyzed for safety and tolerability. Age-related macular degeneration (AMD) was selected as a model disease to evaluate efficacy. The RheoNet registry was successfully established recording 7722 rheopheresis treatments of 1110 patients, including 833 AMD patients. The mean age of patients was 72 years. Adverse events (AE) were reported in 5.67% of treatments, but termination of the treatment session was only required in 0.48%. Transient hypotension was the most frequently reported AE. No age-related increase in AE was observed. Ophthalmological data of 428 eyes (of 279 treated patients) with dry AMD could be analyzed; 85 eyes of 55 untreated AMD patients served as the control. At 6.75 ± 5.25 months post-baseline, 42% of the treated eyes had improved visual acuity. The proportion of eyes with a decline in visual acuity was 17%, compared to 40% in the untreated controls (P < 0.01). The RheoNet registry has been successfully established and data analysis revealed that rheopheresis is a safe outpatient treatment for microcirculatory disorders. Moreover, RheoNet currently provides the largest evaluation of the efficacy of rheopheresis for dry AMD. Registry analysis contributes to a safe and appropriate use of rheopheresis in clinical practice.     

Hybrid Procedures: Adverse Events and Procedural Characteristics—Results of a Multi-institutional Registry

Introduction. Procedural cooperation between cardiac surgeon and interventional cardiologist to facilitate interventions such as device delivery or angioplasty (hybrid procedure) has become increasingly common in the management of patients with congenital heart disease. Design. Data were prospectively collected using a multicenter registry (C3PO). Between February 2007 and December 2008, seven institutions submitted data regarding 7019 cardiac catheterization procedures. Procedural data and adverse events (AEs) of 128 hybrid procedures were evaluated. Results. There was significant variability in the number of hybrid procedures per center, ranging from one to 89 with a median of eight. A total of 60% of interventional (vs. strictly diagnostic) hybrid procedures were performed by one center. The median weight was 3.7 kg (0.7–86 kg). Single-ventricle circulation was present in 60% of the procedures. Hybrid procedures included: patent ductus arteriosus (PDA) stent placement (n = 55), vascular rehabilitation (n = 25), ventricular septal defect (VSD) device closure (n = 7), valvotomy (n = 3), and diagnostic hybrid procedures (n = 38). Sixteen AEs occurred in 15/128 (12%) procedures. These included minor or trivial AEs (n = 9), moderate AEs (n = 5), major AEs (n = 1), and catastrophic AEs (n = 1). The type of AE documented included arrhythmias (n = 6), hypoxia or hypotension (n = 3), vessel or cardiac trauma (n = 2), and other events (n = 5). Of documented AEs, 9/16 (56%) were classified as not preventable, 6/16 (38%) as possibly preventable, and 1/16 (6%) as preventable. The incidence of AE related to PDA stent placement with surgical exposure (5/50, 10%) was significantly lower when compared with PDA stent placement performed percutaneously (4/5, 80%, P= .002). Conclusion. Hybrid procedures appear to have a low incidence of associated major AEs. PDA stent placement performed as a palliation of hypoplastic left heart syndrome (HLHS) or complex single/two ventricle patients may have a lower incidence of AEs if performed using a direct approach with surgical exposure rather than a percutaneous approach. Accurate definitions of these innovative procedures are required to facilitate prospective data collection.     

Efficacy of Different Low‐Density Lipoprotein Apheresis Methods

Abstract: Low‐density lipoprotein (LDL) apheresis is a treatment option in patients with coronary heart disease and drug resistant hypercholesterolemia. Various apheresis systems based on different elimination concepts are currently in use. We compared the efficacy of 4 different apheresis systems concerning the elimination of lipoproteins. The study included 7 patients treated by heparin extracorporeal LDL precipitation (HELP), 10 patients treated by immunoadsorption, 8 patients treated by dextran‐sulfate adsorption, and 4 patients treated by cascade filtration. Ten subsequent aphereses were evaluated in patients undergoing regular apheresis for more than 6 months. Total cholesterol decreased by approximately 50% with all 4 systems. LDL cholesterol (LDL‐C) (64–67%) and lipoprotein a [Lp(a)] (61–64%) were decreased more effectively by HELP, immunoadsorption, and dextran‐sulfate apheresis than by the less specific cascade filtration system [LDL‐C reduction 56%, Lp(a) reduction 53%]. Triglyceride concentrations were reduced by 40% (dextran‐sulfate) to 49% (cascade filtration) and high‐density lipoproteins (HDL) by 9% (dextran‐sulfate) to 25% (cascade filtration). On the basis of plasma volume treated, HELP was the most efficient system (LDL‐C reduction 25.0%/L plasma), followed by dextran‐sulfate (21.0%/L plasma), cascade (19.4%/L plasma), and immunoadsorption (17.0%/L plasma). However, a maximal amount of 3 L plasma can be processed with HELP due to concomitant fibrinogen reduction while there is no such limitation with immunoadsorption. Therefore, the decision of which system should be used in a given patient must be individualized taking the pre‐apheresis LDL concentration, concomitant pharmacotherapy, and fibrinogen concentration into account.     

Low-Density Lipoprotein Apheresis for Prevention and Regression of Atherosclerosis: Clinical Results

Abstract: Hypercholesterolemia can be adequately controlled by appropriate diet and maximum lipid lowering drug therapy in most patients. Nevertheless, there exists a group of patients, including those with familial hypercholesterolemia (FH), who remain at high risk for the development or progression of premature coronary heart disease (CHD). For these patients additional measures such as surgery and low-density lipoprotein (LDL) apheresis have to be considered. The objective of this multicenter trial, which included 30 clinical centers (28 in Germany and one each in Scotland and Luxembourg), was to determine if repeated LDL apheresis using the Liposorber LAIS system (Kaneka Corporation, Osaka, Japan) could lead to an additional acute and time averaged lowering of total cholesterol (TC) and LDL-cholesterol (LDL-C) in severely hypercholesterolemic patients whose cholesterol levels could not be controlled by appropriate diet and maximum drug therapy. A total of 6,798 treatments were performed on 120 patients, including 8 with homozygous FH, 75 with heterozygous FH, and 37 with unclassified FH or other hyperlipidemias from 1988 through 1994. The mean TC and mean LDL-C levels at baseline were 410.0 mg/dl and 333.9 mg/dl, respectively. LDL apheresis was performed once a week or at least once every 2 weeks in all patients. During treatment with the Liposorber system the mean acute percentage reduction was 52.6% for TC and 63.1% for LDL-C. Very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) were also substantially reduced to 60.6% and 47.5%, respectively. Fibrinogen, a potential risk factor for CHD, was reduced by 26.2%. In contrast, the mean acute reduction of high density lipoprotein (HDL) was only 3.4%. During the course of the treatment, the time averaged levels of TC and LDL-C were reduced by approximately 39% and 50%, respectively, compared to baseline levels. The adverse events (AEs) were those generally associated with extra-corporeal treatments. The most common AE was hypotension, with 69 episodes corresponding to 1 % of all treatments reported in 44 of the 120 patients treated. All other kinds of AEs occurred in less than 0.2% of the treatments. The treatment with the Liposorber LA-15 system was overall well tolerated. It should be noted, however, that a more severe type of hypotensive reaction associated with flush, bradycardia, and dyspnea was reported in patients taking concomitant angiotensin converting enzyme (ACE) inhibitor medication. Except for such anaphylactoid-like reactions associated with the intake of ACE inhibitors, the Liposorber LA-15 system represents a safe and effective therapeutic option for patients suffering from severe hypercholesterolemia that could not be adequately controlled by diet and maximum drug therapy.     

Effects of losartan on blood pressure and humoral factors in a patient who suffered from anaphylactoid reactions when treated with ACE inhibitors during LDL apheresis.

In a patient who was taking an angiotensin-converting-enzyme inhibitor, low-density lipoprotein (LDL) apheresis with dextran-sulfate cellulose provoked hypotension accompanied by lacrimation and blurred vision. Hypotension was eliminated by changing the anticoagulant from heparin to a protease inhibitor, nafamostat mesilate. A study was undertaken to clarify whether an antagonist of angiotensin type 1-receptor, losartan, could be safely used in the same patient during LDL apheresis treatment. Blood pressure and humoral factors were compared between the apheresis sessions with losartan and those without. Although angiotensin II and bradykinin plasma levels during LDL apheresis were significantly greater with losartan than without, blood pressure reduction by losartan was mild and unpleasant symptoms were not induced. Losartan was thus safely used for this patient during treatment by LDL apheresis. The greater rise in bradykinin levels during apheresis with losartan might be ascribable to angiotensin type 2-receptor stimulation.     

Association between oral antidiabetic use, adverse events and outcomes in patients with type 2 diabetes

Objective:  To quantify adverse events (AEs) associated with the use of metformin (MET), sulphonylureas (SUs) and thiazolidinediones (TZDs) in a usual care setting, and to assess the relationship of AEs to treatment patterns and glycaemic response in patients with type 2 diabetes.
Research design and methods:  An electronic medical record database was used to identify patients with type 2 diabetes age ≥18 years from 1996 to 2005. Patients naïve to oral antidiabetic therapy were followed for 395 days postinitiation of MET, SU or TZD treatment. AEs related to study drugs were evaluated during the follow-up period. Baseline and follow-up A1C levels were compared by drug regimen. Associations between the change in A1C, drug regimen changes and AEs were evaluated.
Results:  A total of 14 512 patients (mean age 60.8 years, 52.9% female) were identified. During the follow-up period, 12.7% of patients experienced an AE (8.6% MET, 15.9% SU and 19.8% TZD patients). SU and TZD patients were more likely to experience an AE than MET (p < 0.001) patients. AEs did not significantly influence A1C outcomes, although MET and SU patients experiencing an AE were more likely to add-on therapy (odds ratio (OR) = 1.34 and OR = 1.37, respectively; p < 0.05) than those without an AE. MET patients with AEs were more likely to switch therapy (OR = 1.91; p < 0.05) than those without an AE.
Conclusions:  The occurrence of AEs did not significantly impact glycaemic response to therapy. However, AEs may lead to greater treatment switches for patients receiving MET and add-on therapy for MET-treated and SU-treated patients.     

Patient Selection for Intensive Blood Pressure Management Based on Benefit and Adverse Events

BackgroundIntensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients.ObjectivesThe aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment.MethodsThis was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment.ResultsAmong 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = ?0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality.ConclusionsSPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062)     

Storage of platelets in additive solutions: effects of phosphate

BACKGROUND AND OBJECTIVES: In a previous study, low adenine nucleotide levels and a reduced rate of glycolysis were found in platelet concentrates (PCs) prepared by apheresis and stored in a platelet additive solution (PAS). Our objective was to investigate whether the use of PAS with or without phosphate can influence platelet metabolism in a similar way. MATERIALS AND METHODS: The in vitro effects of storage in either plasma or a PAS (T-Sol or PAS-III, both containing citrate, acetate and sodium chloride, PAS-III containing also phosphate) of buffy-coat-derived pooled platelet concentrates (BC-PCs) and apheresis platelets were investigated. The use of PAS implies inclusion of some plasma (20 or 35%). Paired studies over 7 days included investigation of cell counts, pH, PO2, PCO2, bicarbonate, glucose, lactate, adenine nucleotides, and extracellular adenylate kinase activity as a marker for disintegration of platelets. The expected concentration of phosphate in T-Sol is 0.6-1.8 mmol/l (with CPD plasma) and 0.2-0.6 mmol/l (with ACD plasma), and in PAS-III, 15-25 mmol/l (calculated values). RESULTS: BC-PCs were compared during storage in 35% CPD plasma and 65% PAS (T-Sol or PAS-III) (experiment 1), or alternatively 20% CPD plasma and 80% PAS (T-Sol or PAS-III) (experiment 3). In both studies, PAS-III shows similar and significantly higher rates of glycolysis in terms of consumption of glucose (0.06 vs. 0.04 mmol/day/10(11) platelets) and production of lactate (0.11 vs. 0.07 mmol/day/10(11) platelets) compared with T-Sol. Levels of pH and adenine nucleotides were similar when 35% plasma was used. With only 20% plasma, significantly higher levels of adenine nucleotides were found with PAS-III compared to T-Sol. The storage of apheresis platelets in 35% ACD plasma and 65% PAS (either T-Sol or PAS-III) (experiment 5) gave significantly higher values for PAS-III compared to T-Sol with regard to consumption of glucose (0.08 vs. 0.06 mmol/day/10(11) platelets), production of lactate (0.14 vs. 0.11 mmol/day/10(11) platelets) and adenine nucleotide levels. CONCLUSION: With respect to apheresis PCs stored in media containing ACD plasma, our results suggest that the differences found are related to the concentration of phosphate. The results for BC-PCs stored in media containing CPD plasma suggest that PAS-III is preferable to T-Sol as the PAS at plasma concentrations below 35%. The mechanism behind the phenomena observed with BC-PCs is not known.     

Changes in Plasma Levels of Cyclic Nucleotides During Low-Density Lipoprotein Apheresis

Abstract: The negative charges of dextran sulfate (DS) used for low-density lipoprotein (LDL) apheresis activate the intrinsic coagulation pathway, accompanied by the production of bradykinin. This study was undertaken to see whether cyclic nucleotide plasma levels are affected by DS LDL apheresis. Previously, we showed the rise in plasma levels of prostaglandins and nitric oxide derivatives accompanied by the rise in bradykinin levels. The physiologic effects of prostaglandins and nitric oxide become manifest through the intracellular signal of cyclic nucleotides. The plasma levels of the cyclic nucleotides (cyclic adenosine monophosphate [cAMP] and cyclic guanosine monophosphate fcGMP]) were examined when either of 2 anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. The plasma levels of cAMP during LDL apheresis using heparin were 9.2 ± 0.3 (mean ± SE) 12.4 ± 0.6, 12.0 ± 0.5, and 12.1 ± 0.3 pmol/ml, respectively, at the 0,1,000,2,000, and 3,000 ml stages. The rise in cAMP levels was suppressed during apheresis using NM. There were no significant increases in cGMP during apheresis with heparin or with NM. There were significant negative correlations between changes in cAMP and those in the blood pressure. These findings suggest that bradykinin generated during apheresis exerts some physiologic effects via activation of the adenylate cyclase dependent pathway.     

Treatment of hyperlipidemia with a modified low density lipoprotein apheresis system with dextran sulfate

Many low density lipoprotein (LDL) apheresis systems have been applied to patients with hyperlipidemia, but these systems usually work on the basis of complicated equipment and the cost of treatment is expensive. In order to achieve effective treatment of hyperlipidemia at a lower cost, we developed a new LDL apheresis system with dextran sulfate (LAS-DS). In this study, 50 patients with hyperlipidemia were treated 120 times with the new LAS-DS. In each treatment, 600 +/- 100 mL of plasma (equal to approximately 25% of the total plasma of patients) was collected by apheresis, and DS solution and calcium chloride solution were added into the collected plasma as LDL absorber and catalyzer, respectively. DS selectively binds LDL cholesterol (LDL-C) under the catalysis of calcium ion and the LDL-C-DS complex is removed by centrifugation. The treated plasma was transfused back into the patients and the excessive calcium in the plasma was removed by the cation exchange column integrated in the transfusion set. After treatment with our new system, the acute mean LDL-C reduction was 97% in the apheresis plasma of hyperlipidemia patients. The corresponding reduction was 55.2% and 69.4% for total cholesterol and total triglyceride. There were insignificant reductions of high density lipoprotein cholesterol (HDL-C) and albumin. The new LDL apheresis system with DS that we developed is very simple to operate without relying on complicated equipment, and it can achieve significant clinical results at a much lower cost compared with existing systems. Based on this study we think the new system can provide a safe, effective and much cheaper means for the treatment of hyperlipidemia patients.     

Changes In Plasma Levels of Nitric Oxide Derivative During Low-Density Lipoprotein Apheresis

Abstract: The negative charges of dextran-sulfate (DS) used for low-density lipoprotein (LDL) apheresis activates the intrinsic coagulation pathway, in which plasma kallikrein acts on high-molecular-weight kininogen (HMWK) to produce large amounts of bradykinin. This study was undertaken to see whether bradykinin generated during DS LDL apheresis has some physiologic effects in vivo. The plasma levels of bradykinin and nitric oxide derivatives (NOx) were examined when either of 2 anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. Although anticoagulative action by NM depends on the inhibition of thrombin activity, this substance also inhibits the activity of plasma kallikrein. During apheresis using heparin, the marked increase in bradykinin levels (before apheresis, 18 ± 3 (mean ± SE, n = 5) pg/ml; after apheresis 470 ± 140, p < 0.01) was associated with the increase in NOx (before apheresis 50 ± 11 pg/ml; after apheresis 66 ± 15). Interestingly, these changes in bradykinin and NOx levels were suppressed during apheresis using NM. The changes in plasma NOx levels were negatively correlated with those in blood pressures. These findings suggest that bradykinin generated during apheresis exerts some physiologic effects by means of activation of endothelium-derived relaxant factor (EDRF). Our results support the view that bradykinin produced during DS LDL apheresis has physiologic significance.—     

Recognition of intercenter differences may help develop best practice

The Swedish Apheresis Registry is a National Quality Registry and performing intercenter comparisons can be done as one task. The purpose of this study was to evaluate differences in adverse effects (AE) associated with plasma exchange (PE) for the development of best practice. Six hundred and twenty reports of AE related to a total of 12,461 apheresis procedures performed during 1996-2002 were analyzed, and eight Swedish university hospital centers that reported AE every year were compared. About 70% of all PE in Sweden were performed in centers that also reported AE. During this period, there was no change in the proportion of PE procedures with AE, but there was a decrease in the frequency of prematurely interrupted procedures (2.1% to 1.3%, P = 0.003). The mean frequency of moderate and severe AE was 5%. Adverse effects were more common when PE was performed in patients with Guillain-Barré syndrome (GBS; 10%) or thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS; 8%) than in patients with macroglobulinemia/hyperviscosity syndromes (2%). In the eight centers, there was a four-fold difference in AE between the centers with the highest and the lowest frequency. The frequency of AE in GBS, TTP-HUS and macroglobulinemia/hyperviscosity syndromes differed four-fold, while the frequency of specified symptoms differed more than four-fold. The indications and the choice of substitution fluids could explain some of these differences. The results of the study have initiated changes in practice. The identification of significant intercenter differences in the frequency and symptoms of AE has started improvement in current PE practices.     

Influence of Single Low‐Density Lipoprotein Apheresis on the Adhesion Molecules Soluble Vascular Cellular Adhesion Molecule‐1, Soluble Intercellular Adhesion Molecule‐1, and P‐Selectin

Abstract: The aim of our study was to investigate the influence of single low‐density lipoprotein apheresis (heparin extracorporeal low‐density lipoprotein precipitation [HELP]procedure) on plasma concentrations of soluble adhesion molecules (sAMs) such as soluble vascular cellular adhesion molecule‐1 (sVCAM‐1), soluble intercellular adhesion molecule‐1 (sICAM‐1), and P‐selectin in patients with familial heterozygous hypercholesterolemia and documented coronary artery disease enrolled in a chronic weekly HELP apheresis. Before HELP apheresis, the mean plasma concentration of sVCAM‐1 was 515 ± 119 ng/ml, 204 ± 58 ng/ml for sICAM‐1, and 112 ± 45 ng/ml for P‐selectin. After single HELP apheresis, plasma concentrations of sAM declined significantly by 32 ± 7%, 18 ± 15%, and 33 ± 25% for sVCAM‐ 1,sICAM‐1 and P‐selectin, respectively. After a 1 week interval, sAM concentrations rose to approximately the initial values. The concentrations of all sAMs studied were significantly lower in the plasma leaving than entering the filter. Due to filtration, the decline in plasma level of sVCAM‐1, sICAM‐1, and P‐selectin was 62 ± 19%, 51 ± 39%, and 67 ± 22%, respectively. In addition to lipid reduction, single HELP apheresis significantly lowers plasma concentrations of sVCAM‐1, sICAM‐1, and P‐selectin.     

Comparison of Different Low Density Lipoprotein Apheresis Machines on Brain Natriuretic Peptide Levels in Patients With Familial Hypercholesterolemia

B-type natriuretic peptide (BNP) is a hormone released from cardiac ventricles during episodes of hemodynamic overload. Low density lipoprotein (LDL) apheresis, a procedure for patients with familial hypercholesterolemia (FH) and coronary artery disease (CAD), lowers plasma cholesterol and immediately reduces blood viscosity and coronary vascular resistance while improving myocardial blood flow and microvascular perfusion. Previous studies have demonstrated the ability of LDL apheresis to reduce BNP chronically. We undertook this study to evaluate the difference in reduction of BNP levels following a single treatment with two dissimilar LDL apheresis devices. We conducted a prospective trial involving 27 patients (19 F; age = 59 ± 9 years) with FH who received at least 6 months of bi-weekly LDL apheresis therapy with either the Secura heparin extracorporeal LDL precipitation (HELP) system (N = 17 patients, B. Braun, Inc., Melsungen, Germany) or the Liposorber LA-15 dextran sulfate absorber (DSA) system (N = 10 patients, Kaneka, Inc., Osaka, Japan). We measured BNP levels immediately before and after one treatment of LDL apheresis. Following LDL apheresis, BNP levels were reduced by an average of 40 ± 17% (P < 0.001). Despite treating equal amounts of plasma, the HELP system reduced BNP (45 ± 18%) significantly more than the DSA system (31 ± 11%, P = 0.031). In conclusion, LDL apheresis therapy, possibly through its immediate improvement of vascular flow and/or removal of the peptide from plasma, results in a significant reduction of BNP levels. The increased reduction of BNP by HELP may result from its superior acute alterations of rheological markers.     

Using electronic medical record data to report laboratory adverse events

Despite the importance of adverse event (AE) reporting, AEs are under‐reported on clinical trials. We hypothesized that electronic medical record (EMR) data can ascertain laboratory‐based AEs more accurately than those ascertained manually. EMR data on 12 AEs for patients enrolled on two Children's Oncology Group (COG) trials at one institution were extracted, processed and graded. When compared to gold standard chart data, COG AE report sensitivity and positive predictive values (PPV) were 0–21·1% and 20–100%, respectively. EMR sensitivity and PPV were >98·2% for all AEs. These results demonstrate that EMR‐based AE ascertainment and grading substantially improves laboratory AE reporting accuracy.     

Prostacyclin versus citrate in continuous haemodiafiltration: an observational study in patients with high risk of bleeding

BACKGROUND: The efficacy and safety of prostacyclin (PGI2) and citrate (ACD) anticoagulation were observed and compared during continuous haemodiafiltration. METHODS: Mechanically ventilated patients received either the PGI2 analogue epoprostenol (group A, n = 17) in escalating doses of 4.5-10.0 ng.kg(-1).min(-1) in combination with heparin (6 IU.kg(-1).h(-1)) or 2.2% ACD (group B, n = 15). Blood flow was set to match the circuit-filling volume per unit time equal to the intravascular half-life of PGI2. RESULTS: Median filter lifetimes were 26 h (interquartile range 16-37) in group A (39 filters) and 36.5 h (interquartile range 23-50) in group B (56 filters; p < 0.01). In group A, 4 patients (23.5%, p < 0.05) had the dose reduced due to hypotension. The final mean dose of PGI2 was 8.7 +/- 2.4 ng.kg(-1).min(-1). Four patients in group A (23.5%, p < 0.05) were switched to ACD due to a decrease in platelet count. No bleeding episodes, decrease in platelet count or adverse haemodynamic effects were encountered in group B. The cost of epoprostenol plus low dose heparin (EUR 204.73 +/- 53.04) was significantly higher than the cost of ACD-based anticoagulation (EUR 93.92 +/- 45.2, p < 0.05). CONCLUSION: ACD offers longer filter survival, has no impact on platelet count and is less expensive. Increasing the dose of PGI2 up to the average of 8.7 ng.kg(-1).min(-1) did not increase the haemodynamic side effects.     

Left ventricular thrombosis and arterial embolism in acute anterior myocardial infarction

Abstract. To study left ventricular thrombus (LVT) formation and arterial embolism (AE), 106 consecutive patients with a first acute anterior myocardial infarction (AAMI) underwent two-dimensional echocardiography before discharge. Repeated assessments for detection of AE were performed. Patients were non-randomly allocated to either no heparin, low-dose heparin or high-dose heparin. LVT was found in 25 (26.9%) of 93 patients with technically satisfactory echocardiograms. Left ventricular (LV) wall motion impairment (P = 0.0017) and treatment with either heparin or low-dose heparin (P = 0.0019) were independent predictors of LVT formation. AE, all strokes, occurred in 10 patients (9.4%) and was strongly associated with high age (P = 0.0013). In conclusion. LVT and AE are frequent complications to AAMI. LV wall motion impairment predisposes for LVT and low-dose heparin seems not to prevent these complications.