Evaluation of the use of a heparin dose-response test in dogs to determine the optimal heparin dose during intravascular procedures and assessment of the in vitro heparin response in healthy dogs.

BACKGROUND: No guidelines for administering and monitoring anticoagulants intraprocedurally are currently available in dogs, despite the prevalence of procedures necessitating systemic anticoagulation with heparin. OBJECTIVES: To evaluate an activated clotting time (ACT)-based heparin dose-response (HDR) test to predict the individual required heparin dose in dogs during intravascular procedures, and to investigate both the in vitro heparin - ACT and in vitro heparin - factor anti-Xa activity (anti-Xa) relationships in dogs. METHODS: Blood was collected from eight healthy beagles undergoing a cardiac procedure and utilised to establish baseline ACT and for in vitro evaluation. Subsequently, 100 IU/kg heparin was administered intravenously (IV) and ACT was remeasured (HDR test). The required heparin dose for an ACT target response ≥300 s was calculated for each individual and ACT was remeasured after administration of this dose. For in vitro testing, a serial heparin blood dilution (0-0.5-1-2-4 international unit (IU)/mL) was prepared and ACT and anti-Xa were determined using whole blood and frozen plasma, respectively. RESULTS: The HDR test overestimated the required heparin dose in 3/7 dogs. In vitro, ACT and anti-Xa increased significantly with increasing blood heparin concentration. Heparin - ACT was nonlinear in 4/8 dogs at heparin concentrations >2 IU/mL, whereas heparin - anti-Xa remained linear throughout the tested range. CONCLUSIONS: The HDR test poorly estimated the required heparin dose in dogs. This is most likely attributed to a nonlinear heparin - ACT relationship, as observed in vitro. Anti-Xa is a promising alternative for ACT; however, unavailability as a point-of-care test and lack of in vivo target values restrict its current use.

Assessment of thrombin generation in horses using a calibrated automated thrombogram.

BACKGROUND: The amount of thrombin generated reflects the endogenous thrombin potential (ETP), which depends on the balance of pro- and anticoagulant factors. The calibrated automated thrombogram (CAT) allows for the direct measurement of thrombin generation during the clotting process. OBJECTIVES: (1) To describe the results of the CAT assay in horses, (2) to establish intra-assay and intra- and interindividual variation of thrombin generation in healthy horses, and (3) to compare in vitro low-molecular-weight heparin (LMWH) sensitivity between healthy and sick horses. The hypothesis for the last objective is that inhibition of thrombin generation in sick horses requires higher heparin concentrations. METHODS: The plasma of 10 healthy mixed breed horses was used for the determination of normal thrombin generation parameters (lag time, time to peak, peak thrombin concentration, and ETP). Five of the healthy horses were compared with five horses with systemic inflammatory response syndrome (SIRS). In vitro heparin sensitivity was determined using LMWH. RESULTS: The intra-assay variation was small (<5%) for all parameters. Relatively large intra- and interindividual variation were observed in healthy horses. Four of the five sick horses with SIRS had a thrombogram compatible with a hypercoagulable state. The in vitro heparin sensitivity test suggested decreased sensitivity to LMWH in hypercoagulable states. CONCLUSIONS: The CAT assay could detect coagulopathy in horses. In vivo experiments are needed to confirm that it can be used to monitor responses to LMWH therapy.

Assessment of the effect of pulsed electromagnetic field application on the healing of bone defects in rats with heparin-induced osteoporosis.

Osteoporosis is a systemic skeletal disease characterized by an increase in bone fragility and fracture risk due to low bone mass and deterioration of bone tissue. Application of pulsed electromagnetic fields (PEMF), a non-invasive method with a low complication risk, is known to stimulate bone formation. The present study examines the histomorphometric and biochemical effects of PEMF application on the healing of bone defects in rats with heparin-induced secondary osteoporosis. Briefly, 12-month-old male Sprague-Dawley rats were examined in a prospective, randomized, single-blind study. Osteoporosis was induced by administering a daily dose of 2 IU/g heparin for 33 days. Bone defects were created on the right femur on Day 35. PEMF of an average intensity of 0.8 ± 0.2 mT and a frequency of 7.3 Hz, was applied for 1 h/day, for 28 days following surgery. Bone healing was evaluated by histomorphometric and biochemical analyses. The heparin + PEMF group displayed the largest amount of new bone area (P = .002) and the lowest mean CTx on Day 63 (P = .05). This study demonstrates that heparin administration leads to bone loss and osteoporosis, whereas the application of PEMF decreases this effect.

Glycosaminoglycan / gold nanocluster hybrid nanoparticles as a new sensing platform: Metastatic potential assessment of cancer cells.

A novel fluorescent heparanase assay based on hybrid nano-assembly of gold nanocluster and glycosaminoglycan is developed. The nanoparticle probes are fabricated through the co-assembly of positively charged gold nanoclusters with negatively charged heparin molecules, which is accompanied by a dramatic size change and a 2.5-fold fluorescence enhancement. It is demonstrated that the fluorescence enhancement is due to denser aggregation of Au-thiolate complexes in the hybrid nanoparticle and the fluctuation of the fluorescence intensity is an indicator of the variation in assembly efficiency. Experiments in solution and in cell lysis media showed that the heparanase could turn-off the fluorescence with a high selectivity, which could be utilized for the assessment of heparanase activity and the metastatic potentials of different tumour cells. This assay technique is low cost, easy to prepare, and showing good performance. The co-assembly strategy has potential to be transferable to construct other functional nanomaterial.

Tissue plasminogen activator vs heparin for locking central venous catheters between apheresis procedures.

BACKGROUND: Central venous catheters (CVCs) for apheresis procedures require regular locking/flushes to maintain adequate flow rates. Literature comparing locking solutions for apheresis, where the time interval between procedures can be longer than for hemodialysis (many days to weeks), is lacking. In this study, catheter malfunction rates using recombinant tissue plasminogen activator (rt-PA) vs heparin for locking CVC between apheresis procedures were compared. STUDY DESIGN AND METHODS: A retrospective review of 93 extracorporeal photopheresis procedures in 10 patients was performed at our institution. About 1000 U/mL heparin or 2 mg rt-PA was used as the locking solution. Heparin locks were changed at least once per week and rt-PA locks could be left in place for up to 4 weeks. Following these locks, inadequate blood flow noted on accessing CVC and/or during the procedure was scored on as: no issues, some issues, or significant issues. Binary logistic regression was used to evaluate for potential statistical difference in outcomes. Cost analysis was also performed. RESULTS: No statistically significant difference was noted in outcomes between heparin and rt-PA lock (P value = 0.15). Total cost of heparin lock administration ($91-$362.50) was found to be more than rt-PA lock ($76) when more than one flush was needed between procedures. CONCLUSIONS: For apheresis use, rt-PA and heparin CVC locks seem to have similar outcomes in preventing CVC malfunction. The convenience of not needing any flushes between procedures and overall cost of administering fewer locks favors rt-PA use when the interval between procedures is >7 days.

Assessment of Heparin Anticoagulation Measured Using i-STAT and Hemochron Activated Clotting Time.

OBJECTIVE: Adequate anticoagulation, measured using activated clotting time (ACT), is important during vascular and cardiac surgeries. Unfractionated heparin is the most common anticoagulant used. The purpose of this analysis was to compare the i-STAT ACT (iACT) to the Hemochron ACT (hACT), both of which were then compared to anti-factor Xa (anti-Xa) assay, a representation of heparin level and activity. DESIGN: Prospective study. SETTING: Tertiary care cardiovascular center. PARTICIPANTS: Eleven consecutive elective adult cardiac surgical patients. INTERVENTIONS: Prior to cardiopulmonary bypass, ACTs were measured using i-STAT and Hemochron technologies and compared to each other and to anti-Xa assay prior to and during a cumulative administration of heparin. Data were compared using bias analyses. MEASUREMENTS AND MAIN RESULTS: Heparin (300 U/kg) was administered in quarterly doses. Coagulation labs were collected prior to and 3 minutes after each quarterly dose of heparin. The baseline ACTs for i-STAT and Hemochron were 147 and 142 seconds, respectively. A significant association was found between iACT and hACT (p = 0.002). The iACT measurements underestimated hACT at ACT levels >180 seconds or anti-Xa levels >0.75 U/mL. No significant difference was found between ACT data at anti-Xa levels <0.5 U/mL. CONCLUSION: There was a good association between the iACT and hACT; however, the 2 tests are not equivalent. Overall, the iACT underestimated the hACT. Agreement between the ACT technologies was good at lower ACTs and anti-Xa levels, but declined with an anti-Xa >0.75 U/mL.

Assessment of Heparanase-Mediated Angiogenesis Using Microvascular Endothelial Cells: Identification of λ-Carrageenan Derivative as a Potent Anti Angiogenic Agent.

Heparanase is overexpressed by tumor cells and degrades the extracellular matrix proteoglycans through cleavage of heparan sulfates (HS), allowing pro-angiogenic factor release and thus playing a key role in tumor angiogenesis and metastasis. Here we propose new HS analogs as potent heparanase inhibitors: Heparin as a positive control, Dextran Sulfate, λ-Carrageenan, and modified forms of them obtained by depolymerization associated to glycol splitting (RD-GS). After heparanase activity assessment, 11 kDa RD-GS-λ-Carrageenan emerged as the most effective heparanase inhibitor with an IC50 of 7.32 ng/mL compared to 10.7 ng/mL for the 16 kDa unfractionated heparin. The fractionated polysaccharides were then tested in a heparanase-rich medium-based in vitro model, mimicking tumor microenvironment, to determine their effect on microvascular endothelial cells (HSkMEC) angiogenesis. As a preliminary study, we identified that under hypoxic and nutrient poor conditions, MCF-7 cancer cells released much more mature heparanase in their supernatant than in normal conditions. Then a MatrigelTM assay using HSkMEC cultured under hypoxic conditions in the presence (or not) of this heparanase-rich supernatant was realized. Adding heparanase-rich media strongly enhanced angiogenic network formation with a production of twice more pseudo-vessels than with the control. When sulfated polysaccharides were tested in this angiogenesis assay, RD-GS-λ-Carrageenan was identified as a promising anti-angiogenic agent.

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections.

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment.

Pharmacologic Therapies in Anticoagulation.

Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature.

A PK-PD model-based assessment of sugammadex effects on coagulation parameters.

Exposure-response analyses of sugammadex on activated partial thromboplastin time (APTT) and prothrombin time international normalized ratio (PT(INR)) were performed using data from two clinical trials in which subjects were co-treated with anti-coagulants, providing a framework to predict these responses in surgical patients on thromboprophylactic doses of low molecular weight or unfractionated heparin. Sugammadex-mediated increases in APTT and PT(INR) were described with a direct effect model, and this relationship was similar in the presence or absence of anti-coagulant therapy in either healthy volunteers or surgical patients. In surgical patients on thromboprophylactic therapy, model-based predictions showed 13.1% and 22.3% increases in respectively APTT and PT(INR) within 30min after administration of 16mg/kg sugammadex. These increases remain below thresholds seen following treatment with standard anti-coagulant therapy and were predicted to be short-lived paralleling the rapid decline in sugammadex plasma concentrations.

Optimal medication dosing from suboptimal clinical examples: a deep reinforcement learning approach.

Misdosing medications with sensitive therapeutic windows, such as heparin, can place patients at unnecessary risk, increase length of hospital stay, and lead to wasted hospital resources. In this work, we present a clinician-in-the-loop sequential decision making framework, which provides an individualized dosing policy adapted to each patient's evolving clinical phenotype. We employed retrospective data from the publicly available MIMIC II intensive care unit database, and developed a deep reinforcement learning algorithm that learns an optimal heparin dosing policy from sample dosing trails and their associated outcomes in large electronic medical records. Using separate training and testing datasets, our model was observed to be effective in proposing heparin doses that resulted in better expected outcomes than the clinical guidelines. Our results demonstrate that a sequential modeling approach, learned from retrospective data, could potentially be used at the bedside to derive individualized patient dosing policies.

Anti-coagulation assessment with prothrombin time and anti-Xa assays in real-world patients on treatment with rivaroxaban.

Monitoring of anti-coagulation with the direct factor Xa inhibitor rivaroxaban is considered unnecessary in a routine clinical setting. However, assessment of its anti-coagulant effect may be desirable in certain clinical situations. We assessed prothrombin time (PT) reagents and commercially available anti-Xa assays (Biophen) calibrated for rivaroxaban and heparin in comparison to liquid chromatography-mass spectrometry (LC-MS/MS) measurements of rivaroxaban concentration in samples from patients on treatment with rivaroxaban for stroke prevention in atrial fibrillation. Citrate plasma samples were obtained from 30 randomly selected patients on uninterrupted treatment with rivaroxaban for a minimum of 1 month. The anti-Xa assays, direct Xa inhibitor (DiXa-I®), and Heparin LRT® were conducted for both wide and low calibrations for rivaroxaban. Measurements were compared to LC-MS/MS using correlation, linear regression, intra-class correlation, and Bland-Altman analysis. In 30 patients (9 female) of median age 71.5 years and BMI 26.5 kg/m(2), rivaroxaban concentrations between 2.4 and 625 ng/ml (median 82 ng/ml) were measured by LC-MS/MS. PT reagents were poorly correlated with rivaroxaban concentrations (r (2) = 0.52 and 0.09). Anti-Xa assays DiXa-I (r (2) = 0.95) and Heparin LRT (r (2) = 0.97) were correlated with rivaroxaban in all concentrations, but especially in low concentrations with low calibrations (r (2) = 0.97 and 0.98, respectively). The highest agreement occurred between Heparin LRT and low rivaroxaban concentrations with a mean difference of -5.3 ng/ml (limits of agreement, 12.9 to 2.4 ng/ml). Anti-Xa assays can indirectly determine the concentration of rivaroxaban for a wide range of concentrations in real-world patients. An interpretation of anti-Xa and PT measurements in treatment with rivaroxaban requires knowledge of the local reagents.

Assessment of anti-factor Xa activity of heparin in binary parenteral nutrition admixtures for premature neonates.

An in vitro study was carried out to determine the anti-Xa activity of heparin in binary parenteral nutrition (BPN) admixtures for premature neonates in our neonatal intensive care unit (NICU) after a 24-hour infusion, as well as to assess drug interaction with a 50% glucose solution. Two types of bags were prepared: (1) BPN admixtures (composition defined in the NICU) including sodium heparin at 77 UI/mL and (2) bags containing only G50% with sodium heparin at 193 UI/mL. The anti-Xa activity of heparin was measured in bags at T0, after the 24-hour infusion and in eluates at the outlet of the infusion line after 24hours, using a validated chromogenic anti-Xa method. Comparisons of the mean concentration observed with the theoretical value for anti-Xa activity were performed with the Student t-test. Mean values of anti-Xa activity do not differ significantly from the values expected for all conditions. We found a slight variation in anti-Xa activity when infused over 24hours for both types of bags, with and without in-line filtration, showing that heparin remains stable during this infusion period in both BPN admixtures and G50%.

Assessment of Multiplate platelet aggregometry using citrate, heparin or hirudin in Rhesus macaques.

Electrical impedance aggregometry (EIA) has gained popularity in clinical and research applications. Nonhuman primates are used to study disease and drug-related mechanisms that affect hemostasis, therefore establishing normal EIA parameters are necessary. The anticoagulants sodium heparin, hirudin and sodium citrate and three agonists, ADP, ASPI, and collagen were evaluated. Whole blood from 12 adult male rhesus macaques was collected to evaluate anticoagulants, sodium heparin, hirudin and sodium citrate using three agonists (ADP, ASPI and collagen), on the Multiplate® 5.0 Analyzer. Platelet function was reported for three parameters: Area under the curve (AUC), aggregation, and aggregation velocity. There was a significant difference in mean AUC between citrate and heparin samples, and citrate and hirudin samples regardless of the agonist used. There was no difference in AUC between heparin and hirudin. ADP-activated samples showed an increase in impedance with hirudin samples compared to citrate. Furthermore, heparin and hirudin out-perform citrate as the anticoagulant for EIA in the macaque. Finally, this study demonstrates the utility of the Multiplate® system in this model and provides important insight into anticoagulant choice when using EIA.

Post-heparin LPL activity measurement using VLDL as a substrate: a new robust method for routine assessment of plasma triglyceride lipolysis defects.

BACKGROUND: Determination of lipoprotein lipase (LPL) activity is important for hyperchylomicronemia diagnosis, but remains both unreliable and cumbersome with current methods. Consequently by using human VLDL as substrate we developed a new LPL assay which does not require sonication, radioactive or fluorescent particles. METHODS: Post-heparin plasma was added to the VLDL substrate prepared by ultracentrifugation of heat inactivated normolipidemic human serums, diluted in buffer, pH 8.15. Following incubation at 37°c, the NEFA (non esterified fatty acids) produced were assayed hourly for 4 hours. LPL activity was expressed as µmol/l/min after subtraction of hepatic lipase (HL) activity, obtained following LPL inhibition with NaCl 1.5 mmol/l. Molecular analysis of LPL, GPIHBP1, APOA5, APOC2, APOE genes was available for 62 patients. RESULTS: Our method was reproducible (coefficient of variation (CV): intra-assay 5.6%, inter-assay 7.1%), and tightly correlated with the conventional radiolabelled triolein emulsion method (n = 26, r = 0.88). Normal values were established at 34.8 ± 12.8 µmol/l/min (mean ± SD) from 20 control subjects. LPL activities obtained from 71 patients with documented history of major hypertriglyceridemia showed a trimodal distribution. Among the 11 patients with a very low LPL activity (<10 µmol/l/min), 5 were homozygous or compound heterozygous for LPL or GPIHBP1 deleterious mutations, 3 were compound heterozygous for APOA5 deleterious mutations and the p.S19W APOA5 susceptibility variant, and 2 were free of any mutations in the usual candidate genes. No homozygous gene alteration in LPL, GPIHBP1 and APOC2 genes was found in any of the patients with LPL activity >10 µmol/l/min. CONCLUSION: This new reproducible method is a valuable tool for routine diagnosis and reliably identifies LPL activity defects.

A newly designed total implantable venous access device in rats for research with high efficiency and low cost.

BACKGROUND: In this study, we introduced a newly designed totally implantable device for long-term vascular access in rats and compared its efficacy, related complications, and cost-effectiveness with conventional exteriorized jugular vein catheters. METHODS: Forty adult male Sprague-Dawley rats, weighing 250-300 g, were equally divided into two groups (I and II) and all underwent jugular vein catheterization surgery. The totally implanted device was used in group I and conventional exteriorized catheters were used in group II. The functionality of each catheter was checked every 3 d and evaluation included vascular accessibility, patency, and infection. The weight of the animal and microbial culture from the wound and tube were also monitored. We analyzed the cause of vascular access failure and complications, both mechanical and infectious, and compared related variables. RESULTS: The proportions of 9-d patency and 30-d patency in group I were 90% (18/20) and 75% (15/20), respectively, and in group II 80% (16/20) and 35% (7/20), respectively. There was a statistically significant difference in 30-d patency. The rats in group II were more liable to involve vascular access failure because of catheter dislodgment and had a higher infection rate (P = 0.001). Daily body weight gain was also greater in group I than in group II (2.46 ± 0.59 g/d versus 1.84 ± 0.96 g/d; P = 0.02). CONCLUSIONS: This newly designed and totally implanted device substantially increases the success rate of long-term venous access compared with conventional methods. It reinforces the merits of the subcutaneous port and a tethered swivel system and overall has better performance and reliability. Furthermore, given its low cost and the high level of effectiveness offered, this technology could be a powerful tool to be used in future translational medicine research, especially in cases of long-term intravascular administration.

[Assessment of anti-factor Xa activity for heparin and related products by chromogenic assays and thrombin generation tests].

Anticoagulant therapy is widely used for the prevention and treatment of thromboembolism. In addition to established agents such as warfarin, unfractionated heparin and low-molecular-weight heparins, a variety of new anticoagulant drugs has been introduced for clinical use, including direct thrombin inhibitors and factor Xa inhibitors. These new drugs can be given at fixed doses without the need for routine monitoring of the coagulation profile. However, an assays to evaluate anticoagulant strength would be valuable to prevent undesired hemorrhagic or thromboembolic events during treatment. In the present study, we examined the feasibility of several laboratory monitoring tests, including chromogenic-based anti-factor Xa assay and the thrombin generation test to determine the anticoagulant effect of low-molecular-weight heparins and fonda-parinux. Dose-dependent relationship between anti-factor Xa activity and the concentration of fondaparinux was observed by the chromogenic assays. In the thrombin generation test, the peak parameter seemed to be more informative than the endogenous thrombin potential, which corresponds to the total amount of thrombin activity, to assess the pharmacodynamic effects. In summary, our study suggested that both assays may be useful for quantitative determination of factor Xa activity. Further studies are necessary to develop and establish simpler methods that can be used in routine laboratory testing to monitor treatment with the newer anticoagulant drugs.

Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid hemorrhage: a preliminary assessment.

OBJECT: Aneurysmal subarachnoid hemorrhage (aSAH) predisposes to delayed neurological deficits, including stroke and cognitive and neuropsychological abnormalities. Heparin is a pleiotropic drug that antagonizes many of the pathophysiological mechanisms implicated in secondary brain injury after aSAH. METHODS: The authors performed a retrospective analysis in 86 consecutive patients with Fisher Grade 3 aSAH due to rupture of a supratentorial aneurysm who presented within 36 hours and were treated by surgical clipping within 48 hours of their ictus. Forty-three patients were managed postoperatively with a low-dose intravenous heparin infusion (Maryland low-dose intravenous heparin infusion protocol: 8 U/kg/hr progressing over 36 hours to 10 U/kg/hr) beginning 12 hours after surgery and continuing until Day 14 after the ictus. Forty-three control patients received conventional subcutaneous heparin twice daily as deep vein thrombosis prophylaxis. RESULTS: Patients in the 2 groups were balanced in terms of baseline characteristics. In the heparin group, activated partial thromboplastin times were normal to mildly elevated; no clinically significant hemorrhages or instances of heparin-induced thrombocytopenia or deep vein thrombosis were encountered. In the control group, the incidence of clinical vasospasm requiring rescue therapy (induced hypertension, selective intraarterial verapamil, and angioplasty) was 20 (47%) of 43 patients, and 9 (21%) of 43 patients experienced a delayed infarct on CT scanning. In the heparin group, the incidence of clinical vasospasm requiring rescue therapy was 9% (4 of 43, p = 0.0002), and no patient suffered a delayed infarct (p = 0.003). CONCLUSIONS: In patients with Fisher Grade 3 aSAH whose aneurysm is secured, postprocedure use of a low-dose intravenous heparin infusion may be safe and beneficial.

[A comparative and technical assessment of the HELP system (heparin extracorporeal LDL precipitation) and cascade filtration (CF) for the treatment of high plasma lipids]. / Valutazione comparativa e tecnica tra il sistema di Precipitazione Extracorporea delle LDL con Eparina (H.E.L.P) e la Filtrazione a Cascata (CF) nel trattamento delle ipercolesterolemie.

Extracorporeal techniques for the removal of plasma lipids, known as LDL-apheresis, have improved treatment of atherosclerotic lesions in patients with familial hyperlipidemia (FH). In the homozygous form, such treatment is to be considered a life-saving therapy, and in heterozygous forms, which are widely distributed in the population, it is also used when there is a high risk of coronary atherogenic lesions and where a dietary and pharmacological approach has failed to satisfy the objective of a LDL-C 2.6 mmol/L. Of the various techniques available, we believe that cascade filtration (CF) and extracorporeal LDL precipitation with heparin (HELP) are the methods of choice for technical reasons, clinical efficacy and safety. HELP provides, at long-term follow-up, a 5% greater decrease in LDL-C and Lp (a) compared to CF, and about 10% increase in fibrinogen removal resulting in decreased blood viscosity. Conversely, CF produces a concomitant elimination of up to 20% of HDL-C, whereas HELP results in around 5% elimination. CF determines a loss of protein which over time can impact negatively on the protein profile, while HELP results in negligible protein loss. Finally, a significant dampening effect on the intermediate products of inflammation, which initiate the process of vessel atheroma development, has been documented only with HELP. Therefore, the HELP procedure appears to inhibit the development of atheromatous plaques via several different routes.

Bioenergetic gain of citrate anticoagulated continuous hemodiafiltration--a comparison between 2 citrate modalities and unfractionated heparin.

PURPOSE: To determine bioenergetic gain of 2 different citrate anticoagulated continuous hemodiafiltration (CVVHDF) modalities and a heparin modality. MATERIALS AND METHODS: We compared the bio-energetic gain of citrate, glucose and lactate between 29 patients receiving 2.2% acid-citrate-dextrose with calcium-containing lactate-buffered solutions (ACD/Ca(plus)/lactate), 34 on 4% trisodium citrate with calcium-free low-bicarbonate buffered fluids (TSC/Ca(min)/bicarbonate), and 18 on heparin with lactate buffering (Hep/lactate). RESULTS: While delivered CVVHDF dose was about 2000 mL/h, total bioenergetic gain was 262 kJ/h (IQR 230-284) with ACD/Ca(plus)/lactate, 20 kJ/h (8-25) with TSC/Ca(min)/bicarbonate (P < .01) and 60 kJ/h (52-76) with Hep/lactate. Median patient delivery of citrate was 31.2 mmol/h (25-34.7) in ACD/Ca(plus)/lactate versus 14.8 mmol/h (12.4-19.1) in TSC/Ca(min)/bicarbonate groups (P < .01). Median delivery of glucose was 36.8 mmol/h (29.9-43) in ACD/Ca(plus)/lactate, and of lactate 52.5 mmol/h (49.2-59.1) in ACD/Ca(plus)/lactate and 56.1 mmol/h (49.6-64.2) in Hep/lactate groups. The higher energy delivery with ACD/Ca(plus)/lactate was partially due to the higher blood flow used in this modality and the calcium-containing dialysate. CONCLUSIONS: The bioenergetic gain of CVVHDF comes from glucose (in ACD), lactate and citrate. The amount substantially differs between modalities despite a similar CVVHDF dose and is unacceptably high when using ACD with calcium-containing lactate-buffered solutions and a higher blood flow. When calculating nutritional needs, we should account for the energy delivered by CVVHDF.