-
1.
Evaluation of heparinized syringes for measuring newborn metabolites in neonates with a central arterial line.
Ryckman, KK, Ramesh, A, Cho, H, Oltman, SP, Rogers, EE, Dagle, JM, Jelliffe-Pawlowski, LL
Clinical biochemistry. 2022;:78-81
-
-
Free full text
-
Abstract
Newborn metabolic screening is emerging as a novel method for predicting neonatal morbidity and mortality in neonates born very preterm (<32 weeks gestation). The purpose of our study was to determine if blood collected by an electrolyte-balanced dry lithium heparin syringe, as is routine for blood gas measurements, affects targeted metabolite and biomarker levels. Two blood samples (one collected with a heparinized syringe and the other with a non-heparinized syringe) were obtained at the same time from 20 infants with a central arterial line and tested for 49 metabolites and biomarkers using standard procedures for newborn screening. Overall, the median metabolite levels did not significantly differ by syringe type. However, there was wide variability, particularly for amino acids and immunoreactive trypsinogen, for individual paired samples and therefore, consideration should be given to sample collection when using these metabolites in prediction models of neonatal morbidity and mortality.
-
2.
Combination of dociparstat sodium (DSTAT), a CXCL12/CXCR4 inhibitor, with azacitidine for the treatment of hypomethylating agent refractory AML and MDS.
Huselton, E, Rettig, MP, Campbell, K, Cashen, AF, DiPersio, JF, Gao, F, Jacoby, MA, Pusic, I, Romee, R, Schroeder, MA, et al
Leukemia research. 2021;:106713
-
-
Free full text
-
Abstract
Leukemia stem cells utilize cell adhesion molecules like CXCR4/CXCL12 to home to bone marrow stromal niches where they are maintained in a dormant, protected state. Dociparstat sodium (DSTAT, CX-01) is a low anticoagulant heparin with multiple mechanisms of action, including inhibition of the CXCR4/CXCL12 axis, blocking HMGB1, and binding platelet factor 4 (PF-4). We conducted a pilot study adding DSTAT to azacitidine for patients with AML or MDS unresponsive to or relapsed after prior hypomethylating agent therapy, hypothesizing that DSTAT may improve response rates. Twenty patients were enrolled, with a median of 2 prior lines of therapy and 6 cycles of prior hypomethylating agents. Among fifteen patients evaluable for response, there was 1 complete remission, and 3 marrow complete remissions, for a response rate of 27 % among evaluable patients (20 % overall). Hematologic improvement was observed in 5 additional patients. The median overall survival for all enrolled patients was 205 days (95 % CI 119-302). While cytopenias and infections were common, these were not out of proportion to what would be expected in this population of patients undergoing treatment with azacitidine alone. In summary, this trial demonstrated the feasibility of combining DSTAT with azacitidine, with several responses observed, suggesting this combination warrants further study.
-
3.
Design and Rationale of a Randomized, Double-Blind, Placebo-Controlled, Phase 2/3 Study Evaluating Dociparstat in Acute Lung Injury Associated with Severe COVID-19.
Lasky, JA, Fuloria, J, Morrison, ME, Lanier, R, Naderer, O, Brundage, T, Melemed, A
Advances in therapy. 2021;(1):782-791
-
-
Free full text
-
Abstract
INTRODUCTION The COVID-19 global pandemic caused by the novel coronavirus, SARS-CoV-2, and the consequent morbidity and mortality attributable to progressive hypoxemia and subsequent respiratory failure threaten to overrun hospital critical care units globally. New agents that address the hyperinflammatory "cytokine storm" and hypercoagulable pathology seen in these patients may be a promising approach to treat patients, minimize hospital stays, and ensure hospital wards and critical care units are able to operate effectively. Dociparstat sodium (DSTAT) is a glycosaminoglycan derivative of heparin with robust anti-inflammatory properties, with the potential to address underlying causes of coagulation disorders with substantially reduced risk of bleeding compared to commercially available heparin. METHODS This study is a randomized, double-blind, placebo-controlled, phase 2/3 trial to determine the safety and efficacy of DSTAT added to standard of care in hospitalized adults with COVID-19 who require supplemental oxygen. Phase 2 will enroll 12 participants in each of two dose-escalating cohorts to confirm the safety of DSTAT in this population. Following review of the data, an additional 50 participants will be enrolled. Contingent upon positive results, phase 3 will enroll approximately 450 participants randomized to DSTAT or placebo. The primary endpoint is the proportion of participants who survive and do not require mechanical ventilation through day 28. DISCUSSION Advances in standard of care, recent emergency use authorizations, and positive data with dexamethasone have likely contributed to an increasing proportion of patients who are surviving without the need for mechanical ventilation. Therefore, examining the time to improvement in the NIAID score will be essential to provide a measure of drug effect on recovery. Analysis of additional endpoints, including supportive biomarkers (e.g., IL-6, HMGB1, soluble-RAGE, D-dimer), will be performed to further define the effect of DSTAT in patients with COVID-19 infection. TRIAL REGISTRATION ClinicalTrials.gov identifier; NCT04389840, Registered 13 May 2020.
-
4.
Is inhaled prophylactic heparin useful for prevention and Management of Pneumonia in ventilated ICU patients?: The IPHIVAP investigators of the Australian and New Zealand Intensive Care Society Clinical Trials Group.
Bandeshe, H, Boots, R, Dulhunty, J, Dunlop, R, Holley, A, Jarrett, P, Gomersall, CD, Lipman, J, Lo, T, O'Donoghue, S, et al
Journal of critical care. 2016;:95-102
Abstract
PURPOSE To determine whether prophylactic inhaled heparin is effective for the prevention and treatment of pneumonia patients receiving mechanical ventilation (MV) in the intensive care unit. METHODS A phase 2, double blind randomized controlled trial stratified for study center and patient type (non-operative, post-operative) was conducted in three university-affiliated intensive care units. Patients aged ≥18years and requiring invasive MV for more than 48hours were randomized to usual care, nebulization of unfractionated sodium heparin (5000 units in 2mL) or placebo nebulization with 0.9% sodium chloride (2mL) four times daily with the main outcome measures of the development of ventilator associated pneumonia (VAP), ventilator associated complication (VAC) and sequential organ failure assessment scores in patients with pneumonia on admission or who developed VAP. TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry ACTRN12612000038897. RESULTS Two hundred and fourteen patients were enrolled (72 usual care, 71 inhaled sodium heparin, 71 inhaled sodium chloride). There were no differences between treatment groups in terms of the development of VAP, using either Klompas criteria (6-7%, P=1.00) or clinical diagnosis (24-26%, P=0.85). There was no difference in the clinical consistency (P=0.70), number (P=0.28) or the total volume of secretions per day (P=.54). The presence of blood in secretions was significantly less in the usual care group (P=0.005). CONCLUSION Nebulized heparin cannot be recommended for prophylaxis against VAP or to hasten recovery from pneumonia in patients receiving MV.
-
5.
In vitro comparison of the novel, dual-acting FIIa/FXa-inhibitor EP217609C101, unfractionated heparin, enoxaparin, and fondaparinux in preventing cardiac catheter thrombosis.
Kaeberich, A, Raaz, U, Vogt, A, Maedgefessel, L, Neuhart, E, Krezel, C, Drouget, L, Hauroeder, B, Buerke, M, Werdan, K, et al
Journal of thrombosis and thrombolysis. 2014;(2):118-30
Abstract
Efficient and safe anticoagulation is crucial in patients requiring percutaneous coronary intervention (PCI) or extracorporeal circulation during cardiac surgery. Although new anticoagulant strategies have emerged for PCI as alternatives to the established treatment with heparins, the development of new anticoagulants with an improved efficacy/safety ratio is still necessary. Our study compared the efficacy of the novel, dual-acting, neutralizable FIIa/FXa-inhibitor EP217609C101 (EP) at 2, 1.2, 0.9, and 0.6 μg/ml to unfractionated heparin (UFH), enoxaparin, and fondaparinux in preventing cardiac catheter thrombosis under in vitro conditions. Blood drawn by venepunction from healthy male volunteers (n = 10) pretreated with 500 mg aspirin orally was treated with the anticoagulant to test and continuously circulated through a cardiac catheter for 60 min or until the catheter became blocked by thrombotic debris. Anticoagulant efficacy was assessed by thrombus weight, electron microscopic features of the developing thrombi, and laboratory parameters. Whereas UFH, enoxaparin, EP 2, and EP 1.2 μg/ml secured maximum circulation times, statistically significant premature catheter occlusions were observed for EP 0.9, EP 0.6 μg/ml, and fondaparinux. The UFH group and both high-dose concentrations of EP showed significantly lower thrombus weights than the low-dose concentrations of EP and fondaparinux, (p ≤ 0.05). On electron microscopic analysis of the thrombotic debris no differences were observed in erythrocyte deposition between UFH, enoxaparin, and all EP concentrations tested. A significant reduction in fibrin deposition was achieved by UFH and EP 2 μg/ml but no significant differences in platelet deposition were found, except for a significant reduction for EP 0.6 μg/ml. Our in vitro study showed that EP217609C101 is a promising new drug that is dose-dependently superior to classical (UFH, enoxaparin) and newer (fondaparinux) drugs in preventing heart catheter thrombosis.
-
6.
On- and post-treatment symptom relief by repeated instillations of heparin and alkalized lidocaine in interstitial cystitis.
Nomiya, A, Naruse, T, Niimi, A, Nishimatsu, H, Kume, H, Igawa, Y, Homma, Y
International journal of urology : official journal of the Japanese Urological Association. 2013;(11):1118-22
Abstract
OBJECTIVES To examine outcomes of intravesical instillations of heparin and alkalized lidocaine in patients with interstitial cystitis. METHODS Patients with interstitial cystitis refractory to conventional therapies were given a solution of 20 000 U heparin, 5 mL 4% lidocaine and 25 mL 7% sodium bicarbonate, intravesically, weekly for 12 weeks consecutively. The treatment was regarded as "effective", when patients rated "slightly improved" or "better" on a seven-graded scale of global response assessment. Other assessment measures included O'Leary and Sant's symptom index and problem index, visual analog scale for pain, and frequency volume chart variables. RESULTS A total of 32 patients were enrolled in the study. The average age was 63.3 years. All participants had received hydrodistension 2.2 times on average, and fulfilled National Institute of Diabetes and Digestive and Kidney Diseases criteria. The therapy was effective in 60.0% of the patients at the fourth instillation, in 76.7% at the last instillation, and 90.0%, 46.7% and 16.7% at 1, 2 and 6 months after the last instillation, respectively. Most of other assessment measures improved significantly at the fourth instillation and further beyond until the end of therapy. On termination of therapy, the efficacy gradually diminished, yet mostly maintained statistical significance by 2 months post-instillation. No severe adverse events occurred. CONCLUSIONS A 12-week course of weekly intravesical instillations of heparin combined with alkalized lidocaine is safe and effective in relieving symptoms in interstitial cystitis patients. The effect of the treatment is maintained for 6 months. Further studies are required to optimize the number of instillations and maintenance intervals in order to maximize the therapeutic potential of simple or combined instillations in the management of interstitial cystitis.
-
7.
Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial.
Hetzel, GR, Schmitz, M, Wissing, H, Ries, W, Schott, G, Heering, PJ, Isgro, F, Kribben, A, Himmele, R, Grabensee, B, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011;(1):232-9
Abstract
BACKGROUND Continuous venovenous haemofiltration (CVVH) in the intensive care setting requires anticoagulation to prevent clotting of the extracorporeal circuit. Several protocols avoiding heparin and using regional citrate anticoagulation have been developed to diminish bleeding risks. However, data from randomized trials comparing citrate anticoagulation with systemic heparinization are very limited. METHODS One hundred and seventy-four patients on mechanical ventilation, requiring renal replacement therapy for acute renal failure, were included in this prospective randomized multicentre trial comparing regional citrate with systemic heparin. The study was performed at nine different intensive care units at university or academic teaching hospitals. The participants were randomized to either CVVH using regional citrate anticoagulation or CVVH using systemic anticoagulation with unfractionated heparin. The primary outcome was to compare treatment efficacy represented by the patients' acid base status on Day 3 and on each consecutive day. Several parameters of safety and efficacy were analysed as secondary outcomes. RESULTS Comparison of standard bicarbonate from Day 3 to Day 11 revealed no difference between both treatment modalities. Use of citrate resulted in less systemic anticoagulation, a lower risk of bleeding and a longer haemofilter patency. Episodes of hypercalcaemia, hypocalcaemia and the need for additional bicarbonate infusions occurred more often under citrate. The patients' high mortality was not influenced by the mode of anticoagulation. CONCLUSIONS Citrate may be used as a regional anticoagulant and the only buffering agent in CVVH with adequate treatment efficacy and safety. However, neither citrate nor heparin anticoagulation should be regarded as a therapeutic standard, since there is no advantage of one of these substances with regard to patient mortality.
-
8.
Prospective, randomized trial of two different modalities of flushing central venous catheters in pediatric patients with cancer.
Cesaro, S, Tridello, G, Cavaliere, M, Magagna, L, Gavin, P, Cusinato, R, Zadra, N, Franco Zanon, G, Zanesco, L, Carli, M
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009;(12):2059-65
Abstract
PURPOSE There are limited prospective data on whether the method of flushing affects the complication rate of tunnelled central venous catheters (CVCs). PATIENTS AND METHODS During a 25-month period, 203 pediatric patients who had newly placed Broviac-Hickman CVCs were randomly assigned to standard flushing with heparin solution or to experimental flushing with normal saline via a positive-pressure cap. RESULTS Two hundred twenty-one complications were recorded among 75,249 CVC-days (2.94 per 1,000 CVC-days). A higher incidence of CVC occlusion (83 v 41 episodes; P = .0002) and bacteremia (24 v 9; P = .01) were found in the experimental arm. The cumulative probability of developing at least one CVC complication was higher in the experimental arm than in the standard arm (65.1% [95% CI, 55% to 75%] v 43.8% [95% CI, 34% to 54%], respectively; P = .01). No difference was found in either the cause or the frequency of premature removal of CVCs between the two study arms. After a median follow-up of 360 days (range, 4 to 1,073), CVC survival was similar: 77% (95% CI, 66% to 84%) for the experimental arm and 69% (95% CI, 53% to 80%) for the standard arm (P = .7). The factors associated with the occurrence of CVC complication were a diagnosis of leukemia/lymphoma, double-lumen CVC, and experimental flushing. The only factor significantly associated with premature removal of a CVC was a diagnosis of leukemia/lymphoma (hazard rate, 2.3; 95% CI, 1.1 to 4.7). CONCLUSION An increased complication rate was found with normal saline flushing, but additional investigation is warranted to clarify whether it is related to saline use or to once-a-week flushing.
-
9.
Dosing lepirudin in patients with heparin-induced thrombocytopenia and normal or impaired renal function: a single-center experience with 68 patients.
Tschudi, M, Lämmle, B, Alberio, L
Blood. 2009;(11):2402-9
-
-
Free full text
-
Abstract
The recommended dose (bolus 0.4 mg/kg followed by 0.15 mg/kg per hour) of lepirudin, a direct thrombin inhibitor licensed for treatment of heparin-induced thrombocytopenia (HIT), is too high. Starting in 2001, we omitted the bolus and reduced maintenance dose by at least one-third. Analyzing 53 HIT patients treated between January 2001 and February 2007, we observed that therapeutic anticoagulation intensity already 4 hours after lepirudin start had been reached with the following initial lepirudin doses (median): 0.078 mg/kg per hour [creatinine clearance (CrCl) more than 60 mL/min], 0.040 mg/kg per hour (CrCl 30-60 mL/min), and 0.013 mg/kg per hour (CrCl < 30 mL/min). The efficacy of this treatment was documented by increasing platelets and decreasing D-dimers. Based on this experience, we derived a lepirudin dosing regimen, which was prospectively evaluated treating 15 HIT patients between March 2007 and February 2008. We show that omitting the initial lepirudin bolus and administering 0.08 mg/kg per hour in patients with CrCl more than 60 mL/min, 0.04 mg/kg per hour in patients with CrCl 30-60 mL/min, and 0.01 to 0.02 mg/kg per hour in those with CrCl less than 30 mL/min is efficacious and safe, as documented by increasing platelet counts, decreasing D-dimer levels, and rare thrombotic (1 of 46) and major bleeding (4 of 46) complications.
-
10.
A method to reduce saline and heparin in intraoperative cerebral angiography: a preliminary report.
Mihara, F, Yoshiura, T, Noguchi, T, Togao, O, Morioka, T, Sasaki, T, Honda, H
Radiation medicine. 2005;(8):588-9
Abstract
PURPOSE To reduce saline and heparin in continuous catheter perfusion in intraoperative cerebral angiography, a method using a syringe pump was tried. MATERIALS AND METHODS Ten patients with brain arteriovenous malformation (AVM) underwent intraoperative cerebral angiography. Seven internal carotid arteries (ICAs) and six vertebral arteries (VAs) were catheterized in these patients. Continuous catheter perfusion was performed at a low rate of 3 mL/hr with saline containing 8,000 units of heparin per liter using a syringepump. RESULTS Mean duration of catheter perfusion was 8.3 +/- 4.0 hrs (range, 3.0 to 15.7 hrs). Mean volume of saline was 25.0 +/- 11.9 mL (range, 9 to 47 mL) per catheter. Mean dosage of heparin was 200.0 +/- 94.9 units (range, 72 to 376 units) per catheter. No complications due to intraoperative angiography were observed in this trial. CONCLUSION Reduction of the saline volume and heparin dosage was possible in intraoperative cerebral angiography by the continuous perfusion of a small amount of high-concentration heparinized saline using a syringe pump.