The usage and outcomes of dextran in the treatment of acute deep venous thrombosis

Objectives In this study, we retrospectively compared the outcomes of patients with acute deep vein thrombosis treated with dextran 40 infusion and unfractionated heparin with those of patients treated with unfractionated heparin alone. Methods We evaluated 104 patients with the diagnosis of acute deep vein thrombosis. The pain complaints of the patients at the time of admission and the pain complaints in the calf with dorsiflexion of the foot were evaluated with the visual analogue pain scale, and the calf diameter of affected limbs was measured. Fifty five patients had dextran 40 infusion and unfractionated heparin treatment concomitantly (Group HD), while 49 patients had unfractionated heparin treatment (Group H). Heparin dose was adjusted to obtain 1.5- to 2.5-fold of normal activated partial thromboplastin time in both groups. Oral anticoagulant, warfarin sodium, was administered in the first day and resumed. Unfractionated heparin infusion therapy was resumed until international normalized ratio values of 2–2.5 were obtained. Dextran 40 infusion therapy was administered for 3 days. Calf diameters, current pain, and calf pain at foot dorsiflexion were recorded at 48 h and 72 h. 65 patients were distal, and 39 patients were proximal and popliteal acute DVT. None of the patients had phlegmasia. All were acute DVT. Results At 48 and 72 h of therapy, it was determined that the decrease of the calf diameter and the pain were more significant both at 48th and 72nd hours in the Group HD. The calf circumference change, especially at 72 h, was 2.58 ± 0.39 cm in the group receiving heparin + dextran, while it was 1.76 ± 0.56 cm in the group receiving only heparin. ( p = 0.000). While there were only 1.24 ± 1.02 people in the group that received dextran at 72 h, leg pain persisted in 3.35 ± 1.11 people in the other group. ( p = 0.000). Evaluation was made only with calf vein diameter measurement. When patients with Homan’s sign were evaluated for their calf pain at foot dorsiflexion; both groups had decreased pain at 48th and 72nd hours. Conclusion In this study, we observed that the use of dextran 40 infusion therapy concomitantly with unfractionated heparin accelerates recovery substantially and decreases patient complaints significantly in early stages. In particular, reduction in leg pain and calf circumference reduction were more adequate in the dextran group. The early decrease in the calf circumference will have clinical consequences such as less heparin intake, earlier return to normal life, and a decrease in the total cost of treatment. Since the antithrombotic and anticoagulant effects of dextran are well known, we think that its use in this treatment as well as venous thromboembolism prophylaxis should be discussed.

Using nutrient-rich solutions and adding multiple cytoprotective agents as new strategies to develop lung preservation solutions

Commonly, donor lungs are preserved with low potassium dextran glucose solution at low temperature. We hypothesized that adding nutrients and/or cytoprotective agents to preservation solutions improves donor lung quality. Human lung epithelial cells and human pulmonary microvascular endothelial cells cultured at 37ºC with serum containing medium were switched to designated testing solutions at 4ºC with 50% O2 for different cold ischemic time, followed by switching back to serum containing culture medium at 37ºC to simulate reperfusion. We found that bicarbonate buffer system should be avoided in preservation solution. When pH was maintained at physiological levels, cell culture media showed better cell survival than in low potassium dextran glucose solution. Phosphate buffered cell culture media were further improved by adding colloid dextran 40. When rat donor lungs were preserved at 4ºC for 24 h, RPMI-1640(p) medium plus dextran 40 or adding cytoprotective agents (alpha 1 antitrypsin, raffinose and glutathione) to low potassium dextran glucose solution prevented alveolar wall swelling, apoptosis, activation of endothelial cells and cellular edema. Using nutrient-rich solution and/or adding multiple cytoprotective agents is a new direction for designing and developing organ preservation solutions. Cell culture model, as a screening tool reduces the use of animals and provides potential underlying mechanisms.

O59: USE OF DEXTRAN 40 FOLLOWING PANCREAS TRANSPLANT MAY REDUCE EARLY INFLAMMATION AND SIGNIFICANT BLEEDING COMPARED TO A HEPARIN-BASED PROTOCOL

Introduction Dextran 40 (D40) is a synthetic colloid with anticoagulant properties, which is commonly used instead of heparin following pancreas transplantation, however there is a lack of evidence over which is more effective. Graft thrombosis and pancreatitis, which may be mediated through micro or macrothrombosis within the graft, remain significant complications following pancreas transplantation. We hypothesised that D40 reduces inflammation through its antithrombotic pro-microcirculatory effects. We aimed to evaluate D40 compared to a heparin-based protocol by comparing post-operative complications and post-transplant levels of inflammation. Method Data were collected retrospectively for pancreas transplant patients between December 2009 and August 2018 – 26 patients had been treated with the pre-Dextran protocol and 37 had received D40. Post-operative complications and inflammatory markers (WCC, CRP and amylase) on post-operative days 1, 2, 3 and 7 were compared between the two groups. Potential confounders were also recorded. Result Patients in the D40 group had similar thrombosis rates but were less likely to have had substantial post-operative bleeding compared to the heparin-based protocol. The group who received D40 had significantly lower CRP and WCC on days 2, 3 and 7. The differences on days 3 and 7 remained when the results were adjusted for the significant confounders - cold ischaemic time and donor age. Conclusion D40 appears to be as effective as IV heparin at preventing graft thrombosis following pancreas transplant, and to confer a reduced risk of bleeding. It may also reduce post-operative inflammatory processes, leading to reduced graft pancreatitis. Take-home message Using Dextran 40 as an anticoagulant after pancreas transplantation is as effective as IV heparin at preventing graft thromboses and has a reduced risk of bleeding.

Study and Determination of Aluminum in Dextran 40 Glucose Injection by ICP-MS

Background: Aluminum (Al) is classified as other element by ICH, and its permitted daily exposure (PDE) has not been established. As it might cause compromised renal function, guidelines, regional regulations and practices needs to be addressed. According to the United States Pharmacopeia 41 and the Japanese Pharmacopoeia 17, the aluminum content of large-volume parenterals (LVPs) used in total parenteral nutrition (TPN) therapy must not exceed 25 ng mL-1. Therefore, the package insert of LVPs used in TPN therapy must state the content of aluminum. Objective: A new microwave assisted acid digestion pretreatment together with inductively coupled plasma mass spectrometry (ICP-MS) method was developed for the determination of aluminum content in Dextran 40 Glucose Injection. The method was successfully applied for quality evaluation of commercial Dextran 40 Glucose Injection. Method: Samples were digested by a mixture of nitric acid and hydrochloric acid, with the assistance of microwave. After that, ICP-MS in KED mode was employed to analyze the samples. Results: The method showed a good linearity (r2=0.9999) within the range of 2~100 ng mL-1, with the limit of detection and quantitation of 0.482 ng mL-1 and 1.61 ng mL-1, respectively. A good precision was obtained with relative standard deviation (RSD) of 8.8% (n=6). The spike recoveries with low, middle and high Al content in 9 sample were 102.2%~107.4%. Conclusion: The developed method was successfully applied for the analysis of Al content in 44 batches of Dextran 40 Glucose Injection produced by 9 pharmaceutical companies from domestic or international enterprises. The Al content of Dextran 40 Glucose Injection varied greatly between different enterprises or different batches. Meanwhile, among total of 44 batches, the Al content in 3 batches of Dextran 40 Glucose Injection exceeded the limitation of 25 ng mL-1, which might cause potential safety problems.