Lepirudin 50mg powder for solution for injection vials

Background Argatroban, lepirudin, desirudin, bivalirudin, and danaparoid are commonly used to manage heparin-induced thrombocytopenia related complications. However, the most suitable drug for this condition still remains controversial. Aim of the review This Bayesian network meta-analysis study compared the most common anticoagulant drugs used in the management of heparin-induced thrombocytopenia. Method All clinical trials comparing two or more anticoagulant therapies for suspected or confirmed heparin-induced thrombocytopenia were considered for inclusion. Studies concerning the use of heparins or oral anticoagulants were not considered. Data concerning hospitalisation length, thromboembolic, major, and minor haemorrhagic events, and mortality rate were collected. The network analyses were made through the STATA routine for Bayesian hierarchical random-effects model analysis with standardised mean difference (SMD) and log odd ratio (LOR) effect measures. Results Data from a total of 4338 patients were analysed. The overall mean age was 62.31 ± 6.6 years old. Hospitalization length was considerably shorter in favour of the argatroban group (SMD: - 1.70). Argatroban evidenced the lowest rate of major (LOR: - 1.51) and minor (LOR: - 0.57) haemorrhagic events. Argatroban demonstrated the lowest rate of thromboembolic events (LOR: 0.62), and mortality rate (LOR: - 1.16). Conclusion Argatroban performed better overall for selected patients with HIT. Argatroban demonstrated the shortest hospitalization, and lowest rate of haemorrhages, thromboembolisms, and mortality compared to bivalirudin, lepirudin, desirudin, and danaparoid.

Abstract licence: CC BY

Heparin-induced thrombocytopenia type II (HIT II), as stated in the literature, occurs in about 3% of all patients and in 0.1-5% of surgical patients. Thrombosis develops in 20-64% of patients with HIT. The mortality rate in HIT II has not decreased using non-heparin treatment with anticoagulants such as argatroban and lepirudin. An improved understanding of the pathophysiology of HIT may help identify targeted therapies to prevent thrombosis without subjecting patients to the risk of intense anticoagulation. The review will summarize the current knowledge about the pathogenesis of HIT II, potential new therapeutic targets related to it, and new treatments being developed. HIT II pathogenesis involves multi-step immune-mediated pathways dependent on the ratio of PF4/heparin and platelet, monocyte, neutrophil, and endothelium activation. For years, only platelets were known to take part in HIT II development. A few years ago, specific receptors and signal-induced pathways in monocytes, neutrophils and endothelium were revealed. It had been shown that the cells that had become active realised different newly formed compounds (platelet-released TF, TNFα, NAP2, CXCL-7, ENA-78, platelet-derived microparticles; monocytes-TF-MPs; neutrophils-NETs), leading to additional cell activation and consequently thrombin generation, resulting in thrombosis. Knowledge about FcγIIa receptors on platelets, monocytes, neutrophils and FcγIIIa on endothelium, chemokine (CXCR-2), and PSGL-1 receptors on neutrophils could allow for the development of a new non-anticoagulant treatment for HIT II. IgG degradation, Syk kinase and NETosis inhibition are in the field of developing new treatment possibilities too. Accordingly, IdeS and DNases-related pathways should be investigated for better understanding of HIT pathogenesis and the possibilities of being the HIT II treatment targets.

Abstract licence: CC BY

Complement analysis necessitates strict control of pre-analytical blood handling, including time, temperature, and additives. Here, we compared complement function and activation status across five different serum preparations and two plasma preparations. Serum was collected from ten healthy volunteers using glass tubes without additives, tubes with a silica clot activator (with or without a gel separator), and tubes containing thrombin (with or without a gel separator). Plasma was collected in the presence of EDTA or the thrombin inhibitor lepirudin. Serum and plasma aliquots were snap-frozen in liquid nitrogen and stored at -80 °C. Complement functional analysis was performed using Wieslab and Hycult Biotech pathway-specific assays. Complement activation was determined by quantifying specific activation markers: C1s/C1-INH, MASP-1/C1-INH, C3bc, C3bBbP, and sC5b-9. All serum samples exhibited increased complement activation compared to EDTA and lepirudin plasma, with serum tubes containing thrombin and gel separators showing the highest levels of complement activation. However, normal complement function was observed in all serum preparations, indicating that the complement activation and consumption that occurred did not affect complement functional analysis. While all tested serum tubes provided accurate functional activity, the type of tube and the presence of additives like thrombin and gel separators significantly influenced the degree of complement activation. We recommend preparing functionally active serum either in glass tubes or in silica clot activator tubes, and avoiding gel separators. For complement activation studies, lepirudin plasma is preferable over serum due to its complement functional capacity, low level of complement activation, and lack of excessive hemostatic activation.

Abstract licence: CC BY