Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition

Comparison of efficacy of three subanesthetic doses of ketamine in allaying procedural discomfort during establishment of subarachnoid block: A randomized double-blind trial

Background: Procedural discomfort is experienced by patients during the establishment of subarachnoid block even after good preoperative counseling and adequate premedication. To enhance comfort, procedural sedation that would provide good analgesia, faster recovery, and amnesia is necessary. Materials and Methods: Patients with American Society of Anesthesiologists Status I and II posted for elective surgeries under subarachnoid block were premedicated with injection midazolam 0.05 mg/kg and preloaded with 10 ml/kg ringer lactate solution. They were randomized into three groups of 30 each. Group K0.3 received ketamine 0.3 mg/kg, Group K0.4 received ketamine 0.4 mg/kg and Group K0.5 received ketamine 0.5 mg/kg intravenously. University of Michigan sedation score, ease of positioning, prick response, verbal response, hallucinations, recall of procedure, and patient satisfaction were evaluated. Results: There was statistically significant difference in sedation among the three groups. Increased dose necessitated help of two persons to position the patient, which showed statistically significant difference. Verbal response was seen early in Group K0.3 (4.67 ± 2.84 min). There was no recall of experience of subarachnoid block procedure in any of the groups in spite of back muscle contraction or patient movement. Hence, all patients in all three groups were satisfied and were willing to undergo subarachnoid block, if the situation arises. Conclusion: Ketamine in the dose of 0.3 mg/kg provided sufficient sedation for allaying procedural discomfort due to less sedation, less positional difficulty, early verbal response, no hallucinations, no recall of performance of procedure, and good patient satisfaction