1.
Efficacy and safety of nafamostat mesilate anticoagulation in blood purification treatment of critically ill patients: a systematic review and meta-analysis
Lin Y, Shao Y, Liu Y, Yang R, Liao S, Yang S, Xu M, He J
Renal failure. 2022;44(1):1263-1279
Abstract
BACKGROUND Nafamostat mesilate (NM), a broad-spectrum and potent serine protease inhibitor, can be used as an anticoagulant during extracorporeal circulation, as well as a promising drug effective against coronavirus disease 2019 (COVID-19). We conducted a systematic meta-analysis to evaluate the safety and efficacy of NM administration in critically ill patients who underwent blood purification therapy (BPT). METHODS The Cochrane Library, Web of Science and PubMed were comprehensively searched from inception to August 20, 2021, for potential studies. RESULTS Four randomized controlled trials (RCTs) and seven observational studies with 2723 patients met the inclusion criteria. The meta-analysis demonstrated that conventional therapy (CT) significantly increased hospital mortality compared with NM administration (RR = 1.25, p = 0.0007). In subgroup analyses, the in-hospital mortality of the NM group was significantly lower than that of the anticoagulant-free (NA) group (RR = 1.31, p = 0.002). The CT interventions markedly elevated the risk ratio of bleeding complications by 45% (RR = 1.45, p = 0.010) compared with NM interventions. In another subgroup analysis, NM used exhibited a significantly lower risk of bleeding complications than those of the low-molecular-weight heparin (LMWH) used (RR = 4.58, p = 0.020). The filter lifespan was decreased significantly (MD = -10.59, p < 0.0001) in the NA groups compared with the NM groups. Due to the poor quality of the included RCTs, these results should be interpreted with caution. CONCLUSION Given the better survival outcomes, lower risk of bleeding, NM anticoagulation seems to be a safe and efficient approach for BPT patients and could yield a favorable filter lifespan. More multi-center RCTs with large samples are required for further validation of this study.
2.
Therapeutic Plasma Exchange Protects Patients with Sepsis-Associated Disseminated Intravascular Coagulation by Improving Endothelial Function
Weng J, Chen M, Fang D, Liu D, Guo R, Yang S
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2021;27:10760296211053313
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Abstract
The mortality rate of sepsis-associated disseminated intravascular coagulation (DIC) is high. This study aimed to explore the efficacy of therapeutic plasma exchange (TPE) in sepsis-associated DIC patients by improving endothelial function. A total of 112 sepsis-associated DIC patients were randomly divided into the TPE group (n = 40), the heparin (HP) group (n = 36), and the SHAM group (n = 36). The SHAM group received conventional treatment; the HP group was treated with HP based on conventional treatment; and the TPE group received conventional treatment plus TPE. The differences in thromboelastogram (TEG), platelet (PLT), coagulation function, and the endothelial cell (EC) injury biomarkers at 6 h, 24 h, 48 h, 72 h, and 7 days after TPE were compared among the three groups, and the three groups were compared in terms of Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sepsis-Related Organ Failure Assessment (SOFA) score, the length of intensive care unit (ICU) hospitalization, 28-day mortality rate, 28-day cumulative survival rate, the incidence of bleeding events, the incidence of acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS). The efficacy of TPE is superior to the HP in increasing PLT, improving coagulation function, increasing the 28-day cumulative survival rate, and reducing the length of ICU hospitalization, 28-day mortality, and the incidence of bleeding events, AKI, and ARDS with statistically significant differences (P < .05). Moreover, the effect of TPE outperforms HP on the EC injury biomarkers with statistically significant differences (P < .05). Our results suggest that TPE may be more effective than HP in the treatment of patients with sepsis-associated DIC. The possible mechanism is via improving endothelial function.
PICO Summary
Population
Patients with sepsis-associated disseminated intravascular coagulation (DIC), (n= 112).
Intervention
Therapeutic plasma exchange (TPE), (n= 40).
Comparison
Heparin (HP), (n= 36); conventional treatment (n= 36).
Outcome
The efficacy of TPE was superior to the HP in increasing platelet, improving coagulation function, increasing the 28-day cumulative survival rate, and reducing the length of intensive care unit hospitalization, 28-day mortality, and the incidence of bleeding events, acute kidney injury and acute respiratory distress syndrome with statistically significant differences. The effect of TPE outperformed HP on the endothelial cell injury biomarkers with statistically significant differences.
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Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura
Cataland SR, Kourlas PJ, Yang S, Geyer S, Witkoff L, Wu H, Masias C, George JN, Wu HM
Blood Advances. 2017;1((23)):2075-2082.
Abstract
Although steroids are routinely used as an adjunct to plasma exchange (PEX) therapy in the treatment of immune-mediated thrombotic thrombocytopenic purpura (iTTP), limited data regarding their efficacy or effect on ADAMTS13 biomarkers are available. We report the results of a prospective, randomized study that compared the effectiveness of prednisone or cyclosporine (CSA) as adjuncts to PEX in the treatment of iTTP. A total of 26 of the planned 72 subjects were enrolled and treated from November 2007 until February 2014 before the study was halted after a planned interim analysis. Fourteen patients were randomly assigned to the prednisone arm, and 12 to the CSA arm of the study. One patient died in each arm of the study, and 2 patients in the prednisone arm of the study failed to achieve a response and crossed over to the CSA arm, leaving 11 patients in each arm of the study evaluable for the primary end point of exacerbation. One of the 11 prednisone-treated subjects (9%) suffered an exacerbation, whereas 3 of the 11 (27%) patients in the CSA arm suffered an exacerbation. Although there was no significant difference in the exacerbation rate, suppression of the anti-ADAMTS13 antibodies and improvement in ADAMTS13 activity in the first month after stopping PEX were significantly better in the prednisone-treated subjects. Side effects were manageable and comparable in both arms of the study. These data demonstrate the superiority of prednisone over CSA as an adjunct to PEX in the suppression of the anti-ADAMTS13 antibodies and improvement in ADAMTS13 activity. This trial was registered at www.clinicaltrials.gov as #NCT00713193.