Fibrinogen concentrate in surgery

Fibrinogen is a plasma glycoprotein synthesised by the liver which plays a critical role in haemostasis by acting as an endogenous substrate for fibrin formation and by inducing clot formation and platelet aggregation

The use of fibrinogen concentrate for the management of trauma-related bleeding. A systematic review and meta-analysis

Haemorrhage following injury is associated with significant morbidity and mortality. The role of fibrinogen concentrate in trauma-induced coagulopathy has been the object of intense research in the last 10 years and has been systematically analysed in this review. A systematic search of the literature identified six retrospective studies and one prospective one, involving 1,650 trauma patients. There were no randomised trials. Meta-analysis showed that fibrinogen concentrate has no effect on overall mortality (risk ratio: 1.07, 95% confidence interval: 0.83-1.38). Although the metaanalytic pooling of the current literature evidence suggests no beneficial effect of fibrinogen concentrate in the setting of severe trauma, the quality of data retrieved was poor and the final results of ongoing randomised trials will help to further elucidate the role of fibrinogen concentrate in traumatic bleeding

Inhibitors in Patients with Congenital Bleeding Disorders Other Than Hemophilia

The most worrying complication of replacement therapy for severe hemophilia A and B is currently the occurrence of inhibitory alloantibodies against infused factor VIII and factor IX, respectively. Inhibitors compromise the management of hemorrhage in affected patients, with a considerable increase in complications, disability, and costs. While these alloantibodies have been extensively studied in the past years in hemophilia A and B, those occurring in patients with other inherited bleeding disorders are less well characterized and still poorly understood, mostly due to the rarity of these hemorrhagic conditions. This narrative review will deal with inhibitors arising in patients with inherited bleeding disorders other than "classical" hemophilia, focusing in particular on those developing in patients with congenital deficiency of coagulation factor V, factor VII, factor XI, and factor XIII

Fatal Myocarditis in Course of Plasmodium falciparum Infection: Case Report and Review of Cardiac Complications in Malaria

We describe a fatal case of imported malaria where the sole finding revealed at the postmortem evaluation was an acute lymphocytic myocarditis with myocardiolysis. This case recalls the potential importance of myocardial injury in the prognosis of malaria and prompts a reevaluation of current perspectives on the pathogenesis of severe falciparum infection. In the light of this, we have reviewed the cases of cardiac complications in malaria published to date

Safety of intravenous tranexamic acid in patients undergoing major orthopaedic surgery. A meta-analysis of randomised controlled trials

Among the various pharmacological options to decrease peri-operative bleeding, tranexamic acid appears to be one of the most interesting. Several trials have consistently documented the efficacy of this synthetic drug in reducing the risk of blood loss and the need for allogeneic blood transfusion in patients undergoing total hip and knee arthroplasty. The safety of intravenous tranexamic acid in major orthopaedic surgery, particularly regarding the risk of venous thromboembolism, was systematically analysed in this review. A systematic search of the literature identified 73 randomised controlled trials involving 4,174 patients and 2,779 controls. The raw overall incidence of venous thromboembolism was 2.1% in patients who received intravenous tranexamic acid and 2.0% in controls. A meta-analytic pooling showed that the risk of venous thromboembolism in tranexamic acid-treated patients was not significantly different from that of controls (risk difference: 0.01%, 95% confidence interval [CI]: -0.05%, 0.07%; risk ratio: 1.067, 95% CI: 0.760-1.496). Other severe drug-related adverse events occurred very rarely (0.1%). In conclusion, the results of this systematic review and meta-analysis show that intravenous tranexamic acid is a safe pharmacological treatment to reduce blood loss and transfusion requirements in patients undergoing major orthopaedic surgery

The use of viscoelastic haemostatic assays in non-cardiac surgical settings. a systematic review and meta-analysis

Background: Thrombelastography (TEG) and rotational thromboelastometry (ROTEM) are viscoelastic haemostatic assays (VHA) which exploit the elastic properties of clotting blood. The aim of this systematic review and meta-analysis was to evaluate the usefulness of these tests in bleeding patients outside the cardiac surgical setting. Materials and methods: We searched the Cochrane Library, MEDLINE, EMBASE and SCOPUS. We also searched clinical trial registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. Results: We found 4 randomised controlled trials (RCTs) that met our inclusion criteria with a total of 229 participants. The sample size was small (from 28 to 111 patients) and the follow-up periods very heterogenous (from 4 weeks to 3 years). Pooled data from the 3 trials reporting on mortality (199 participants) do not show any effect of the use of TEG on mortality as compared to standard monitoring (based on the average treatment effect from a fixed-effects model): Risk Ratio (RR) 0.71; 95% Confidence Interval (CI): 0.43 to 1.16. Likewise, the use of VHA does not reduce the need for red blood cells (mean difference -0.64; 95% CI: -1.51 to 0.23), platelet concentrates (mean difference -1.12; 95% CI: -3.25 to 1.02), and fresh frozen plasma (mean difference -0.91; 95% CI: -2.02 to 0.19) transfusion. The evidence on mortality and other outcomes was uncertain (very low-certainty evidence, down-graded due to risk of biases, imprecision, and inconsistency). Conclusions: Overall, the certainty of the evidence provided by the trials was too low for us to be certain of the benefits and harms of viscoelastic haemostatic assay in non-cardiac surgical settings. More, larger, and better-designed RCTs should be carried out in this area

β-Glucan Antigenemia Assay for the Diagnosis of Invasive Fungal Infections in Patients With Hematological Malignancies: A Systematic Review and Meta-Analysis of Cohort Studies From the Third European Conference on Infections in Leukemia (ECIL-3)

This Third European Conference on Infections in Leukemia meta-analysis of high-quality hemato-oncological cohort studies shows that 2 consecutive positive 1,3-β-D-glucan assays have high specificity and both positive and negative predictive values but low sensitivity for diagnosis of invasive fungal infectio

Safety and efficacy of tranexamic acid for prevention of obstetric haemorrhage. An updated systematic review and meta-analysis

Background. A number of clinical systematic review and meta-analysis have been published on the use of tranexamic in the obstetric setting. The aim of this meta-analysis was to evaluate the safety and effectiveness of tranexamic acid in reducing blood loss when given prior to caesarean delivery. Materials and methods. We searched the Cochrane Wounds Specialized Register, Cochrane Central, MEDLINE (through PUBMED), Embase, and SCOPUS electronic databases. We also searched clinical trials registries for ongoing and unpublished studies, and checked reference lists to identify additional studies. We used no restrictions with respect to language and date of publication. Two review authors independently performed study selection, "Risk of bias" assessment, and data extraction. Initial disagreements were resolved by discussion, or by including a third review author when necessary. Results. We found 18 randomised controlled trials (RCTs) that met our inclusion criteria. Overall, 1,764 women receiving intravenous tranexamic acid for prevention of bleeding following caesarean sections and 1,793 controls receiving placebo were enrolled in the 18 RCTs evaluated. The use of tranexamic acid compared to controls (placebo or no intervention) reduces post-partum haemorrhage >400 mL (risk ratio [RR] 0.40, 95% confidence interval [CI] 0.24-0.65; 5 trials with a total of 786 participants), severe post-partum haemorrhage >1,000 mL (RR 0.32, 95% CI: 0.12-0.84; 5 trials with a total of 1,850 participants), and need for red blood cell transfusion (RR 0.30, 95% CI: 0.18-0.49; 10 trials with a total of 1,873 participants). No particular safety concerns on the use of this antifibrinolytic agent emerged from the analysis of the 18 RCTs included. Discussion. Overall, the results of this meta-analysis support the evidence of a beneficial effect of tranexamic acid in reducing blood loss and need for blood transfusion in pregnant women undergoing caesarean section

COVID-19-associated coagulopathy

Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently recognized as a systemic disorder inducing a prothrombotic state. The molecular mechanisms underlying the hypercoagulable state seen in patients with COVID-19 is still incompletely understood, although it presumably involves the close link between inflammatory and hemostatic systems. The laboratory coagulation monitoring of severely ill COVID-19 patients is mandatory to identify those patients at increased thrombotic risk and to modulate thromboprophylaxis accordingly. In this review, we summarize the current understanding on the pathogenesis, epidemiology, clinical and laboratory features and management of coagulopathy associated with COVID-19