Real-World Data Analysis of Patients Affected by Immune-Mediated Thrombotic Thrombocytopenic Purpura in Italy.

Background: The therapeutic management of immune-mediated thrombotic thrombocytopenic purpura (iTTP) has recently benefited from the introduction of caplacizumab, an agent directed at the inhibition of platelet aggregation. This real-world analysis investigated the epidemiology and the demographic and clinical characteristics of iTTP patients in Italy before and after caplacizumab introduction in 2020. Methods: Hospitalized adults with iTTP were included using the administrative databases of healthcare entities covering 17 million residents. Epidemiological estimates of iTTP considered the 3-year period before and after caplacizumab introduction. After stratification by treatment with or without caplacizumab, iTTP patients were characterized for their baseline features. Results: The annual incidence before and after 2020 was estimated in the range of 4.3-5.8 cases/million and 3.6-4.6 cases/million, respectively. From 2018 to 2022, 393 patients with iTTP were included, and 42 of them were treated with caplacizumab. Caplacizumab-treated patients showed better clinical outcomes, with tendentially shorter hospital stays and lower mortality rates (no treated patients died at either 1 month or 3 months after caplacizumab treatment initiation, compared to 10.5% and 11.1% mortality rates at 1 and 3 months, respectively, of the untreated ones). Conclusions: These findings may suggest that caplacizumab advent provided clinical and survival benefits for patients with iTTP.

Treatment of immune-mediated thrombotic thrombocytopenic purpura without plasma exchange.

Not available.

Caplacizumab use for immune thrombotic thrombocytopenic purpura: the Milan thrombotic thrombocytopenic purpura registry.

•Data on caplacizumab use for thrombotic thrombocytopenic purpura (TTP) in Italy are missing.•Twenty-six Italian patients were treated with caplacizumab for an acute immune TTP episode.•Caplacizumab was effective in treating acute TTP in the Italian real-world clinical setting.•Two major bleeds leading to drug discontinuation were observed.

Viscoelastic coagulation testing in Neonatal Intensive Care Units: advantages and pitfalls in clinical practice.

The expression "developmental hemostasis" indicates the age-related physiological changes occurring during the maturational process of the hemostatic system. Despite the quantitative and qualitative alterations, the neonatal hemostatic system is competent and well-balanced. Conventional coagulation tests do not provide reliable information as they only explore the procoagulants during the neonatal period. In contrast, viscoelastic coagulation tests (VCTs), such as viscoelastic coagulation monitoring (VCM), thromboelastography (TEG or ClotPro), and rotational thromboelastometry (ROTEM), are point-of-care assays that provide a quick, dynamic and global view of the hemostatic process, allowing prompt and individualized therapeutic intervention when necessary. Their use in neonatal care is on the increase and they could help monitor patients at risk of hemostatic derangement. In addition, they are crucial for anticoagulation monitoring during extracorporeal membrane oxygenation. Moreover, implementing VCT-based monitoring could optimize blood product use.

A retrospective study on the use of low-molecular-weight heparin for prevention of pregnancy-related recurrent venous thromboembolism and obstetrical complications.

BACKGROUND: The risk of venous thromboembolism (VTE) is increased during pregnancy and it is further increased together with pregnancy complications in women with personal history of VTE and thrombophilia abnormalities. It is unclear how the use of low-molecular-weight heparin (LMWH) may prevent such complications. OBJECTIVE: To evaluate the potential benefits and risks of the use of LMWH for prevention of pregnancy-related VTE and obstetrical complications in the first pregnancy after a previous VTE. METHODS: This retrospective cohort study includes fertile women referred to the Thrombosis Center from January 2000 to September 2018 for a thrombophilia work-up, after having had at least one previous VTE and one pregnancy thereafter. Data on pregnancy-related recurrent VTE, pregnancy outcomes and the use of LMWH were collected. RESULTS: Among 208 women, no thrombosis or major bleeding was recorded in 138 pregnancies conducted with LMWH, whereas 10 VTE (14%) were recorded in 70 pregnancies conducted without. Nine women (90%) with recurrent VTE had had a previous hormone-related event. The incidence of miscarriage was lower in pregnancies with LMWH than in those without (11% vs. 26%, relative risk 0.4, 95% confidence interval: 0.2-0.8), whereas late obstetrical complications and terminations were similar in the two groups. The prevalence of terminations was doubled in women with thrombophilia (12%) than in those without (6%). CONCLUSIONS: LMWH prophylaxis during pregnancy appears to be effective and safe for the prevention of recurrent VTE and may reduce the incidence of miscarriage.

Evaluation of an automated platelet aggregation method for detection of congenital or acquired platelet function defects.

BACKGROUND: Light transmission aggregometry (LTA) is the most widely used laboratory method for an initial screening of patients with a suspected platelet function defect (PFD), and its use has also been proposed for assessing the efficacy of antiplatelet treatment (APT). An automated LTA method has been developed by Sysmex (Kobe, Japan) on a routine coagulation analyzer (CS-2400), together with a new research parameter called PAL (platelet aggregation level) to evaluate patients on APT. MATERIALS AND METHODS: We evaluated the performance of CS-2400 compared to a stand-alone lumi-dual-aggregometer device in the diagnosis of PFD and in assessing the efficacy of APT. For these purposes, the study population was represented by a cohort of 23 patients with a previous diagnosis of PFD and a cohort of 28 patients on APT. RESULTS: Compared to healthy volunteers, patients with PFD showed a statistically significant reduction (p<0.05) in the maximal %light transmission, irrespective of the agonist used, both with the CS-2400 and the lumi-dual-aggregometer. As regards PFD patients, CS-2400 was effective in identifying the more severe defects, with a good sensibility and specificity, but less effective in identifying milder forms of PFD, such as platelet secretion defects. Patients on APT showed a statistically significant (p=0.001) reduced median %light transmission and PAL scores compared to healthy controls. DISCUSSION: Thanks to this LTA technology, CS-2400, a routine coagulation analyzer widely available in routine laboratories, could prove useful for initial assessment of patients with a suspected PFD. Moreover, the PAL scores were a fairly accurate reflection of the platelet response to APT.

Hemostasis in neonatal ECMO.

Extracorporeal membrane oxygenation (ECMO) is a life-saving support for cardio-respiratory function. Over the last 50 years, the extracorporeal field has faced huge technological progress. However, despite the improvements in technique and materials, coagulation problems are still the main contributor to morbidity and mortality of ECMO patients. Indeed, the incidence and survival rates of the main hemorrhagic and thrombotic complications in neonatal respiratory ECMO are relevant. The main culprit is related to the intrinsic nature of ECMO: the contact phase activation. The exposure of the human blood to the non-endothelial surface triggers a systemic inflammatory response syndrome, which chronically activates the thrombin generation and ultimately leads to coagulative derangements. Pre-existing illness-related hemostatic dysfunction and the peculiarity of the neonatal clotting balance further complicate the picture. Systemic anticoagulation is the management's mainstay, aiming to prevent thrombosis within the circuit and bleeding complications in the patient. Although other agents (i.e., direct thrombin inhibitors) have been recently introduced, unfractionated heparin (UFH) is the standard of care worldwide. Currently, there are multiple tests exploring ECMO-induced coagulopathy. A combination of the parameters mentioned above and the evaluation of the patient's underlying clinical context should be used to provide a goal-directed antithrombotic strategy. However, the ideal algorithm for monitoring anticoagulation is currently unknown, resulting in a large inter-institutional diagnostic variability. In this review, we face the features of the available monitoring tests and approaches, mainly focusing on the role of point-of-care (POC) viscoelastic assays in neonatal ECMO. Current gaps in knowledge and areas that warrant further study will also be addressed.

The usefulness of D-dimer as a predictive marker for mortality in patients with COVID-19 hospitalized during the first wave in Italy.

BACKGROUND: The coronavirus disease 2019 (COVID-19) presents an urgent threat to global health. Identification of predictors of poor outcomes will assist medical staff in treatment and allocating limited healthcare resources. AIMS: The primary aim was to study the value of D-dimer as a predictive marker for in-hospital mortality. METHODS: This was a cohort study. The study population consisted of hospitalized patients (age >18 years), who were diagnosed with COVID-19 based on real-time PCR at 9 hospitals during the first COVID-19 wave in Lombardy, Italy (Feb-May 2020). The primary endpoint was in-hospital mortality. Information was obtained from patient records. Statistical analyses were performed using a Fine-Gray competing risk survival model. Model discrimination was assessed using Harrell's C-index and model calibration was assessed using a calibration plot. RESULTS: Out of 1049 patients, 507 patients (46%) had evaluable data. Of these 507 patients, 96 died within 30 days. The cumulative incidence of in-hospital mortality within 30 days was 19% (95CI: 16%-23%), and the majority of deaths occurred within the first 10 days. A prediction model containing D-dimer as the only predictor had a C-index of 0.66 (95%CI: 0.61-0.71). Overall calibration of the model was very poor. The addition of D-dimer to a model containing age, sex and co-morbidities as predictors did not lead to any meaningful improvement in either the C-index or the calibration plot. CONCLUSION: The predictive value of D-dimer alone was moderate, and the addition of D-dimer to a simple model containing basic clinical characteristics did not lead to any improvement in model performance.

External validation of risk scores to predict in-hospital mortality in patients hospitalized due to coronavirus disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) presents an urgent threat to global health. Prediction models that accurately estimate mortality risk in hospitalized patients could assist medical staff in treatment and allocating limited resources. AIMS: To externally validate two promising previously published risk scores that predict in-hospital mortality among hospitalized COVID-19 patients. METHODS: Two prospective cohorts were available; a cohort of 1028 patients admitted to one of nine hospitals in Lombardy, Italy (the Lombardy cohort) and a cohort of 432 patients admitted to a hospital in Leiden, the Netherlands (the Leiden cohort). The endpoint was in-hospital mortality. All patients were adult and tested COVID-19 PCR-positive. Model discrimination and calibration were assessed. RESULTS: The C-statistic of the 4C mortality score was good in the Lombardy cohort (0.85, 95CI: 0.82-0.89) and in the Leiden cohort (0.87, 95CI: 0.80-0.94). Model calibration was acceptable in the Lombardy cohort but poor in the Leiden cohort due to the model systematically overpredicting the mortality risk for all patients. The C-statistic of the CURB-65 score was good in the Lombardy cohort (0.80, 95CI: 0.75-0.85) and in the Leiden cohort (0.82, 95CI: 0.76-0.88). The mortality rate in the CURB-65 development cohort was much lower than the mortality rate in the Lombardy cohort. A similar but less pronounced trend was found for patients in the Leiden cohort. CONCLUSION: Although performances did not differ greatly, the 4C mortality score showed the best performance. However, because of quickly changing circumstances, model recalibration may be necessary before using the 4C mortality score.

Plasma Exchange in a Patient with Immune Thrombocytopenia Associated with Antiphospholipid Syndrome Hospitalized for COVID-19.

Thrombocytopenia is a common feature of antiphospholipid syndrome (APS) and rarely requires treatment. Here we present the case of a 71-year-old man hospitalized for severe immune thrombocytopenia (ITP) secondary to APS and concomitant SARS-CoV-2 infection. The patient was successfully treated with systemic corticosteroids, intravenous immunoglobulins, and plasma exchange (PEX). Few data are published on the use of plasma exchange in the treatment of thrombocytopenia in non-catastrophic APS. In the setting of acute infection when immunosuppressive therapies might be contraindicated, plasma exchange may be considered an effective therapeutic option. SARS-CoV-2 infection may be a trigger for a relapse of immune thrombocytopenia.