Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms

We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment

Adverse Outcome in Non-Severe COVID-19: Potential Diagnostic Coagulation Tests

COVID-19-associated coagulopathy (CAC) identifies the coagulation changes in coronavirus disease 2019 (COVID-19) and is responsible for thrombosis. CAC has been studied in critical and severe stage COVID-19 disease through tests including the D-Dimer (DD), prothrombin time (PT), thromboplastin partial time (PTT), platelet count, fibrinogen (Fib), and platelet factor 4 (PF4) tests. However, these tests have some limitations. The aim of this study was to identify more accurate warning tests for early recognition of CAC and to prevent its deterioration to disseminated intravascular coagulation (DIC). First, we measured Interleukin-1α (IL-1α) and IL-8, and tissue factor pathway inhibitor (TFPI) as inflammation and endothelial damage markers, respectively. Second, we measured thrombin antithrombin complex (TAT), β-Thromboglobulin (β-TG), and thromboelastometric parameters including clotting time (CT), clot formation time (CFT), clot firmness (MCF), and clot lysis at 30 min (LY-30), as markers of coagulation and platelet activation. This study included 100 non-severe patients with COVID-19 that developed pulmonary embolism (PE) compared to 80 healthy patients. IL-1α and IL-8, and TFPI were higher as well as TAT and β-TG and thromboelastometric parameters, indicating hypercoagulability. If confirmed in other studies, these results could help in predicting the deterioration of non-severe COVID-19 disease, thereby reducing hospitalizations and health costs

Impact of Anti-Endothelial Cell Antibodies (AECAs) in Patients with Polycythemia Vera and Thrombosis

Polycythemia vera (PV) causes thrombosis. Erythrocytosis and cell adhesiveness are responsible for thrombosis. JAK2V617F causes inflammation and autoimmunity; however, whether or not autoimmunity or inflammation causes thrombosis has yet to be proven. In 60 PV patients, we analyzed JAK2V671F and its allele burden, autoimmune Th17 cells, interleukin-17 (IL-17), anti-endothelial cell antibodies (AECAs), endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and von Willebrand factor antigen (VWF: Ag). Fifty blood donors were used as the controls. All patients were on phlebotomy-maintaining hematocrit <45% and aspirin. Of the 60 patients, 40 had thrombosis. Those patients with thrombosis had a higher JAK2V617F allele burden than those without thrombosis, andTh17 cells and IL-17 were also higher in patients with thrombosis. Interestingly, we observed a high AECA IgG ELISA ratio (ER) in patients with thrombosis, which was normal in patients without thrombosis. We found high ELAM-1 and ICAM-1 as well as high VWF:Ag in patients with thrombosis compared to patients without thrombosis. AECA-positive sera from patients with thrombosis showed enhanced binding to cytokine-treated HUVEC and a positive antibody-dependent cellular cytotoxicity, suggesting that AECA may contribute to vascular injury. A positive correlation between AECAs, allele burden, and thrombosis was found. These results suggest that autoimmunity may be an additional mechanism in PV thrombogenesis

Adverse Outcome in Non-Severe COVID-19: Potential Diagnostic Coagulation Tests

COVID-19-associated coagulopathy (CAC) identifies the coagulation changes in coronavirus disease 2019 (COVID-19) and is responsible for thrombosis. CAC has been studied in critical and severe stage COVID-19 disease through tests including the D-Dimer (DD), prothrombin time (PT), thromboplastin partial time (PTT), platelet count, fibrinogen (Fib), and platelet factor 4 (PF4) tests. However, these tests have some limitations. The aim of this study was to identify more accurate warning tests for early recognition of CAC and to prevent its deterioration to disseminated intravascular coagulation (DIC). First, we measured Interleukin-1α (IL-1α) and IL-8, and tissue factor pathway inhibitor (TFPI) as inflammation and endothelial damage markers, respectively. Second, we measured thrombin antithrombin complex (TAT), β-Thromboglobulin (β-TG), and thromboelastometric parameters including clotting time (CT), clot formation time (CFT), clot firmness (MCF), and clot lysis at 30 min (LY-30), as markers of coagulation and platelet activation. This study included 100 non-severe patients with COVID-19 that developed pulmonary embolism (PE) compared to 80 healthy patients. IL-1α and IL-8, and TFPI were higher as well as TAT and β-TG and thromboelastometric parameters, indicating hypercoagulability. If confirmed in other studies, these results could help in predicting the deterioration of non-severe COVID-19 disease, thereby reducing hospitalizations and health costs

How to prevent intraoperative risks and complications in laparoscopic splenectomy

Dalla sua introduzione nel 1992, la splenectomia laparoscopica (LS) è diventata la tecnica di scelta per la rimozione chirurgica della milza in diversi centri. La procedura, tuttavia, è associata a rischi e complicanze, sia durante l'intervento chirurgico che in fase post-operatoria. Sebbene l'incidenza delle complicanze intra-operatorie non sia nota, i rischi intraoperatori in pazienti sottoposti a splenectomia laparoscopica non sono infrequenti. In questo articolo, abbiamo esaminato la letteratura sui rischi e le complicanze durante la splenectomia laparoscopica e ricordiamo, sulla base della nostra serie e dell’esperienza segnalata da altri autori, come prevenire, ove possibile, tali complicanz

Laparoscopic splenectomy in patients under the age of eighteen. Experience in 18 cases

Background. Pediatric surgery is now in the forefront of minimal access procedures. Although pediatric surgeons have been skeptic about laparoscopic splenectomy, recently minimally invasive approach for spleen removal has been revaluated also in young patients. Purpose of this study was to report Authors’ personal experience in patients under eighteen who underwent laparoscopic splenectomy. Results of the procedure were evaluated. Patients and ethods. A retrospective review was undertaken in 18 splenectomised patients under the age of eighteen. Indications were hereditary spherocytosis in 10 patients, β-thalassemia in 4, idiopathic thrombocytopenic purpura in 3 and a splenic cyst in 1 child. Results. No intra-operative complications occurred. No conversion to open surgery was reported. During the follow-up one case of portal vein thrombosis, treated by medical therapy, was encountered and no other postoperative complications were observed. Conclusions. Laparoscopic approach has to be preferable for all those children undergoing spleen surgery. In experienced hands, it is of beneficial effects with a very reasonable rate of complications

Digital Droplet PCR in Hematologic Malignancies: A New Useful Molecular Tool

Digital droplet PCR (ddPCR) is a recent version of quantitative PCR (QT-PCR), useful for measuring gene expression, doing clonality assays and detecting hot spot mutations. In respect of QT-PCR, ddPCR is more sensitive, does not need any reference curve and can quantify one quarter of samples already defined as “positive but not quantifiable”. In the IgH and TCR clonality assessment, ddPCR recapitulates the allele-specific oligonucleotide PCR (ASO-PCR), being not adapt for detecting clonal evolution, that, on the contrary, does not represent a pitfall for the next generation sequencing (NGS) technique. Differently from NGS, ddPCR is not able to sequence the whole gene, but it is useful, cheaper, and less time-consuming when hot spot mutations are the targets, such as occurs with IDH1, IDH2, NPM1 in acute leukemias or T315I mutation in Philadelphia-positive leukemias or JAK2 in chronic myeloproliferative neoplasms. Further versions of ddPCR, that combine different primers/probes fluorescences and concentrations, allow measuring up to four targets in the same PCR reaction, sparing material, time, and money. ddPCR is also useful for quantitating BCR-ABL1 fusion gene, WT1 expression, donor chimerism, and minimal residual disease, so helping physicians to realize that “patient-tailored therapy” that is the aim of the modern hematology