Search

Background: Patients hospitalized with acute heart disease [acute myocardial infarction (MI); heart disease exacerbation] may require red blood cell (RBC) transfusion. These patients are at increased risk for morbidity and mortality. Hematological biomarkers may help to identify increased mortality risk. The aim of the study was to evaluate the association between hematological biomarkers and survival in these patients., Methods: A historical cohort study of all patients admitted to an internal medicine department, who were diagnosed with acute heart disease and requiring RBC transfusion, was carried out in a tertiary medical center between 2009-2014. The association between hematological biomarkers and 30-, 90-day and 5-year mortality was studied., Results: A total of 254 patients (median age 80 years, IQR 74-86.25; 40.9% females; acute MI 24.8%), were included. During the 5-year follow-up 212(83.5%) patients died. In a multivariate analysis the lower platelet to neutrophil ratio (PNR) was significantly associated with increased 30-, 90-day and 5-year mortality (p<0.001, 0.041, 0.003 respectively). A higher red cell distribution width (RDW) was significantly associated with 30- and 90-day mortality (p=0.003, 0.023 respectively), while higher neutrophil to lymphocyte ratio (NLR) was associated with increased 30-day and 5-year mortality (p= 0.036, 0.033 respectively)., Conclusions: Hematological biomarkers may help to identify increased mortality risk of acute heart disease patients, receiving RBC transfusions in an internal medicine department., Competing Interests: Conflicts of interest The authors have no conflicting interests to declare., (Copyright © 2021 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: In December 2020 the Israeli Health Ministry began a mass vaccination campaign with the BNT162b2 vaccine. This was an important step in overcoming the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic. Autoimmune phenomenon have been described after receiving vaccinations., Patients/methods: Here we describe a case series of patients who developed acquired Thrombotic Thrombocytopenic Purpura, a rare autoimmune disease, within several days of receiving the BNT162b2 vaccine., Conclusions: A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity should be evaluated in patients with history of aTTP before and after any vaccination, especially the SARS-CoV-2 vaccination, and immunosuppression treatment should be considered before vaccination in cases of low ADAMTS13 activity. Patients should be closely monitored after the vaccine for clinical situation and laboratory data. Post vaccination thrombocytopenia assessment should include immune thrombocytopenic purpura, vaccine-induced immune thrombotic thrombocytopenia and acquired thrombotic thrombocytopenic purpura., (© 2021 International Society on Thrombosis and Haemostasis.)

Introduction: The myeloproliferative neoplasms (MPN) are clonal diseases that confer an increased risk of thrombohemorrhagic complications. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease associated with an increased thrombotic risk. Small PNH clones are prevalent in aplastic anemia and myelodysplastic syndrome patients, but their prevalence in MPN patients is unknown., Patients and Methods: Consecutive patients with MPN followed up at a single center were recruited. PNH clones were analyzed in erythrocytes and white blood cells by flow cytometry., Results: PNH clones were detected in 2% of patients and were more common in JAK2 V617F positive patients. We could not detect any differences in clinical manifestations or complications in patients either with or without PNH clones because of the small patient numbers., Conclusion: The prevalence of PNH clones in MPN is similar to that described in myelodysplastic syndromes. Whether PNH clones influence MPN phenotype and complications should be studied prospectively in larger patient cohorts and over long-term follow-up., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase with important roles in hematopoietic progenitor cell survival and proliferation. It is mutated in approximately one-third of AML patients, mostly by internal tandem duplications (ITDs). Adaptor protein Lnk is a negative regulator of hematopoietic cytokine signaling. In the present study, we show that Lnk interacts physically with both wild-type FLT3 (FLT3-WT) and FLT3-ITD through the SH2 domains. We have identified the tyrosine residues 572, 591, and 919 of FLT3 as phosphorylation sites involved in direct binding to Lnk. Lnk itself was tyrosine phosphorylated by both FLT3 ligand (FL)-activated FLT3-WT and constitutively activated FLT3-ITD. Both shRNA-mediated depletion and forced overexpression of Lnk demonstrated that activation signals emanating from both forms of FLT3 are under negative regulation by Lnk. Moreover, Lnk inhibited 32D cell proliferation driven by different FLT3 variants. Analysis of primary BM cells from Lnk-knockout mice showed that Lnk suppresses the expansion of FL-stimulated hematopoietic progenitors, including lymphoid-primed multipotent progenitors. The results of the present study show that through direct binding to FLT3, Lnk suppresses FLT3-WT/ITD-dependent signaling pathways involved in the proliferation of hematopoietic cells. Therefore, modulation of Lnk expression levels may provide a unique therapeutic approach for FLT3-ITD-associated hematopoietic disease.

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and primary myelofibrosis show an inherent tendency for transformation into leukemia (MPN-blast phase), which is hypothesized to be accompanied by acquisition of additional genomic lesions. We, therefore, examined chromosomal abnormalities by high-resolution single nucleotide polymorphism (SNP) array in 88 MPN patients, as well as 71 cases with MPN-blast phase, and correlated these findings with their clinical parameters. Frequent genomic alterations were found in MPN after leukemic transformation with up to 3-fold more genomic changes per sample compared with samples in chronic phase (P < .001). We identified commonly altered regions involved in disease progression including not only established targets (ETV6, TP53, and RUNX1) but also new candidate genes on 7q, 16q, 19p, and 21q. Moreover, trisomy 8 or amplification of 8q24 (MYC) was almost exclusively detected in JAK2V617F(-) cases with MPN-blast phase. Remarkably, copy number-neutral loss of heterozygosity (CNN-LOH) on either 7q or 9p including homozygous JAK2V617F was related to decreased survival after leukemic transformation (P = .01 and P = .016, respectively). Our high-density SNP-array analysis of MPN genomes in the chronic compared with leukemic stage identified novel target genes and provided prognostic insights associated with the evolution to leukemia.

Symptoms of posttraumatic stress disorder (PTSD) and risk factors for recurrent ischemia were evaluated in 65 survivors of a myocardial infarction (MI) at baseline and 6 months afterward. PTSD patients had more uncontrolled cardiovascular risk factors at baseline. Patients with PTSD (N=14) were offered trauma-focused cognitive-behavior treatment (CBT) plus a nonspecific intervention to improve adherence to medical recommendations. Adherence to aspirin improved in recipients of the nonspecific intervention (N=8); PTSD symptoms and cardiovascular risk improved in patients who received CBT (N=6). PTSD may be a treatable risk factor for poor post-MI outcome. Further research is needed to evaluate treatment options.