Immunological HCV-Associated Thrombocytopenia: Short Review

Infection with Hepatitis C virus (HCV) is affecting about 3% of the world's population, leading to liver damage, end-stage liver disease, and development of hepatocellular carcinoma, being thus the first indication for liver transplantation in the USA. Apart from the cirrhotic-liver-derived clinical signs and symptoms several conditions with immunological origin can also arise, such as, glomerulonephritis, pulmonary fibrosis, and thrombocytopenia. HCV-related autoimmune thrombocytopenia shows specific pathogenetic characteristics as well as symptoms and signs that differ in severity and frequency from symptoms in patients that are not HCV infected. Aim of this short paper is to estimate the epidemiological characteristics of the disease, to investigate the pathogenesis and clinical manifestation, and to propose treatment strategies according to the pertinent literature

Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype.- Pfizer Pharmaceuticals(undefined

A clinicopathological study of b-cell differentiation markers and transcription factors in classical Hodgkin lymphoma

Although most cases of Classical Hodgkin lymphoma (CHL) are cured, a significant minority experiences refractoriness to treatment. The investigation of biological markers could ameliorate the predictive capacity of clinical staging systems. The aim of our study was the detection of the B-cell differentiation markers and transcription factors in CHL in order to define subgroups with different histogenesis and prognosis. We evaluated 107 cases of CHL for BCL6, CD79a, MUM1/IRF4 and B-cell transcription factors BOB.1, OCT.2 expression by immunohistochemistry. Statistical analysis was performed using the Fisher’s exact test, the Mann-Whitney test, the Kaplan-Meier method and the log rank test. Univariate and multivariate regression analyses were performed to identify variables with a significant effect on survival. CD79a was expressed in 5.8%, BCL6 in 14.7%, MUM1/IRF4 in 92.3%, BOB.1 in 53.4% and OCT.2 in 12.6% of cases. There was not any significant association between CD79a and BCL6 expression and clinical characteristics. Univariate analysis has shown that age ? 45, stage III/IV and MUM/IRF4 negative status were associated with significantly shorter time to disease progression (TTP) and overall survival (OS). On multivariate analysis the lack of MUM/IRF4 expression was associated with significantly shorter TTP while age ? 45 and the presence of extralymphatic sites with significantly shorter OS. In conclusion our study has confirmed that MUM1/IRF4 is expressed in most cases of CHL and the lack of this expression may indicate an aggressive clinical behaviorΠαρόλο που η πλειοψηφία των περιπτώσεων κλασικού λεμφώματος Hodgkin οδηγείται σε ίαση μετά από θεραπεία, μια μικρή μειονότητα παρουσιάζει ανθεκτικότητα στην θεραπεία. Η ανεύρεση βιολογικών δεικτών με προγνωστική σημασία θα μπορούσε να βελτιώσει την έκβαση των ασθενών αυτών. Σκοπός της μελέτης μας ήταν η διερεύνηση της έκφρασης δεικτών Β λεμφοκυτταρικής διαφοροποίησης και μεταγραφικών παραγόντων στο κλασικό λέμφωμα Hodgkin με σκοπό την ταυτοποίηση ομάδων με διαφορετική ιστογένεση και πρόγνωση. Μελετήσαμε 107 περιπτώσεις κλασικού λεμφώματος Hodgkin ως προς την έκφραση των CD79a, BCL6, MUM1/IRF4 και των μεταγραφικών παραγόντων BOB.1, OCT.2 με ανοσοϊστοχημεία. Η στατιστική ανάλυση πραγματοποιήθηκε με τη χρήση του Fisher’s exact test, του Mann-Whitney test, της μεθόδου Kaplan-Meier, του log rank test, της μονοπαραγοντικής και πολυπαρογοντικής ανάλυσης παλινδρόμησης κατά Cox. Το CD79a εκφράσθηκε σε ποσοστό 5.8%, η BCL6 σε 14.7%, το MUM1/IRF4 σε 92.3%, το BOB.1 σε 53.4% και το OCT.2 σε 12.6% των περιπτώσεων. Δεν βρέθηκε κάποια σημαντική συσχέτιση μεταξύ της έκφρασης των CD79a και BCL6 και των κλινικοεργαστηριακών παραμέτρων. Η μονοπαραγοντική ανάλυση έδειξε ότι η ηλικία ? 45, τα στάδια (III/IV) και η απουσία έκφρασης του MUM/IRF4 σχετίζονται με χειρότερη επιβίωση ελεύθερη νόσου και συνολική επιβίωση. Ακολούθως η πολυπαραγοντική ανάλυση έδειξε ότι η απουσία έκφρασης του MUM/IRF4 σχετίζεται με χειρότερη επιβίωση ελεύθερη νόσου ενώ η ηλικία ? 45 και η εξωλεμφαδενική νόσος με χειρότερη συνολική επιβίωση. Συμπερασματικά η παρούσα μελέτη επιβεβαίωσε την έκφραση του MUM/IRF4 στην πλειοψηφία των περιπτώσεων κλασικού Hodgkin και ανέδειξε οτι η απουσία έκφρασης του φαίνεται να σχετίζεται με επιθετικότερη βιολογική συμπεριφορ

A Brief Review of 50 Years of Perioperative Thrombosis and Hemostasis Management

Perioperative thrombosis and hemostasis management has changed dramatically over the past 50 years. From two anticoagulants and one anti-aggregant, the number of currently available drugs has recently increased several-fold, leaving clinicians with the problem of choosing the optimal agent. Individualized preoperative assessment of bleeding risk based on bleeding history and testing limited to high-risk patients is an emerging concept. Based on the identification of risk factors for venous thromboembolism (VTE), pharmacologic and non-pharmacologic strategies for perioperative VTE prophylaxis have had a major impact on patient outcome. For patients undergoing surgery who are treated with anticoagulants and anti-aggregants, “bridging” strategies have been proposed. Bleeding management strategies have shifted focus from replacing lost blood volume to new approaches aimed at preventing blood loss, reducing the potential complications of blood loss, and preventing the transfusion of blood products. For some areas of perioperative thrombosis and hemostasis management, randomized controlled trial (RCT) data are emerging, but the database remains insufficient to date. Clearly, more RCTs need to be published for perioperative thrombosis and hemostasis management to become an evidence-based approach. Semin Hematol 50:79-87. (C) 2013 Published by Elsevier Inc

Immunological HCV-Associated Thrombocytopenia: Short Review

Infection with Hepatitis C virus (HCV) is affecting about 3% of the world’s population, leading to liver damage, end-stage liver disease, and development of hepatocellular carcinoma, being thus the first indication for liver transplantation in the USA. Apart from the cirrhotic-liver-derived clinical signs and symptoms several conditions with immunological origin can also arise, such as, glomerulonephritis, pulmonary fibrosis, and thrombocytopenia. HCV-related autoimmune thrombocytopenia shows specific pathogenetic characteristics as well as symptoms and signs that differ in severity and frequency from symptoms in patients that are not HCV infected. Aim of this short paper is to estimate the epidemiological characteristics of the disease, to investigate the pathogenesis and clinical manifestation, and to propose treatment strategies according to the pertinent literature

Current trends in platelet transfusions practice: The role of ABO-RhD and human leukocyte antigen incompatibility

Platelet transfusions have contributed to the revolutionary modern treatment of hypoproliferative thrombocytopenia. Despite the long-term application of platelet transfusion in therapeutics, all aspects of their optimal use (i.e., in cases of ABO and/or Rh (D incompatibility) have not been definitively determined yet. We reviewed the available data on transfusion practices and outcome in ABO and RhD incompatibility and platelet refractoriness due to anti-human leukocyte antigen (HLA) antibodies. Transfusion of platelets with major ABO-incompatibility is related to reduced posttransfusion platelet (PLT) count increments, compared to ABO-identical and minor, but still are equally effective in preventing clinical bleeding. ABO-minor incompatible transfusions pose the risk of an acute hemolytic reaction of the recipient that is not always related to high anti-A, B donor titers. ABO-identical PLT transfusion seems to be the most effective and safest therapeutic strategy. Exclusive ABO-identical platelet transfusion policy could be feasible, but alternative approaches could facilitate platelet inventory management. Transfusion of platelets from RhD positive donors to RhD negative patients is considered to be effective and safe though is associated with low rate of anti-D alloimmunization due to contaminating red blood cells. The prevention of D alloimmunization is recommended only for women of childbearing age. HLA alloimmunization is a major cause of platelet refractoriness. Managing patients with refractoriness with cross-matched or HLA-matched platelets is the current practice although data are still lacking for the efficacy of this practice in terms of clinical outcome. Leukoreduction contributes to the reduction of both HLA and anti-D alloimmunization

A Successful Mother and Neonate Outcome for a Woman with Essential Thrombocytosis and FV Leiden Heterozygosity

Essential thrombocytosis (ET) and FV Leiden heterozygosity represent an acquired and hereditable hypercoagulable state, respectively. An uncommon case of coexistence of ET and FV Leiden heterozygosity in a 36-year-old pregnant woman and her successful pregnancy outcome is described. She was considered to be at high risk of thrombosis during her pregnancy and she was treated with both prophylactic dose of LMWH and aspirin daily throughout her pregnancy and for a 6-week period postpartum. The efficacy of the anticoagulation treatment was monitored in various time points not only by measuring anti-Xa levels and D-Dimers but also with new coagulation methods such as rotation thromboelastometry and multiplate. Global assessment of coagulation using additional newer laboratory tests might prove useful in monitoring coagulation pregnancies at high risk for thrombosis

Clotting Factor Deficiencies as an Underlying Cause of Abnormal Uterine Bleeding in Women of Reproductive Age: A Literature Review

Clotting Factor deficiencies are rare disorders with variations in clinical presentation and severity of symptoms ranging from asymptomatic to mild to life-threatening bleeding. Thus, they pose a diagnostic and therapeutic challenge, mainly for the primary health care providers, general practitioners, and gynecologists who are more likely to first encounter these patients. An additional diagnostic challenge arises from the variable laboratory presentations, as PT, PTT, and BT are not always affected. The morbidity is higher among women of reproductive age since Abnormal Uterine Bleeding–specifically Heavy Menstrual Bleeding–is one of the most prevalent manifestations of these disorders, and in some cases of severe deficiencies has led to life-threatening episodes of bleeding requiring blood transfusions or even immediate surgical intervention. Physician awareness is important as, in the case of some of these disorders–i.e., Factor XIII deficiency–prophylactic treatment is available and recommended. Although uncommon, the potential for rare bleeding disorders and for hemophilia carrier states should be considered in women with HMB, after more prevalent causes have been excluded. Currently, there is no consensus on the management of women in these instances and it is reliant on the physicians’ knowledge

Importance of Direct Antiglobulin Test (DAT) in Cord Blood: Causes of DAT (+) in a Cohort Study

The direct antiglobulin test (DAT) is the cornerstone of the diagnosis of hemolytic disease of the newborn (HDN). The aim of this study was to review the incidence and causes of positive DAT in cord blood in relation to development of HDN. Methods: We retrospectively reviewed all results of DAT, which is routinely performed in cord blood samples, along with the laboratory and infants' medical records. Results: DAT was positive in 70/2695 (2.59%) cases. In 64/70 (91.43%) cases, DAT positivity was attributed to ABO incompatibility. There were 50/218 (22.93%) DAT (+) cases in the A/O group and 13/97 (13.40%) cases in the B/O group (p = 0.0664). Two DAT (+) cases were attributed to maternal alloimmunization (anti-Fya and anti-JKb, respectively), and one to maternal IgG autoantibodies that developed after methyldopa treatment. Among the 70 DAT (+) cases, 30 (42.86%) cases required phototherapy with no difference between the A/O and B/O groups. The duration of phototherapy in the B/O group was significantly longer than in the A/O group (p = 0.024). There was a trend of correlation of increasing strength of DAT positivity with phototherapy need. No false positive DAT case was detected. Conclusions: Although ABO incompatibility remains the main reason of DAT (+), other causes (e.g., alloimmunization, drugs) should also be explored. The relevant impact of DAT (+) on HDN development should be considered