Obstetric outcomes in pregnant COVID-19 women: the imbalance of von Willebrand factor and ADAMTS13 axis.

Background: Thrombotic microangiopathy has been invoked as one of the most important mechanisms of damage in COVID-19 patients. Protease ADAMTS13 is a marker of microangiopathy responsible for controlling von Willebrand multimers size. Von Willebrand factor/ADAMTS13 ratio has been found impaired in COVID-19 patients outside pregnancy.

Focus on Key Issues in Immune Thrombotic Thrombocytopenic Purpura: Italian Experience of Six Centers.

Immune-mediated thrombotic thrombocytopenic purpura is a rare and challenging hematological disease caused by the antibody anti-ADAMTS13. Though the mortality rate has decreased considerably in recent years, fatalities still remain unacceptable. This study aimed at further adding to the existing knowledge of this medical challenge.

The Prognostic Value of ADAMTS-13 and von Willebrand Factor in COVID-19 Patients: Prospective Evaluation by Care Setting.

Background: Endothelial dysfunction, coupled with inflammation, induces thrombo-inflammation. In COVID-19, this process is believed to be associated with clinical severity. Von Willebrand factor (VWF), and a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS-13), are strong markers of endothelial dysfunction.

Anemone study: prevalence of risk factors for superficial vein thrombosis in a large Italian population of blood donors.

Knowledge of the distribution of risk factors for superficial thrombosis (SVT) in low-risk population is fundamental to improve the prevention of the disease in each individual and high-risk settings of patients. Exact frequency data for the low-risk population are scarce, but could be useful for optimal use of prophylactic strategies against venous thrombosis. Blood donors represent a low-risk population, because are healthier than the general population.

Thromboelastography parameters in Italian pregnant women: do antithrombotic drugs change reference values?

This study was carried out to explore hemostasis modifications occurring in pregnant women and thromboelastography profiles in those taking antithrombotic drugs. An exploratory study was carried out in the period from March 2017 to May 2018. Caucasian women from Southern Italy were recruited during a routine obstetric assessment.

Identification of novel mutations in patients with fibrinogen disorders and genotype/phenotype correlations.

Background: Congenital fibrinogen disorders are caused by variants occurring within the fibrinogen gene cluster. We describe ten subjects with disease-causative variants, adding information on such disorders.

Materials And Methods: Ten subjects were referred to our Centre because of likely hypo/dysfibrinogenaemia.

Antiphospholipid Antibodies in a General Obstetric Population: Clinical Impact on Pregnancy Outcome and Relationship with the M2 Haplotype in the Annexin A5 (ANXA5) Gene.

Antiphospholipid (aPL) antibodies are recognised risk factors for adverse obstetric outcomes. Recently, carriers of the M2 haplotype in the gene have been shown to have a higher susceptibility to develop aPL antibodies. In a general obstetric population, we prospectively evaluated the possible relationship between: (1) aPL antibodies and M2 haplotype; and (2) aPL antibodies and/or M2 haplotype and obstetric outcomes.

Factor XI gene variants in factor XI-deficient patients of Southern Italy: identification of a novel mutation and genotype-phenotype relationship.

Congenital Factor XI (FXI) deficiency shows a high variability in clinical phenotype. To date, many allele variants have been shown to cause this bleeding disorder. However, the genotype-phenotype relationship is difficult to establish.

Modulation of factors involved in placental haemostasis and angiogenesis by low-molecular-weight-heparins.

Purpose: In placentae from uneventful pregnancies a direct relationship between expression of tissue factor (TF) and tissue-factor pathway inhibitor type 2 (TFPI2) was found, as well as between TF and vascular endothelial growth factor (VEGF). Furthermore, placentae from gestational vascular complications (GVCs) lack these correlations. Aims of the present study are (1) to evaluate a possible role of low-molecular-weight-heparins (LMWHs) in the modulation of the expression of TF, TFPI, TFPI2 and VEGF in placentae from thrombophilic women and (2) to study the possible role of endothelium in the placental expression of markers involved in haemostasis and angiogenesis.

Pharmacogenetics of dabigatran etexilate interindividual variability.

Introduction: Dabigatran etexilate is given in fixed doses without coagulation monitoring for the prevention of blood clots in at risk adults. A high inter-individual variability in blood concentrations of the active metabolite of dabigatran has been reported. ABCB1 and CES1 exert an important effect in the metabolism of dabigatran etexilate and allele variants at these two loci are likely to play a pivotal role.

Clinical utility of antithrombotic prophylaxis in ART procedures: an Italian experience.

Background: The usefulness of antithrombotic prophylaxis in management of Assisted Reproductive Technologies (ART) is questionable.

Objectives: We prospectively examined the contribution of an antithrombotic prophylaxis in influencing clinical pregnancy and live-birth in an unselected cohort of women approaching ART.

Patients/methods: 1107 women with fertility problems and a valid indication for ART were recruited.

A reliable and rapid tool for plasma quantification of 18 psychotropic drugs by ESI tandem mass spectrometry.

A simple liquid chromatographic tandem mass spectrometry (LC-MS/MS) method has been developed for simultaneous analysis of 17 basic and one acid psychotropic drugs in human plasma. The method relies on a protein precipitation step for sample preparation and offers high sensitivity, wide linearity without interferences from endogenous matrix components. Chromatography was run on a reversed-phase column with an acetonitrile-H₂O mixture.

An unreported mutation within protein Z gene is associated with very low protein levels in women with fetal loss.

Gene variant intron C G-42A of protein Z is significantly associated with the occurrence of fetal loss. A previously unreported sporadic missense mutation within exon 8 is described in a patient with very low protein Z levels.

Antithrombotic prophylaxis during pregnancy in women with deficiency of natural anticoagulants.

Prevalence of obstetric complications in women with deficiency of natural anticoagulants is difficult, because these defects are very rare in general population. Furthermore, the available data on prophylactic intervention in such individuals to decrease the obstetric risk are also very limited. To evaluate in a setting of women with rare hereditary thrombophilias, deficiency of antithrombin, protein C or protein S whether thromboprophylaxis during pregnancy could affect foeto-maternal outcome.

Gain-of-function gene mutations and venous thromboembolism: distinct roles in different clinical settings.

Objective: To calculate the prevalence of common gain of function gene mutations in patients with different clinical manifestations of venous thromboembolism.

Design And Setting: Case-control study in two hospitals in Italy.

Participants: 387 patients with venous thromboembolism and 286 controls.

Symptomatic venous thromboembolism and thrombophilic status in adult acute leukemia: a single-center experience of 114 patients at diagnosis.

Inherited and acquired thrombophilia are associated with venous thromboembolic events (TE). The prevalence of inherited and acquired prothrombotic risk factors and the incidence of symptomatic TE were evaluated in a cohort of 114 adult acute leukemia patients. The most frequent prothrombotic risk factor was hyperhomocysteinemia which occurred in 46.

Inherited abnormalities of fibrinogen: 10-year clinical experience of an Italian group.

Inherited abnormalities of fibrinogen present a high variability in penetrance and expressivity, and clinical manifestations vary from severe bleeding or thrombosis to asymptomatic This variability makes clinical and genetic counseling more difficult. We report the experience of a clinical group working in specialist centers in Southern Italy on a series of consecutive patients presenting with congenital abnormalities of fibrinogen. Over 10 years, 18 patients were diagnosed to carry a congenital abnormality of fibrinogen.

Polymorphisms in factor II and factor VII genes modulate oral anticoagulation with warfarin.

Background And Objectives: There is very considerable inter-individual variability in warfarin dosages necessary to achieve target therapeutic anticoagulation. The variability is largely genetically determined but can only partly be explained by genetic variability in the cytochrome CYP2C9 locus. Polymorphisms within the genes coding for vitamin K-dependent proteins have been suggested to predict sensitivity to warfarin therapy.

Protein Z levels and unexplained fetal losses.

We evaluated protein Z plasma levels in a group of women with fetal losses (n = 124) and compared them with those in a group of women (n = 60) with uneventful pregnancies. We found that protein Z deficiency is not associated with otherwise unexplained fetal losses.

Homocysteine and antiphospholipid antibodies in a woman undergoing ovarian follicular stimulation: prospective clinical and laboratory evaluation.

This is the case of a 28-year-old woman in apparently good health, who had an ischemic stroke and significant proteinuria developed during her first attempt of in vitro fertilization. She was evaluated for inherited and acquired thrombophilia and tested positive for high titer of antiphospholipid antibodies and mild hyperhomocysteinemia. The potential thrombotic risks associated with in vitro fertilization will be discussed.