Anti-PF4 immunothrombosis without proximate heparin or adenovirus vector vaccine exposure.

Platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies and anti-PF4 antibodies cause heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), respectively. Diagnostic and treatment considerations differ somewhat between HIT and VITT. We identified patients with thrombocytopenia and thrombosis without proximate heparin exposure or adenovirus-based vaccination who tested strongly positive by PF4/polyanion enzyme-immunoassays and negative/weakly positive by heparin-induced platelet activation (HIPA) test but strongly positive by PF4-induced platelet activation (PIPA) test (ie, VITT-like profile).

Erratum to 'A comparative study in type 2 von Willebrand disease patients using four different platelet-dependent von Willebrand factor assays.' [Research and Practice in Thrombosis and Haemostasis Volume 7, Issue 3, March 2023, 100139].

[This corrects the article DOI: 10.1016/j.rpth.

A comparative study in patients with type 2 von Willebrand disease using 4 different platelet-dependent von Willebrand factor assays.

Background: Several assays are now available to evaluate platelet-dependent von Willebrand factor (VWF) activity.

Objective: To report the results obtained using 4 different assays in patients with von Willebrand disease (VWD) carrying variants mainly in the A1 domain, which is critical for VWF binding to glycoprotein Ib (GPIb) and ristocetin.

Methods: We evaluated 4 different assays, 2 gain-of-function mutant GPIb binding (VWF:GPIbM) and 2 ristocetin cofactor (VWF:RCo) assays, in 76 patients with type 2 VWD.

von Willebrand factor neutralizing and non-neutralizing alloantibodies in 213 subjects with type 3 von Willebrand disease enrolled in 3WINTERS-IPS.

Background: Type 3 von Willebrand disease (VWD) is the most severe form of this disease owing to the almost complete deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived products containing VWF or recombinant VWF rarely cause the development of alloantibodies against VWF that may be accompanied by anaphylactic reactions.

Objective: The objective of this study was to assess the prevalence of anti-VWF alloantibodies in subjects with type 3 VWD enrolled in the 3WINTERS-IPS.

Genetic determinants of enhanced von Willebrand factor clearance from plasma.

Background: Enhanced von Willebrand factor (VWF) clearance from plasma is associated with von Willebrand disease (VWD). However, the genetic background of this disease mechanism is not well defined.

Objective: To determine VWF variants that are associated with reduced VWF survival.

Successful Chemical Synovectomy in a Patient with Acquired von Willebrand Syndrome with Chronic Synovitis Due to Recurrent Knee Hemarthrosis: A Case Report.

Acquired von Willebrand syndrome (AVWS) is a rare, non-hereditary bleeding disorder related to heterogeneous medical conditions such as hematological malignancies and cardiovascular and autoimmune diseases. We describe the clinical course of a 62-year-old man with polycythemia vera who experienced post-traumatic knee and leg swelling due to hemarthrosis. He was treated at another center with low molecular weight heparin due to misdiagnosed deep vein thrombosis further exacerbating the ongoing bleeding.

Phenotypic and genetic characterizations of the Milan cohort of von Willebrand disease type 2.

von Willebrand disease (VWD) type 2 is caused by qualitative abnormalities of von Willebrand factor (VWF). This study aimed to determine the genotypic and phenotypic characterizations of a large VWD type 2 cohort from Milan. We included 321 patients (54% female) within 148 unrelated families from 1995 to 2021.

Rise of levels of von Willebrand factor and factor VIII with age: Role of genetic and acquired risk factors.

Background: Von Willebrand factor (VWF) levels are regulated by genetic and acquired factors. The acquired factors are mostly related to age and could be mediators of the age effect on VWF levels.

Objectives: To disentangle the role of genetic (sex, blood group) and acquired factors (comorbidities, body mass index, reduced kidney function, hormone use, and inflammation) in regulating von Willebrand factor antigen (VWF:Ag) and factor VIII activity (FVIII:C) levels in the normal population.

Increasing levels of von Willebrand factor and factor VIII with age in patients affected by von Willebrand disease.

Essentials VWF and FVIII increase with age in patients affected by VWD. VWF and FVIII increase in type 1 and in low levels of VWF patients. VWF and FVIII do not increase in type 1 Vicenza.

How I treat gastrointestinal bleeding in congenital and acquired von Willebrand disease.

Gastrointestinal (GI) bleeding is distinctive of severe von Willebrand disease (VWD), generally arising in older patients; in most cases, blood transfusion and hospitalization are required. The presence of arteriovenous malformations is often described when endoscopic examinations are performed. Patients with congenital type 3, 2A, and 2B are those most frequently affected by this symptom, possibly due to the loss of high-molecular-weight multimers of von Willebrand factor (VWF).

Management of rare acquired bleeding disorders.

Autoantibodies toward clotting factors may develop in people suffering from autoimmune or neoplastic diseases, after drug intake or even in subjects without apparent conditions. They are more commonly directed against factor VIII (FVIII) or von Willebrand factor leading to acquired hemophilia A or acquired von Willebrand syndrome, respectively. Rarely, autoantibodies develop against other clotting factors, such as fibrinogen, FII, FV, FVII, FX, FXI, and FXIII.

A two-step approach (Enzyme-linked immunosorbent assay and confirmation assay) to detect antibodies against von Willebrand factor in patients with Acquired von Willebrand Syndrome.

Background: Acquired von Willebrand Syndrome is a rare bleeding disorder, which arises in individuals with no personal or family history of bleeding, associated with lymphoproliferative and myeloproliferative disorders or other diseases.

Aim: To develop a two-step approach assay to detect autoantibodies against VWF and to verify their prevalence in AVWS.

Methods: AVWS definition: negative personal or family history of bleeding diathesis, VWF below normal range and recent history of bleeding manifestations.

Normal reference ranges of antithrombin, protein C and protein S: effect of sex, age and hormonal status.

Introduction: Antithrombin (AT), protein C (PC) and protein S (PS) deficiencies are risk factors for venous thromboembolism. Overlapping values between heterozygous carriers and normal individuals often make a correct classification of a deficiency difficult. The aim of this study was to investigate the effect of sex, age, menopause and hormone therapy on natural anticoagulant plasma levels in a large group of healthy individuals, and to evaluate the need of separate reference ranges.

Laboratory diagnostic outcome applying detection criteria recommended by the Scientific and Standardization Committee of the ISTH on Lupus Anticoagulant.

This study shows the diagnostic outcome of an APTT-based and two dRVVT-based commercial confirmatory integrated tests with the application of the recommendations by the Scientific and Standardization Committee (SSC) on Lupus anticoagulant (LA)/antiphospholipid syndrome (APS) of the International Society on Thrombosis and Haemostasis (ISTH) issued in 2009 concerning the cut-off values for the screening, mixing and confirmatory tests for the detection of LA and the mandatory need to perform mixing tests of patient plasma with pooled normal plasma. The study population included 565 patients collected from a large central coagulation laboratory, for which the attending physicians requested LA detection. One-hundred-six healthy subjects (HS) and 131 selected patients on oral anticoagulant therapy (OAT) were included as negative controls.

Risk factors for postpartum hemorrhage in a cohort of 6011 Italian women.

Introduction: Postpartum hemorrhage is responsible for 25% of maternal pregnancy-related deaths and it is the first cause of maternal morbidity and mortality worldwide.

Objective: To define the prevalence of postpartum hemorrhage and associated risk factors after vaginal birth and to develop a risk model that improves postpartum hemorrhage prediction.

Patients And Methods: All women who underwent a vaginal delivery at the Obstetric Unit of a large University hospital in Milan (Italy) between July 2007 and September 2009 were enrolled.

Coagulation testing before epidural analgesia at delivery: cost analysis.

Background: The usefulness of coagulation tests performed before epidural analgesia for surgery or to alleviate labour pain is controversial. The aims of this study were: (1) to evaluate the prevalence of abnormal tests in a large cohort of healthy pregnant women and their association with epidural hematoma; (2) to assess the approach of the anesthesiologists to women with abnormal tests; (3) to evaluate the cost of performing coagulation tests before epidural analgesia in all healthy pregnant women.

Methods: Data regarding epidural analgesia, epidural hematoma, PT, APTT, fibrinogen and platelet count were extracted from medical charts.

Standardization of lupus anticoagulant. Feasibility study of a calibration model to minimize between-method variability.

Background: Results for lupus anticoagulant (LA) are currently expressed as ratio of patient-to-normal clotting times (LA-ratio). Yet, numerical results do vary according to the method used for testing, thus making difficult the between-method comparison of results. We hypothesized that the standardization model currently used for the INR for patients on oral-anticoagulants (OAT) would be of value also for LA standardization.

Maternal and fetal thrombophilia in intrauterine growth restriction in the presence or absence of maternal hypertensive disease.

Intrauterine growth restriction (IUGR) depends on the placental capacity to transfer oxygen and nutrients from the maternal to the fetal circulation. Placental insufficiency may be caused by impairment of the maternal or fetal circulation by a thrombotic event, possibly associated with thrombophilic disorders. The goals of our study were to define the role of maternal/fetal gain-of-function factor V Leiden and prothrombin G20210A mutations in the development of IUGR and to evaluate whether maternal pregnancy-induced hypertensive diseases would modify any such association.

A new chromogenic assay (HemosIL ThromboPath) is sensitive to major prothrombotic risk factors affecting the protein C pathway. Results of a multicenter study.

The HemosIL ThromboPath assay (Instrumentation Laboratory) is a new chromogenic assay designed to globally evaluate the functionality of the protein C (PC) pathway. It is based on the ability of endogenous APC generated after activation of PC by a snake venom extract (Protac) to reduce the thrombin generation induced by a reagent containing tissue factor. The aim of this multicenter study involving three laboratories was to evaluate the test sensitivity to PC pathway abnormalities by retrospectively testing frozen plasma samples obtained in the different laboratories.