A Systematic Review of Efficacy and Safety of Plasma-Derived von Willebrand Factor/Factor VIII Concentrate (Voncento) in von Willebrand Disease.

Background:  For the treatment of von Willebrand disease (VWD), von Willebrand factor (VWF) concentrates can be used in on-demand, long-term prophylaxis, and surgical prophylaxis regimens.

Methods:  This systematic literature review was conducted to evaluate the efficacy, consumption, and safety of plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Voncento/Biostate) for the treatment of patients with any inherited VWD type. An electronic search was conducted in MEDLINE and Cochrane Library databases on VWD therapies.

Multicolor flow cytometry in clinical samples for platelet signaling assessment.

Background: Availability of multichannel cytometers and specific commercial antibodies makes flow cytometry a new option to simultaneously assess multiple intracellular platelet signaling pathways for clinical purposes, in small volume of blood or low platelet count.

Objectives: To describe a multicolor flow cytometry with fluorescent barcoding technique for screening signaling pathways downstream membrane receptors of major platelet agonists (adenosine diphosphate, thrombin, thromboxane, and collagen).

Methods: By comparison with immunoblotting, we first selected the target phosphoproteins, AKT, P38MAPK, LIMK, and SPL76; the times of stimulation; and phosphoflow barcoding conditions.

Management of rare inherited bleeding disorders: Proposals of the French Reference Centre on Haemophilia and Rare Coagulation Disorders.

Introduction: The rare coagulation disorders may present significant difficulties in diagnosis and management. In addition, considerable inter-individual variation in bleeding phenotype is observed amongst affected individuals, making the bleeding risk difficult to assess in affected individuals. The last international recommendations on rare inherited bleeding disorders (RIBDs) were published by the United Kingdom Haemophilia Centre Doctors' Organisation in 2014.

Continuous Infusion of Factor VIII and von Willebrand Factor in Surgery: Trials with pdFVIII LFB or pdVWF LFB in Patients with Bleeding Disorders.

Background:  A plasma-derived factor VIII product (pdFVIII; Factane 100 or 200 IU/mL) and a plasma-derived von Willebrand factor product (pdVWF; Wilfactin 100 IU/mL) are approved for replacement therapy by intravenous bolus injections in hemophilia A (HA) and von Willebrand disease (VWD), respectively. However, in situations requiring intensive treatment, continuous infusion (CI) may be desirable to better control target plasma factor levels.

Aim:  To evaluate the perioperative hemostatic efficacy and safety of these concentrates administered by CI.

Effectiveness of long-term prophylaxis using pdFVIII/VWF concentrate in patients with inherited von Willebrand disease.

Background: Patients with symptomatic von Willebrand disease (VWD) should be offered long-term prophylaxis (LTP) to prevent recurrent bleedings. Our objective was to evaluate the effectiveness and safety of Voncento®, a plasma-derived FVIII/VWF concentrate (ratio 1:2.4), administrated in LTP.

Report of surgeries, their outcome and the thrombin generation assay in patients with Factor XI deficiency: A retrospective single-centre study.

Background: In patients with FXI deficiency, the risk of surgery-related bleeding is poorly correlated with plasma FXI activity (FXI:C); the latter can therefore not be used as a reliable predictor of bleeding in surgeries.

Objectives: The aim of this retrospective study was to determine whether thrombin generation assay (TGA) could be used to evaluate the risk of surgery-related bleeding in FXI-deficient patients. TGA parameters were compared to FXI:C values, haemostatic treatments and surgical outcomes.

Acquired factor V inhibitor: a nation-wide study of 38 patients.

Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency <50% associated with inhibitor activity.

Effectiveness and safety of hFVIII/VWF concentrate (Voncento) in patients with inherited von Willebrand disease requiring surgical procedures: the OPALE multicentre observational study.

Background: In patients with moderate to severe qualitative and quantitative von Willebrand disease (VWD), even minor surgical procedures can be associated with a risk of life-threatening bleeding. Treatment strategies vary according to the levels of von Willebrand factor (VWF) and Factor VIII (FVIII). The aim of this study was to evaluate the effectiveness and the safety of Voncento (CSL Behring, Marburg, Germany), a plasma-derived FVIII/VWF concentrate (ratio 1:2.

Comparative Analysis of a French Prospective Series of 144 Patients with Heparin-Induced Thrombocytopenia (FRIGTIH) and the Literature.

Background:  Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatments, and only a few large patient cohorts have been reported. In this study, biological and clinical data from 144 French patients with HIT were analyzed in comparison with the literature.

Methods:  The diagnosis of HIT was confirmed in all patients by an immunoassay combined with serotonin release assay.

Gynecological and obstetric outcome in the French cohort of women with factor XIII deficiency.

Introduction: Congenital factor XIII deficiency is a very rare bleeding disorder affecting 33 patients in France. Besides its role in fibrin clot stabilization, factor XIII is involved in placental attachment. Fetal miscarriages represent a frequent and concerning issue for these patients.

Pregnancy-related thrombosis risk in patients with protein C deficiency and comparison with pregnant women with heterozygous factor V Leiden mutation.

: The risk of pregnancy-related venous thromboembolism is high in patients with inherited thrombophilia. The aim of this study was to compare the risk of pregnancy related-venous thromboembolism of women with protein C (PC) deficiency to patients with heterozygous factor V Leiden mutation. 145 consecutive pregnant women with confirmed PC deficiency or heterozygous factor V Leiden mutation were prospectively enrolled in the study.

A Prolonged Treatment Response in Acquired Von Willebrand Syndrome.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder. We report herein a case of AVWS due to a monoclonal gammopathy of undetermined significance, in which a transient but prolonged response to a treatment by intravenous immunoglobulin (IVIG) was observed. The diagnosis was fortuitously made in a preoperative setting for neurosurgery, after biological exploration of an isolated prolonged activated partial thromboplastin time.

Congenital factor XIII deficiency: comprehensive overview of the FranceCoag cohort.

This FranceCoag network study assessed 33 patients with congenital factor XIII (FXIII) deficiency presenting FXIII levels <10 iu/dl. Diagnosis was based on abnormal bleeding in 29 patients, a positive family history in 2, recurrent miscarriages in 1 and was fortuitous in 1. Eighteen patients (62·1%) presented life-threatening umbilical or intracranial haemorrhages (ICH).

Differential diagnosis of neonatal alloimmune thrombocytopenia: Type 2B von Willebrand disease.

At birth, severe thrombocytopenia without context of infection should mainly suggest neonatal alloimmune thrombocytopenia (NAIT), especially in case of a platelet count below 20 GL. We report two cases of severe neonatal thrombocytopenia, first suspected as being NAIT. Both had a platelet count below 20 GL with platelet clumps.

Pre-analytical effects of pneumatic tube system transport on routine haematology and coagulation tests, global coagulation assays and platelet function assays.

Introduction: Pneumatic tube system (PTS) in hospitals is commonly used for the transport of blood samples to clinical laboratories, as it is rapid and cost-effective. The aim was to compare the effects on haematology samples of a newly acquired ~2km-long PTS that links 2 hospitals with usual transport (non-pneumatic tube system, NPTS).

Methods: Complete blood cell count, routine coagulation assays, platelet function tests (PFT) with light-transmission aggregometry and global coagulation assays including ROTEM® and thrombin generation assay (TGA) were performed on blood samples from 30 healthy volunteers and 9 healthy volunteers who agreed to take aspirin prior to blood sampling.

Correlation between laboratory coagulation testing and thromboelastometry is modified during management of trauma patients.

Background: Thromboelastometry (ROTEM, Pentapharm GmbH, Munich, Germany) is increasingly being used to make a diagnosis of coagulopathy and to guide hemostatic therapy (HT). Although ROTEM parameters and standard laboratory test (SLT) correlated well before administration of HT, it is not known if this correlation persists after hemostatic resuscitation.

Methods: A retrospective analysis of prospectively collected data from a trauma registry (2011-2014) was performed.

Progressive endothelial damage revealed by multilevel von Willebrand factor plasma concentrations in atrial fibrillation patients.

Aims: Abnormal plasma concentrations of von Willebrand factor (vWF), a marker of prothrombotic risk, have been found in atrial fibrillation (AF) patients, but the extent of this variation is not clear. This study aimed to investigate the effect of different clinical forms of AF on plasma concentrations of vWF at different levels of the circulatory tree, both intracardiac and extracardiac.

Methods And Results: Peripheral (Pf), left atrial (LA), and coronary sinus (CS) blood samples were obtained during cardiac catheterization from 52 patients with paroxysmal AF (PAF), 36 with persistent AF (PsAF), and 17 control subjects (Ct) with left-sided accessory pathway Wolff-Parkinson-White syndrome.

Utility of a point-of-care device for rapid determination of prothrombin time in trauma patients: a preliminary study.

Background: Rapid and accurate determination of prothrombin time in trauma patients may help to faster control of bleeding induced coagulopathy. The goal of this prospective observational study was to investigate the accuracy of bedside measurements of prothrombin time by the mean of a point-of-care device (INRatio) in trauma patients.

Methods: Fifty blood samples were drawn at admission and during the acute care phase for standard coagulation assays (prothrombin time, International Normalized Ratio [INR], and fibrinogen) and INRatio testing (INR(A)) from 48 trauma patients.

Early coagulopathy in trauma patients: an on-scene and hospital admission study.

Purpose: Amongst trauma patients, early coagulopathy is common on hospital admission. No studies have evaluated the initial coagulation status in the pre-hospital setting. We hypothesise that the coagulopathic process begins at the time of trauma.

[Assessment of the interest of using confirmatory test in ELISA with use of high concentration of heparin-induced thrombocytopenia].

Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy caused by an antibody against heparin/Platelet Factor 4 (PF4) complex. It complicates the treatment with unfractionated heparin (UFH). The aim of the study was to assess the interest of using confirmatory test in ELISA with use of high concentration of heparin (100 UI/mL) in patients (n=15) with discordance between platelet activation test and ELISA test.