ABSTRACT
Background: Factor (F)XI deficiency is a rare bleeding disorder with a poor correlation between bleeding tendency and FXI level. Management of pregnant women with FXI deficiency is not clearly established, especially regarding neuraxial analgesia (NA). Objectives: A retrospective multicenter observational study was conducted in French hemostasis centers on pregnant women with FXI of <60 IU/dL. Methods: Data to report were (i) FXI levels before pregnancy and at time of delivery, (ii) type of NA and delivery management modalities, and (iii) possible complications related to NA and bleeding complications. Results: Three hundred fourteen pregnancies in patients with FXI deficiency of <60 IU/dL were reported (from 20 centers); among them, 199 NA procedures have been completed (137 epidurals and 61 spinals, 1 had both). The period of childbirth was mostly from 2014 to 2020 (281/314; 89.5%). Congenital FXI deficiency was established with certainty by investigators in 32.8% patients (n = 103). Previous bleedings were described in 20.4% of the patients (64/314; 45.3% cutaneous, 31.3% gynecologic, and 15.6% postsurgical). Thirteen deliveries had an NA procedure with FXI of <30 IU/dL, 42 with FXI of 30-40 IU/dL, and 118 with FXI of 40-60 IU/dL. Median FXI levels at delivery in the epidural and spinal groups were not significantly different but were significantly lower in the group without NA by medical staff contraindications. There were no complications related to NA. A 17.5% postpartum hemorrhage or excessive postpartum bleeding incidence was reported, which is consistent with previous data. Conclusion: Our data support the use of a 30 IU/dL FXI threshold for NA, as suggested by the French proposals published in August 2023.
ABSTRACT
The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society of Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals on the management of antiplatelet therapy for non-elective invasive procedures or bleeding complications. The proposals were discussed and validated by a vote; all proposals could be assigned with a high strength. Emergency management of oral antiplatelet agents (APA) requires knowledge on their pharmacokinetic/pharmacodynamics parameters, evaluation of the degree of the alteration of haemostatic competence and the associated bleeding risk. Platelet function testing may be considered. When APA-induced bleeding risk may worsen the prognosis, measures should be taken to neutralise antiplatelet therapy by considering not only the efficacy of available means (which can be limited for prasugrel and even more for ticagrelor) but also the risks that these means expose the patient to. The measures include platelet transfusion at the appropriate dose and haemostatic agents (tranexamic acid; rFVIIa for ticagrelor). When possible, postponing non-elective invasive procedures at least for a few hours until the elimination of the active compound (which could compromise the effect of transfused platelets) or if possible a few days (reduction of the effect of APA) should be considered.
Subject(s)
Hemorrhage/chemically induced , Hemorrhage/therapy , Hemostasis, Surgical/methods , Platelet Aggregation Inhibitors/adverse effects , Anesthesia , Critical Care , France , Hemostasis , Hemostatics/therapeutic use , Humans , Platelet Aggregation Inhibitors/pharmacokinetics , Platelet Function Tests , Platelet Transfusion , Prasugrel Hydrochloride/adverse effects , Prognosis , Societies, Medical , Ticagrelor/adverse effectsSubject(s)
Blood Coagulation Disorders/drug therapy , Hematologic Agents/administration & dosage , Kasabach-Merritt Syndrome/drug therapy , Sirolimus/administration & dosage , Administration, Oral , Case-Control Studies , Child, Preschool , Drug Administration Schedule , Female , Humans , Infant , Infant, Newborn , Male , Platelet Count , Treatment OutcomeABSTRACT
INTRODUCTION: Factor XIII (FXIII) deficiency is a rare hemorrhagic disorder whose early diagnosis is crucial for appropriate treatment and prophylactic supplementation in cases of severe deficiency. International guidelines recommend a quantitative FXIII activity assay as first-line screening test. FXIII antigen measurement may be performed to establish the subtype of FXIII deficiency (FXIIID) when activity is decreased. METHODS: The aim of this multicenter study was to evaluate the analytical and diagnostic levels of performance of a new latex immunoassay, K-Assay® FXIII reagent from Stago, for first-line measurement of FXIII antigen. Results were compared to those obtained with the Berichrom® FXIII chromogenic assay for measurement of FXIII activity. Of the 147 patient plasma samples, 138 were selected for analysis. RESULTS: The accuracy was very good, with intercenter reproducibility close to 7%. Five groups were defined on FXIII activity level (<5% (n = 5), 5%-30% (n = 23), 30%-60% (n = 17), 60%-120% (n = 69), above 120% (n = 24)), without statistical differences between activity and antigen levels (P value >0.05). Correlation of the K-Assay® with the Berichrom® FXIII activity results was excellent (r = 0.919). Good agreement was established by the Bland and Altman method, with a bias of +9.4% on all samples, and of -1.4% for FXIII levels lower than 30%. One patient with afibrinogenemia showed low levels of Berichrom® FXIII activity but normal antigen level and clot solubility as expected. CONCLUSIONS: The measurement of FXIII antigen using the K-Assay® is a reliable first-line tool for detection of FXIII deficiency when an activity assay is not available.
Subject(s)
Factor XIII Deficiency/blood , Factor XIII/analysis , Factor XIII/metabolism , Female , France , Humans , MaleSubject(s)
Hemophilia A/diagnosis , Molecular Diagnostic Techniques , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Senegal , Young AdultABSTRACT
Obturator muscles haematoma are rarely reported. The most often reported cases are primary pyomyositis or posttraumatic haematomas occurring during pelvic fractures. We firstly report herein two cases of spontaneous obturator internus haematoma (OIH) in two haemophiliacs with inhibitor. Clinical data and imaging of two patients treated in our clinic are reported here according to previously defined criteria of OIH in posttraumatic situation. Both patients were children suffering from severe and moderate haemophilia A, respectively, with an inhibitor at the time of the event. The clinical feature was marked by an iliopelvic pain letting discussing hip haemarthrosis, appendicitis or iliopsoas haematoma. For both patients ultrasonography (US) failed to provide the diagnosis. Careful and repeated clinical examinations eventually lead to suspect obturator haematoma which was confirmed by abdominopelvic computed tomography (CT) and magnetic resonance imaging (MRI). Respectively, high dose of FVIII or rFVIIa regimen allowed a rapid control of the muscular bleeding in the low and high responder inhibitor patients. Spontaneous OIH may be added to the differential diagnosis of iliopelvic pain in severe forms of haemophilia. US still often performed at first in such case remains unhelpful; abdominopelvic CT or MRI should be performed to discriminate among different diagnoses, including OIH which stays probably undiagnosed.
Subject(s)
Hematoma/etiology , Hemophilia A/complications , Psoas Muscles , Adolescent , Child , Humans , MaleABSTRACT
Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. The HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to assess this new method. First, the analytical performance of VWF:AC on an automated coagulo-meter (ACLTop) was determined, and then this new method was compared with VWF:RCo and the platelet function analyzer (PFA100) for 160 patients referred for VWD screening. The VWF:AC achieved acceptable precision with within-run and between-run coefficients of variation ranging from 2.3% to 14.1%, and linearity from 10% to 100%. Despite some marked differences between VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The good analytical performance, and the sensitivity and specificity of VWF:AC to detect VWF deficiency renders it a suitable method for VWD screening. Our findings support VWF:AC use for the diagnostic work-up of VWD, paying close attention to concomitant clinical signs and bleeding score, as recommended for VWD.
Subject(s)
Blood Coagulation Tests/standards , von Willebrand Diseases/diagnosis , von Willebrand Factor/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Area Under Curve , Automation , Blood Coagulation Tests/methods , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , ROC Curve , Sensitivity and Specificity , Young AdultSubject(s)
Hemorrhagic Disorders/blood , Hemostasis/physiology , Infant, Premature, Diseases/blood , Thrombophilia/blood , Blood Coagulation Factors/metabolism , Blood Coagulation Tests , Humans , Infant, Newborn , Infant, Premature, Diseases/surgery , Platelet Function Tests , Preoperative Care , Risk FactorsABSTRACT
The development of inhibitors following factor VIII replacement therapy is a serious complication in severe inherited haemophilia. Whereas significant experience, notably in orthopaedic surgery, is now obtained with the use of bypassing agents in haemophilia with high-titre inhibitor, new surgical challenges might occur due to patients' increasing life expectancy. A 56-year-old severe haemophilia A patient with a high-titre inhibitor was diagnosed for probable right temporoparietal malignant glioneuronal tumour on cerebral magnetic resonance imaging (MRI) (4 cm x 3 cm cerebromeningeal tumour with perilesional oedema and transfalcial herniation) requiring total resection. Then recombinant activated FVII (rFVIIa) was chosen as the haemostatic agent: bolus of 270 microg kg(-1) every 2 h during the first 24 h, 180 microg kg(-1) every 3, 4 and 6 h, respectively, at days 2-3, from days 4-10 and finally from days 11-15. Tranexamic acid was associated. Pre- and postoperative courses were uneventful, the surgical procedure being assessed at optimal haemostatic condition without any unusual haemorrhage on MRI controls, diffuse intravascular coagulation criteria or thromboembolic event. Intensive rFVIIa therapy has shown to be safe and effective in this first reported neurosurgery about a malignant tumour exhibiting to a high-bleeding risk notably in haemophilia with high-titre inhibitor. The use of lower doses of rFVIIa might have been possible; however, in the absence of accurate test for monitoring rFVIIa therapy, the potentially life-threatening complications of this procedure required maximum haemostasis with high rFVIIa doses.
Subject(s)
Blood Coagulation Factor Inhibitors/blood , Cerebral Ventricle Neoplasms/surgery , Factor VIIa/therapeutic use , Hemophilia A/drug therapy , Cerebral Ventricle Neoplasms/immunology , Hemostasis, Surgical , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Postoperative Hemorrhage/prevention & control , Prothrombin Time , Recombinant Proteins/therapeutic useABSTRACT
Nonbacterial purpura fulminans (PF) is rare, usually follows viral infection in young children, and is characterized by specific coagulation disorders, requiring specific therapy. Following a transient rash, a 2-year-old previously healthy girl developed PF without haemodynamic impairment. Laboratory data revealed disseminated intravascular coagulation and a severe transient protein S deficiency. Antiprotein S autoantibodies and active human herpesvirus-6 (HHV6) replication were demonstrated. Purpuric skin lesions spread very rapidly despite broad-spectrum antibiotics and right leg amputation. Plasmapheresis and intravenous immunoglobulins gave complete clinical recovery and normalization of protein S level within 10 days, with progressive clearance of antiprotein S autoantibodies. Transient severe protein S deficiencies have previously been reported in patients with nonbacterial PF, usually after varicella infection. This is the first documented case of PF after HHV6 infection.
Subject(s)
Autoimmune Diseases/complications , Purpura Fulminans/virology , Roseolovirus Infections/complications , Amputation, Surgical , Autoimmune Diseases/therapy , Child, Preschool , Disseminated Intravascular Coagulation/etiology , Female , Heparin/therapeutic use , Herpesvirus 6, Human/isolation & purification , Herpesvirus 6, Human/physiology , Humans , Immunoglobulins/therapeutic use , Leg/surgery , Plasmapheresis/methods , Polymerase Chain Reaction , Protein S/analysis , Protein S Deficiency/etiology , Protein S Deficiency/therapy , Purpura Fulminans/therapy , Treatment Outcome , Virus ReplicationABSTRACT
PURPOSE: Danaparoid is a safe and effective drug for the treatment of heparin-induced thrombocytopenia (HIT). We describe an uncommon complication: danaparoid cross-reactivity with HIT antibodies. DESIGN AND SETTING: A retrospective observational multicenter study on HIT was conducted in France. In this study concerning HIT patients treated with lepirudin, 12 patients were treated with lepirudin because danaparoid cross-reacted with the heparin-dependent antibodies. RESULTS: Three groups of situations can be separated. In a first group, four patients received a short course of danaparoid until their initial functional HIT assay showed a cross-reactivity between danaparoid and HIT antibodies. One patient presented a fatal thrombotic complication but the relationship between this thrombotic complication and danaparoid cross-reactivity cannot be certain. In a second group, four patients received for 4 days at least a danaparoid treatment while the initial functional test did not show any danaparoid cross-reactivity. During danaparoid treatment, no significant increase of platelet count was observed and two patients presented a fatal thrombotic complication. In a third group, cross-reactivity between danaparoid and HIT antibodies was not checked before danaparoid therapy. During danaparoid treatment, no significant increase of platelet count was observed and the four patients developed a venous thromboembolic complication. CONCLUSION: Absence of any increase in platelet count after 3 to 5 days of danaparoid therapy and/or the occurrence of a new thrombotic event should lead to danaparoid cross-reactivity suspicion. However, before attributing thrombotic complications to danaparoid cross-reactivity, it is crucial to verify that the patients received the recommended danaparoid dosage regimen.
Subject(s)
Anticoagulants/adverse effects , Chondroitin Sulfates/pharmacology , Dermatan Sulfate/pharmacology , Heparin/adverse effects , Heparitin Sulfate/pharmacology , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Aged , Anticoagulants/administration & dosage , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Chondroitin Sulfates/administration & dosage , Chondroitin Sulfates/therapeutic use , Cross Reactions , Dermatan Sulfate/administration & dosage , Dermatan Sulfate/therapeutic use , Female , Hemostasis/drug effects , Heparin/administration & dosage , Heparin/pharmacology , Heparin/therapeutic use , Heparitin Sulfate/administration & dosage , Heparitin Sulfate/therapeutic use , Hirudins , Humans , Intensive Care Units , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/immunology , Recombinant Proteins/therapeutic use , Retrospective StudiesABSTRACT
Measurements of the velocity profile of water flowing on a glass surface using fluorescent nanoparticles and single fluorescent molecules as velocity probes show that the no slip boundary condition holds down to at least 10 nm from the surface. For water flowing on a hydrophobic solid surface, silanized glass, the no slip boundary condition fails, and a slip length of 45 nm is measured. These velocity measurements are complemented with atomic force microscopy measurements of dissipation on a small sphere oscillating near the surface with results in agreement with the velocity profiles.
ABSTRACT
Drag on a cylinder can be enhanced in the presence of polymers. This enhancement is directly related to the interaction of the polymers with the flow around the obstacle. The presence of the polymers modifies the flow in the vicinity of the cylinder giving rise to a band of higher shear, large molecular elongations and large velocity fluctuations. The measured drag on the cylinder is directly related to the modification of the flow field by the presence of the polymers.
Subject(s)
DNA, Viral/chemistry , Polymers/chemistry , Bacteriophage T4/chemistry , Bacteriophage T4/genetics , Bacteriophage lambda/chemistry , Bacteriophage lambda/genetics , Dimethylpolysiloxanes/chemistry , Polyethylene Glycols/chemistry , Silicones/chemistry , Sucrose/chemistry , ViscosityABSTRACT
Several recently developed detection techniques opened studies of individual metal nanoparticles (1-100 nm in diameter) in the optical far field. Eliminating averaging over the broad size and shape distributions produced by even the best of current synthesis methods, these studies hold great promise for gaining a deeper insight into many of the properties of metal nanoparticles, notably electronic and vibrational relaxation. All methods are based on detection of a scattered wave emitted either by the particle itself, or by its close environment. Direct absorption and interference techniques rely on the particle's scattering and have similar limits in signal-to-noise ratio. The photothermal method uses a photo-induced change in the refractive index of the environment as an additional step to scatter a wave with a different wavelength. This leads to a considerable improvement in signal-to-background ratio, and thus to a much higher sensitivity. We briefly discuss and compare these various techniques, review the new results they generated so far, and conclude on their great potential for nanoscience and for single-molecule labelling in biological assays and live cells.
Subject(s)
Metals/chemistry , Microscopy/methods , Nanostructures/ultrastructure , Absorption , Light , Scattering, RadiationABSTRACT
Heparin-induced thrombocytopenia (HIT) occurs in nearly 3% of patients treated with heparin after cardiopulmonary bypass (CPB). HIT carries a risk of severe thrombotic complications, and must be diagnosed rapidly. To identify simple criteria for estimating the probability of HIT after CPB, we retrospectively analyzed the files of 84 patients with suspected HIT after CPB and we analyzed the usefulness of several variables collected at the time of HIT suspicion to estimate HIT probability. HIT was confirmed in 35 cases and ruled out in 49 cases, on the basis of a platelet increment after heparin withdrawal, detection of heparin-dependent antibodies, and absence of other clear cause of thrombocytopenia. A biphasic platelet count from CPB to the first day of suspected HIT, an interval of >/= 5 days from CPB to the first day of suspected HIT, and a CPB duration of = 118 min were independent risk factors for HIT. These variables were combined to create a post-CPB HIT probability score. The score correctly identified 34/35 HIT patients and 28/49-non-HIT patients. This score, which can be applied as soon as HIT is suspected after CPB, has very good negative predictive value (97%). Prospective studies are required to confirm these findings.
Subject(s)
Cardiopulmonary Bypass/adverse effects , Heparin/adverse effects , Predictive Value of Tests , Probability , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Aged , Antibodies/blood , Diagnosis, Differential , Female , Heparin/immunology , Humans , Male , Middle Aged , Platelet Count , Retrospective Studies , Risk FactorsABSTRACT
Cardiac surgery with extracorporeal circulation induces major alterations of haemostasis and requires high level of anticoagulation, usually achieved by unfractionated heparin infusion. Optimization of anticoagulant regimen, through adapted biological monitoring, can probably improve postoperative course, at least for postoperative haemostatic status. Despite increasing knowledge on extracorporeal circulation-induced haemostatic abnormalities and the development of new biological devices for heparin monitoring, the optimal level of anticoagulation remains matter of debate, as well as the monitoring procedures. This critical review presents the current available data on heparin anticoagulation and monitoring in this specific context, and underlines the pending issues about anticoagulation management during extracorporeal bypass.
Subject(s)
Anticoagulants/therapeutic use , Coronary Artery Bypass , Extracorporeal Circulation , Heparin/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/blood , Cardiac Surgical Procedures , Drug Resistance , Hemostasis/physiology , Heparin/administration & dosage , Heparin/blood , Humans , Monitoring, IntraoperativeABSTRACT
We present a simple method to stretch DNA molecules close to a surface without any chemical modification of either the molecules or the surface. By adjusting the pH of the solution, only the extremities of DNA molecules are tethered to a glass coverslip made hydrophobic, while stretching is achieved using a hydrodynamic flow. These extended molecules provide a very favorable template for DNA-protein interaction studies by purely optical means. Pursuing these experiments requires first a full characterization of the thermally driven fluctuations of the tethered DNA molecules. For this purpose, these fluctuations were recorded by fluorescence microscopy and were analyzed in terms of normal modes. Our experimental results are well described by a model accounting for the nonlinear elastic behavior of the chain. Remarkably, the proximity of the molecules to a rigid surface does not alter the main features of their dynamics, and our results are in agreement with previous studies on extended DNA in viscous solutions.