RESUMEN
A young patient experienced a generalized seizure during the placement of an axillary plexus block. The mechanisms, essentially the presumed intravascular administration, which led to the local anesthetic toxicity as the cause of this event, are discussed. This case is an example of how visualization of the anatomy by ultrasound can give a false impression when certain details are not respected. It is assumed that the main mechanism in this case was venous compression by the ultrasound transducer.
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Anestesia de Conducción , Plexo Braquial , Bloqueo Nervioso , Anestésicos Locales/efectos adversos , Plexo Braquial/diagnóstico por imagen , Humanos , Inyecciones , Bloqueo Nervioso/efectos adversos , ConvulsionesRESUMEN
Linkage analysis in autosomal inherited von Willebrand disease (VWD) is important to diagnose the carriers and reduce the burden of severe type VWD. The study was designed to identify the carriers and estimate the frequency of variable number of tandem repeats (VNTR) instability in VWD families. Carrier detection was performed in eight recessive type 3 VWD (VWD3) families using VNTRs VWF1 and VWF2, RsaI (789Thr/Ala) linkage markers, multimer analysis and DNA sequencing. Moreover, five dominant VWD families were studied through DNA sequencing and multimer analysis. Frequency of VWF VNTR instability was investigated in 20 VWD families. In VWD3 families, a total of 22 (81.5%) carriers were identified using VWF1 and VWF2 markers. However, only 13(48.1%) carriers were identified through RsaI markers. Mutation screening revealed 22(81.5%) carriers in VWD3 and 4 (33.3%) carriers in VWD2 families. In comparison to DNA sequencing, the accuracy of VWF1 and VWF2 markers in VWD3 was 85.7% while RsaI could identify 68.2% carriers accurately. Mutations p.R1205H and p.C1272R were identified as de novo in families. Multimer analysis confirmed the identified carriers in VWD2 families. Three VWD families were found to be carrying VNTR instability for VWF1 and VWF2 locus. VNTRs could be an effective linkage markers for carrier detection in VWD3 families. However, in the event of germline de novo mutations and VNTR instability, it may confound risk of misdiagnosis of carriers. Multimer analysis could be an alternative way of carrier detection in dominant type 2A and type 2B VWD families.
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Portador Sano/diagnóstico , Análisis Mutacional de ADN , Ligamiento Genético/genética , Marcadores Genéticos/genética , Mutación de Línea Germinal/genética , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/genética , Femenino , Sitios Genéticos/genética , Inestabilidad Genómica/genética , Humanos , Masculino , Linaje , Secuencias Repetidas en Tándem/genéticaRESUMEN
Effects of desmopressin (DDAVP) in platelet disorders and primary haemostasis cannot be attributed solely to the increase in FVIII/VWF (von Willebrand factor), as VWF/FVIII concentrates have no effect in these circumstances. Microparticles (MP) can support haemostasis by expression of phospholipids, tissue factor and VWF on their surface. We hypothesized that significant amounts of VWF are bound to MP after DDAVP administration and that consequently depletion of MP should influence VWF:Ag and VWF:RCo plasma levels. Platelet-poor plasma was either obtained well from healthy controls or before and after DDAVP administration from patients with von Willebrand's disease (type 1 or possible type 1) or patients with other bleeding disorders as controls. Concentrations of MP and VWF parameters were determined before and after MP depletion by different methods (magnetic bead selection, plasma microfiltration, ultracentrifugation). Platelet MP and VWF-bearing MP were significantly increased after DDAVP. MP depletion by magnetic bead selection led to a significant reduction in VWF:Ag (-18.0%) and VWF:RCo (-27.7%) plasma levels without changes in VWF multimer composition. As results were similar for DDAVP control subjects, the amount of VWF bound to circulating microparticles was significantly higher after DDAVP administration compared with healthy controls (reduction -11.7%). DDAVP leads to a release of microparticles and increases the amount of VWF bound to microparticles which might explain the clinical efficacy of DDAVP in platelet disorders.
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Plaquetas/metabolismo , Micropartículas Derivadas de Células/metabolismo , Desamino Arginina Vasopresina/administración & dosificación , Hemostasis/efectos de los fármacos , Hemostáticos/administración & dosificación , Enfermedad de von Willebrand Tipo 1/tratamiento farmacológico , Factor de von Willebrand/metabolismo , Adulto , Anexina A5/sangre , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Adulto Joven , Enfermedad de von Willebrand Tipo 1/sangreRESUMEN
The first meeting of international specialists in the field of von Willebrand disease (VWD) was held in the Åland islands in 1998 where Erik von Willebrand had first observed a bleeding disorder in some members of a family from Föglö and a summary of the meeting was published in 1999. The second meeting was held in 2010 and a report of the meeting was published in 2012. Topics covered included progress in understanding of VWD over the last 50 years; multimers; classification of VWD; pharmacokinetics and laboratory assays; genetics; treating the paediatric patient; prophylaxis; geriatrics; gene therapy and treatment guidelines. This third meeting held over 3 days covered the structure and function of von Willebrand factor (VWF); type 1 VWD, the most common form of the disease; a lifespan of pharmacokinetics in VWD; detecting inhibitors in VWD patients; and special challenges in understanding and treating the female VWD patient.
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Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/terapia , Animales , Factor VIII/metabolismo , Femenino , Humanos , Enfermedades de von Willebrand/genética , Enfermedades de von Willebrand/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
von Willebrand's disease (VWD) is probably the most common bleeding disorder, with some studies indicating that up to 1% of the population may have the condition. Over recent years interest in VWD has fallen compared to that of haemophilia, partly the result of focus on blood-borne diseases such as HIV and hepatitis. Now the time has come to revisit VWD, and in view of this some 60 international physicians with clinical and scientific interest in VWD met over 4 days in 2010 in the Åland islands to discuss state-of-the-art issues in the disease. The Åland islands are where Erik von Willebrand had first observed a bleeding disorder in a number of members of a family from Föglö, and 2010 was also the 140th anniversary of his birth. This report summarizes the main papers presented at the symposium; topics ranged from genetics and biochemistry through to classification of VWD, pharmacokinetics and laboratory assays used in the diagnosis of the disease, inhibitors, treatment guidelines in different age groups including the elderly who often have comorbid conditions that present challenges, and prophylaxis. Other topics included managing surgeries in patients with VWD and the role of FVIII in VWF replacement, a controversial subject.
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Factor VIII/uso terapéutico , Enfermedades de von Willebrand/terapia , Factor de von Willebrand/uso terapéutico , Factor VIII/farmacocinética , Terapia Genética , Humanos , Guías de Práctica Clínica como Asunto , Países Escandinavos y Nórdicos , Reino Unido , Estados Unidos , Enfermedades de von Willebrand/clasificación , Enfermedades de von Willebrand/metabolismo , Factor de von Willebrand/metabolismo , Factor de von Willebrand/farmacocinéticaAsunto(s)
Factor IX/genética , Factor VIIa/uso terapéutico , Hemartrosis/diagnóstico , Hemofilia B/diagnóstico , Inhibidor de Coagulación del Lupus/sangre , Pruebas de Coagulación Sanguínea , Preescolar , Factor IX/metabolismo , Factor IX/uso terapéutico , Hemartrosis/etiología , Hemartrosis/prevención & control , Hemofilia B/complicaciones , Hemofilia B/tratamiento farmacológico , Humanos , Lactante , Masculino , Mutación/genéticaRESUMEN
BACKGROUND: Aortic valve (AV) defects can destroy high molecular weight multimers (HMWM) of von Willebrand factor (VWF), leading to acquired von Willebrand syndrome (aVWS) type IIA. This syndrome is considered a cause for increased perioperative bleeding in AV surgery. If diagnosed before operation, administration of VWF/FVIII concentrates is recommended. However, there is currently no evidence that the VWF HMWM defect persists during surgery long enough to require haemostatic therapy. We hypothesized that the preoperative VWF HMWM defect corrects already during cardiopulmonary bypass (CPB) before any haemostatic therapy. METHODS: This prospective observational study enrolled 17 patients undergoing AV surgery, either isolated or associated with mitral valve or aorta surgery, and also 10 patients undergoing coronary artery bypass surgery (CABG) for comparison. VWF HMWM, VWF antigen (VWF:Ag) concentration, and collagen-binding capacity (VWF:CB) were measured before operation, directly after weaning from CPB, and on the first postoperative day. RESULTS: In 12 of the 17 subjects undergoing AV surgery (71%), VWF HMWM were abnormally absent before operation. At the end of CPB, VWF HMWM were normal in 15 of AV subjects (88%), and was normal in 16 subjects on the first postoperative day. VWF:Ag and VWF:CB were within or above the normal range at all three times. Two out of 10 subjects undergoing CABG (20%) had preoperative deficits of VWF HMWM that normalized after operation. CONCLUSIONS: Preoperative VWF HMWM defects corrected at the end of CPB in the absence of haemostatic therapy in most patients undergoing AV surgery. Diffuse bleeding occurring after CPB is unlikely to be related to persisting type 2A von Willebrand syndrome; other causes of coagulopathy should be suspected. Administration of VWF/FVIII concentrates appears unnecessary in this setting.
Asunto(s)
Válvula Aórtica/cirugía , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/cirugía , Enfermedad de von Willebrand Tipo 2/etiología , Adulto , Anciano , Pruebas de Coagulación Sanguínea/métodos , Transfusión Sanguínea , Puente de Arteria Coronaria , Femenino , Enfermedades de las Válvulas Cardíacas/sangre , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios/métodos , Estudios Prospectivos , Enfermedad de von Willebrand Tipo 2/sangre , Enfermedad de von Willebrand Tipo 2/terapia , Factor de von Willebrand/inmunología , Factor de von Willebrand/metabolismoRESUMEN
Von Willebrand factor (VWF) is an adhesive, multi-functional huge multimerized protein with multiple domains harboring binding sites for collagen, platelet glycoprotein receptors and coagulation factor VIII (FVIII). The functional domains enable VWF to bind to the injured vessel wall, to recruit platelets to the site of injury by adhesion and aggregation and to bind and protect FVIII, an important cofactor of the coagulation cascade. VWF function in primary haemostasis is located in particular in the arterial and micro-circulation. This environment is exposed to high shear forces with hydrodynamic shear rates ranging over several orders of magnitude from 10⻹ to 105 s-1 and requires particular mechanisms to enable platelet adhesion and aggregation under these variable conditions. The respective VWF function is strictly correlating with its multimer size. Lack or reduction of large VWF multimers is seen in patients with von Willebrand disease (VWD) type 2A which correlates with reduction of both VWF:platelet GPIb-binding and VWF:collagen binding and a bleeding phenotype. To prevent unlimited platelet adhesion and aggregation which is the cause of the microangiopathic disorder thrombotic thrombocytopenic purpura (TTP), VWF function is regulated by its specific protease ADAMTS13. Whereas a particular susceptibility of VWF to ADAMTS13 proteolysis is the cause of a frequent VWD type 2A phenotype, lack or dysfunction of ADAMTS13, either acquired by ADAMTS13 antibodies or by inherited ADAMTS13 deficiency (Upshaw-Schulman Syndrome), causes TTP. Therefore VWD and TTP represent the opposite manifestations of VWF related disorders, tightly linked to each other.
Asunto(s)
Proteínas ADAM/inmunología , Coagulación Sanguínea/inmunología , Hemostasis/inmunología , Enfermedades de von Willebrand/inmunología , Factor de von Willebrand/inmunología , Proteína ADAMTS13 , Animales , Humanos , Modelos InmunológicosRESUMEN
Deficiency or mutation of von Willebrand factor (VWF) leads to a coagulation disorder (von Willebrand disease; VWD) which requires a lifelong therapy. For avoiding maternal complications treatment may be necessary also in pregnancy, but placental transfer to the fetus might impact its coagulation system and evoke undesired side effects. As VWF is a very large molecule it may be assumed that it does not pass the placental barrier. To prove this hypothesis the materno-fetal transfer of recombinant VWF (rVWF) has been analyzed ex vivo in a total of 21 valid dual side placenta perfusions. Three groups of five placentas each have been perfused with physiological and up to ten-fold increased concentrations of rVWF for 2 h. Six placentas have been used for control perfusions. A series of different control parameters has been assessed for documentation of intactness and functionality of the placenta and the perfusion system. In not a single analysis, independent of time and concentration, rVWF was detected in the fetal circuit. In the maternal circuit VWF concentration decreased slightly during perfusion. These results demonstrate that recombinant VWF does not pass the human placenta.
Asunto(s)
Intercambio Materno-Fetal , Placenta/metabolismo , Factor de von Willebrand/farmacocinética , Adulto , Femenino , Humanos , Técnicas In Vitro , Perfusión , Embarazo , Proteínas Recombinantes/farmacocinética , Adulto JovenRESUMEN
We report on a 15-year-old girl referred to us for dyspnea. Investigations revealed multiple pulmonary emboli originating from iliac vein thrombosis. As under heparin therapy, d-dimers rose again and the thrombus grew significantly in size while platelet count decreased by >30%. A diagnosis of heparin-induced thrombocytopenia (HIT) type II was suspected, heparin-treatment was stopped and lepirudin therapy was started successfully at a doses of 0.15 mg/kg bw/hr.
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Anticoagulantes/efectos adversos , Fibrinolíticos/uso terapéutico , Heparina/efectos adversos , Vena Ilíaca , Embolia Pulmonar/tratamiento farmacológico , Trombocitopenia/inducido químicamente , Trombosis/tratamiento farmacológico , Adolescente , Anticoagulantes/uso terapéutico , Diagnóstico Diferencial , Relación Dosis-Respuesta a Droga , Femenino , Heparina/uso terapéutico , Hirudinas , Humanos , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Embolia Pulmonar/diagnóstico , Proteínas Recombinantes/uso terapéutico , Recurrencia , Trombosis/diagnóstico , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler , Vena Cava InferiorRESUMEN
UNLABELLED: Heparin-induced thrombocytopenia (HIT II) in childhood is rare. Suspected HIT II requires immediate diagnostic and therapeutic measures in order to avoid potentially life threatening complications. Heparin must be stopped immediately. We report on a 6-year old boy who required cardiac surgery due to tetralogy of Fallot. To our knowledge he had been exposed to heparin for the first time during cardiac catheterization on the day before surgery. Preoperatively, platelet count was normal. Postoperatively (3 days after heparin exposure), he developed pulmonary and renal failure and required inotropic cardiac support and dialysis. He also developed progressive (severe) thrombocytopenia under heparin therapy on day 2-3 postoperatively. The dialysis filter required daily exchanges due to clotting despite increasing heparin doses. The first ELISA for HIT on postop day 4 was negative. 3 days later a repeated test was positive. Von Willebrand factor antigen and D-dimers were markedly increased. The patient was immediately switched to lepirudin and subsequently stabilized slowly. No major systemic thrombosis occurred. After lepirudin treatment for 6 weeks the patient was fully recovered and HIT II-testing was negative again. CONCLUSION: In children with progressive thrombocytopenia in the setting of heparin exposure and signs of major or micro thrombosis HIT II must be ruled out. Even if a first early test turns out negative repeated testing should be performed. Lepirudin anticoagulation is effective and should be monitored correctly. Platelet transfusion should be avoided in HITII.
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Anticoagulantes/uso terapéutico , Heparina/efectos adversos , Tetralogía de Fallot/cirugía , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Niño , Hirudinas , Humanos , Masculino , Periodo Posoperatorio , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
To determine the frequency and clinical relevance of acquired von Willebrand syndrome (aVWS) due to antiepileptic therapy by valproic acid, we investigated 50 consecutive children in three neuropediatric institutions. Coagulation factors were determined in local laboratories before and three times after starting therapy with valproic acid. Parameters of von Willebrand factor (VWF) were additionally investigated in a reference laboratory including multimeric analysis. Significant changes in the coagulation system were found concerning fibrinogen (decreased from 287 +/- 70 mg/dl to 222 +/- 67 mg/dl; p < 0.001) and platelet count. Changes of VWF parameters were also found but no patient developed laboratory defined aVWS. We conclude that the bleeding tendency observed in some children undergoing antiepileptic therapy with valproic acid is not due to aVWS.
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Anticonvulsivantes/efectos adversos , Ácido Valproico/efectos adversos , Enfermedades de von Willebrand/inducido químicamente , Factor de von Willebrand/metabolismo , Niño , Factor VIII/metabolismo , Humanos , Convulsiones/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Enfermedades de von Willebrand/epidemiologíaRESUMEN
UNLABELLED: We have prospectively evaluated the biologic response to desmopressin (DDAVP) in 28 children with type 2 von Willebrand disease (VWD) in correlation with the phenotype and the molecular defect of VWF. The diagnosis of VWD type 2 was mainly based on VWF functional parameters and/or an aberrant VWF multimer pattern. Seventeen different mutations were identified (6 of them novel). No response with respect to the functional parameters VWF:RCo and/or VWF:CB was seen in patients with severe abnormality of the VWF multimer pattern. One patient with VWD type 2A phenotype IIC Miami did not respond with respect to VWF:CB, but showed a good response of VWF:Ag and FVIII:C as expected. Interestingly he showed a persistently high level of VWF:Ag and FVIII:C up to 4 hours after DDAVP infusion. Patients with minor alterations of multimer structure and particular mutations responded well to DDAVP, whereas patients with normal multimer structure but a defect in platelet dependent functional parameters did not respond with VWF:RCo. CONCLUSION: Children with VWD type 2 show a variable response to desmopressin depending on the mutation that correlates with the functional defect and the presence or absence as well as the half-life of large VWF multimers. Our data emphasize the usefulness of DDAVP testing even in patients with VWD type 2, possibly with the exception of VWD type 2B.
Asunto(s)
Desamino Arginina Vasopresina/uso terapéutico , Enfermedades de von Willebrand/tratamiento farmacológico , Niño , Hemostáticos/uso terapéutico , Humanos , Mutación , Fenotipo , Enfermedades de von Willebrand/genética , Factor de von Willebrand/genéticaRESUMEN
BACKGROUND: Von Willebrand disease type 3 VWD is an autosomal-recessively inherited severe bleeding disorder with a homogeneous phenotype on the basis of very heterogeneous genotypes. Many different molecular defects have been reported to date. We tried to assess the molecular background of Indian and Greek patients with VWD type 3 by doing a complete VWF gene screen in all index patients. MATERIALS AND METHODS: We investigated 21 unrelated Indian and six Greek patients with type 3 VWD. Mutation screening was done by PCR and direct sequencing of the coding VWF exons 2-52 including flanking intron sequences. RESULTS: The diagnosis of VWD type 3 could be confirmed by the detection of null alleles or two mutations each in 22 patients. In one patient only one heterozygous mutation was identified. In four patients no mutations were identified for unknown reasons. Most of the defects cause null alleles. Eight patients had homozygous nonsense mutations - R1659X (6 patients), W553X (1 patients) and L1267X (1 patient); 2 patients were compound heterozygous - R324X/R373X and N318K/Q565X; 3 patients had small insertions - 3259insT, 3737insCC and 7173insT; 2 patients had small deletions - 3938delG and 1381delG; 2 patients had a duplication of 8 bp (duplAGTGTGGA) in exon 28 and a missense mutation (R273W) in exon 7; one patient had a heterozygous mutation K1794E (second mutation not identified); 5 patients had gene conversions between VWF and its pseudogene (117 bp to 335 bp in length corresponding to the 5' end of exon 28). The mutations as part of the gene conversion were - S1263P, P1266L, V1279I, Q1311X, A1317, I1343V, V1360A, and F1369I. CONCLUSION: VWD type 3 is caused by a broad variety of mutations distributed over the entire VWF sequence. As expected most mutations cause null alleles (16/23). The most common molecular defects found were gene conversions and R1659X in exon 28.
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Mutación , Enfermedades de von Willebrand/genética , Factor de von Willebrand/genética , Adolescente , Adulto , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Grecia , Humanos , India , MasculinoRESUMEN
von Willebrand disease (VWD) is a complex congenital bleeding disorder that is characterized by different quantitative and/or qualitative defects in von Willebrand factor (VWF). The diagnosis of VWD remains a challenge to the treating physician because of clinical and laboratory variability; many patients are oligosymptomatic and no single laboratory test is entirely diagnostic. Thus, a combination of patient medical history as well as several laboratory tests must be utilized to accurately diagnose and characterize the disease. The introduction of molecular techniques in the last two decades has greatly improved the ability to characterize the genetic variants of the disease. In contrast, however, progress in improving methods to classify the disease phenotype has been much slower. The current 'gold standard' for classifying VWD is the evaluation of VWF multimers, which enables the different types and subtypes of the disease to be discriminated. However, this method is technically demanding, not easy to standardize, and has not improved considerably over the last 25 years. This article reviews the current methods used to diagnose and characterize VWD and issues in the treatment of this complex disease.
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Enfermedades de von Willebrand/diagnóstico , Diagnóstico Diferencial , Factor VIII/uso terapéutico , Humanos , Mutación , Enfermedades de von Willebrand/clasificación , Enfermedades de von Willebrand/tratamiento farmacológico , Factor de von Willebrand/genética , Factor de von Willebrand/uso terapéuticoAsunto(s)
Sustitución de Aminoácidos/genética , Mutación/genética , Enfermedad de von Willebrand Tipo 2/genética , Factor de von Willebrand/química , Factor de von Willebrand/genética , Niño , Exones/genética , Factor VIII/genética , Femenino , Células HEK293 , Homocigoto , Humanos , Irán , Masculino , Proteínas Mutantes/metabolismo , Linaje , Fenotipo , Estructura Terciaria de Proteína , Proteínas Recombinantes/metabolismo , Enfermedad de von Willebrand Tipo 2/sangreRESUMEN
Von Willebrand disease (VWD) is known for its marked heterogeneity which was already recognized by von Willebrand in 1926. The basis of phenotypic differentiation are quantitative and qualitative or functional differences between the different types and subtypes of VWD. Clinical relevant facts for the practioner on diagnosis and therapy of von Willebrand disease and von Willebrand syndrome are presented.
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Enfermedades de von Willebrand/terapia , Factor de von Willebrand/fisiología , Desamino Arginina Vasopresina/farmacología , Factor VIII/fisiología , Hemostasis/efectos de los fármacos , Hemostasis/fisiología , Hemostáticos/farmacología , Humanos , Fenotipo , Agregación Plaquetaria/efectos de los fármacos , Ristocetina/farmacología , Enfermedades de von Willebrand/clasificación , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/genética , Factor de von Willebrand/genéticaRESUMEN
Essentials Bleeding complications during congenital heart disease surgery in neonatal age are very common. We report the perioperative incidence of acquired von Willebrand syndrome (aVWS) in 12 infants. aVWS was detected in 8 out of 12 neonates and infants intraoperatively after cardiopulmonary bypass. Ten patients received von Willebrand factor concentrate intraoperatively and tolerated it well. SUMMARY: Background Cardiac surgery of the newborn and infant with complex congenital heart disease (CHD) is associated with a high rate of intraoperative bleeding complications. CHD-related anatomic features such as valve stenoses or patent arterial ducts can lead to enhanced shear stress in the blood stream and thus cause acquired von Willebrand syndrome (aVWS). Objective To evaluate the intraoperative incidence and impact of aVWS after cardiopulmonary bypass (CPB) in neonates and infants with complex CHD. Patients/Methods We conducted a survey of patients aged < 12 months undergoing complex cardiac surgery in our tertiary referral center. Twelve patients, whose blood samples were analyzed for aVWS before CPB and immediately after discontinuation of CPB on a routine basis, were eligible for the analysis. von Willebrand factor antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo), collagen binding activity (VWF:CB), VWF:multimers and factor VIII activity (FVIII:C) were determined. Results aVWS was diagnosed by VWF multimer analysis in 10 out of 12 patients (83%) prior to surgery and intraoperatively at the end of CPB in 8 out of 12 patients (66%). Ten patients received VWF/FVIII concentrate intraoperatively as individual treatment attempts during uncontrolled bleeding. They tolerated it well without intraoperative thrombotic events. One patient suffered a transient postoperative cerebral sinuous vein thrombosis. Conclusions aVWS is of underestimated incidence in complex CHD surgery. These data may offer a new approach to reduce the risk of severe bleedings and to achieve hemostasis during high-risk pediatric cardiac surgery by tailoring the substitution with von Willebrand factor concentrate.
Asunto(s)
Cardiopatías Congénitas/cirugía , Enfermedades de von Willebrand/complicaciones , Pruebas de Coagulación Sanguínea , Procedimientos Quirúrgicos Cardíacos , Constricción Patológica/complicaciones , Conducto Arterioso Permeable , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/complicaciones , Hemorragia/complicaciones , Humanos , Incidencia , Lactante , Recién Nacido , Periodo Intraoperatorio , Periodo Perioperatorio , Enfermedades de von Willebrand/sangre , Enfermedades de von Willebrand/diagnóstico , Factor de von Willebrand/análisisRESUMEN
Essentials New VWF activity assays are increasingly used but information on their comparability is limited. This is an ISTH SSC-organized study (expert labs, 5 countries) to compare all available assays. VWF activity by six assays correlated well with each other. The new assays show improved characteristics - minor differences are noted. SUMMARY: Background Several new assays have become available to measure von Willebrand factor (VWF) activity. The new assays appear to have improved performance characteristics compared with the old reference standard, ristocetin cofactor activity (VWF:RCo), but information is limited about how they compare with VWF:RCo and each other. Methods The von Willebrand factor Subcommittee of the International Society for Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee (SSC) designed a collaborative study involving expert laboratories from several countries to compare available tests with each other and with VWF:RCo. Eight laboratories from five countries were provided with blinded samples from normal healthy individuals and well-characterized clinical cases. Laboratories measured VWF activity using all tests available to them; data from six laboratories, not affected by thawing during transportation, are included in this study. Results All tests correlated well with VWF:RCo activity (r-values ranged from 0.963 to 0.989). Slightly steeper regression lines for VWF:Ab and VWF:GPIbM were clinically insignificant. The new assays showed improved performance characteristics. Of the commercially available assays, the VWF:GPIbR using the AcuStar system was the most sensitive and could reliably detect VWF activity below 1 IU dL-1 . The lower limit of the measuring interval for the VWF:GPIbM and the VWF:GPIbR assays was in the 3-4 and 3-6 IU dL-1 range, respectively. Inter-laboratory variation was also improved for most new assays. Conclusion All VWF activity assays correlated well with each other and the VWF:RCo assay. The slight differences in characteristics found in the COMPASS-VWF study will assist the VWF community in interpreting and comparing activity results.
RESUMEN
Three preparations of purified von Willebrand factor (vWF), obtained from unrelated patients affected by type IIB von Willebrand disease, were found to have normal sialic acid content (between 129 and 170 nmol/mg of vWF, as compared with 158 +/- 17 nmol/mg in four normal preparations) and to induce platelet aggregation in the presence of physiologic levels of divalent cations and without addition of ristocetin. A monoclonal antibody that blocks the vWF binding domain of the platelet glycoprotein (GP)Ib caused complete inhibition of IIB vWF-induced aggregation. In contrast, a monoclonal antibody that blocks the receptor for adhesive proteins on the platelet GPIIb/IIIa complex failed to inhibit the initial response of platelets to high concentrations of IIB vWF. Moreover, IIB vWF caused agglutination of formalin-fixed platelets that was blocked only by the anti-GPIb antibody, suggesting that the binding of vWF to GPIb, even in the absence of ristocetin, results in platelet-platelet interaction that is followed by exposure of the GPIIb/IIIa receptors for adhesive proteins. Endogenous ADP, normally active platelet metabolism and fibrinogen binding to GPIIb/IIIa were necessary for maximal and irreversible platelet aggregation. In the absence of fibrinogen, however, aggregation was mediated by vWF binding to GPIIb/IIIa. A 52/48-kD tryptic fragment containing the GPIb binding domain of normal vWF completely blocked the aggregation induced by all three IIB vWF preparations. The present study defines in detail the mechanisms involved in IIB vWF-induced platelet aggregation. Moreover, it establishes that the GPIb binding domain of normal and IIB vWF are closely related and that desialylation is not required for the direct interaction of IIB vWF with GPIb.