Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 85
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Thromb Haemost ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073230

RESUMO

BACKGROUND: Data on the effect of ABO blood group (ABO), von Willebrand factor (VWF) levels, and age on factor VIII (FVIII) in non-severe haemophilia A (HA) is scarce. OBJECTIVE: To investigate if ABO, VWF levels, and age have an influence on the variability of FVIII levels and consequently on the assessment of severity in non-severe HA. PATIENTS/METHODS: Eighty-nine patients with non-severe HA and 82 healthy controls were included. Data on ABO was collected and FVIII clotting activity (FVIII:C) with one-stage clotting assay (FVIII:C OSA) and chromogenic substrate assay (FVIII:C CSA), FVIII antigen (FVIII:Ag) and VWF antigen (VWF:Ag) and activity (VWF:Act) were determined. RESULTS: In HA, FVIII:C OSA and CSA and FVIII:Ag were not different between non-O (n = 42, median 15.5, interquartile range 10.4-24.0; 10.0, 6.8-26.0 and 15.2, 10.7-24.9) and O (n = 47, 14.1, 9.0-23.0; 10.0, 5.0-23.0 and 15.2, 9.3-35.5), whereas in healthy controls, non-O individuals had significantly higher FVIII levels. FVIII: C showed no relevant correlation with VWF levels in HA, but we observed strong correlations in healthy controls. Age had only a minor influence in HA, but had a considerable impact on FVIII:C in healthy controls. In multivariable regression analysis ABO, VWF:Ag and age were not associated with FVIII:C in HA, whereas this model explained 61.3% of the FVIII:C variance in healthy controls. CONCLUSIONS: We conclude that in non-severe HA ABO and VWF levels do not substantially influence the variability of FVIII levels and age has only minor effects on it, which is important information for diagnostic procedures.

2.
Liver Int ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052552

RESUMO

BACKGROUND AND AIMS: Non-O blood type (BT) is a risk factor for thromboses, which has been attributed to its effects on von Willebrand factor (VWF)/factor VIII (FVIII) levels. Although high VWF/FVIII may be risk factors for portal vein thrombosis (PVT) in patients with advanced chronic liver disease (ACLD), the impact of BT on PVT is unknown. We aimed to assess (I) whether non-O-BT is a risk factor for PVT and (II) whether non-O-BT impacts VWF/factor VIII in patients with ACLD. METHODS: Retrospective analysis comprising two cohorts: (I) "US" including all adult liver transplantations in the US in the MELD era and (II) "Vienna" comprising patients with a hepatic venous pressure gradient (HVPG) ≥6 mmHg. RESULTS: (I) The "US cohort" included 84 947 patients (non-O: 55.43%). The prevalence of PVT at the time of listing (4.37% vs 4.56%; P = .1762) and at liver transplantation (9.56% vs 9.33%; P = .2546) was similar in patients with O- and non-O-BT. (II) 411 patients were included in the "Vienna cohort" (non-O: 64%). Mean HVPG was 18(9) mmHg and 90% had an HVPG ≥10 mmHg. Patients with non-O-BT had slightly increased VWF levels (318(164)% vs 309(176)%; P = .048; increase of 23.8%-23.9% in adjusted analyses), but this difference was driven by patients with less advanced disease. However, non-O-BT explained only 1% of the variation in VWF and had no effect on FVIII. CONCLUSIONS: Although non-O-BT impacts VWF in patients with early stage ACLD, its contribution to VWF variation is considerably smaller than in the general population. Moreover, non-O-BT had no impact on FVIII. These findings may explain the absence of an association between non-O-BT and PVT in patients with advanced cirrhosis.

3.
J Thromb Haemost ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073229

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication of cancer. Elevated D-Dimer is associated with an increased risk of cancer-associated VTE. Whether changes in D-Dimer over time harbor additional prognostic information that may be exploited clinically for dynamic prediction of VTE is unclear. OBJECTIVES: To explore the potential role of longitudinal D-Dimer trajectories for personalized prediction of cancer-associated VTE. PATIENTS/METHODS: 167 patients with active malignancy were prospectively enrolled (gastrointestinal: n=59 (35%), lung: n=56 (34%), brain: n=50 (30%), others: n=2 (1%); metastatic disease: n=74 (44%)). D-Dimer (median=0.8µg/mL [25th -75th percentile: 0.4-2.0]) was measured at baseline and during 602 monthly follow-up visits. Joint models of longitudinal and time-to-event data were implemented to quantify the association between D-Dimer trajectories and prospective risk of VTE. RESULTS: VTE occurred in 20 patients (250-day VTE risk=12.1%, 95%CI: 7.8-18.5). D-Dimer increased by 34%/month (0.47µg/mL/month, 95%CI: 0.22-0.72, p<0.0001) in patients who developed VTE, but remained constant in patients who did not develop VTE (change/month=-0.06µg/mL/month, 95%CI: -0.15-0.02, p=0.121). In joint modeling, a doubling of the D-Dimer trajectory was associated with a 2.8-fold increase in the risk of VTE (Hazard ratio=2.78, 95%CI: 1.69-4.58, p<0.0001). This finding was independent of established VTE risk factors. Highly personalized, dynamic predictions of VTE conditional on individual patients' D-Dimer trajectories could be obtained. CONCLUSIONS: D-Dimer increases before the onset of cancer-associated VTE, but remains constant over time in patients without VTE. This study represents proof-of-concept that longitudinal trajectories of D-Dimer may advance the personalized assessment of VTE risk in the oncologic setting.

4.
Res Pract Thromb Haemost ; 3(3): 503-514, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31294335

RESUMO

Background: Cancer-associated venous thromboembolism (VTE) is an important complication in the course of a malignant disease. Low ADAMTS-13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13) and increased von Willebrand Factor (VWF) levels in cancer patients have been described numerously. Objectives: Investigation of the influence of ADAMTS-13 and VWF on the probability of VTE and survival in malignancy. Patients/Methods: In the framework of the ongoing prospective Cancer and Thrombosis Study (CATS) ADAMTS-13 activity and VWF antigen levels were investigated in cancer patients. Results: In total, 795 patients with various tumor types (364 female/431 male, median age 62 years) were included; of those, 56 developed VTE and 359 patients died during a median follow-up time of 730 days. The hazard ratio (HR) of VTE per doubling of VWF level was 1.56 (95% confidence interval [CI] 1.13-2.16) in multivariable competing risk analysis. ADAMTS-13 levels showed no correlation with the incidence of VTE in univariate competing risk analysis. The HR of mortality per doubling of VWF level was 1.46 (95% CI 1.28-1.66) and per SD increment of ADAMTS-13was 0.90 (95% CI 0.81-1.00) in multivariable Cox regression analysis. Patients with VWF >75th percentile and concomitant low (<25th percentile) or medium (25-75th percentile) ADAMTS-13 values had the highest probability of mortality (HR 4.31 and 4.75, respectively). Conclusions: High VWF levels were significantly associated with the risk of developing VTE in cancer patients, whereas ADAMTS-13 was not. Low ADAMTS-13 and increased VWF levels were independently associated with worse overall survival.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31177280

RESUMO

Acquired von Willebrand syndrome is a frequently encountered complication of continuous flow ventricular assist devices, which may lead to clinically relevant bleeding in up to 30% of patients after continuous flow ventricular assist device implantation. As standard anticoagulation strategies may be detrimental, individualized treatment is called for, as described in our patient on the HeartMate III® left ventricular assist device.

6.
Blood Adv ; 3(5): 769-776, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30837214

RESUMO

Lupus anticoagulant (LA) has been associated with pregnancy complications and pregnancy loss. Identification of predictive factors could aid in deciding on therapeutic management. To identify risk factors for adverse pregnancy outcomes in high-risk women with persistently positive LA, we prospectively followed 82 women of childbearing age, of whom 23 had 40 pregnancies within the Vienna Lupus Anticoagulant and Thrombosis Study. Pregnancy complications occurred in 28/40 (70%) pregnancies, including 22 (55%) spontaneous abortions (<10th week of gestation [WOG]: n = 12, 10th to 24th WOG: n = 10) and 6 deliveries <34th WOG (15%, 3 due to severe preeclampsia/HELLP [hemolysis, elevated liver enzymes, and a low platelet count] syndrome, 3 due to placental insufficiency). One abortion was followed by catastrophic antiphospholipid syndrome. Neither a history of pregnancy complications nor of thrombosis, or prepregnancy antiphospholipid antibody levels were associated with adverse pregnancy outcomes. In logistic regression analysis, higher age was associated with a lower risk of adverse pregnancy outcome (per 5 years' increase: odds ratio [OR] = 0.41, 95% confidence interval [CI]: 0.19-0.87), a high Rosner index (index of circulating anticoagulant) predicted an increased risk (OR = 4.51, 95% CI: 1.08-18.93). Live birth rate was 15/28 (54%) in women on the combination of low-molecular-weight heparin and low-dose aspirin and 3/12 (25%) in those with no treatment or a single agent. We conclude that the risk of severe, even life-threatening pregnancy complications and adverse pregnancy outcomes is very high in women with persistent LA. A high Rosner index indicates an increased risk. Improved treatment options for women with persistently positive LA are urgently needed.

7.
Int J Lab Hematol ; 41(3): 404-411, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30860669

RESUMO

BACKGROUND: Haemolysis, lipaemia and hyperbilirubinaemia represent important challenges in the coagulation laboratory. Test results are influenced not only by the degree of the interfering substance but also by the detection system. METHODS: We investigated the interference of free haemoglobin, triglycerides and bilirubin on a "modified activated protein C (APC) resistance test," protein C activity and protein S (antigen and activity) with two coagulation analysers, the STA-R Evolution and the ACL TOP. RESULTS: Haemolysis interfered with all assays on the STA-R Evolution resulting in higher levels of protein C activity and lower levels of protein S and a decreased APC ratio compared with baseline levels. On the ACL TOP, haemolysis only diminished protein S antigen levels and the APC ratio. Lipaemia increased protein C activity and protein S activity levels on the STA-R Evolution, whereas APC-R decreased on the ACL TOP and protein S antigen could not be measured in any lipaemic samples. Hyperbilirubinaemia caused an increase in protein C activity and in protein S antigen and a decrease in APC-R on the STA-R Evolution, whereas a decline of protein C activity, of protein S antigen and of the APC-R could be observed in icteric samples on the ACL TOP. CONCLUSIONS: Our data show that the degree of interference associated with haemolysis, lipaemia and hyperbilirubinaemia is different in several assays. Some assay limitations were not reproduced, and limitations stated in kit inserts cannot be assumed to apply to all analysers.


Assuntos
Testes de Coagulação Sanguínea/métodos , Testes de Coagulação Sanguínea/normas , Coagulação Sanguínea , Proteína C/metabolismo , Transdução de Sinais , Resistência à Proteína C Ativada , Bilirrubina/sangue , Hemoglobinas , Hemólise , Humanos , Hiperbilirrubinemia/sangue , Hiperlipidemias/sangue , Proteína S , Reprodutibilidade dos Testes
8.
Int J Lab Hematol ; 40(6): 645-654, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30033570

RESUMO

INTRODUCTION: New methods for coagulation tests require careful assessment before routine use. We evaluated the analytical performance of five new coagulation assays for measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT). METHODS: PT Rec, PT Owren, aPTT, aPTT Lupus and aPTT Screen assays (Roche Diagnostics) were evaluated on cobas t 711 and cobas t 511 analysers (Roche Diagnostics) at four European centres. Analytical performance and method comparisons with relevant commercially available assays were performed to Clinical Laboratory Standards Institute guidelines using residual anonymized samples. Lot-to-lot comparison and equivalency of the cobas t analysers were also assessed; reference ranges were determined using samples from apparently healthy volunteers. RESULTS: Overall, coefficients of variation were ≤1.3% for within-run precision and ≤6.3% for total reproducibility across all sites. Deming regression analyses showed good agreement between each assay (cobas t 711) and respective comparator method (Pearson's r: 0.964-0.999, n > 120 samples/assay/site). Passing-Bablok regression analyses demonstrated equivalence of the two cobas t platforms for use with each assay (Pearson's r ≥ 0.995). Lot-to-lot consistency was high for all assays and comparisons (Pearson's r ≥ 0.998). Reference ranges (2.5th-97.5th percentiles; n = 200 samples/assay) in seconds were 8.4-10.6 (PT Rec), 18.2-27.2 (PT Owren), 23.6-30.6 (aPTT), 24.1-31.7 (aPTT Lupus) and 23.9-33.2 (aPTT Screen). CONCLUSION: Based on the excellent analytical performance and good agreement with relevant comparator methods, the five coagulation assays on the novel cobas t 711 and cobas t 511 analysers are suitable for routine use in core laboratories.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Tempo de Protrombina/métodos , Kit de Reagentes para Diagnóstico , Feminino , Humanos , Masculino , Tempo de Tromboplastina Parcial/métodos
9.
Int J Lab Hematol ; 40(6): 637-644, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30033683

RESUMO

INTRODUCTION: New laboratory methods to measure haemostatic function require careful assessment before routine use. We evaluated the analytical performance of four new coagulation assays for the measurement of fibrinogen by Clauss assay, prothrombin time-derived fibrinogen, thrombin time and D-dimer levels. METHODS: The four assays were evaluated on the cobas t 711 and cobas t 511 analysers at four centres in Europe. Analytical performance and method comparisons with other commercially available assays were performed according to Clinical and Laboratory Standards Institute guidelines (EP09-A3, EP05-A3) using residual anonymized human sodium citrate (3.2% [0.109M]) plasma samples. Lot-to-lot variability and the equivalency of each assay on the cobas t 711 and cobas t 511 analysers were also assessed. RESULTS: Overall, coefficients of variance were ≤4.1% and ≤8.6% for within-run precision and total reproducibility, respectively. Method comparison experiments showed good or acceptable agreement for each assay compared with their respective comparator method, and equivalency was demonstrated for the two cobas t platforms (Pearson's correlation coefficient ≥0.991). A high level of consistency was observed between lots for all four assays (Pearson's correlation coefficient ≥0.994). CONCLUSION: This multicentre study demonstrates excellent analytical performance for four new coagulation assays on the cobas t 711 and cobas t 511 analysers.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Tempo de Protrombina/métodos , Kit de Reagentes para Diagnóstico , Feminino , Humanos , Masculino , Tempo de Tromboplastina Parcial/métodos
10.
Clin Chim Acta ; 482: 124-135, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29626437

RESUMO

INTRODUCTION: Practical and ethical challenges as well as time and costs have restricted the generation of pediatric reference intervals. Therefore, pediatric reference intervals on coagulation parameters based on solid evidence are still scarce. Furthermore, reference intervals by age-group cannot reflect the dynamics of age and sex specific coagulation values during childhood. This study is the first to close this gap and provide continuous age and sex dependent reference intervals during childhood in hemostasis. METHODS: We used an innovative indirect method for providing continuous reference intervals for five common coagulation parameters: Activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin clotting time (TT), fibrinogen (FIB) and antithrombin (AT). Calculations were performed using retrospective laboratory data from pediatric patients between 2005 and 2015 of two major Austrian hospitals, resulting in a total of 195.360 measurements (aPTT: 55,100; PT: 35,492; TT: 35,295; FIB: 49,789; AT: 19,684). RESULTS: This multicenter study provides calculations of continuous reference intervals for five common coagulation parameters in a large pediatric cohort, accounting for age and gender. CONCLUSION: To the best of our knowledge, this is the first multicenter study, determining continuous pediatric coagulation reference intervals based on a large retrospective dataset.


Assuntos
Testes de Coagulação Sanguínea/normas , Coagulação Sanguínea , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Valores de Referência , Estudos Retrospectivos
11.
Arch Pathol Lab Med ; 142(8): 992-997, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29624078

RESUMO

CONTEXT: - Coagulation testing is challenging and depends on preanalytic factors, including the citrate buffer concentration used. OBJECTIVE: - To better estimate preanalytic effects of the citrate buffer concentration in use, the difference between results obtained by samples with 3.2% and 3.8% citrate was evaluated. DESIGN: - In a prospective observational study with 76 volunteers, differences related to the citrate concentration were evaluated. For both buffer concentrations, reference range intervals were established according to the recommendations of the C28-A3 guideline published by the Clinical and Laboratory Standards Institute. RESULTS: - In our reagent-analyzer settings, most parameters evaluated presented good comparability between citrated samples taken with 3.2% and 3.8% trisodium buffer. The ellagic acid containing activated partial thromboplastin time reagent (aPTT-FS) indicated a systemic and proportional difference between both buffer concentrations, leading to an alteration in its reference ranges. Further, a confirmation test for lupus anticoagulant assessment (Staclot LA) showed only a moderate correlation ( rρ = 0.511) with a proportional deviation between both citrate concentrations. Further, a statistically significant difference was found in the diluted Russell viper venom time confirmation testing, coagulation factors V and VIII, and the protein C activity, which was found to be of minor clinical relevance. CONCLUSIONS: - With caution regarding the potential impact of the reagent-analyzer combination, our findings demonstrate the comparability of data assessed with 3.2% and 3.8% buffered citrated plasma. As an exception, the aPTT-FS and the Staclot LA assay were considerably affected by the citrate concentration used. Further studies are required to confirm our finding using different reagent-analyzer combinations.


Assuntos
Testes de Coagulação Sanguínea/métodos , Citrato de Sódio , Tampões (Química) , Voluntários Saudáveis , Humanos , Estudos Prospectivos , Valores de Referência
12.
Clin Exp Med ; 18(3): 325-336, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29417256

RESUMO

The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42). Plasma clot formation and lysis were recorded continuously on a photometer after addition of an activation mix (tissue factor 2 pmol/l and tissue plasminogen activator 333 ng/ml). We used linear regression and ANCOVA for correlation analysis. Clot formation lag phase was prolonged in the presence of anticoagulants in a concentration-dependent manner for DOACs (dabigatran Spearman r = 0.74; rivaroxaban r = 0.78; apixaban r = 0.72, all p < 0.0001), INR dependent for phenprocoumon (r = 0.59, p < 0.0001), anti-Xa level dependent in LMWH samples (r = 0.90, p < 0.0001). Maximum rate of clot formation and peak clot turbidity were reduced in the presence of anticoagulants, but correlated only moderately with the comparator measures of anticoagulation. The clot lysis time was inversely correlated with DOAC concentrations in the presence of recombinant thrombomodulin. A direct ex vivo comparison between the effects of different classes of anticoagulants is possible with turbidimetric measurement of plasma clot formation and lysis. Anticoagulation inhibited clot formation in a plasma concentration manner for DOACs, INR dependent for phenprocoumon, and anti-Xa dependent for LMWH. Susceptibility to fibrinolysis increased with increasing DOAC concentrations.


Assuntos
Anticoagulantes/farmacologia , Fibrilação Atrial/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/fisiopatologia , Estudos de Casos e Controles , Dabigatrana/farmacologia , Inibidores do Fator Xa/farmacologia , Feminino , Tempo de Lise do Coágulo de Fibrina , Heparina de Baixo Peso Molecular/farmacologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Femprocumona/farmacologia , Plasma/efeitos dos fármacos , Plasma/metabolismo , Pirazóis/farmacologia , Piridonas/farmacologia , Rivaroxabana/farmacologia , Tromboplastina/farmacologia , Ativador de Plasminogênio Tecidual/farmacologia
13.
Scand J Clin Lab Invest ; 77(8): 651-657, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29081243

RESUMO

BACKGROUND AND AIMS: The aim of this study was to assess the circadian variation and the between- and within-subject variation in 10 healthy subjects over a period of 8 weeks by ROTEM®. We further evaluated the influence of elevated body mass index and the effect of low molecular weight heparin and antithrombin on clot formation. METHODS: Citrated blood samples were analysed in the NATEM® test system. The clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF) and the maximum lysis (ML) were assessed. RESULTS: Duplicate measurements showed that 23% of the CT and 31% of the CFT measurements had a coefficient of variation (CV) greater than 10%. The within-subject CV was 16% for the CT and 30% for the CFT. The MCF was fairly constant (6%), whereas ML showed more variation (18%). The between-subject CV was 6% for the CT and 20% for the CFT. Analytical variability was improved by summing up CT and CFT. Compared to morning values, CT, CFT and the sum of CT + CFT were shortened in the afternoon. High body mass index was associated with faster clotting. High concentrations of antithrombin had similar effects on clot formation as 0.2 IU/ml of enoxaparin. CONCLUSIONS: To overcome the influence of diurnal variation, we recommend obtaining blood samples at specified times in the morning. The within-subject variation should be taken into account, when serial measurements of drug effects are required.


Assuntos
Coagulação Sanguínea , Adulto , Índice de Massa Corporal , Ritmo Circadiano , Humanos , Masculino , Tromboelastografia , Adulto Jovem
14.
Biochem Med (Zagreb) ; 27(3): 030705, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28900368

RESUMO

INTRODUCTION: Lupus anticoagulant (LAC) testing is challenging. Most data are derived from a well-controlled study environment with potential alterations to daily routines. The aim of this retrospective cohort study was to assess the capacity of various LAC screening tests and derived mixing tests to predict a positive result in subsequent confirmation tests in a large cohort of patients. MATERIALS AND METHODS: In 5832 individuals, we retrospectively evaluated the accuracy of the aPTT-A, aPTT-LAscreen, aPTT-FS and dRVVTscreen and of their derived mixing tests in detecting a positive confirmation test result within the same blood specimen. The group differences, degree of correlation and the predictive accuracy of LAC coagulation tests were analysed using the Mann-Whitney U test, the Spearman-rank-correlation and by area under the receiver operating characteristic curve (ROC-AUC) analysis. ROC-AUCs were compared with the Venkatraman´s permutation test. RESULTS: The pre-test probability of patients with clinically suspected LAC was 36% in patients without factor deficiency or anticoagulation therapy. The aPTT-LAscreen showed the best diagnostic accuracy with a ROC-AUC of 0.84 (95% CI: 0.82 - 0.86). No clear advantage of the dRVVT-derived mixing test was detectable when compared to the dRVVTscreen (P = 0.829). Usage of the index of circulating anticoagulant (ICA) did not improve the diagnostic power of respective mixing tests. CONCLUSIONS: Among the parameters evaluated, aPTT-LAscreen and derived mixing test parameters were the most accurate tests. In our study cohort, neither other mixing test nor the ICA presented any further advantage in LAC diagnostics.


Assuntos
Anticoagulantes/sangue , Anticoagulantes/metabolismo , Inibidor de Coagulação do Lúpus/sangue , Inibidor de Coagulação do Lúpus/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Coagulação Sanguínea/fisiologia , Feminino , Testes Hematológicos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Adulto Jovem
15.
Thromb Res ; 158: 134-137, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28892658

RESUMO

We report four children from different families with homozygous antithrombin (AT) deficiency type II affecting the heparin binding site (p.Leu131Phe mutation). All children had severe spontaneous venous and/or arterial thromboembolic events shortly after birth. This report intends to raise awareness among clinicians about this rare but severe condition. When thrombosis occurs in an otherwise healthy newborn, a severe congenital thrombophilic disorder should be considered. In homozygous AT deficiency type II, AT activity is typically reduced but may also be in the normal range, posing a diagnostic challenge. Rapid diagnosis is important to initiate appropriate therapy. Standard anticoagulation with heparin may prove ineffective in severe AT deficiency, requiring substitution of AT concentrate and early switch to alternative anticoagulants such as vitamin K antagonists.


Assuntos
Trombofilia/complicações , Trombose/etiologia , Feminino , Humanos , Recém-Nascido , Masculino , Trombose/patologia
16.
Ann Hematol ; 96(6): 1023-1031, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28361296

RESUMO

Data regarding outcome and therapy of pregnancies in patients with homozygous antithrombin (AT) deficiency are very rare. We conducted a retrospective, descriptive investigation with emphasis on the obstetric history of eight women with homozygous AT deficiency heparin-binding site (HBS), who had at least one pregnancy. The aim of the study was to get a better insight into the outcome and identify suitable management procedures of pregnancy in this rare disease. All patients suffered from homozygous AT deficiency caused by the mutation c.391C>T p.Leu131Phe in the AT gene (SERPINC1). The women reported in total 23 pregnancies; one pregnancy was excluded because of induced abortion. We found that only seven out of the 22 analyzed pregnancies ended with a live infant, all of them were born preterm. Among the 15 negative outcomes, seven were early pregnancy losses and eight were intrauterine fetal deaths. We found no clear association between treatment protocols and outcome. Eight pregnancies were not treated at all; all of them ended with pregnancy loss. We conclude that homozygous AT deficiency HBS, a form of severe thrombophilia, is associated with high risk of pregnancy loss and preterm delivery. Rigorous anticoagulation and/or replacement of AT during pregnancy may improve the outcome.


Assuntos
Aborto Espontâneo/genética , Antitrombina III/genética , Mutação , Complicações Hematológicas na Gravidez/genética , Trombofilia/genética , Adolescente , Adulto , Anticoagulantes/uso terapêutico , Sítios de Ligação/genética , Feminino , Heparina/metabolismo , Heparina/uso terapêutico , Homozigoto , Humanos , Recém-Nascido , Nascimento Vivo , /estatística & dados numéricos , Gravidez , Complicações Hematológicas na Gravidez/tratamento farmacológico , Nascimento Prematuro , Estudos Retrospectivos , Fatores de Risco , Trombofilia/tratamento farmacológico , Adulto Jovem
17.
BMC Med ; 15(1): 54, 2017 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-28279213

RESUMO

BACKGROUND: Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death. Understanding the determinants of thrombotic risk in patients with LA may pave the way towards targeted thromboprophylaxis. In the Vienna Lupus Anticoagulant and Thrombosis Study (LATS), we systematically evaluate risk factors for thrombotic events in patients with LA. METHODS: We followed 150 patients (mean age: 41.3 years, female gender: n = 122 (81.3%), history of thrombosis or pregnancy complications: n = 111 (74.0%)), who tested repeatedly positive for LA until development of thrombosis, death, or censoring. The primary endpoint was a composite of arterial or venous thrombotic events (TEs). RESULTS: During a median follow-up of 9.5 years (range: 12 days-13.6 years) and 1076 person-years, 32 TEs occurred (arterial: n = 16, venous: n = 16; cumulative 10-year TE incidence: 24.3%). A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07--5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42-13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14-5.02) emerged as independent risk factors of both arterial and venous thrombotic risk. A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22). CONCLUSIONS: Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.


Assuntos
Inibidor de Coagulação do Lúpus/efeitos adversos , Trombose/epidemiologia , Trombose/etiologia , Adulto , Doenças Cardiovasculares/complicações , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
18.
Eur J Emerg Med ; 24(5): 340-346, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26703757

RESUMO

OBJECTIVE: To assess the prevalence, characteristics and prognosis of overt disseminated intravascular coagulation (DIC) in adult emergency department (ED) patients and identify markers of poor outcome. MATERIALS AND METHODS: In a chart review study, we analysed the occurrence of overt DIC in all patients (n=1 001 727) attending the University's ED from 2003 to 2014 applying the ISTH DIC score. The primary outcome measure was 30-day mortality. Logistic regression analysis was used to determine predictors of mortality. RESULTS: The initial inter-rater reliability in the diagnosis of DIC was 0.85 [κ; 95% confidence interval (CI), 0.77-0.92]. The main DIC precipitators were malignancy (47%), cardiovascular diseases (CVD, 27%) and sepsis (16%). Hyperfibrinolytic DIC occurred in 27% of patients and was over-represented in those with cardiac arrest (68%). Thirty-day mortality (52%) was inversely associated with fibrinogen levels on admission [adjusted odds ratio, 0.49; 95% CI: 0.30-0.82; P=0.006]. Afibrinogenaemia implied an even 10-fold increased risk of dying (crude odds ratio, 10.0; 95% CI: 3.2-31.4; P<0.001). D-dimer and platelet count had no predictive value. Appropriate ICD-10 coding for DIC was present in only 1.8% of cases. CONCLUSION: Overt DIC is a rare but underdiagnosed event in ED patients. In this collective, cardiac arrest is a dominant cause of DIC presenting with a fibrinolytic phenotype. The degree of hypofibrinogenaemia on admission strongly and linearly predicted early death.


Assuntos
Coagulação Intravascular Disseminada/diagnóstico , Serviço Hospitalar de Emergência , Coagulação Intravascular Disseminada/epidemiologia , Coagulação Intravascular Disseminada/mortalidade , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Prevalência , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
Ann Hematol ; 96(3): 489-495, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28018998

RESUMO

In more than 50% of patients with a mild-to-moderate bleeding tendency, no underlying cause can be identified (bleeding of unknown cause, BUC). Data on parameters of fibrinolysis in BUC are scarce in the literature and reveal discrepant results. It was the aim of this study to investigate increased fibrinolysis as a possible mechanism of BUC. We included 270 patients (227 females, median age 44 years, 25-75th percentile 32-58) with BUC and 98 healthy controls (65 females, median age 47 years, 25-75thpercentile 39-55). Tissue plasminogen activator (tPA-) antigen and activity, plasminogen activator inhibitor type-1 (PAI-1), tPA-PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI), α2-antiplasmin, and D-dimer were determined. While PAI-1 deficiency was equally frequent in patients with BUC and controls (91/270, 34%, and 33/98, 34%, p = 0.996), tPA activity levels were more often above the detection limit in patients than in controls (103/213, 48%, and 23/98, 23%, p < 0.0001). We found lower levels of tPA-PAI-1 complexes (6.86 (3.99-10.00) and 9.11 (7.17-13.12), p < 0.001) and higher activity of TAFI (18.61 (15.80-22.58) and 17.03 (14.02-20.02), p < 0.001) and α2-antiplasmin (102 (94-109) and 98 (90-106], p = 0.003) in patients compared to controls. Detectable tPA activity (OR 3.02, 95%CI 1.75-5.23, p < 0.0001), higher levels of TAFI (OR 2.57, 95%CI 1.48-4.46, p = 0.0008) and α2-antiplasmin (OR 1.03, 95%CI 1.01-1.05, p = 0.011), and lower levels of tPA-PAI-1 complexes (OR 0.90, 95%CI 0.86-0.95, p < 0.0001) were independently associated with BUC in sex-adjusted logistic regression analyses. We conclude that the fibrinolytic system can play an etiological role for bleeding in patients with BUC.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Fibrinólise/fisiologia , Hemorragia/sangue , Hemorragia/diagnóstico , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Dig Liver Dis ; 48(10): 1194-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27476467

RESUMO

BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection was revolutionized within the last years. Interferon free antiviral regimens are not accessible without limitations. Combination of peginterferon/ribavirin with first generation direct acting antivirals is less effective and associated with serious adverse events. AIM: We have shown that vWF-Ag is associated with portal hypertension and treatment response to PEG/RBV and we evaluated if vWF-Ag is a predictive marker for treatment response and safety in patients with triple therapy. METHODS: 222 HCV-GT 1 patients and DAA based triple therapy were included in this retrospective, multicenter study. RESULTS: Median vWF-Ag levels were 167.0% [IQR: 124.0-210.0%]. Significantly higher levels were seen in patients without SVR; median 190% [IQR: 146.0-259.5%] versus SVR: 142.5% [IQR: 114.3-196.8%], p<0.001. Furthermore levels of vWF-Ag were identified as independent predictor of non SVR; (OR: 1.009; 95%CI: 1.016-1.3, p=0.005). In patients with cirrhosis elevated vWF-Ag levels were associated with increased incidence of SAEs (OR: 1.016; 95%CI: 1.004-1.028; p=0.007). Best cut off for prediction of SAEs was vWF-Ag>281.5% with a sensitivity of 78% and a specificity of 90%. CONCLUSION: Baseline vWF-Ag levels predict outcome of DAA based treatment in HCV-1 patients and identify patients with a risk of SAEs. Therefore vWF-Ag may be an additional marker for selecting patients for interferon free therapeutic regimens.


Assuntos
Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Cirrose Hepática/patologia , Ribavirina/efeitos adversos , Fator de von Willebrand/análise , Adulto , Antivirais/uso terapêutico , Áustria , Biomarcadores , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/sangue , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Ribavirina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA