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1.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542014

RESUMO

A 32-year-old multiparous obese woman was referred to our center at 37 weeks of twin gestation. She was referred for birth planning following an accidentally discovered high international normalised ratio (INR) in routine preoperative labs. Her history was significant for recurrent pregnancy-associated deep venous thrombosis as well as two early pregnancy losses. Further work-up revealed transaminitis, mild splenomegaly and high lupus anticoagulant titre. A multidisciplinary team of physicians from the high-risk pregnancy, anaesthesiology, haematology, gastroenterology and hepatology departments put a management plan; it culminated into uncomplicated delivery of the patient by repeated caesarian section. The team was also able to figure out the cause of the patient's high INR that is associated with thrombophilia rather than haemophilia.


Assuntos
Deficiência do Fator VII/complicações , Coeficiente Internacional Normatizado , Trombofilia/complicações , Trombose Venosa , Adulto , Antineoplásicos Fitogênicos/uso terapêutico , Cesárea , Deficiência do Fator VII/genética , Feminino , Humanos , Inibidor de Coagulação do Lúpus/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Plasma , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/tratamento farmacológico , Silibina/uso terapêutico , Trombofilia/genética , Trombose Venosa/complicações , Trombose Venosa/genética
3.
Am J Case Rep ; 21: e926623, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32807764

RESUMO

BACKGROUND COVID-19 was declared a pandemic in March 2020 in the United States. It has been associated with high mortality and morbidity all over the world. COVID-19 can cause a significant inflammatory response leading to coagulopathy and this hypercoagulable state has been associated with worse clinical outcomes in these patients. The published data regarding the presence of lupus anticoagulant in critically ill COVID-19-positive patients is limited and indicates varying conclusions so far. CASE REPORT Here, we present a case of a 31-year-old man who was admitted to the hospital with COVID-19 pneumonia, complicated with superadded bacterial empyema and required video-assisted thoracoscopic surgery with decortication. This patient also had prolonged prothrombin time on preoperative labs, which was not corrected with mixing study. Further workup detected positive lupus anticoagulant and anti-cardiolipin IgM along with alteration in other coagulation factor levels. The patient was treated with fresh frozen plasma and vitamin K before surgical intervention. He had an uneventful surgical course. He received prophylactic-dose low molecular weight heparin for venous thromboembolism prophylaxis and did not experience any thrombotic events while hospitalized. CONCLUSIONS COVID-19 infection creates a prothrombotic state in affected patients. The formation of micro-thrombotic emboli results in significantly increased mortality and morbidity. Routine anticoagulation with low molecular weight heparin can prevent thrombotic events and thus can improve patient outcomes. In patients with elevated prothrombin time, lupus anticoagulant/anti-cardiolipin antibody-positivity should be suspected, and anticoagulation prophylaxis should be continued perioperatively for better outcomes.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Empiema Pleural/virologia , Inibidor de Coagulação do Lúpus/sangue , Pneumonia Viral/complicações , Adulto , Antifibrinolíticos/uso terapêutico , Cardiolipinas/imunologia , Tubos Torácicos , Infecções por Coronavirus/diagnóstico , Empiema Pleural/diagnóstico por imagem , Empiema Pleural/terapia , Humanos , Imunoglobulina M/sangue , Coeficiente Internacional Normatizado , Masculino , Pandemias , Tempo de Tromboplastina Parcial , Plasma , Pneumonia Viral/diagnóstico , Tempo de Protrombina , Tomografia Computadorizada por Raios X , Tromboembolia Venosa/prevenção & controle , Vitamina K/uso terapêutico
4.
Transplant Proc ; 52(9): 2715-2718, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32713821

RESUMO

Very few cases of lung transplant patients affected by coronavirus disease 2019 (COVID-19) have been reported to date. A 31-year-old patient who underwent bilateral lung transplantation for cystic fibrosis in 2012 was admitted for severe acute lower limb pain. He had a confirmed exposure to COVID-19 and a 3-week history of upper respiratory tract infection. Whole-body computed tomography (CT) angiography revealed an occlusion of the 2 common femoral arteries. CT angiography detected an intracardiac thrombus in the left ventricle. Chest CT angiography showed ground-glass opacities consistent with COVID-19. A bilateral femoral surgical embolectomy using Fogarty catheter was successfully performed. Specific reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 performed on an extracted thrombus was negative, but IgM antibodies specific for COVID-19 were detected. Cardiac magnetic resonance imaging demonstrated a subendocardial and almost transmural late gadolinium enhancement in the mid and distal inferolateral and inferior wall segments, consistent with a nonrecent myocardial infarction and an apical centimetric thrombus adjacent to the lesion. Thrombophilia laboratory tests found the presence of a positive lupus anticoagulant. Treatment with low-molecular-weight heparin and aspirin was prescribed. On day 13, the patient was discharged from the hospital. This case underlines the need to be vigilant with respect to the thrombotic complications of COVID-19 and raises the issue of thrombosis prevention in COVID-19 patients.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Inibidor de Coagulação do Lúpus/sangue , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Trombose/etiologia , Adulto , Betacoronavirus , Artéria Femoral/patologia , Humanos , Isquemia/etiologia , Extremidade Inferior/irrigação sanguínea , Transplante de Pulmão , Masculino , Pandemias , Transplantados
6.
Cochrane Database Syst Rev ; 5: CD012852, 2020 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-32358837

RESUMO

BACKGROUND: Aspirin and heparin are widely used as preventive strategy to reduce the high risk of recurrent pregnancy loss in women with antiphospholipid antibodies (aPL). This review supersedes a previous, out-of-date review that evaluated all potential therapies for preventing recurrent pregnancy loss in women with aPL. The current review focusses on a narrower scope because current clinical practice is restricted to using aspirin or heparins, or both for women with aPL in an attempt to reduce pregnancy complications. OBJECTIVES: To assess the effects of aspirin or heparin, or both for improving pregnancy outcomes in women with persistent (on two separate occasions) aPL, either lupus anticoagulant (LAC), anticardiolipin (aCL) or aß2-glycoprotein-I antibodies (aß2GPI) or a combination, and recurrent pregnancy loss (two or more, which do not have to be consecutive). SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (3 June 2019), and reference lists of retrieved studies. Where necessary, we attempted to contact trial authors. SELECTION CRITERIA: Randomised, cluster-randomised and quasi-randomised controlled trials that assess the effects of aspirin, heparin (either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH]), or a combination of aspirin and heparin compared with no treatment, placebo or another, on pregnancy outcomes in women with persistent aPL and recurrent pregnancy loss were eligible. All treatment regimens were considered. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion criteria and risk of bias. Two review authors independently extracted data and checked them for accuracy and the certainty of the evidence was assessed using the GRADE approach. MAIN RESULTS: Eleven studies (1672 women) met the inclusion criteria; nine randomised controlled trials and two quasi-RCTs. The studies were conducted in the USA, Canada, UK, China, New Zealand, Iraq and Egypt. One included trial involved 1015 women, all other included trials had considerably lower numbers of participants (i.e. 141 women or fewer). Some studies had high risk of selection and attrition bias, and many did not include sufficient information to judge the risk of reporting bias. Overall, the certainty of evidence is low to very low due to the small numbers of women in the studies and to the risk of bias. The dose and type of heparin and aspirin varied among studies. One study compared aspirin alone with placebo; no studies compared heparin alone with placebo and there were no trials that had a no treatment comparator arm during pregnancy; five studies explored the efficacy of heparin (either UFH or LMWH) combined with aspirin compared with aspirin alone; one trial compared LMWH with aspirin; two trials compared the combination of LMWH plus aspirin with the combination of UFH plus aspirin; two studies evaluated the combination of different doses of heparin combined with aspirin. All trials used aspirin at a low dose. Aspirin versus placebo We are very uncertain if aspirin has any effect on live birth compared to placebo (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.71 to 1.25, 1 trial, 40 women, very low-certainty evidence). We are very uncertain if aspirin has any effect on the risk of pre-eclampsia, pregnancy loss, preterm delivery of a live infant, intrauterine growth restriction or adverse events in the child, compared to placebo. We are very uncertain if aspirin has any effect on adverse events (bleeding) in the mother compared with placebo (RR 1.29, 95% CI 0.60 to 2.77, 1 study, 40 women). The certainty of evidence for these outcomes is very low because of imprecision, due to the low numbers of women involved and the wide 95% CIs, and also because of risk of bias. Venous thromboembolism and arterial thromboembolism were not reported in the included studies. Heparin plus aspirin versus aspirin alone Heparin plus aspirin may increase the number of live births (RR 1.27, 95% CI 1.09 to 1.49, 5 studies, 1295 women, low-certainty evidence). We are uncertain if heparin plus aspirin has any effect on the risk of pre-eclampsia, preterm delivery of a live infant, or intrauterine growth restriction, compared with aspirin alone because of risk of bias and imprecision due to the low numbers of women involved and the wide 95% CIs. We are very uncertain if heparin plus aspirin has any effect on adverse events (bleeding) in the mother compared with aspirin alone (RR 1.65, 95% CI 0.19 to 14.03, 1 study, 31 women). No women in either the heparin plus aspirin group or the aspirin alone group had heparin-induced thrombocytopenia, allergic reactions, or venous or arterial thromboembolism. Similarly, no infants had congenital malformations. Heparin plus aspirin may reduce the risk of pregnancy loss (RR 0.48, 95% CI 0.32 to 0.71, 5 studies, 1295 women, low-certainty evidence). When comparing LMWH plus aspirin versus aspirin alone the pooled RR for live birth was 1.20 (95% CI 1.04 to 1.38, 3 trials, 1155 women). In the comparison of UFH plus aspirin versus aspirin alone, the RR for live birth was 1.74 (95% CI 1.28 to 2.35, 2 trials, 140 women). AUTHORS' CONCLUSIONS: The combination of heparin (UFH or LMWH) plus aspirin during the course of pregnancy may increase live birth rate in women with persistent aPL when compared with aspirin treatment alone. The observed beneficial effect of heparin was driven by one large study in which LMWH plus aspirin was compared with aspirin alone. Adverse events were frequently not, or not uniformly, reported in the included studies. More research is needed in this area in order to further evaluate potential risks and benefits of this treatment strategy, especially among women with aPL and recurrent pregnancy loss, to gain consensus on the ideal prevention for recurrent pregnancy loss, based on a risk profile.


Assuntos
Aborto Habitual/prevenção & controle , Anticorpos Antifosfolipídeos/sangue , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Heparina/uso terapêutico , Resultado da Gravidez , Aborto Habitual/sangue , Anticorpos Anticardiolipina/sangue , Anticoagulantes/efeitos adversos , Aspirina/efeitos adversos , Viés , Quimioterapia Combinada , Feminino , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Nascimento Vivo , Inibidor de Coagulação do Lúpus/sangue , Placebos/uso terapêutico , Pré-Eclâmpsia/prevenção & controle , Gravidez , Complicações Hematológicas na Gravidez/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , beta 2-Glicoproteína I/imunologia
8.
Clin Immunol ; 214: 108388, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32200114

RESUMO

Anti-phospholipid antibodies (aPL) and lupus anticoagulant (LAC) represent diagnostic criteria for systemic lupus erythematosus (SLE) and underlie anti-phospholipid syndrome (APS) in patients with and without SLE. 526 healthy controls and 1633 SLE and 1835 primary APS (PAPS) patients were evaluated. LAC was assessed by hexagonal phase phospholipid neutralization assay (HPPNA), diluted Russell viper venom test (dRVVT), and platelet neutralization procedure (PNP). ß2-glycoprotein-I and cardiolipin IgG, IgM, and IgA antibodies (aCL-IgG, aCL-IgM, aCL-IgA) were measured. 222/1633 SLE patients had APS based on the nine-test panel, which afforded the highest sensitivity (74%) and negative predictive value (90%) but lowest specificity (52%). HPPNA was the most sensitive individual test at 52%. The nine-test panel yielded the greatest sensitivity for aPL detection (70%) relative to HPPNA, the most sensitive individual test (36%) in PAPS. Superior sensitivity of a nine-test aPL panel has major implications for preventing potentially fatal thrombotic events in SLE and PAPS.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/etiologia , Humanos , Inibidor de Coagulação do Lúpus/sangue , Lúpus Eritematoso Sistêmico/sangue , Testes de Função Plaquetária , Valor Preditivo dos Testes , Tempo de Protrombina , Estudos Retrospectivos , Sensibilidade e Especificidade , Trombose/prevenção & controle , beta 2-Glicoproteína I/sangue
9.
Int J Lab Hematol ; 42(1): 46-51, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31821738

RESUMO

INTRODUCTION: Detection of lupus anticoagulant (LA), an antiphospholipid (aPL) antibody, in a clotting time test is an important finding for diagnosis of antiphospholipid syndrome (APS). However, confirmation of LA requires several different testing procedures, some of which can be difficult and require time. We report here a simple and highly specific method for detecting LA. MATERIALS AND METHODS: We examined 66 plasma samples obtained from LA-positive (LA) and 75 from LA-negative (non-LA) subjects, which included patients with acquired hemophilia and coagulation disorders, as well as from 43 healthy volunteer samples as normal controls. Activated partial thromboplastin time (APTT) was determined by adding 20 mmol of CaCl2 (Ca-APTT) or 25 mmol of a mixture of Mg and Ca (Mg-APTT). The ratio of Mg-APTT/Ca-APTT was then calculated and used as the Mg/Ca Index. RESULTS: The Mg/Ca Index value for the LA group was significantly lower than that for the non-LA and normal control groups (P < .0001). When the cutoff value of the Mg/Ca Index was less than 1.00, the sensitivity of LA determination using the Mg-APTT assay was 80.3%, while specificity was 100%. CONCLUSION: Our findings indicate that the present Mg-APTT assay is a simple yet highly specific method for LA detection.


Assuntos
Síndrome Antifosfolipídica/sangue , Inibidor de Coagulação do Lúpus/sangue , Magnésio/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome Antifosfolipídica/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial
10.
Am J Clin Pathol ; 153(2): 229-234, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31598704

RESUMO

OBJECTIVES: Lupus anticoagulant (LAC) is typically associated with thrombosis but also rarely with hemorrhage. Some patients exhibit a prozone effect on LAC testing. Antiphosphatidylserine/prothrombin (aPS/PT) antibodies may provide a mechanism for both hemorrhage and prozone effect. Our goal was to evaluate whether antibody specificities, isotypes, and titers were associated with LAC prozone effect, factor II levels, hemorrhage, and thrombosis. METHODS: Patients with prozone effect noted on LAC testing were entered into a database over 3 years. Factor II activity and aPS/PT antibody testing were performed when a sufficient residual sample was available. RESULTS: All patients with LAC prozone effect and antibody testing were positive for at least 1 class of aPS/PT antibodies. In addition, aPS/PT IgG titers were significantly associated with thrombosis and significantly inversely associated with factor II levels. CONCLUSIONS: In prozone effect patients, aPS/PT antibodies are associated with LAC prozone effect as well as thrombosis and decreased factor II levels.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Inibidor de Coagulação do Lúpus/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Protrombina/análise , Trombose/etiologia , Adulto Jovem
11.
Am J Hematol ; 95(1): 117-128, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674066

RESUMO

Coagulation testing underpins the investigation of hemostasis and/or monitoring of anticoagulation therapy for prevention and/or treatment of thrombosis related pathology. Assessment of coagulation results requires comparison against a normal reference range or interval (NRR/NRI). Results flagged as "abnormal" (ie, above the NRR/NRI for patients not on anticoagulant therapy), typically require further evaluation. eg, follow up or reflexive testing is used to identify the reason for prolongation, especially when supported by clinical context (eg, bleeding). Mixing tests may have utility to help identify the pathway of follow-up testing (ie, towards investigation of factor deficiencies, or else inhibitors), and are also useful for investigation of lupus anticoagulants (LA). In general, mixing tests that "correct" tend to suggest the presence of factor deficiencies, where as those that do not correct suggest the presence of "inhibitors". Various approaches can be used to identify correction/non-correction, and all have strengths and limitations. Furthermore, eventual identification of causal factor deficiencies or even "inhibitors" may (eg, factor VIII or IX deficiencies or inhibitors) or may not (eg, factor XII deficiency) be clinically important. Ultimately, mixing studies performed in view of appropriate clinical scenarios (eg, bleeding patient) and for LA investigations in symptomatic patients will have best utility.


Assuntos
Testes de Coagulação Sanguínea/métodos , Inibidor de Coagulação do Lúpus/sangue , Algoritmos , Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea/normas , Hemostasia , Humanos
12.
Ann Rheum Dis ; 79(3): 363-369, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31826855

RESUMO

OBJECTIVES: To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci. RESULTS: SLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9×10-86 and OR 7.48 (6.73 to 8.32), p=2.2×10-304 for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3×10-5), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10-2), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10-5), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10-3), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10-2), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10-3), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10-2), anti-ß2-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10-3) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10-2) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7×10-2), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10-2), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10-7), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10-3) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10-2) in high to low quartile comparison. CONCLUSIONS: A high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.


Assuntos
Predisposição Genética para Doença/epidemiologia , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Medição de Risco/estatística & dados numéricos , Índice de Gravidade de Doença , Adulto , Anticorpos Anticardiolipina/sangue , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/mortalidade , Inibidor de Coagulação do Lúpus/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/mortalidade , Nefrite Lúpica/mortalidade , Masculino , Pessoa de Meia-Idade , Prevalência , Risco , Fatores de Risco , Taxa de Sobrevida , beta 2-Glicoproteína I/imunologia
13.
J Thromb Thrombolysis ; 49(2): 334-336, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31515751

RESUMO

Association of acquired factor II deficiency and lupus anticoagulant is a rare disease that can be related to sudden, severe or fatal haemorrhage. We present a 74-years-old woman with history of myelodysplastic syndrome, admitted to the Emergency Department due to spontaneous mucocutaneous bleeding. Coagulation assays revealed prolonged prothrombin time and activated partial thromboplastin time with evidence of an immediate acting inhibitor. Antithrombotic therapy usage, drug ingestion, disseminated intravascular coagulation, liver dysfunction and sepsis were excluded. Patient was admitted for close monitoring and etiological evaluation. A comprehensive bleeding diathesis workup was performed showing factor II levels severely decreased and transient positive lupus anticoagulant. Immunosuppression with methylprednisolone lasted for 3 days, followed by prednisolone. After 20 days she was discharged and follow-up was scheduled. Early diagnosis of lupus anticoagulant hypoprothrombinemia syndrome is critical, as it may result in fatal complications if not treated appropriately. There is no consensus regarding the best treatment, most being based on immunosuppression.


Assuntos
Hemorragia/sangue , Hemorragia/diagnóstico por imagem , Hipoprotrombinemias/sangue , Hipoprotrombinemias/diagnóstico por imagem , Inibidor de Coagulação do Lúpus/sangue , Idoso , Feminino , Hemorragia/etiologia , Humanos , Hipoprotrombinemias/complicações
14.
Int J Rheum Dis ; 22(12): 2185-2190, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31749332

RESUMO

BACKGROUND AND PURPOSE: The mechanism of glomerular microthrombosis (GMT) in patients with lupus nephritis (LN) is largely unknown. The aim of this study is to investigate the association between antiphospholipid antibodies (aPLs) and factor Bb in LN patients with GMT. METHODS: Patients with biopsy-proven LN hospitalized from July 2015 to July 2018 in our hospital were selected for this study. Levels of lupus anticoagulant (LAC), anticardiolipin antibodies (aCLs), anti-ß2-glycoprotein I (anti-ß2-GPI) antibodies and factor Bb were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy. RESULTS: A total of 25 LN patients with GMT and 76 LN patients without GMT were included in this study. In LN patients with GMT, the presence of anti-ß2GPI and LAC were both significantly higher than in those without GMT (P < .001 and P = .039, respectively). The level of factor Bb was also higher in LN patients with GMT than in those without GMT (P = .021). In the correlation analysis, Bb level was positively correlated with serum creatinine (r = 0.28, P = .014), activity index (r = 0.24, P = .021) GMT (r = 0.65, P < .001) and IgG-anti-ß2GPI (r = 0.771, P < .001). CONCLUSIONS: Our work suggests that aPLs, especially IgG-anti-ß2GPI, may play a role in the progress of GMT, and this process might involve alternative complement activation.


Assuntos
Anticorpos Anticardiolipina/sangue , Fator B do Complemento/análise , Imunoglobulina G/sangue , Glomérulos Renais/imunologia , Inibidor de Coagulação do Lúpus/sangue , Nefrite Lúpica/imunologia , Trombose/imunologia , Microglobulina beta-2/imunologia , Adulto , Biomarcadores/sangue , Ativação do Complemento , Feminino , Humanos , Glomérulos Renais/patologia , Nefrite Lúpica/sangue , Nefrite Lúpica/diagnóstico , Masculino , Pessoa de Meia-Idade , Trombose/sangue , Trombose/diagnóstico , Adulto Jovem
15.
Thromb Res ; 184: 86-91, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31710863

RESUMO

INTRODUCTION: Lupus Anticoagulant testing using dilute Russell Viper Venom Time (dRVVT) is challenging in patients receiving Direct Oral AntiCoagulants (DOAC) due to potential false positive results. In a multicenter study, we evaluated the in vitro removal of DOAC by activated charcoal (DOAC remove®), allowing reliable dRVVT testing. MATERIALS AND METHODS: Patient samples were analyzed before and after treatment with DOAC remove®: 49 apixaban, 48 rivaroxaban, 24 dabigatran and 30 none. DOAC plasma concentrations were measured using anti-Xa or diluted thrombin time assays. In a subset of 28 samples, DOAC concentrations were also measured using HPLC-MS/MS following treatment with DOAC remove®. DRVVT was performed using STA-Staclot dRVVT Screen®/Confirm® (Stago) or LAC-Screening®/Confirmation® (Siemens). RESULTS: Baseline median [min-max] concentrations were 94 [<20-479] for apixaban, 107 [<20-501] for rivaroxaban and 135 ng/mL [<20-792] for dabigatran; dRVVT screen ratio/confirm ratio was positive in 47, 90 and 42% of apixaban, rivaroxaban and dabigatran samples. Treatment with DOAC remove® did not affect dRVVT results in non-DOAC patients while it resulted in DOAC concentrations <20 ng/mL in 82, 98 and 100% of samples, respectively. Concentrations were <5 ng/mL with HPLC-MS/MS in 5 out of 10, 8 out of 10 and 7 out of 8 samples, respectively. DOAC remove® corrected DOAC interference with dRVVT assays in 76, 85 and 95% of the patients, respectively. CONCLUSION: For dRVVT testing in DOAC patients, we suggest the use of DOAC remove® for every rivaroxaban sample, whereas it might only be used in positive apixaban and dabigatran samples. A residual DOAC interference cannot be ruled out in case of persisting dRVVT positive results after treatment with DOAC remove®.


Assuntos
Anticoagulantes/uso terapêutico , Testes de Coagulação Sanguínea/métodos , Carvão Vegetal/uso terapêutico , Inibidor de Coagulação do Lúpus/sangue , Administração Oral , Anticoagulantes/farmacologia , Carvão Vegetal/farmacologia , Feminino , Humanos , Masculino
16.
Lupus ; 28(12): 1460-1467, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31594451

RESUMO

Whether the presence or absence of antiphospholipid antibodies (aPL) in patients with lupus nephritis (LN) is associated with differences in clinical outcomes remains unclear. We reviewed LN patients at a single centre during 2000-2017, and compared the clinical features and long-term outcomes between patients who were seropositive or seronegative for aPL. aPL was detected in 53/149 (35.6%) patients with biopsy-proven LN, and anticardiolipin IgM, anticardiolipin IgG, anti-ß2 glycoprotein I and lupus anticoagulant was detected in 18.8%, 18.1%, 10.7% and 8.1%, respectively. Follow-up was 155.8 ± 61.0 months, and was similar between aPL-seropositive and -seronegative patients. aPL seropositivity persisted in 94.3% of patients during remission. aPL-seropositive patients showed inferior patient survival (91% and 85% at 10 and 15 years, respectively, compared to 99% and 95% in aPL-seronegative patients; p = 0.043). Nine (6.0%) patients died during follow-up, including six aPL-seropositive (four thrombotic events and two bleeding complications related to anticoagulation) and three aPL-seronegative patients. aPL seropositivity was associated with more rapid decline in estimated glomerular filtration rate (-1.44 mL/min/year compared to -0.38 mL/min/year in aPL-seronegative patients; p = 0.027) and inferior long-term renal survival (82% and 74% at 10 and 15 years, respectively, compared to 91% and 87% in aPL-seronegative patients; p = 0.034). aPL-seropositive patients also had a higher incidence of thrombotic events and miscarriage (32.1% and 13.2%, respectively, compared to 16.7% and 2.1% in the aPL-seronegative group; p = 0.030 and 0.006). We concluded that aPL seropositivity was associated with inferior long-term patient and renal survival and more frequent thrombotic events and miscarriage in LN patients.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/complicações , Nefrite Lúpica/sangue , Nefrite Lúpica/patologia , Aborto Espontâneo/etiologia , Adulto , Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Feminino , Taxa de Filtração Glomerular , Hemorragia/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Rim/fisiopatologia , Inibidor de Coagulação do Lúpus/sangue , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Trombose/induzido quimicamente , beta 2-Glicoproteína I/sangue
18.
Int J Lab Hematol ; 41(6): 738-744, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31487115

RESUMO

INTRODUCTION: Direct oral factor Xa inhibitors (xabans) induce false positive results for lupus anticoagulant (LA) diagnosis. Consequently, it is suggested not to perform LA testing in xabans patients although it may be useful in selected patients. In this monocentric study, we evaluated xabans impact at trough levels (ie, just before the next intake) on LA diagnosis in treated patients using dilute Russell viper venom time (dRVVT) and two LA sensitive activated partial thromboplastin time (aPTT). METHODS: Sixty patients receiving rivaroxaban (30) or apixaban (30) were included. Plasma concentrations were measured using specific anti-Xa assays. LA testing was performed using one dRVVT (LAC-Screening® /Confirm® ; Siemens) and two LA sensitive aPTT-based assays (Hemosil® Silica Clotting Time (SCT) Screen/Confirm; Werfen and Dade® Actin® Factor Sensitivity FSL/FS (Actin F); Siemens). RESULTS: Median [min-max] concentrations were 23 [<18-68] for rivaroxaban and 42 ng/mL [19-99] for apixaban. dRVVT was positive in 93% of rivaroxaban and 40% of apixaban samples. SCT was positive in 40 and 30% and Actin F in 17 and 20% of samples respectively. Xabans affected more significantly dRVVT than aPTT-based assays (P < .001) with less false positive results with apixaban than with rivaroxaban samples irrespective of the assay used. CONCLUSION: lupus anticoagulant diagnosis in rivaroxaban and apixaban samples drawn at trough levels remains questionable whenever positive results are obtained. If LA testing in apixaban samples might be useful to rule-out LA using dRVVT and/or aPTT-based assays, the wide majority of rivaroxaban samples would give false positive results.


Assuntos
Inibidores do Fator Xa/administração & dosagem , Inibidor de Coagulação do Lúpus/sangue , Administração Oral , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Testes de Coagulação Sanguínea/métodos , Testes de Coagulação Sanguínea/normas , Inibidores do Fator Xa/uso terapêutico , Reações Falso-Positivas , Humanos , Tempo de Tromboplastina Parcial , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridonas/farmacologia , Piridonas/uso terapêutico , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico
19.
Int J Lab Hematol ; 41(6): 726-730, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31523903

RESUMO

INTRODUCTION: The confirmation time interval for the presence of antiphospholipid antibodies (aPL) has been extended to 12 weeks as epiphenomenal antibodies may disappear after 6 weeks. Our aim was to analyse extended persistence of aPL positivity beyond the 12-week interval. METHODS: We retrospectively analysed our database of 23 856 aPL test samples collected between 2005 and 2017 from 17 367 consecutive patients. Two groups of patients were identified among aPL-positive patients, confirmed at 12 weeks: with or without extended persistence beyond confirmatory testing. Percentages of extended persistence are given according to the initial aPL positivity profiles, and baseline laboratory variables are compared between the two groups. RESULTS: Three hundred and twenty-seven patients confirmed aPL-positive had subsequent testing. The vast majority of them displayed extended persistence in the long term: 89.6% and up to 97.9% for patients with initial triple positivity. In extended persistent positive patients, there were more LA-positive initial samples, and baseline LA test values and IgG aCL titres were higher than in nonpersistent positive patients. CONCLUSION: Data from a large database of an aPL referral laboratory showed that the time interval of 12 weeks defining persistence of aPL positivity was appropriate for the majority of patients. Furthermore, we found baseline features associated with extended persistence.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Adulto , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Feminino , Humanos , Inibidor de Coagulação do Lúpus/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
20.
Clin Appl Thromb Hemost ; 25: 1076029619872556, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523979

RESUMO

The effect of direct oral anticoagulants (DOACs) on laboratory tests dependent on the production of their targets, factor IIa and factor Xa (FXa), is a well-known problem and can cause both false positive and negative results. Therefore, the correct interpretation of tests performed in patients receiving DOACs is necessary to avoid misclassification and subsequent clinical consequences. However, even with significant experience, there are situations where it is not possible to assess the influence of some methods. Particularly important is the situation in the diagnosis of lupus anticoagulants using the dilute Russell viper venom timetest, which is based on direct FXa activation. A very promising solution to this situation is offered by the DOAC laboratory balancing procedure DOAC-Stop. For evaluating the effectiveness of this procedure, 60 (20 apixaban, 20 dabigatran, and 20 rivaroxaban) patients treated with DOACs were enrolled. All patient samples were analyzed for the presence of individual DOAC types and subsequently subjected to the DOAC-Stop procedure.We evaluated its effectiveness by our own high-performance liquid chromatography-coupled tandem mass spectrometrymethod, which simultaneously sets all high-sensitivity DOACs. Unlike coagulation tests based on the determination of the residual effects of DOACs on target enzymes, which is complicated by extensive interindividual variation, this methodology is highly specific and sensitive.The DOAC-Stop procedure eliminated dabigatran from 99.5%, rivaroxaban from 97.9%, and apixaban from 97.1% of participants in our group. Residual amounts did not exceed 2.7 ng/mL for dabigatran, 10.9 ng/mL for rivaroxaban, or 13.03 ng/mL for apixaban, which are safe values that do not affect either screening or special coagulation tests.


Assuntos
Cromatografia Líquida/métodos , Inibidores do Fator Xa/análise , Espectrometria de Massas em Tandem/métodos , Antitrombinas , Coagulação Sanguínea/efeitos dos fármacos , Dabigatrana/análise , Dabigatrana/farmacologia , Dabigatrana/uso terapêutico , Inibidores do Fator Xa/farmacologia , Inibidores do Fator Xa/uso terapêutico , Humanos , Inibidor de Coagulação do Lúpus/sangue , Métodos , Pirazóis/análise , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridonas/análise , Piridonas/farmacologia , Piridonas/uso terapêutico , Rivaroxabana/análise , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico
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