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1.
Semin Thromb Hemost ; 46(7): 845-849, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32877961

RESUMO

Over the past few months, Coronavirus Disease 2019 (COVID-19) has spread across much of the world leading to a pandemic. Many infected individuals do not experience signs or symptoms, or experience only mild symptoms, whilst a subset experience severe disease, which is often fatal. A number of laboratory tests have been found to be abnormal in hospitalized patients, and some studies suggest some of these tests can predict an unfavorable outcome. These include markers of acute phase reaction (elevated C-reactive protein, erythrocyte sedimentation rate, white blood cell count, fibrinogen, procalcitonin, factor VIII, von Willebrand factor), signs of tissue injury (elevated lactic dehydrogenase, alanine aminotransferase, cardiac troponins), changes in hemostasis and coagulation (elevated D-dimer, prolonged prothrombin time, decreased platelets, decreased antithrombin, elevated factor VIII and von Willebrand factor), and decreased lymphocytes. Additional studies are needed to confirm the most ideal panel of tests, and to confirm the efficiency of laboratory tests to predict clinical outcome, as well as the ideal anticoagulation management.


Assuntos
Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Anticoagulantes/sangue , Betacoronavirus , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Infecções por Coronavirus/diagnóstico , Cuidados Críticos , Hematologia/normas , Humanos , Unidades de Terapia Intensiva , Pandemias , Prognóstico , Risco , Resultado do Tratamento
2.
Am J Hematol ; 95(12): 1522-1530, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32833259

RESUMO

Coagulopathy causes morbidity and mortality in patients with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Yet, the mechanisms are unclear and biomarkers are limited. Early in the pandemic, we observed markedly elevated factor V activity in a patient with COVID-19, which led us to measure factor V, VIII, and X activity in a cohort of 102 consecutive inpatients with COVID-19. Contemporaneous SARS-CoV-2-negative controls (n = 17) and historical pre-pandemic controls (n = 260-478) were also analyzed. This cohort represents severe COVID-19 with high rates of ventilator use (92%), line clots (47%), deep vein thrombosis or pulmonary embolism (DVT/PE) (23%), and mortality (22%). Factor V activity was significantly elevated in COVID-19 (median 150 IU/dL, range 34-248 IU/dL) compared to contemporaneous controls (median 105 IU/dL, range 22-161 IU/dL) (P < .001)-the strongest association with COVID-19 of any parameter studied, including factor VIII, fibrinogen, and D-dimer. Patients with COVID-19 and factor V activity >150 IU/dL exhibited significantly higher rates of DVT/PE (16/49, 33%) compared to those with factor V activity ≤150 IU/dL (7/53, 13%) (P = .03). Within this severe COVID-19 cohort, factor V activity associated with SARS-CoV-2 load in a sex-dependent manner. Subsequent decreases in factor V were linked to progression toward DIC and mortality. Together, these data reveal marked perturbations of factor V activity in severe COVID-19, provide links to SARS-CoV-2 disease biology and clinical outcomes, and nominate a candidate biomarker to investigate for guiding anticoagulation therapy in COVID-19.

3.
Am J Hematol ; 95(12): 1479-1485, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32780525

RESUMO

Coronavirus disease 2019 (COVID-19) may cause a hypercoagulable state. The D-dimer is frequently elevated in COVID-19, but other markers of coagulation activation, including the prothrombin fragment 1.2 (PF1.2) are poorly described. We studied hospitalized adults with COVID-19 and PF1.2 measurements performed at any time during hospitalization. We evaluated the relationship between PF1.2 and synchronously measured D-dimer. We utilized receiver operating characteristic (ROC) analysis to evaluate optimal thresholds for diagnosing thrombosis and multivariable logistic regression to evaluate association with thrombosis. A total of 115 patients were included [110 (95.7%) critically ill]. Both PF1.2 and D-dimer were moderately positively correlated (r = 0.542, P < .001) but significant discordance was observed in elevation of each marker above the laboratory reference range (59.0% elevated PF1.2 vs 98.5% elevated D-dimer). Median PF1.2 levels were higher in patients with thrombosis than those without (611 vs 374 pmol/L, P = .006). In ROC analysis, PF1.2 had superior specificity and conferred a higher positive likelihood ratio in identifying patients with thrombosis than D-dimer (PF1.2 threshold of >523 pmol/L: 69.2% sensitivity, 67.7% specificity; >924 pmol/L: 37.9% sensitivity, 87.8% specificity). In multivariable analysis, a PF1.2 >500 pmol/L was significantly associated with VTE [adjusted odds ratio (OR) 4.26, 95% CI, 1.12-16.21, P = .034] and any thrombotic manifestation (adjusted OR 3.85, 95% CI, 1.39-10.65, P = .010); conversely, synchronously measured D-dimer was not significantly associated with thrombosis. 90.6% of patients with a non-elevated PF1.2 result did not develop VTE. So, PF1.2 may be a useful assay, and potentially more discriminant than D-dimer, in identifying thrombotic manifestations in hospitalized patients with COVID-19.

4.
Clin Appl Thromb Hemost ; 26: 1076029620943671, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702995

RESUMO

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.


Assuntos
Afro-Americanos , Betacoronavirus , Infecções por Coronavirus/etnologia , Pandemias , Pneumonia Viral/etnologia , Trombofilia/etnologia , Tromboembolia Venosa/etnologia , Afro-Americanos/genética , Anemia Falciforme/sangue , Anemia Falciforme/etnologia , Anticoagulantes/uso terapêutico , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/genética , Ensaios Clínicos como Assunto , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Fator VIII/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Estudos de Associação Genética , Predisposição Genética para Doença , Disparidades em Assistência à Saúde , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Seleção de Pacientes , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Polimorfismo de Nucleotídeo Único , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etnologia , Fatores de Risco , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
5.
Thromb Haemost ; 120(7): 1116-1127, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32572866

RESUMO

Delayed identification of coagulopathy and bleeding increases the risk of organ failure and death in hospitalized patients. Timely and accurate identification of impaired coagulation at the point-of-care can proactively identify bleeding risk and guide resuscitation, resulting in improved outcomes for patients. We test the accuracy of a novel optical coagulation sensing approach, termed iCoagLab, for comprehensive whole blood coagulation profiling and investigate its diagnostic accuracy in identifying patients at elevated bleeding risk. Whole blood samples from patients (N = 270) undergoing conventional coagulation testing were measured using the iCoagLab device. Recalcified and kaolin-activated blood samples were loaded in disposable cartridges and time-varying intensity fluctuation of laser speckle patterns were measured to quantify the clot viscoelastic modulus during coagulation. Coagulation parameters including the reaction time (R), clot progression time (K), clot progression rate (α), and maximum clot strength (MA) were derived from clot viscoelasticity traces and compared with mechanical thromboelastography (TEG). In all patients, a good correlation between iCoagLab- and TEG-derived parameters was observed (p < 0.001). Multivariate analysis showed that iCoagLab-derived parameters identified bleeding risk with sensitivity (94%) identical to, and diagnostic accuracy (89%) higher than TEG (87%). The diagnostic specificity of iCoagLab (77%) was significantly higher than TEG (69%). By rapidly and comprehensively permitting blood coagulation profiling the iCoagLab innovation is likely to advance the capability to identify patients with elevated risk for bleeding, with the ultimate goal of preventing life-threatening hemorrhage.

7.
Thromb Haemost ; 120(5): 793-804, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369850

RESUMO

BACKGROUND: Accurate diagnosis of symptomatic low von Willebrand factor (VWF) remains a major challenge in von Willebrand disease (VWD). However, present tests do not adequately take into account flow forces that, at very high shear rates, reveal a weakness in the VWF-platelet glycoprotein glycoprotein Ib bond in normal subjects. The degree of this weakness is greater in symptomatic, but not asymptomatic, low VWF. OBJECTIVE: The aim of this study is to distinguish patients with symptomatic low VWF (levels in the 30-50 IU/dL range) from those with asymptomatic low VWF and normal subjects. METHODS: We measured platelet adhesion (PA)/aggregation in our novel microfluidic flow system that permits real-time assessment of PA (surface coverage) and PA/aggregation (V, aggregate volume) using epifluorescence digital videomicroscopy in flowing noncitrated whole blood at 4,000 second-1. Blood samples from 24 low VWF patients and 15 normal subjects were collected into plastic tubes containing 4 U/mL enoxaparin. MetaMorph software was used to quantify rates of PA and V increase. RESULTS: Rates of PA increase showed a bimodal distribution, with values for 16/24 patients (Group I) all below the 2.5th percentile of normal, and values for 8/24 patients (Group II) similar to controls. Bleeding scores (mean ± standard error) were 5.50 ± 0.45 versus 2.75 ± 0.45 (p = 0.00077), and 10 clinically significant bleeding events were observed in seven versus zero (p = 0.0295) Group I and Group II subjects, respectively. CONCLUSION: The present approach may offer a definitive means to distinguish symptomatic low VWF from either asymptomatic low VWF or normal controls.


Assuntos
Adesividade Plaquetária , Agregação Plaquetária , Testes de Função Plaquetária , Doenças de von Willebrand/diagnóstico , Fator de von Willebrand/metabolismo , Adolescente , Adulto , Doenças Assintomáticas , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Técnicas Analíticas Microfluídicas , Microscopia de Vídeo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estresse Mecânico , Fatores de Tempo , Adulto Jovem , Doenças de von Willebrand/sangue , Doenças de von Willebrand/complicações
8.
Arch Pathol Lab Med ; 144(11): 1401-1407, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101451

RESUMO

CONTEXT.­: Apixaban causes a false increase in activated protein C resistance (APCR) ratios and possibly protein S activity. OBJECTIVE.­: To investigate whether this increase can mask a diagnosis of factor V Leiden (FVL) or protein S deficiency in an actual population of patients undergoing apixaban treatment and hypercoagulation testing. DESIGN.­: During a 4.5-year period involving 58 patients, we compared the following 4 groups: heterozygous for FVL (FVL-HET)/taking apixaban, wild-type/taking apixaban, heterozygous for FVL/no apixaban, and normal APCR/no apixaban. Patients taking apixaban were also tested for protein S functional activity and free antigen (n = 40). RESULTS.­: FVL-HET patients taking apixaban had lower APCR ratios than wild-type patients (P < .001). Activated protein C resistance in FVL-HET patients taking apixaban fell more than 3 SD below the cutoff of 2.2 at which the laboratory reflexes FVL DNA testing. No cases of FVL were missed despite apixaban. In contrast to rivaroxaban, apixaban did not interfere with the assessment of protein S activity (mean activity 93.9 IU/dL, free antigen 93.1 IU/dL, P = .39). A total of 3 of 40 patients (8%) had low free protein S antigen (30, 55, and 57 IU/dL), with correspondingly similar activity results (27, 59, and 52 IU/dL, respectively). Apixaban did not cause a missed diagnosis of protein S deficiency. CONCLUSIONS.­: Despite apixaban treatment, APCR testing can distinguish FVL-HET from healthy patients, rendering indiscriminate FVL DNA testing of all patients on apixaban unnecessary. Apixaban did not affect protein S activity.

9.
J Thromb Haemost ; 18(1): 17-22, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894660

RESUMO

Hereditary deficiency of antithrombin, a natural anticoagulant, causes a thrombophilia with a high risk for venous thromboembolism. Guidance for laboratory testing to diagnose antithrombin deficiency include the use of an activity assay for initial testing, performing an antigen test and activity-to-antigen ratio when the activity level is low, using pediatric reference ranges until the age of 6 months, excluding acquired causes of low antithrombin (e.g. liver dysfunction, proteinuria, heparin, disseminated intravascular coagulation, thrombosis, surgery) or falsely normal/elevated results (e.g. argatroban, bivalirudin, dabigatran in factor IIa-based assays; rivaroxaban, apixaban, edoxaban, but not betrixaban in Xa-based assays). Molecular testing, if available, may help determine the risk for thrombosis as this might vary among the different mutations. Moreover, it will identify mutations that can be missed by traditional activity assays. Strategies for interpreting laboratory test results are provided.

10.
J Thromb Haemost ; 17(12): 2123-2130, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31420903

RESUMO

BACKGROUND: Accurate diagnosis of heparin-induced thrombocytopenia (HIT) is essential to ensure timely treatment and prevent complications. Current diagnostic assays include enzyme-linked immunosorbent assays (ELISAs) and rapid immunoassays (RIs). RIs offer fast turnaround times but were not significantly represented in previous external proficiency testing challenges. OBJECTIVES: To use external proficiency testing to assess qualitative concordance for heparin/PF4 antibody detection. METHODS: From 2013 to 2017, the External Quality Control for Assays and Tests (ECAT) Foundation distributed 10 samples internationally. RESULTS: In total, 437 laboratories submitted 3149 results. ELISAs accounted for 1484 (47%) responses with RIs accounting for 1665 (53%) responses. RI use increased over the 5-year period. ELISAs classified 96% of both consensus positive and consensus negative samples concordantly. The coefficient of variation (CV) for positive sample optical densities (ODs) ranged from 35% to 50% when combining ELISA assay methods together. Quantitative RIs classified 97% of consensus-positive and 98% of consensus-negative samples concordantly. Qualitative RIs had a higher proportion of discordant responses and classified 88% of consensus-positive samples and 73% of consensus-negative samples concordantly. Of RIs only latex immunoassays and IgG specific chemiluminescent assays identified > 95% of samples concordantly with consensus. CONCLUSION: Quantitative RIs and ELISAs classify > 95% of samples concordantly. The ODs from different ELISA methods vary considerably and are not interchangeable. Qualitative RI use is increasing despite a greater proportion of discordant classifications. This includes a higher than expected number of negative classifications for consensus-positive samples among many RIs, challenging their use as "rule out" tests.


Assuntos
Anticorpos/sangue , Anticoagulantes/efeitos adversos , Ensaio de Imunoadsorção Enzimática/normas , Heparina/efeitos adversos , Ensaio de Proficiência Laboratorial , Fator Plaquetário 4/imunologia , Radioimunoensaio/normas , Testes Sorológicos/normas , Trombocitopenia/diagnóstico , Anticoagulantes/imunologia , Austrália , Biomarcadores/sangue , Europa (Continente) , Heparina/imunologia , Humanos , Israel , América do Norte , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Trombocitopenia/imunologia
12.
Am J Hematol ; 94(6): 697-709, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30916798

RESUMO

Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non-specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/efeitos adversos , Fator Xa/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Anticoagulantes/uso terapêutico , Humanos , Guias de Prática Clínica como Assunto
14.
Int J Lab Hematol ; 41(3): 325-330, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30735311

RESUMO

INTRODUCTION: Patients with Type 1 von Willebrand disease (VWD) have reduced amounts of von Willebrand factor (VWF) in their blood. Desmopressin (DDAVP) has been used to raise the blood levels of VWF in these patients. However, not all patients with Type 1 VWD are known to respond to DDAVP therapy. We sought to compare the levels of Factor VIII, VWF antigen (VWF:Ag), VWF ristocetin cofactor (VWF:RCo), and fibrinogen at different time points after administration of DDAVP. METHODS: A retrospective analysis was conducted at a single institution on 89 patients with Type 1 VWD who received a single intravenous dose of 0.3 µg/kg DDAVP. Levels of Factor VIII, VWF:Ag, VWF:RCo, and fibrinogen were measured before and then 30, 60, 90, and 120 minutes after completion of DDAVP administration. RESULTS: Median levels of Factor VIII, VWF:Ag, and VWF:RCo were significantly elevated (P < 0.001) at 30 (175 IU/dL, 111 IU/dL, 127 IU/dL), 60 (218 IU/dL, 138 IU/dL, 139 IU/dL), and 90 (212 IU/dL, 134 IU/dL, 130 IU/dL) minutes time points when compared to their respective baseline values (71 IU/dL, 54 IU/dL, 54 IU/dL). At 60 minutes, 96% of subjects were responders, but three subjects failed to respond at any time point. CONCLUSION: Measurement of levels of Factor VIII, VWF:Ag, and VWF:RCo, optimally at 60 minutes after the DDAVP infusion, is sufficient to confirm a patient as a responder in a DDAVP challenge test. Curtailing the number of time points of measurement will result in significant savings in cost and time to patients and their providers.


Assuntos
Desamino Arginina Vasopressina/uso terapêutico , Doença de von Willebrand Tipo 1/sangue , Doença de von Willebrand Tipo 1/tratamento farmacológico , Adulto , Biomarcadores , Coagulação Sanguínea , Fatores de Coagulação Sanguínea , Testes de Coagulação Sanguínea/métodos , Desamino Arginina Vasopressina/administração & dosagem , Feminino , Hemostáticos/farmacocinética , Hemostáticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Doença de von Willebrand Tipo 1/diagnóstico , Fator de von Willebrand
15.
Crit Care Explor ; 1(8): e0024, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32166266

RESUMO

Determining whether a patient has taken a direct oral anticoagulant (DOAC) is critical during the periprocedural and preoperative period in the emergency department. However, the inaccessibility of complete medical records, along with the generally inconsistent sensitivity of conventional coagulation tests to these drugs, complicates clinical decision making and puts patients at risk of uncontrollable bleeding. In this study, we evaluate the utility of inhibitor-II-X (i-II-X), a novel, microfluidics-based diagnostic assay for the detection and identification of Factor Xa inhibitors (FXa-Is) in an acute care setting. Design: First-in-human, 91-patient, single-center retrospective pilot study. Setting: Emergency room. Patients: Adult patients admitted into the emergency department, which received any clinician-ordered coagulation test requiring a 3.2% buffered sodium citrate blood collection tube. Interventions: None. Measurements and Main Results: Plasma samples from patients admitted to the emergency department were screened for the use of FXa-Is, including apixaban and rivaroxaban, within the past 24 hours using our new i-II-X microfluidic test. i-II-X results were then compared with results from conventional coagulation tests, including prothrombin time (PT) and international normalized ratio (INR), which were ordered by treating clinicians, and an anti-Xa assay for rivaroxaban. The i-II-X test detected DOACs in samples collected from the emergency department with 95.20% sensitivity and 100.00% specificity. Unlike PT and INR, i-II-X reliably identified patients who had prolonged clotting times secondary to the presence of a FXa-I. Conclusions: The i-II-X test overcomes the limitations of currently available coagulation tests and could be a useful tool by which to routinely screen patients for DOACs in emergency and critical care settings. Our new diagnostic approach is particularly relevant in clinical situations where medical records may be unavailable, or where precautions need to be taken prior to invasive interventions, such as specific reversal agent administration.

16.
Ann Hematol ; 98(3): 581-588, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30446804

RESUMO

The thrombopoietin receptor agonist romiplostim is used for the long-term treatment of chronic immune thrombocytopenia (ITP). ITP patients have an increased thrombotic risk, which could be exacerbated if romiplostim increased platelet hyperreactivity or caused spontaneous platelet aggregation. To investigate this possibility, this study examined platelet function in romiplostim-treated ITP patients and healthy subjects. Light transmission platelet aggregometry utilizing arachidonic acid, collagen, epinephrine, ristocetin, ADP, and saline (to assess spontaneous aggregation) was performed for each subject. In addition, the ADP AC50 (ADP concentration that induced half-maximal aggregation) was determined for each patient as a sensitive measurement of altered platelet reactivity. Fifteen ITP patients and 7 healthy subjects entered the study. All ITP patients had active disease and were receiving weekly romiplostim as the sole ITP-directed therapy. Platelet aggregation in response to the strong agonists arachidonic acid, collagen, and ristocetin was not significantly different between ITP patients and healthy subjects (P = 0.2442, P = 0.0548, and P = 0.0879, respectively). Platelet aggregation in response to weak agonists was significantly reduced in ITP patients compared with that in healthy subjects: median (range) aggregation to ADP, 45% (15-84%) versus 89% (70-95%) (P = 0.0010), and epinephrine, 21% (1.6-90%) versus 88% (79-94%) (P = 0.0085). The median AC50 of ADP was threefold higher in ITP patients versus that in healthy subjects (6.3 µM vs 2.1 µM) (P = 0.0049). Significant spontaneous aggregation was not observed in any patient. Platelets from romiplostim-treated ITP patients do not show evidence for spontaneous aggregation or hyperreactivity, but instead have a modestly reduced aggregation response to ADP and epinephrine.


Assuntos
Transtornos Plaquetários/induzido quimicamente , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Difosfato de Adenosina/farmacologia , Adulto , Idoso , Ácido Araquidônico/farmacologia , Colágeno/farmacologia , Epinefrina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Púrpura Trombocitopênica Idiopática/sangue , Receptores de Trombopoetina/agonistas , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Ristocetina/farmacologia , Trombofilia/induzido quimicamente , Trombopoetina/efeitos adversos , Trombopoetina/farmacologia , Adulto Jovem
17.
Platelets ; 29(6): 574-582, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29863946

RESUMO

Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessing distinct ultrastructural abnormalities in inherited platelet disorders (IPDs). Nevertheless, PTEM remains mainly a research tool due to the lack of standardized procedures, a validated dense granule (DG) count reference range, and standardized image interpretation criteria. The aim of this study was to standardize and validate PTEM as a clinical laboratory test. Based on previously established methods, we optimized and standardized preanalytical, analytical, and postanalytical procedures for both whole mount (WM) and thin section (TS) PTEM. Mean number of DG/platelet (plt), percentage of plts without DG, platelet count (PC), mean platelet volume (MPV), immature platelet fraction (IPF), and plt light transmission aggregometry analyses were measured on blood samples from 113 healthy donors. Quantile regression was used to estimate the reference range for DG/plt, and linear regression was used to assess the association of DG/plt with other plt measurements. All PTEM procedures were standardized using commercially available materials and reagents. DG interpretation criteria were established based on previous publications and expert consensus, and resulted in improved operator agreement. Mean DG/plt was stable for 2 days after blood sample collection. The median within patient coefficient of variation for mean DG/plt was 22.2%; the mean DG/plt reference range (mid-95th %) was 1.2-4.0. Mean DG/plt was associated with IPF (p = .01, R2 = 0.06) but not age, sex, PC, MPV, or plt maximum aggregation or primary slope of aggregation (p > .17, R2 < 0.02). Baseline ultrastructural features were established for TS-PTEM. PTEM was validated using samples from patients with previously established diagnoses of IPDs. Standardization and validation of PTEM procedures and interpretation, and establishment of the normal mean DG/plt reference range and PTEM baseline ultrastructural features, will facilitate implementation of PTEM as a valid clinical laboratory test for evaluating ultrastructural abnormalities in IPDs.


Assuntos
Plaquetas/metabolismo , Microscopia Eletrônica de Transmissão/métodos , Valores de Referência , Humanos
18.
Clin Chem Lab Med ; 57(1): 115-126, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-29668440

RESUMO

Quality in diagnostic testing represents a key target of laboratory medicine, for which an assurance around the quality of testing is expected from all involved in the process. Laboratories attempt to assure the quality of their testing by various processes, but especially by performance of internal quality control and external quality assessment (EQA). This is especially true for tests of hemostasis and coagulation. EQA in general provides information on test accuracy and on evaluation of long-term laboratory performance. EQA providers support laboratory performance by various means, including distribution of material for testing of analytes ("proficiency testing"), educational support through expert advice, distribution of publications or case series. Participation in EQA is often a laboratory accreditation requirement. This review aims to identify some of the strengths and weaknesses of EQA, and targets attempts towards harmonization of EQA practice, in order to achieve the best outcome for participant laboratories and, thus, for patients and their clinical care providers.


Assuntos
Hemostasia , Ensaio de Proficiência Laboratorial/normas , Garantia da Qualidade dos Cuidados de Saúde/normas , Coagulação Sanguínea , Humanos
19.
Blood Coagul Fibrinolysis ; 29(2): 184-188, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29356700

RESUMO

: Coagulation laboratories have largely stopped transporting whole blood specimens on ice, due to adverse effects on factor VIII, von Willebrand factor, and the prothrombin time. However, it is unknown whether ice should be required or avoided for other coagulation assays. Furthermore, the amount of time that specimens remain stable during transportation at room temperature (RT) is also largely unknown for many coagulation tests. Therefore, this study investigated specimen stability on ice and RT for a comprehensive panel of coagulation tests. One tube of whole blood from each volunteer (n = 22) was centrifuged immediately (time 0), one was stored for 4 h on ice, and one was stored for 4 h at RT before centrifugation. Among time 0, 4 h on ice, and 4 h at RT samples, no statistically significant differences were found for fibrinogen, activated protein C resistance, thrombin time, reptilase time, antithrombin activity, chromogenic protein C, factor XII, and antiplasmin activity. Prothrombin time, activated partial thromboplastin time, factors IX, XI, protein S activity, and plasminogen activity showed statistically, but not clinically, significant differences. On ice, the only analytes that showed clinically significant changes (≥6.0% from time 0) were factors VII, VIII, von Willebrand factor antigen, and ristocetin cofactor, which were 14.0% higher, and 19.2, 9.5, and 18.8% lower than time 0, respectively. At RT, all analytes were stable except factor VIII was 9.4% lower than time 0. Only factors II, V, X, and PTT-LA lupus anticoagulant showed a possible slight benefit from ice, but the statistically significant differences were not clinically significant. Ice did not substantially benefit any of the coagulation assays. All tests were stable at RT, except more study is needed regarding factor VIII.


Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Testes de Coagulação Sanguínea/métodos , Temperatura Baixa , Humanos , Fatores de Tempo
20.
Arch Pathol Lab Med ; 142(1): 70-74, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28920711

RESUMO

CONTEXT: - Rivaroxaban causes a false increase in activated protein C resistance (APCR) ratios and protein S activity. OBJECTIVE: - To investigate whether this increase masks a diagnosis of factor V Leiden (FVL) or protein S deficiency in a "real-world" population of patients undergoing rivaroxaban treatment and hypercoagulation testing. DESIGN: - During a 2.5-year period, we compared 4 groups of patients (n = 60): FVL heterozygous (FVL-HET)/taking rivaroxaban, wild-type/taking rivaroxaban, FVL-HET/no rivaroxaban, and normal APCR/no rivaroxaban. Patients taking rivaroxaban were tested for protein S functional activity and free antigen (n = 32). RESULTS: - The FVL-HET patients taking rivaroxaban had lower APCR ratios than wild-type patients ( P < .001). For FVL-HET patients taking rivaroxaban, mean APCR was 1.75 ± 0.12, versus 1.64 ± 0.3 in FVL-HET patients not taking rivaroxaban ( P = .005). Activated protein C resistance in FVL-HET patients fell more than 3 SDs below the cutoff of 2.2 at which the laboratory reflexes FVL DNA testing. No cases of FVL were missed despite rivaroxaban. In contrast, rivaroxaban falsely elevated functional protein S activity, regardless of the presence or absence of FVL ( P < .001). A total of 4 of 32 patients (12.5%) had low free protein S antigen (range, 58%-67%), whereas their functional protein S activity appeared normal (range 75%-130%). Rivaroxaban would have caused a missed diagnosis of all cases of protein S deficiency during the study if testing relied on the protein S activity assay alone. CONCLUSIONS: - Despite rivaroxaban treatment, APCR testing can distinguish FVL-HET from normal patients, rendering indiscriminate FVL DNA testing of all patients on rivaroxaban unnecessary. Free protein S should be tested in patients taking rivaroxaban to exclude hereditary protein S deficiency.


Assuntos
Resistência à Proteína C Ativada/diagnóstico , Fator V/genética , Inibidores do Fator Xa/uso terapêutico , Deficiência de Proteína S/diagnóstico , Rivaroxabana/uso terapêutico , Resistência à Proteína C Ativada/tratamento farmacológico , Resistência à Proteína C Ativada/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Testes de Coagulação Sanguínea , Inibidores do Fator Xa/efeitos adversos , Reações Falso-Negativas , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteína S/análise , Deficiência de Proteína S/sangue , Rivaroxabana/efeitos adversos , Adulto Jovem
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