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INTRODUCTION: Diagnosing hemophilia B (HB) carrier status is important to manage bleeding in carriers and to prevent bleeding in potential offspring. Without a family history of hemophilia, diagnosing HB carrier status is challenging. Genetic testing is the gold-standard, however it is reserved for individuals with a high suspicion of carrier status. AIMS: To describe the distribution of activated partial thromboplastin time (aPTT) and factor IX coagulant (FIX:C) levels in HB carriers and assess the ratio of FIX:C to other Vitamin K dependent factors (FII:C, FVII:C, FX:C) as an indicator of HB carrier status. METHODS: In this retrospective, single-centre cohort study, subjects were included if they were obligate or genetically proven HB carriers. Distributions of aPTT and FIX:C were described and the relationship between FIX:C levels in carriers and severity of familial HB was analysed. Ratios of FIX:C to FII:C, FVII:C, FX:C were calculated. RESULTS: Seventy-two female HB carriers (median age: 34 years; IQR 24-43) were included. Median aPTT and FIX:C levels were 33.0 s [IQR 30.0-37.0] and 57 IU/dL [IQR 43-74]. Fifteen carriers (21%) had mild HB (FIX:C levels of 10-40 IU/dL). FIX:C levels trended higher in carriers of mild HB versus carriers of moderate/severe HB. In six carriers, the median ratio of FIX:C to other Vitamin K dependent factors was 0.44, with 92% of ratios being ≤ 0.75. CONCLUSION: aPTT and FIX:C levels were unreliable in diagnosing HB carrier status. A low ratio of FIX:C to other Vitamin K dependent factors may be a useful marker of HB carrier status.
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Factor IX , Hemofilia B , Vitamina K , Humanos , Hemofilia B/sangre , Hemofilia B/diagnóstico , Hemofilia B/genética , Factor IX/metabolismo , Factor IX/genética , Factor IX/análisis , Femenino , Adulto , Tiempo de Tromboplastina Parcial/métodos , Estudios Retrospectivos , Adulto Joven , Heterocigoto , Estudios de Cohortes , MasculinoRESUMEN
INTRODUCTION: Non-factor replacement therapies are emerging as prophylactic treatment options in haemophilia A or B (HA/HB) with and without inhibitors. Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody preventing factor (F)Xa inhibition and enhancing thrombin generation. Based on experience with other non-factor therapies and extended half-life products, there is a focus on potential interference with common clinical coagulation assays used to monitor patients treated with concizumab. AIM: To evaluate the impact of concizumab on standard clinical coagulation assays. METHODS: Plasma samples (normal, HA/HB with/without inhibitors) in the presence/absence of added concizumab (250-16,000 ng/mL) were analysed in clinical assays including activated partial thromboplastin time (aPTT), prothrombin time (PT), FVIII and FIX one-stage clot and chromogenic substrate assay, assays for detecting FVIII or FIX inhibitors and other assays for coagulation factors. RESULTS: Concizumab did not impact PT assays, but resulted in a small shortening of aPTT (up to 5 s in haemophilia plasma and 0.4 s in normal plasma). Concizumab had no, or only a minor impact on FVIII and FIX activity assays or Bethesda inhibitor assays. FXI and FXII activity in normal plasma, as measured by single factor aPTT-based assay, was significantly increased in the presence of concizumab (+11% each). This was also the case for FVII and FX measured by PT-based assays using plasma with 25% of FVII or FX (+64% and +22%, respectively). CONCLUSION: The presence of concizumab did not, or only slightly, influence the outcome of standard clinical coagulation assays relevant for HA and HB.
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Anticuerpos Monoclonales Humanizados , Hemofilia A , Humanos , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Pruebas de Coagulación Sanguínea/métodos , Hemofilia A/tratamiento farmacológico , Hemofilia A/sangre , Hemofilia B/tratamiento farmacológico , Hemofilia B/sangre , Coagulación Sanguínea/efectos de los fármacos , Tiempo de Tromboplastina Parcial/métodosRESUMEN
In unfractionated heparin (UFH) monitoring during extracorporeal circulation, the traditional measures of activated clotting time (ACT) or activated partial thromboplastin time (APTT) may diverge, confounding anticoagulant adjustments. We aimed to explore the factors explaining this discrepancy in children and young adults. This retrospective observational study, conducted at an urban regional tertiary hospital, included consecutive pediatric patients who received UFH during extracorporeal circulation (continuous kidney replacement therapy or extracorporeal membrane oxygenation) between April 2017 and March 2021. After patients whose ACT and APTT were not measured simultaneously or who were also taking other anticoagulants were excluded, we analyzed 94 samples from 23 patients. To explain the discrepancy between ACT and APTT, regression equations were created using a generalized linear model (family = gamma, link = logarithmic) with ACT as the response variable. Other explanatory variables included age, platelet count, and antithrombin. Compared to APTT alone as an explanatory variable, the Akaike information criterion and pseudo-coefficient of determination improved from 855 to 625 and from 0.01 to 0.42, respectively, when these explanatory variables were used. In conclusion, we identified several factors that may explain some of the discrepancy between ACT and APTT in the routinely measured tests. Evaluation of these factors may aid in appropriate adjustments in anticoagulation therapy.
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Circulación Extracorporea , Heparina , Humanos , Heparina/farmacología , Heparina/uso terapéutico , Femenino , Masculino , Niño , Estudios Retrospectivos , Circulación Extracorporea/métodos , Adolescente , Tiempo de Tromboplastina Parcial/métodos , Preescolar , Adulto Joven , Adulto , Lactante , Anticoagulantes/uso terapéutico , Anticoagulantes/farmacología , Coagulación Sanguínea/efectos de los fármacos , Tiempo de Coagulación de la Sangre Total/métodosRESUMEN
INTRODUCTION: An investigation of the suitability of reagents for measuring FVIII products in a one-stage clotting assay (OSA) showed variations in their FVIII activity (FVIII:C). Most studies have focused on the activated partial thromboplastin time (APTT) reagent rather than FVIII-deficient plasma (F8DP), even though the APTT-based OSA is comprised of APTT reagents and factor-deficient plasma. AIM: A single-centre study was conducted to clarify variations in measurements of FVIII products in an OSA using a total of 12 reagent combinations, including four APTT reagents and three types of F8DP. METHODS: FVIII:C in nine types of FVIII product-spiked plasma was measured using an OSA with four different APTT reagents and three types of F8DP. RESULTS: F8DP-dependent variations were found in addition to differences derived from APTT reagents. Variations in target recovery (TR) were observed for NovoEight®, Eloctate®, and Jivi®. Reduced TR for Jivi was found only for Pathromtin SL in combination with congenital F8DP (F8DP-3). This lower TR was not observed with alternative manufacturing lots of F8DP-3. The reduced TR for Jivi might be related to impaired contact activation due to lower factor XI activity in F8DP-3. CONCLUSION: In addition to APTT reagents, variations in F8DPs used for OSAs can also affect FVIII:C results. F8DPs as well as the APTT reagent used for OSA should be chosen with caution, and laboratories should evaluate reagents for F8DPs as they currently do for APTT reagents, especially when lot changes occur.
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Factor VIII , Humanos , Factor VIII/análisis , Tiempo de Tromboplastina Parcial/métodos , Tiempo de Tromboplastina Parcial/normas , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/normas , Coagulación Sanguínea , Indicadores y Reactivos , Reproducibilidad de los ResultadosRESUMEN
Acquired factor XI deficiencies due to factor-specific inhibitors are rare and may be associated with lupus anticoagulant. We report a 63-year-old male with suspected postsurgical bleeding, prior surgical site infection, an isolated prolonged activated partial thromboplastin time, and a positive lupus anticoagulant. Although the factor II assay was normal, factor VIII and IX assays initially demonstrated nonparallelism with factor activity that consistently increased to normal reference ranges with serial dilutions. A discrepancy in factor XI activity results was discovered when the in-house method demonstrated undetectable activity (<3%); send-out testing using different instrument/reagent combinations revealed the presence of factor XI activity between 70% and 76%. The patient received surgical follow-up and was subsequently discharged home. Given the differential in vitro inhibition of factor XI activity on our initial in-house testing, this case highlights the importance of recognizing factor assay interference in the presence of a known lupus anticoagulant inhibitor, with strategies to mitigate potentially erroneous results.
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Factor XI , Inhibidor de Coagulación del Lupus , Humanos , Inhibidor de Coagulación del Lupus/sangre , Masculino , Persona de Mediana Edad , Factor XI/antagonistas & inhibidores , Pruebas de Coagulación Sanguínea/métodos , Deficiencia del Factor XI/sangre , Tiempo de Tromboplastina Parcial/métodosRESUMEN
OBJECTIVES: This study aimed to determine the test performances of rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-based clot waveform analysis (aPTT-CWA) compared with the International Society on Thrombosis and Hemostasis disseminated intravascular coagulation (ISTH-DIC) score for diagnosis of overt disseminated intravascular coagulation (ODIC) in critically ill children. Prognostic indicators of DIC complications were also evaluated. DESIGN: A prospective cross-sectional observational study was conducted. ROTEM and aPTT-CWA were assessed alongside standard parameters based on the ISTH-DIC score and natural anticoagulants. Both conventional and global hemostatic tests were repeated on days 3-5 for nonovert DIC. SETTING: PICU of the Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. SUBJECTS: Infants and children who were admitted to PICU with underlying diseases predisposed to DIC, such as sepsis, malignancy, major surgery, trauma, or severe illness, were included in the study between July 1, 2021, and November 30, 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-four children were enrolled in this study. The prevalence of ODIC was 20.3%. Regarding ROTEM parameters, using EXTEM clot formation time (CFT) cutoff of greater than 102 seconds provided sensitivity and specificity of 90.9% and 80.9%, respectively, for diagnosing ODIC, with the area under the curve (AUC) of 0.86. In the case of aPTT-CWA performance, no biphasic waveform was observed, whereas both maximum coagulation acceleration (Min2) of less than 0.35%/s 2 and maximum coagulation deceleration of less than 0.25%/s 2 demonstrated identical sensitivities of 76.9% and specificities of 79.6%. Combining two global hemostatic tests significantly improved the diagnostic performance (INTEM CFT + EXTEM CFT + Min2 AUC 0.92 [95% CI, 0.80-1.00] vs. EXTEM CFT AUC 0.86 [95% CI, 0.75-0.96], p = 0.034). Bleeding was the most common consequence. In multivariable logistic regression analysis, Min2 of less than 0.36%/s 2 was an independent risk factor for bleeding complications, with an adjusted odds ratio of 15.08 (95% CI, 1.08-211.15, p = 0.044). CONCLUSIONS: ROTEM and aPTT-CWA were valuable diagnostic tools in critically ill children who might require point-of-care tests. Min2 showed significant clinical implications for predicting bleeding events in this population.
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Enfermedad Crítica , Coagulación Intravascular Diseminada , Tromboelastografía , Humanos , Tromboelastografía/métodos , Masculino , Estudios Prospectivos , Femenino , Preescolar , Tailandia/epidemiología , Coagulación Intravascular Diseminada/diagnóstico , Niño , Lactante , Estudios Transversales , Tiempo de Tromboplastina Parcial/métodos , Unidades de Cuidado Intensivo Pediátrico , Pruebas en el Punto de Atención , Sensibilidad y Especificidad , Adolescente , Sistemas de Atención de Punto , Recién NacidoRESUMEN
BACKGROUND: We aim to determine the clinical utility of reflex coagulation investigations (RCI) for prolonged lupus insensitive activated partial thromboplastin time (aPTT) at our institution. METHODS: We retrospectively reviewed all potential RCI (lupus insensitive aPTT of ≥32s) from April 2014 to June 2019. Our diagnostic algorithm requires completion of RCI only if samples had no interfering medications to explain a prolonged aPTT and were either from a preoperative sample or from a patient presenting with unexplained bleeding. Appropriate RCI samples undergo further investigations with one-stage factor activity testing for factors 8(FVIII), 9(FIX), and 11(FXI) reflexively. Data were obtained through electronic medical records to capture clinical characteristics, laboratory findings, prophylactic hemostatic replacement, and bleeding outcomes. RESULTS: Three thousand and three hundreds seventeen samples from 2940 distinct patients were considered as potential RCI during the study period. 263/3317 (8%) samples had RCI completed. Of those, 55/263 (21%) had abnormal factor testing, with the majority from preoperative setting (43/55; 78%). 5/43 (12%) patients were referred to hematology for preoperative evaluation. 5/43 patients received preoperative hemostatic support. A total of 5 patients (5/43) developed postop bleeding. Six patients (6/55) had RCI for unexplained bleeding, and five patients (83%) had a newly identified clinically significant bleeding disorder. CONCLUSION: Reflex coagulation investigations benefited patients presenting with unexplained bleeding as this expedited the diagnosis and management of clinically significant bleeding disorders. RCI for preoperative evaluation infrequently led to additional hemostatic support/referral to hematology. The lack of additional workup for an abnormal factor activity level suggests laboratory alert fatigue as a potential contributory factor.
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Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/normas , Coagulación Sanguínea , Tiempo de Tromboplastina Parcial/métodos , Tiempo de Tromboplastina Parcial/normas , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Toma de Decisiones Clínicas , Pruebas Diagnósticas de Rutina , Manejo de la Enfermedad , Humanos , Cuidados Preoperatorios/métodosRESUMEN
INTRODUCTION: An algorithmic approach, termed the prolonged clot time profile (PROCT), consisting of initial screening with prothrombin time (PT) and activated partial thromboplastin time (aPTT), reflexive mixing studies if indicated, and follow-up assays depending on initial testing results, offers an efficient approach to delineate the etiology of a prolonged PT/aPTT. Herein, we present the outcomes of the PROCT in the outpatient setting. METHODS: In this retrospective study, we reviewed medical records of consecutive outpatients who had prolonged PT and/or aPTT noted in the routine coagulation laboratory and who had PROCT ordered in our institutional Special Coagulation Laboratory between 2010 and 2017. RESULTS: One hundred and six patients, median age 55 years (IQR 30-67), met our study criteria. Twenty-nine patients had normal PT/aPTT, while 77 had persistent abnormalities and underwent reflexive testing. A prolonged PT, aPTT, or PT and aPTT was noted in 27 (35%), 27 (35%), and 23 (30%) respectively. Forty-nine (64%) had an acquired condition, 17 (22%) had a congenital condition, 7 (9%) had unclear etiology, and 4 (5%) were the result of laboratory artifact. The most common known cause of an isolated prolonged PT in our study was vitamin K deficiency in 8 (10%), the most common cause of an isolated prolonged aPTT was lupus anticoagulant in 4 (5%), and the most common cause of prolonged PT and aPTT was liver disease in 11 (14%). CONCLUSION: Prolonged PT/aPTT have a wide range of causes, including artifactual prolongation or abnormalities in secondary hemostasis due to both inherited and acquired conditions.
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Instituciones de Atención Ambulatoria , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Adulto , Anciano , Trastornos de la Coagulación Sanguínea/etiología , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/normas , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Tiempo de Tromboplastina Parcial/métodos , Tiempo de Tromboplastina Parcial/normas , Tiempo de Protrombina/métodos , Tiempo de Protrombina/normas , Valores de Referencia , Estudios RetrospectivosRESUMEN
BACKGROUND: Coagulation system is heavily involved into the process of infective endocarditis (IE) vegetation formation and can facilitate further embolization. In this study we aimed to assess the coagulation and platelet state in IE implementing a wide range of standard and global laboratory assays. We also aim to determine whether prothrombotic genetic polymorphisms play any role in embolization and mortality in IE patients. METHODS: 37 patients with IE were enrolled into the study. Coagulation was assessed using standard coagulation assays (activated partial thromboplastin time (APTT), prothrombin, fibrinogen, D-dimer concentrations) and integral assays (thromboelastography (TEG) and thrombodynamics (TD)). Platelet functional activity was estimated by flow cytometry. Single nuclear polymorphisms of coagulation system genes were studied. RESULTS: Fibrinogen concentration and fibrinogen-dependent parameters of TEG and TD were increased in patients indicating systemic inflammation. In majority of patients clot growth rate in thrombodynamics was significantly shifted towards hypercoagulation in consistency with D-dimers elevation. However, in some patients prothrombin, thromboelastography and thrombodynamics were shifted towards hypocoagulation. Resting platelets were characterized by glycoprotein IIb-IIIa activation and degranulation. In patients with fatal IE, we observed a significant decrease in fibrinogen and thrombodynamics. In patients with embolism, we observed a significant decrease in the TEG R parameter. No association of embolism or mortality with genetic polymorphisms was found in our cohort. CONCLUSIONS: Our findings suggest that coagulation in patients with infective endocarditis is characterized by general hypercoagulability and platelet pre-activation. Some patients, however, have hypocoagulant coagulation profile, which presumably can indicate progressing of hypercoagulation into consumption coagulopathy.
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Endocarditis/patología , Activación Plaquetaria/genética , Activación Plaquetaria/fisiología , Trombofilia/genética , Trombofilia/patología , Adulto , Anciano , Plaquetas/fisiología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Hemostasis/fisiología , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial/métodos , Polimorfismo de Nucleótido Simple/genética , Protrombina/análisis , Tromboelastografía/métodosRESUMEN
INTRODUCTION: Argatroban is licensed for patients with heparin-induced thrombocytopenia and is conventionally monitored by activated partial thromboplastin time (APTT) ratio. The target range is 1.5 to 3.0 times the patients' baseline APTT and not exceeding 100 s, however this baseline is not always known. APTT is known to plateau at higher levels of argatroban, and is influenced by coagulopathies, lupus anticoagulant and raised FVIII levels. It has been used as a treatment for COVID-19 and Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). Some recent publications have favored the use of anti-IIa methods to determine the plasma drug concentration of argatroban. METHODS: Plasma of 60 samples from 3 COVID-19 patients and 54 samples from 5 VITT patients were tested by APTT ratio and anti-IIa method (dilute thrombin time dTT). Actin FS APTT ratios were derived from the baseline APTT of the patient and the mean normal APTT. RESULTS: Mean APTT ratio derived from baseline was 1.71 (COVID-19), 1.33 (VITT) compared to APTT ratio by mean normal 1.65 (COVID-19), 1.48 (VITT). dTT mean concentration was 0.64â µg/ml (COVID-19) 0.53â µg/ml (VITT) with poor correlations to COVID-19 baseline APTT ratio r2 = 0.1526 p <0.0001, mean normal r2 = 0.2188 p < 0.0001; VITT baseline APTT ratio r2 = 0.04 p < 0.001, VITT mean normal r2 = 0.0064 p < 0.001. CONCLUSIONS: We believe that dTT is a superior method to monitor the concentration of argatroban, we have demonstrated significant differences between APTT ratios and dTT levels, which could have clinical impact. This is especially so in COVID-19 and VITT.
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Arginina/análogos & derivados , Tratamiento Farmacológico de COVID-19 , Tiempo de Tromboplastina Parcial/métodos , Ácidos Pipecólicos/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Sulfonamidas/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Anciano , Arginina/farmacología , Arginina/uso terapéutico , COVID-19/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácidos Pipecólicos/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , SARS-CoV-2 , Sulfonamidas/farmacología , Trombocitopenia/inducido químicamente , Trombosis/inducido químicamenteRESUMEN
OBJECTIVES: The aim of this study was to investigate the incidence of deep vein thrombosis (DVT) and the preoperative and intraoperative risk factors associated with DVT in glioma patients METHODS: We conducted a retrospective analysis of data obtained from glioma patients at Sanbo Hospital (Beijing, China) between 2018 and 2021. Symptomatic DVT was confirmed by Doppler ultrasonography. Multivariable logistic regression analysis was used to identify preoperative and intraoperative characteristics associated with DVT. Basic clinical variables and laboratory results were analyzed. RESULTS: A total of 492 glioma patients were included. Of these, 73 (14.84%) developed DVT, and three (0.61%) developed DVT and pulmonary embolism (PE). Multivariate analyses revealed that the following factors were highly predictive of post-operative DVT: older age ranges of 46--55 years (odds ratio [OR]: 2.94; 95% confidence interval [CI]: 1.41--6.13; p = 0.004), 56--65 years (OR: 7.86; 95% CI: 3.63--17.03; p < 0.001), and > 65 years (OR: 4.94; 95% CI: 1.83--13.33; p = 0.002); partial thromboplastin time (APTT; OR: 0.91; 95% CI: 0.84--1.00; p = 0.040); D-dimer (OR: 2.21; 95% CI: 1.28--3.82; p = 0.005); and surgery duration (OR: 2.87; 95% CI: 1.6 --5.07; p < 0.001) CONCLUSIONS: Older age, preoperative APTT, D-dimer, and surgery duration independently increased the risk of developing postoperative DVT. These findings may facilitate the development of a thrombosis risk score that will allow physicians to develop individualized strategies to prevent DVT as early as possible.
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Neoplasias Encefálicas/cirugía , Craneotomía/efectos adversos , Glioma/cirugía , Monitoreo Intraoperatorio/métodos , Complicaciones Posoperatorias/epidemiología , Trombosis de la Vena/epidemiología , Adulto , Factores de Edad , Anciano , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/diagnóstico por imagen , Craneotomía/métodos , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Glioma/sangre , Glioma/diagnóstico por imagen , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial/métodos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico por imagen , Cuidados Preoperatorios/métodos , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Trombosis de la Vena/sangre , Trombosis de la Vena/diagnóstico por imagenRESUMEN
OBJECTIVES: Extracorporeal membrane oxygenation provides large surface exposure to human blood leading to coagulation activation. Only limited clinical data are available on contact activation and coagulation factor XII activity in extracorporeal membrane oxygenation patients. DESIGN: Prospective cohort study. SETTING: Three medical ICUs at the Medical University of Vienna. PATIENTS: Adult patients receiving venovenous or venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in coagulation factor XII activity in response to extracorporeal membrane oxygenation. Secondary outcomes included the prevalence of reduced coagulation factor XII activity (< 60%) among patients receiving extracorporeal membrane oxygenation and association of coagulation factor XII activity with thromboembolic and bleeding complications. An exploratory endpoint was the association of coagulation factor XII activity and activated partial thromboplastin time in heparinase-treated samples in vitro. Fifty-one patients with a total of 117 samples were included in the study between July 2018 and February 2020. Fifty patients (98%) had reduced coagulation factor XII activity at any timepoint during extracorporeal membrane oxygenation. Median coagulation factor XII activity during extracorporeal membrane oxygenation treatment was 30% (interquartile range, 21.5-41%) and increased after discontinuation (p = 0.047). Patients with thromboembolic complications had higher median coagulation factor XII activity during extracorporeal membrane oxygenation (34% vs 23%; p = 0.023). The odds of a thromboembolic event increased by 200% per tertile of median coagulation factor XII activity (crude odds ratio, 3.034; 95% CI, 1.21-7.63). No association with bleeding was observed. In heparinase-treated samples, coagulation factor XII activity correlated well with activated partial thromboplastin time (r = -0.789; p = 0.007). CONCLUSIONS: We observed a high prevalence of reduced coagulation factor XII activity in adult patients on extracorporeal membrane oxygenation, which may confound activated partial thromboplastin time measurements and limit its clinical usefulness for monitoring and titrating anticoagulation with unfractionated heparin. Lower coagulation factor XII activity was associated with less thromboembolic complications, which may highlight the potential of coagulation factor XII to serve as a target for anticoagulation in extracorporeal membrane oxygenation.
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Oxigenación por Membrana Extracorpórea/efectos adversos , Factor XII/biosíntesis , Adulto , Austria/epidemiología , Estudios de Cohortes , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/estadística & datos numéricos , Humanos , Tiempo de Tromboplastina Parcial/métodos , Prevalencia , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Vitamin K has long been regarded as a procoagulant drug by physicians, and concerns have been raised with regard to its effects on hemostasis. Although many studies have shown that vitamin K supplementation is safe for thrombotic events, the effect of vitamin K supplementation on the activities of vitamin K dependent procoagulation factors in healthy individuals is not available. OBJECTIVES: This study aimed to investigate whether vitamin K2 supplementation at recommended doses affects the activity of vitamin K dependent procoagulation factors in healthy individuals without any anticoagulation treatment. DESIGN: Forty healthy volunteers between 25 and 40âyears of age were recruited. Menaquinone-7 (MK-7) was administrated at 90âµg for 30âdays. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and blood coagulation factors II, VII, IX, and X activities and Protein induced by vitamin K absence or antagonist-II (PIVKA-II) were measured on days 0 and 30 after MK-7 administration. RESULTS: PT, APTT, and TT showed no significant differences on day 30 when compared with baseline. The activities of coagulation factors II, VII, IX, and X on day 30 showed no significant differences with those at baseline. PIVKA-II levels were unchanged after 30âdays of MK-7 supplementation. CONCLUSIONS: MK-7 supplementation at recommended dosage does not affect vitamin K-dependent coagulation factors' coagulation activity, and does not enhance the carboxylation of prothrombin in healthy individuals. This indicated that MK-7 administration does not alter hemostatic balance in healthy populations without anticoagulation treatment.
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Factores de Coagulación Sanguínea/efectos de los fármacos , Suplementos Dietéticos/normas , Vitamina K 2/farmacología , Adulto , Antifibrinolíticos/farmacología , Antifibrinolíticos/uso terapéutico , Factores de Coagulación Sanguínea/análisis , Suplementos Dietéticos/estadística & datos numéricos , Factor IX/análisis , Factor IX/efectos de los fármacos , Factor VII/análisis , Factor VII/efectos de los fármacos , Factor X/análisis , Factor X/efectos de los fármacos , Femenino , Voluntarios Sanos/estadística & datos numéricos , Humanos , Masculino , Tiempo de Tromboplastina Parcial/métodos , Tiempo de Tromboplastina Parcial/estadística & datos numéricos , Protrombina/análisis , Protrombina/efectos de los fármacos , Tiempo de Protrombina/métodos , Tiempo de Protrombina/estadística & datos numéricos , Tiempo de Trombina/métodos , Tiempo de Trombina/estadística & datos numéricos , Vitamina K 2/uso terapéuticoRESUMEN
PURPOSE: To evaluate the prognostic role of prothrombin time (PT) and activated partial thromboplastin time (APTT) for newly diagnosed multiple myeloma (MM). METHODS: We retrospectively analyzed 354 patients with newly diagnosed MM who received primary treatment in our center. The propensity score matching technique was used to reduce the bias between groups. RESULTS: Among 354 patients, lengthened PT or APTT was observed in 154 (43.5%) patients and 200 (56.5%) patients had normal PT and APTT. Patients with lengthened PT or APTT had significantly shorter median overall survival (OS) (37.5 vs. 73.8 months, p < 0.001) and progression-free survival (PFS) (23.1 vs. 31.6 months, p = 0.001) than those with normal PT and APTT. Univariate Cox proportional hazards regression analyses showed that lengthened PT or APTT was associated with shorter OS (HR = 2.100, 95% CI: 1.525-2.893, p < 0.001). Lengthened PT or APTT was also a poor prognostic factor for OS (HR = 3.183, 95% CI: 1.803-5.617, p < 0.001) in multivariable analyses. The poor effect of lengthened PT or APTT on PFS was confirmed in univariate analysis (HR = 1.715, 95% CI: 1.244-2.365, p = 0.001), but it had no impact on PFS in multivariate analysis (p = 0.197). In the propensity score matching analysis, 154 patients, 77 in each group, were identified. Among 154 matched patients, the OS of patients with lengthened PT or APTT was shorter (38.4 vs. 51.0 months, p = 0.030), but PFS was similar (29.0 vs. 35.0 months, p = 0.248). CONCLUSION: These results demonstrated that lengthened PT or APTT was an independent poor prognostic factor for patients with newly diagnosed MM.
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Mieloma Múltiple/patología , Anciano , Coagulación Sanguínea/fisiología , Pruebas de Coagulación Sanguínea/métodos , Femenino , Humanos , Masculino , Tiempo de Tromboplastina Parcial/métodos , Pronóstico , Supervivencia sin Progresión , Tiempo de Protrombina/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Lupus anticoagulants (LA) are detected by prolongation of clotting times for dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) screening tests. Direct oral anticoagulants (DOACs) can interfere with both screening and confirmatory tests. The present study aimed to investigate the influence of direct factor Xa inhibitors (DiXaIs) on screen, confirm and mixing tests and establish a method for differentiation from other sample types. MATERIALS AND METHODS: A total of 257 samples including nonanticoagulated LA positive, LA positive with DiXaIs, factor deficiency, FVIII inhibitors, warfarin and non-APS DiXaIs were tested. APTT reagents Cephen LS/Cephen and dRVVT reagents LA1/LA2 were used, respectively, to screen/confirm the study group. Index of circulating anticoagulant (ICA) was calculated from clotting times based on the following formula as ICA screening and ICA confirmation. ICA= (1:1 Mix sample - Normal pooled plasma) / Screen patient x 100. An ICA matrix was established which suggested the presence of a DiXaI when both ICA screening and confirmation were above the cut-off. When only ICA screening is elevated, LA is suspected. RESULTS: Sensitivity and specificity of the ICA matrix were 52.2% and 92.8% for DiXaIs and 38.1% and 96.7% for LA in APTT, and 61.2% and 92.9% for DiXaIs and 22.2% and 88.4% for LA in dRVVT, respectively. CONCLUSION: The ICA matrix achieved high specificity with a lower apparent sensitivity for DiXaI samples comparatively to other devices but due only to less interferences: the matrix could contribute to differentiating DiXaIs from LA in samples where anticoagulation status is unknown.
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Inhibidores del Factor Xa/sangre , Inhibidor de Coagulación del Lupus/sangre , Coagulación Sanguínea/efectos de los fármacos , Pruebas de Coagulación Sanguínea/métodos , Inhibidores del Factor Xa/farmacología , Humanos , Inhibidor de Coagulación del Lupus/farmacología , Tiempo de Tromboplastina Parcial/métodos , Tiempo de Protrombina/métodosRESUMEN
CP3000 coagulation analyzer is a high-throughput, fully automated coagulation analyzer. The objective of this study was to evaluate the analytical performance of CP3000 coagulation system for general and special coagulation analyses. Quality control materials and patient samples were used to evaluate the analytical performance of CP3000 coagulation system. Precision, carryover, linearity, comparability with ACL-TOP 700 coagulation system, and verification of reference range were evaluated or performed according to Clinical and Laboratory Standards Institute guidelines. Within-run and between-run precisions were below 5% for both normal and abnormal ranges. There was no detectable carryover. The linearity of antithrombin and fibrinogen were excellent. The comparability between CP3000 and ACL-TOP 700 coagulation systems was acceptable except for activated partial thromboplastin time and thrombin time due to differences in reagent composition. Reference ranges proposed by the manufacturer were verified to be acceptable. CP3000 coagulation system is a reliable system that can be used to perform routine and special coagulation tests rapidly and accurately. Because of its small footprint as an additional advantage, the implementation of CP3000 coagulation system can be efficient in hospital laboratories of various sizes.
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Automatización de Laboratorios/instrumentación , Pruebas de Coagulación Sanguínea/instrumentación , Anticoagulantes/análisis , Coagulación Sanguínea/fisiología , Pruebas de Coagulación Sanguínea/métodos , Servicios de Laboratorio Clínico , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Humanos , Tiempo de Tromboplastina Parcial/instrumentación , Tiempo de Tromboplastina Parcial/métodos , Protrombina/análisis , Valores de Referencia , Reproducibilidad de los Resultados , Tiempo de Trombina/instrumentación , Tiempo de Trombina/métodosRESUMEN
The FVIII activity in patients treated with several extended half-life FVIII (EHL-FVIII) agents different when various activated partial thromboplastin time (APTT) reagents were used. The present study examined the difference in clot waveform analysis (CWA) findings and FVIII activity when various APTT reagents and CWA were used. The CWA including FVIII activity was measured using 12 APTT reagents, and the FIX activation based on a small amount of tissue factor assay (sTF/FIX) were examined in reference plasma (RP), EHL-FVIII (Jivi®) and Kovaltry®. The 3 APTT reagents were associated with high variation in the peak time and height in the CWA when analyzing low concentrations of FVIII. The peak time and height could not be measured with one APTT reagent, and there were marked differences in the CWA findings between Jivi® and Kovaltry® among APTT reagents. Several APTT reagents showed a markedly lower FVIII activity with Jivi® than with Kovaltry®. In the FVIII assay, the peak time measured with sTF/FIX did not differ markedly between Jivi® and Kovaltry®; however, the FVIII activity in Jivi® (as measured by the peak height) tended to be higher than in Kovaltry®. The CWA findings for monitoring Jivi® varied for monitoring Jivi® depending on the APTT reagents used, and sTF/FIX assay may be able to measure the EHL-FVIII.
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Factor VIII/metabolismo , Indicadores y Reactivos/metabolismo , Tiempo de Tromboplastina Parcial/métodos , Plasma/metabolismo , HumanosRESUMEN
INTRODUCTION: Hemolysis, icterus, and lipemia (HIL) are common pre-analytical variables in the clinical laboratory. Understanding their effects on coagulation laboratory results is essential. METHODS: HIL effects on the prothrombin time (PT), activated partial thromboplastin time (APTT), dilute Russell's viper venom time (DRVVT), thrombin time (TT), and protein C chromogenic activity (CFx) were evaluated on the ACL TOP 750 optical analyzer and STA-R Evolution mechanical analyzer (PT and APTT only) by spiking normal donor, patient, and commercial control samples with varying concentrations of hemolysate, bilirubin, or a lipid emulsion. The relative difference or bias compared to the original results was determined. RESULTS: Hemolysis (H) indices up to 900 mg/dL did not affect the APTT, PT, DRVVT Confirm, TT, and CFx; however, H indices above approximately 200 mg/dL resulted in a false-negative DRVVT screen and screen/confirm ratio in samples with a lupus anticoagulant. There was an artifactual prolongation of the PT and APTT when conjugated bilirubin was dissolved in aqueous solvents and not when it was dissolved in dimethyl sulfoxide. Icterus (I) indices up to 45 mg/dL did not result in significant (>15%) bias for all assays evaluated. The PT and APTT assays failed to produce a robust clot curve when the lipemia (L) index exceeded 6000 milliabsorbance units (mAbs), and the TT and DRVVT assays failed when the L index exceeded 3000 mAbs; the CFx assay was unaffected by lipemia. CONCLUSIONS: Verification of the manufacturer's recommended interference thresholds is important since it may avoid inappropriate instrument flagging and/ or sample rejection.
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Pruebas de Coagulación Sanguínea/métodos , Coagulación Sanguínea , Hemólisis , Humanos , Hiperlipidemias/diagnóstico , Ictericia/diagnóstico , Tiempo de Tromboplastina Parcial/métodos , Tiempo de Protrombina/métodosRESUMEN
CONTEXT: Hemophilia A is classified as mild, moderate, and severe based on Factor VIII levels (FVIII). Clot-based assays only detect initiation of thrombin generation, hence FVIII levels may not accurately predict the bleeding risk in all hemophilia patients. The entire process of thrombin generation as measured by global hemostasis tests like activated partial thromboplastin time clot waveform analysis (APTT CWA) and thrombin generation test (TGT) may reflect the actual bleeding phenotype. AIMS: To assess the utility of TGT and CWA as a screening tool to identify bleeders and to evaluate the bleeding phenotype in Hemophilia A. SETTINGS AND DESIGN: Prospective, observational study of 147 consecutive patients referred for coagulation workup. SUBJECTS AND METHODS: Bleeding assessment tool was used to identify bleeders. Patients were classified as severe and nonsevere bleeders based on clinical criteria. TGT was performed by calibrated automated thrombogram, CWA by photo-optical coagulometer and factor levels by one stage clot-based assays. STATISTICAL ANALYSIS USED: The Kruskal-Wallis test with post-hoc analysis was done to examine the difference in CWA/TGT parameters amongst hemophilia classified by FVIII levels. Receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic accuracy of CWA and TGT in discriminating between clinically severe vs nonsevere bleeders. RESULTS: Using ROC derived cut-offs of min1, min2 and peak height of thrombin (PH), the sensitivity (min1:91.67%, min2:91.67%, PH: 97.22%, FVIII: 86.11%) and specificity (min1:100%, min2:100%, PH: 90.91%, FVIII: 90.91%) of CWA/TGT was superior to FVIII to distinguish between clinically severe vs nonsevere bleeders. Phenotypic heterogeneity of bleeding severity was identified in our study population. Clinical severity correlated with CWA/TGT parameters instead of FVIII levels. CONCLUSIONS: CWA and TGT are more effective tools than conventional factor assays to identify clinically severe bleeders and tailor prophylaxis as per bleeding phenotype.
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Hemorragia/metabolismo , Tiempo de Tromboplastina Parcial/normas , Fenotipo , Trombina/análisis , Trombosis , Pruebas de Coagulación Sanguínea/normas , Hemofilia A/diagnóstico , Hemorragia/clasificación , Humanos , Tiempo de Tromboplastina Parcial/métodos , Estudios Prospectivos , Curva ROC , Trombina/metabolismoRESUMEN
BACKGROUND: The use of extracorporeal membrane oxygenator (ECMO) support devices are associated with complications, including bleeding and thrombosis. Unfractionated heparin (UFH) is the gold standard anticoagulant in ECMO patients. Clinically, UFH is monitored through activated clotting time (ACT), activated partial thromboplastin time (aPTT), and anti-factor Xa assay. It is unknown which assay best predicts anticoagulation effects in adults. OBJECTIVE: To assess the correlation of UFH dosing and monitoring using an established protocol. METHODS: A pilot, prospective cohort, historically controlled study was conducted at a tertiary care hospital. Patients ≥18 years-old who received ECMO on the multifaceted anticoagulation protocol were included and compared with those on the conventional method of anticoagulation. The primary end point was to assess the correlation between UFH dose and different monitoring methods throughout 72 hours using the new protocol guided by ACT and anti-factor Xa assay. RESULTS: In each arm, 20 patients were enrolled. The study revealed that anti-factor Xa assay had the largest number of "strong" correlations 11/20 (55%), followed by both aPTT and aPTT ratio 10/20 (50%), and, finally, ACT 2/20 (10%). Concordance between anti-factor Xa assay and the other monitoring parameters in the prospective arm was generally low: 31% with aPTT ratio, 26% with ACT, and 23% with aPTT. CONCLUSION AND RELEVANCE: The adaption of a multifaceted anticoagulation protocol using anti-factor Xa assay may provide a better prediction of heparin dosing in adults ECMO patients compared with the conventional ACT-based protocol. Further studies are needed to assess the safety and different monitoring modalities.