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1.
Am J Hematol ; 97(5): 519-526, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35132672

RESUMEN

Rare cases of COVID-19 vaccinated individuals develop anti-platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a syndrome referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Currently, information on the characteristics and persistence of anti-PF4 antibodies that cause VITT after Ad26.COV2.S vaccination is limited, and available diagnostic assays fail to differentiate Ad26.COV2.S and ChAdOx1 nCoV-19-associated VITT from similar clinical disorders, namely heparin-induced thrombocytopenia (HIT) and spontaneous HIT. Here we demonstrate that while Ad26.COV2.S-associated VITT patients are uniformly strongly positive in PF4-polyanion enzyme-linked immunosorbent assays (ELISAs); they are frequently negative in the serotonin release assay (SRA). The PF4-dependent p-selectin expression assay (PEA) that uses platelets treated with PF4 rather than heparin consistently diagnosed Ad26.COV2.S-associated VITT. Most Ad26.COV2.S-associated VITT antibodies persisted for >5 months in PF4-polyanion ELISAs, while the PEA became negative earlier. Two patients had otherwise unexplained mild persistent thrombocytopenia (140-150 x 103 /µL) 6 months after acute presentation. From an epidemiological perspective, differentiating VITT from spontaneous HIT, another entity that develops in the absence of proximate heparin exposure, and HIT is important, but currently available PF4-polyanion ELISAs and functional assay are non-specific and detect all three conditions. Here, we report that a novel un-complexed PF4 ELISA specifically differentiates VITT, secondary to both Ad26.COV2.S and ChAdOx1 nCoV-19, from both spontaneous HIT, HIT and commonly-encountered HIT-suspected patients who are PF4/polyanion ELISA-positive but negative in functional assays. In summary, Ad26.COV2.S-associated VITT antibodies are persistent, and the un-complexed PF4 ELISA appears to be both sensitive and specific for VITT diagnosis.


Asunto(s)
COVID-19 , Trombocitopenia , Vacunas , Ad26COVS1 , COVID-19/diagnóstico , Vacunas contra la COVID-19/efectos adversos , ChAdOx1 nCoV-19 , Heparina/efectos adversos , Humanos , Factor Plaquetario 4 , Trombocitopenia/inducido químicamente , Trombocitopenia/diagnóstico
2.
Mod Pathol ; 34(7): 1358-1366, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33526873

RESUMEN

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. We identified 105 cases, diagnosed as NK-LL (6), CD56+ acute undifferentiated leukemia (AUL) (6), CD56+ T-lymphoblastic leukemia (T-LL) (51), and CD56+ acute myeloid leukemia (AML) (42). Compared to AUL patients, NK-LL patients were significantly younger (p = 0.021) and presented with higher white blood cell (WBC) (p = 0.037) and platelet counts (p = 0.041). Flow cytometry showed more frequent expression of cytoplasmic CD3 (cCD3, p = 0.064) and CD33, (p = 0.065), while HLA-DR was significantly absent from NK-LL (p = 0.035) compared to AUL. Compared to T-ALL, NK-LL cases showed less frequent cCD3 (p = 0.002), CD4 (p = 0.051), and CD10 expression (p = 0.06). The frequency of abnormal karyotypes was similar between NK-LL, AUL, and T-ALL. The mutational profile differed in four leukemia groups, with a significance enrichment of NOTCH1 (p = 0.002), ETV6 (p = 0.002) and JAK3 (p = 0.02) mutations in NK-LL as compared to AML. As compared to T-ALL, NK-LL cases showed a higher number of total mutations (p = 0.04) and significantly more frequent ETV6 mutations (p = 0.004). Clinical outcome data showed differences in overall survival between all four groups (p = 0.0175), but no difference in event free survival (p = 0.246). In this largest study to date, we find that that NK-LL shows clinical presentation, immunophenotypic and molecular characteristics distinct from AUL, T-ALL, and AML. Our findings suggest NK-LL is a distinct acute leukemia entity and should be considered in the clinical diagnosis of acute leukemias of ambiguous lineage.


Asunto(s)
Células Asesinas Naturales/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adolescente , Anciano , Antígeno CD56/análisis , Niño , Preescolar , Femenino , Humanos , Inmunofenotipificación , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Estudios Retrospectivos
3.
Mod Pathol ; 34(1): 20-31, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32694616

RESUMEN

JAK2, CALR, and MPL are myeloproliferative neoplasm (MPN)-driver mutations, whereas SF3B1 is strongly associated with ring sideroblasts (RS) in myelodysplastic syndrome (MDS). Concomitant mutations of SF3B1 and MPN-driver mutations out of the context of MDS/MPN with RS and thrombocytosis (MDS/MPN-RS-T) are not well-studied. From the cases (<5% blasts) tested by NGS panels interrogating at least 42 myeloid neoplasm-related genes, we identified 18 MDS/MPN-RS-T, 42 MPN, 10 MDS, and 6 MDS/MPN-U cases with an SF3B1 and an MPN-driver mutation. Using a 10% VAF difference to define "SF3B1-dominant," "MPN-mutation dominant," and "no dominance," the majority of MDS/MPN-RS-T clustered in "SF3B1-dominant" and "no dominance" regions. Aside from parameters as thrombocytosis and ≥15% RS required for RS-T, MDS also differed in frequent neutropenia, multilineage dysplasia, and notably more cases with <10% VAF of MPN-driver mutations (60%, p = 0.0346); MPN differed in more frequent splenomegaly, myelofibrosis, and higher VAF of "MPN-driver mutations." "Gray zone" cases with features overlapping MDS/MPN-RS-T were observed in over one-thirds of non-RS-T cases. This study shows that concomitant SF3B1 and MPN-driver mutations can be observed in MDS, MPN, and MDS/MPN-U, each showing overlapping but also distinctively different clinicopathological features. Clonal hierarchy, cytogenetic abnormalities, and additional somatic mutations may in part contribute to different disease phenotypes, which may help in the classification of "gray zone" cases.


Asunto(s)
Calreticulina/genética , Janus Quinasa 2/genética , Enfermedades Mielodisplásicas-Mieloproliferativas/genética , Fosfoproteínas/genética , Factores de Empalme de ARN/genética , Receptores de Trombopoyetina/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación
5.
Pediatr Blood Cancer ; 65(4)2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29230938

RESUMEN

It has been suggested that persons with factor XI deficiency can have a normal activated partial thromboplastin time (aPTT). This notion is based on limited data, especially in children. Because of the central role the aPTT plays in diagnostic algorithms for bleeding disorders, it is important to know if a normal aPTT eliminates the need for factor XI activity testing. Our institutional database contains seven children with factor XI deficiency, of whom four have a normal aPTT. This supports the hypothesis that children with factor XI deficiency can have a normal aPTT. Clinicians may wish to consider this evidence when evaluating children with abnormal bleeding.


Asunto(s)
Algoritmos , Bases de Datos Factuales , Deficiencia del Factor XI/sangre , Deficiencia del Factor XI/diagnóstico , Hemorragia/sangre , Hemorragia/diagnóstico , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Tiempo de Tromboplastina Parcial
8.
Am J Hematol ; 89(7): 781-4, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24676945

RESUMEN

Factor VIII (FVIII) may be measured by three different methodologies in the clinical laboratory: one-stage clotting assay, two-stage clotting assay, and chromogenic assay. These assays differ in ease of use, variety of reagents available, sensitivity to mild hemophilia A, and interference from lupus anticoagulants. This review will outline the methodology for each of the FVIII activity assays, with a discussion of assay interferences and variability. In some cases, chromogenic FVIII activity assays may be preferable to clot-based assays, and these clinical situations will be reviewed as well.


Asunto(s)
Compuestos Cromogénicos/química , Factor VIII/análisis , Factor VIII/química , Humanos
10.
Methods Mol Biol ; 2663: 693-706, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37204746

RESUMEN

Factor XIII (FXIII) is an essential coagulation factor that stabilizes fibrin clots and allows the clot to resist fibrinolysis. Inherited or acquired FXIII deficiency is a severe bleeding disorder with manifestations that can include fatal intracranial hemorrhage. Accurate FXIII laboratory testing is necessary for diagnosis, subtyping, and treatment monitoring. The recommended first-line test is FXIII activity, most commonly performed by commercial ammonia release assays. In these assays, it is important to perform a plasma blank measurement to correct for FXIII-independent ammonia production, which can lead to clinically significant overestimation of FXIII activity. Automated performance of a commercial FXIII activity assay (Technoclone, Vienna, Austria), including blank correction, on the BCS XP instrument is described.


Asunto(s)
Deficiencia del Factor XIII , Trombosis , Humanos , Factor XIII , Amoníaco , Plasma , Automatización
11.
J Med Biochem ; 41(1): 115-121, 2022 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-35431650

RESUMEN

Background: von Willebrand factor (VWF) multimers (VWF:MM) methodologies are technically difficult, laborious, time consuming, non-standardized and results vary between laboratories. A new semi automated VWF:MM assay is available for routine use (Sebia). Due to lack of reference values for VWF:MM fractions, results interpretation can be challenging in some cases. The aim of this study was to determine reference intervals for low molecular weight (LMWM), intermediate molecular weight (IMWM) and high molecular weight (HMWM) multimers. Methods: By the international cooperation initiated between 4 countries (Estonia, Latvia, France, and USA) 131 samples of relatively healthy individuals were analyzed for VWF:MM (in total 51 males and 80 non-pregnant females aged 17-69 years). Reference intervals were calculated according to CLSI C28-A3 standard. Results: The proposed reference intervals for VWF:MM were calculated for LMWM 10.4-22.5%, IMWM 22.6-37.6%, HMWM 45.6-66.6%. Age related differences were seen in IMWM and HMWM (p<0.001 and 0.038). There was no gender related difference observed. Geographically LMWM results of France were different from the other regions (p<0.05). Conclusions: Quantification of VWF:MM fractions, in addition to qualitative assessment of VWF:MM patterns, has the potential to aid in differential diagnosis of von Willebrand disease (VWD) subtypes. The reference values calculated in this study can be used in future research to establish clinical decision limits.

12.
Med Sci Educ ; 32(5): 1045-1054, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36276764

RESUMEN

Introduction: Assessment for learning has many benefits, but learners will still encounter high-stakes decisions about their performance throughout training. It is unknown if assessment for learning can be promoted with a combination model where scores from some assessments are factored into course grades and scores from other assessments are not used for course grading. Methods: At the University of Utah School of Medicine, year 1-2 medical students (MS) completed multiple-choice question quiz assessments and final examinations in six systems-based science courses. Quiz and final examination performance counted toward course grades for MS2017-MS2018. Starting with the MS2020 cohort, quizzes no longer counted toward course grades. Quiz, final examination, and Step 1 scores were compared between ungraded quiz and graded quiz cohorts with independent samples t-tests. Student and faculty feedback was collected. Results: Quiz performance was not different for the ungraded and graded cohorts (p = 0.173). Ungraded cohorts scored 4% higher on final examinations than graded cohorts (p ≤ 0.001, d = 0.88). Ungraded cohorts scored above the national average and 11 points higher on Step 1 compared to graded cohorts, who had scored below the national average (p ≤ 0.001, d = 0.64). During the study period, Step 1 scores increased by 2 points nationally. Student feedback was positive, and faculty felt it improved their relationship with students. Discussion: The change to ungraded quizzes did not negatively affect final examination or Step 1 performance, suggesting a combination of ungraded and graded assessments can effectively promote assessment for learning.

13.
Blood Adv ; 6(2): 405-409, 2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-34649277

RESUMEN

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by somatic mutations in UBA1 and is identified by a genotype-driven method. This condition affects unrelated men with adultonset inflammatory syndromes in association with hematologic manifestations of peripheral cytopenia and bone marrow myeloid dysplasia. Although bone marrow vacuolization restricted to myeloid and erythroid precursors has been identified in patients with VEXAS, the detailed clinical and histopathological features of peripheral blood and bone marrows remain unclear. The current case report describes the characteristic hematologic findings in patients with VEXAS, including macrocytic anemia, thrombocytopenia, marked hypercellular bone marrow with granulocytic hyperplasia, megaloblastic changes in erythroid precursors, and the absence of hematogones in addition to prominent vacuoles in myeloid and erythroid precursor cells. Characterizing the clinical and hematologic features helps to raise awareness and improve diagnosis of this novel, rare, but potentially underrecognized disease. Prompt diagnosis expands the general knowledgeable and understanding of this disease, and optimal management may prevent patients from developing complications related to this refractory inflammatory syndrome and improve the overall clinical outcome.


Asunto(s)
Síndromes Mielodisplásicos , Trastornos Mieloproliferativos , Neoplasias , Humanos , Masculino , Mutación , Síndromes Mielodisplásicos/genética , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/genética , Enzimas Activadoras de Ubiquitina
14.
Arch Pathol Lab Med ; 146(2): 145-153, 2022 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-34133726

RESUMEN

CONTEXT.­: Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios. OBJECTIVE.­: To evaluate the performance of DOAC-specific assays for various concentrations of dabigatran and rivaroxaban, assess the interlaboratory variability in measurement of these DOACs, and investigate the responsiveness of the routine clotting assays to various concentrations of these oral anticoagulants. DESIGN.­: College of American Pathologists proficiency testing survey data from 2013 to 2016 were summarized and analyzed. RESULTS.­: For dabigatran, the interlaboratory coefficient of variation (CV) of ecarin chromogenic assay was broad (ranging from 7.5% to 29.1%, 6.3% to 15.5%, and 6.8% to 9.0% for 100-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The CV for diluted thrombin time for dabigatran was better overall (ranging from 11.6% to 17.2%, 9.3% to 12.3, and 7.1% to 11.2% for 100 ng/mL, 200 ng/mL, and 400 ng/mL, respectively). The rivaroxaban-calibrated anti-Xa assay CVs also showed variability (ranging from 11.5% to 22.2%, 7.2% to 10.9%, and 6.4% to 8.1% for 50-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The prothrombin time (PT) and activated partial thromboplastin time (aPTT) showed variable dose- and reagent-dependent responsiveness to DOACs: PT was more responsive to rivaroxaban and aPTT to dabigatran. The undiluted thrombin time showed maximum prolongation across all 3 dabigatran concentrations, making it too sensitive for drug-level monitoring, but supporting its use as a qualitative screening assay. CONCLUSIONS.­: DOAC-specific assays performed reasonably well. While PT and aPTT cannot be used safely to determine DOAC degree of anticoagulation, a normal thrombin time excludes the presence of dabigatran.


Asunto(s)
Dabigatrán , Rivaroxabán , Administración Oral , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Antitrombinas/farmacología , Pruebas de Coagulación Sanguínea/métodos , Dabigatrán/farmacología , Humanos , Tiempo de Tromboplastina Parcial , Pirazoles , Piridonas , Rivaroxabán/farmacología
15.
Fetal Pediatr Pathol ; 30(2): 71-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21391746

RESUMEN

We report on a case of FG syndrome in an almost 6-year-old boy, diagnosed post-mortem. The description of the intellectual and behavior phenotype provided by the mother, together with the evidence gathered at autopsy, were sufficient to reach a clinical diagnosis. The mother had mild manifestations, including a symptomatic tethered cord, which established her as a carrier of the putative mutation causing the syndrome in the son. The propositus' phenotype did not suggest involvement of the MED12 gene.


Asunto(s)
Agenesia del Cuerpo Calloso , Ano Imperforado , Estreñimiento , Discapacidad Intelectual Ligada al Cromosoma X , Hipotonía Muscular , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Anomalías Múltiples/fisiopatología , Síndrome Acrocallosal/diagnóstico , Síndrome Acrocallosal/genética , Síndrome Acrocallosal/patología , Síndrome Acrocallosal/fisiopatología , Ano Imperforado/diagnóstico , Ano Imperforado/genética , Ano Imperforado/patología , Ano Imperforado/fisiopatología , Autopsia , Preescolar , Estreñimiento/diagnóstico , Estreñimiento/genética , Estreñimiento/patología , Estreñimiento/fisiopatología , Resultado Fatal , Femenino , Humanos , Masculino , Complejo Mediador/genética , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Discapacidad Intelectual Ligada al Cromosoma X/genética , Discapacidad Intelectual Ligada al Cromosoma X/patología , Discapacidad Intelectual Ligada al Cromosoma X/fisiopatología , Hipotonía Muscular/congénito , Hipotonía Muscular/diagnóstico , Hipotonía Muscular/genética , Hipotonía Muscular/patología , Hipotonía Muscular/fisiopatología , Mutación , Linaje
16.
Hematology Am Soc Hematol Educ Program ; 2021(1): 85-91, 2021 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-34889362

RESUMEN

Bleeding disorders with normal, borderline, or nondiagnostic coagulation tests represent a diagnostic challenge. Disorders of primary hemostasis can be further evaluated by additional platelet function testing modalities, platelet electron microscopy, repeat von Willebrand disease testing, and specialized von Willebrand factor testing beyond the usual initial panel. Secondary hemostasis is further evaluated by coagulation factor assays, and factor XIII assays are used to diagnose disorders of fibrin clot stabilization. Fibrinolytic disorders are particularly difficult to diagnose with current testing options. A significant number of patients remain unclassified after thorough testing; most unclassified patients have a clinically mild bleeding phenotype, and many may have undiagnosed platelet function disorders. High-throughput genetic testing using large gene panels for bleeding disorders may allow diagnosis of a larger number of these patients in the future, but more study is needed. A logical laboratory workup in the context of the clinical setting and with a high level of expertise regarding test interpretation and limitations facilitates a diagnosis for as many patients as possible.


Asunto(s)
Trastornos de la Coagulación Sanguínea/diagnóstico , Pruebas de Coagulación Sanguínea , Hemorragia/diagnóstico , Adolescente , Coagulación Sanguínea , Niño , Femenino , Humanos , Masculino , Enfermedades de von Willebrand/diagnóstico
17.
Hematology Am Soc Hematol Educ Program ; 2021(1): 129-133, 2021 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-34889400

RESUMEN

Direct oral anticoagulants (DOACs) are a group of direct coagulation factor inhibitors including both direct thrombin inhibitors and direct factor Xa inhibitors. These medications may cause hemostasis assay interference by falsely increasing or decreasing measured values, depending on the analyte. Considering the potential for DOAC interference in a variety of hemostasis assays is essential to avoid erroneous interpretation of results. Preanalytic strategies to avoid DOAC interference include selecting alternatives to clot-based hemostasis assays in patients taking DOACs when possible and sample collection timed when the patient is off anticoagulant therapy or at the expected drug trough. Clinical laboratories may also provide educational materials that clearly describe possible interferences from DOAC, develop testing algorithms to aid in detection of DOAC in submitted samples, use DOAC-neutralizing agents to remove DOACs before continuing with testing, and write interpretive comments that explain the effects of DOAC interference in hemostasis tests. Using a combination of the described strategies will aid physicians and laboratorians in correctly interpreting hemostasis and thrombosis laboratory tests in the presence of DOACs.


Asunto(s)
Pruebas de Coagulación Sanguínea , Inhibidores del Factor Xa/farmacología , Hemostasis/efectos de los fármacos , Adulto , Coagulación Sanguínea/efectos de los fármacos , Femenino , Humanos , Laboratorios Clínicos , Masculino , Persona de Mediana Edad
18.
Arthroplast Today ; 6(4): 686-688, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32875020

RESUMEN

The D-dimer test is a component of the modified scoring criteria for periprosthetic joint infection (PJI). The performance of the D-dimer test varies greatly among laboratories because of the lack of standardization. Laboratories may use different assays and will produce widely varying results for the same sample. This study used published proficiency testing data from 3903 laboratories to demonstrate the variability in D-dimer results and estimate the misclassification rate of patients using the proposed cutoff for the test as a component of PJI criteria. Given the variability in D-dimer results, a clinically significant percentage of patients are likely to be misclassified. The data illustrate that a universal cutoff for this marker in the context of assessment for PJI is not appropriate. Each site must conduct a study to determine an appropriate cutoff for their unique testing platform.

19.
Arch Pathol Lab Med ; 143(10): 1281-1285, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30702334

RESUMEN

Protein C (PC) deficiency is a heritable or acquired risk factor for thrombophilia, with presentations varying from asymptomatic to venous thromboembolism to neonatal purpura fulminans, a life-threatening disorder. Hereditary PC deficiency is caused by mutation in the PC (PROC) gene located on chromosome 2q14.3. Heterozygous and acquired PC deficiencies are more common than homozygous deficiency. The recommended initial laboratory test measures PC activity using either clot-based or chromogenic methods. There are numerous potential interferences in PC activity testing that may result in either false-positive (falsely low activity) or false-negative (falsely normal or elevated activity) results. In the present review, we discuss common clinical presentations; laboratory testing, with a focus on potential assay interferences; treatment options; and prognosis in patients with PC deficiency.


Asunto(s)
Deficiencia de Proteína C/diagnóstico , Púrpura Fulminante/etiología , Trombofilia/etiología , Tromboembolia Venosa/etiología , Pruebas de Coagulación Sanguínea , Humanos , Mutación , Deficiencia de Proteína C/complicaciones , Deficiencia de Proteína C/fisiopatología , Deficiencia de Proteína C/terapia , Púrpura Fulminante/fisiopatología , Púrpura Fulminante/terapia , Trombofilia/fisiopatología , Trombofilia/terapia , Tromboembolia Venosa/fisiopatología , Tromboembolia Venosa/terapia
20.
Int J Lab Hematol ; 41 Suppl 1: 49-55, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31069983

RESUMEN

Coagulation laboratory external quality assurance (EQA) programs provide information that satisfies regulatory requirements and improves laboratory quality, patient care, and safety. In addition to the value to individual laboratories, data from EQA programs benefits the laboratory community in multiple ways by providing a snapshot of laboratory practice and summarizing the performance of various methods in identifying normal and abnormal specimens and the effects of therapies or interfering substances. This review article aims to summarize and provide examples of some of the important lessons learned from coagulation EQA data, including issues related to non-standardization, imprecision, and the effects of interfering substances.


Asunto(s)
Coagulación Sanguínea , Garantía de la Calidad de Atención de Salud , Control de Calidad , Manejo de Especímenes , Pruebas de Coagulación Sanguínea/métodos , Pruebas de Coagulación Sanguínea/normas , Humanos , Manejo de Especímenes/métodos , Manejo de Especímenes/normas
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