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In the current WHO classification, a T-cell prolymphocytic leukemia (T-PLL) diagnosis requires lymphocytosis of >5 × 109/L, evidence of monoclonality, and TCL1A or MTCP1 rearrangement. However, the 2019 consensus document suggested that in the absence of rearrangement of TCL1-family, the presence of abnormalities involving chromosome 11 (11q22.3; ATM), chromosome 8 (idic(8)(p11), t(8;8), trisomy 8q), 5, 12, 13, 22, or a complex karyotype, as well as involvement specific sites (e.g., splenomegaly, effusions) would suffice for a diagnosis of T-PLL. We present a patient diagnosed with T-PLL with MTCP1 rearrangement who was successfully treated with alemtuzumab followed by consolidative allogeneic unrelated donor stem cell transplantation. Eight years later, the patient presented with inguinal lymphadenopathy with features more akin to peripheral T-cell lymphoma, NOS (PTCL, NOS) of the GATA3 subtype, and there was no evidence of peripheral blood involvement. However, the lymphoma cells were clonally related to those at presentation. Currently, literature on T-PLL-like cases lacking the rearrangement of TCL1A is limited, and the possibility of whether a proportion of such cases could represent PTCL, NOS (with leukemic involvement) needs consideration.
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AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance. METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23 001 pairs of simultaneously measured aPTT/anti-Xa were collected from 699 MCS patients. aPTT and anti-Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT > antiXa 61.5%; aPTT < antiXa 3.0%). Discordance with a high aPTT relative to anti-Xa (aPTT > antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre-albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT > anti-Xa than temporary MCS devices. CONCLUSIONS: aPTT and anti-Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti-Xa.
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Primary T-cell lymphoma (TCL) of the central nervous system (CNS) is a rare and potentially aggressive entity. We describe a case of TCL presenting in the basal ganglia with γδ receptor expression and a remarkably aggressive clinical course. To the best of our knowledge, this is the fifth reported case of γδ TCL presenting in the CNS. We review existing literature, including the previously reported cases of γδ TCL of the CNS. In our case, a 69-year-old male presented with acute onset dysarthria and right-sided weakness, with initial imaging concerning for stroke. Repeat imaging demonstrated a 2.6-cm mass in the left basal ganglia-corona radiata. Pathologic examination of a stereotactic biopsy revealed TCL with γδ receptor phenotype. The patient suffered rapid clinical decline and passed away within 6 weeks of initial diagnosis. This represents an important differential diagnosis and sheds light on the potentially poor prognosis conferred by γδ TCL of the CNS.
Subject(s)
Lymphoma, T-Cell , T-Lymphocytes , Male , Humans , Aged , T-Lymphocytes/pathology , Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/pathology , Central Nervous System/pathology , BiopsyABSTRACT
BACKGROUND: Administering platelets through a rapid infuser is proven to be safe. However, the clinical significance of infusing ABO-incompatible platelets with red blood cells (RBCs) in a rapid infuser remains unclear. There is a theoretical risk that isoagglutinin in the plasma of a platelet unit can interact with RBCs and induce hemolysis. MATERIALS AND METHODS: Seven in vitro studies were performed including five cases (type A RBCs and type O platelets) and two controls (type A RBCs and platelets). Anti-A titers were measured in platelet units. An RBC unit and a platelet unit were mixed in the rapid infuser reservoir and incubated for 30 min. The primary outcome was the presence of hemolysis based on the following parameters: free hemoglobin concentration, hemolysis check, direct antiglobulin test (DAT), and direct agglutination. RESULTS: The post-mix DAT was positive for IgG in all test samples (5/5), and weakly positive for complement in 3/5. The changes in free Hb in test cases between measured and calculated post-mix spanned -2.2 to +3.4 mg/dL. Post-mix hemolysis check was negative in 3/5 and slightly positive in 2/5 cases, with no significant differences compared to the control case. Anti-A titers ranged from 16 to 512 and were not associated with hemolysis. All samples were negative for direct agglutination. CONCLUSION: Our study suggested that mixing ABO-incompatible platelets with RBCs in a rapid infuser does not induce in vitro hemolysis. These findings support the use of rapid infusers regardless of platelet compatibility in support of hemostatic resuscitation.
Subject(s)
ABO Blood-Group System , Hemolysis , Humans , Platelet Transfusion/adverse effects , Blood Group Incompatibility , Blood Platelets , AntibodiesABSTRACT
Hemoglobin disorders are among the most common genetic diseases worldwide. Molecular diagnosis is helpful in cases where the diagnosis is uncertain and for genetic counseling. Protein-based diagnostic techniques are frequently adequate for initial diagnosis. Molecular genetic testing is pursued in some cases, particularly when a definitive diagnosis is not possible and especially for the purpose of assessing genetic risk for couples wanting to have children. The expertise available in the clinical hematology laboratory is essential for the diagnosis of patients with hemoglobin abnormalities. Initial diagnoses are made using protein-based techniques such as electrophoresis and chromatography. Based on these findings, genetic risk to an individual's offspring can be assessed. In the setting of ß-thalassemia and other ß-globin disorders, coincident α-thalassemia may be difficult to diagnose, which can have potentially serious consequences. In addition, unusual forms of ß-thalassemia caused by deletions in the ß-globin locus cannot be definitively characterized using standard techniques. Molecular diagnostic testing has an important role in the diagnosis of hemoglobin disorders and is important in the setting of genetic counseling. Molecular testing also has a role in prenatal diagnosis to identify fetuses affected by severe hemoglobinopathies and thalassemias.
Subject(s)
Hemoglobinopathies , alpha-Thalassemia , beta-Thalassemia , Pregnancy , Female , Child , Humans , beta-Thalassemia/diagnosis , beta-Thalassemia/genetics , Hemoglobinopathies/diagnosis , Hemoglobinopathies/genetics , alpha-Thalassemia/genetics , Prenatal Diagnosis/methods , Molecular Diagnostic Techniques , beta-Globins/geneticsABSTRACT
OBJECTIVES: The US Food and Drug Administration (FDA)-approved CELLSEARCH assay (Menarini Silicon Biosystems) for circulating tumor cells (CTCs) relies on expression of an epithelial cell adhesion molecule to enrich for CTCs. We sought to validate a CTC assay (RareCyte) for clinical use that instead collects a buffy coat preparation enriched for CTCs. METHODS: Normal peripheral blood specimens spiked with cultured breast and prostate cancer cells and 47 clinical samples were used to validate assay performance. Specimens were enriched for buffy coat cells and applied onto 8 glass slides. The slides were immunofluorescently stained and imaged by automated microscopy and computer-aided image analysis. RESULTS: The assay was 100% specific for detecting spiked tumor cells. For samples spiked with 25, 50, and 125 cells, the percentage coefficients of variation were 42%, 21%, and 3.7%, respectively. Linearity studies demonstrated a slope of 0.99, an intercept of 1.6, and R2 of 0.96. Recoveries at the 25-, 50-, and 125-cell levels were 92%, 111%, and 100%, respectively. Clinical samples run on both CELLSEARCH and RareCyte correlated with an R2 of 0.8 after log-transformation and demonstrated 87.5% concordance using the CELLSEARCH criteria for predicting adverse outcomes. CONCLUSIONS: The RareCyte CTC assay has comparable performance to the FDA-cleared method and is ready for further clinical validation studies.
Subject(s)
Neoplastic Cells, Circulating , Prostatic Neoplasms , Biomarkers, Tumor/metabolism , Cell Count , Centrifugation , Humans , Male , Microscopy, Fluorescence , Neoplastic Cells, Circulating/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathologyABSTRACT
Frequent prothrombin time (PT) and international normalized ratio (INR) testing is critical for millions of people on lifelong anticoagulation with warfarin. Currently, testing is performed in hospital laboratories or with expensive point-of-care devices limiting the ability to test frequently and affordably. We report a proof-of-concept PT/INR testing system that uses the vibration motor and camera on smartphones to track micro-mechanical movements of a copper particle. The smartphone system computed the PT/INR with inter-class correlation coefficients of 0.963 and 0.966, compared to a clinical-grade coagulation analyzer for 140 plasma samples and demonstrated similar results for 80 whole blood samples using a single drop of blood (10 µl). When tested with 79 blood samples with coagulopathic conditions, the smartphone system demonstrated a correlation of 0.974 for both PT/INR. Given the ubiquity of smartphones in the global setting, this proof-of-concept technology may provide affordable and effective PT and INR testing in low-resource environments.
Subject(s)
Blood Coagulation Tests/methods , International Normalized Ratio/methods , Prothrombin Time/methods , Smartphone , Thrombosis/diagnosis , Algorithms , Anticoagulants/pharmacology , Blood Coagulation/drug effects , Blood Coagulation Tests/instrumentation , Hemorrhage , Humans , International Normalized Ratio/instrumentation , Point-of-Care Systems , Prothrombin Time/instrumentation , Warfarin/pharmacologyABSTRACT
OBJECTIVES: We compared complete blood count (CBC) with differential and markers of inflammation and coagulation in patients with and without coronavirus disease 2019 (COVID-19) presenting to emergency departments in Seattle, WA. METHODS: We reviewed laboratory values for 1 week following each COVID-19 test for adult patients who received a standard severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) test before April 13, 2020. Results were compared by COVID-19 status and clinical course. RESULTS: In total 1,027 patients met inclusion criteria. Patients with COVID-19 (n = 155) had lower leukocytes (P < .0001), lymphocytes (P < .0001), platelets (P < .0001), and higher hemoglobin (P = .0140) than those without, but absolute differences were small. Serum albumin was lower in patients with COVID-19 (P < .0001) and serum albumin, neutrophil to lymphocyte ratio (NLR), and red cell distribution width (RDW) were each associated with disease severity. NLR did not differ between patients with COVID-19 and those without (P = .8012). CONCLUSIONS: Patients with COVID-19 had modestly lower leukocyte, lymphocyte, and platelet counts and higher hemoglobin values than patients without COVID-19. The NLR, serum albumin, and RDW varied with disease severity, regardless of COVID-19 status.
Subject(s)
Blood Cell Count , Blood Coagulation , COVID-19/blood , Inflammation/blood , Lymphocytes/cytology , Adult , Biomarkers/blood , Blood Cell Count/methods , COVID-19/diagnosis , Emergency Service, Hospital , Humans , Leukocyte Count/methods , Lymphocyte Count/methods , Male , Middle Aged , Neutrophils/cytology , Platelet Count/methods , SARS-CoV-2/pathogenicityABSTRACT
Heparin-induced thrombocytopenia (HIT) is a life-threatening, prothrombotic, antibody-mediated disorder. To maximize the likelihood of recovery, early and accurate diagnosis is critical. Widely available HIT assays, such as the platelet factor 4 (PF4) heparin enzyme-linked immunosorbent assay (ELISA) lack specificity, and the gold-standard carbon 14-labeled serotonin release assay (SRA) is of limited value for early patient management because it is available only through reference laboratories. Recent studies have demonstrated that pathogenic HIT antibodies selectively activate PF4-treated platelets and that a technically simpler assay, the PF4-dependent P-selectin expression assay (PEA), may provide an option for rapid and conclusive results. Based upon predefined criteria that combined 4Ts scores and HIT ELISA results, 409 consecutive adults suspected of having HIT were classified as disease positive, negative, or indeterminate. Patients deemed HIT indeterminate were considered disease negative in the primary analysis and disease positive in a sensitivity analysis. The ability of PEA and SRA to identify patients judged to have HIT was compared using receiver operating characteristic curve statistics. Using these predefined criteria, the diagnostic accuracy of PEA was high (area under the curve [AUC], 0.94; 95% confidence interval [CI], 0.87-1.0) and similar to that of SRA (AUC, 0.91; 95% CI, 0.82-1.0). In sensitivity analysis, the AUCs of PEA and SRA were also similar at 0.88 (95% CI, 0.78-0.98) and 0.86 (95% CI, 0.77-0.96), respectively. The PEA, a technically simple nonradioactive assay that uses â¼20-fold fewer platelets compared with the SRA, had high accuracy for diagnosing HIT. Widespread use of the PEA may facilitate timely and more effective management of patients with suspected HIT.
Subject(s)
Anticoagulants/adverse effects , Heparin/adverse effects , Platelet Factor 4/immunology , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Adult , Aged , Antibodies/immunology , Anticoagulants/immunology , Enzyme-Linked Immunosorbent Assay , Female , Heparin/immunology , Humans , Immunoassay , Male , Middle Aged , P-Selectin/immunology , Prospective Studies , Thrombocytopenia/immunologyABSTRACT
Warfarin is a narrow therapeutic index anticoagulant drug and its use is associated with infrequent but significant adverse bleeding events. The international normalized ratio (INR) is the most commonly used biomarker to monitor and titrate warfarin therapy. However, INR is derived from a functional assay, which determines clotting efficiency at the time of measurement and is susceptible to technical variability. Protein induced by vitamin K antagonist-II (PIVKA-II) has been suggested as a biomarker of long-term vitamin K status, providing mechanistic insights about variation in the functional assay. However, the currently available antibody-based PIVKA-II assay does not inform on the position and number of des-carboxylation sites in prothrombin. The assay presented in this paper provides simultaneous quantification of carboxy and des-carboxy prothrombin that are essential for monitoring early changes in INR and, thus, serves as the superior tool for managing warfarin therapy. Additionally, this assay permits the quantification of total prothrombin level, which is affected by warfarin treatment. Prothrombin recovery from plasma was 95% and the liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was linear (r2 = 0.98) with a dynamic range of 1-100 µg/mL. The assay interday precision was within 20%. A des-carboxy peptide of prothrombin (GNLER) was negatively correlated with active prothrombin (Pearson r = 0.99, P < 0.0001), whereas its association was positively linked with INR values (Pearson r = 0.75, P < 0.015). This novel LC-MS/MS assay for active and inactive prothrombin quantification can be applied to titrate anticoagulant therapy and to monitor the impact of diseases, such as hepatocellular carcinoma on clotting physiology.
Subject(s)
Anticoagulants/adverse effects , Hemorrhage/prevention & control , Prothrombin/analysis , Warfarin/adverse effects , Anticoagulants/administration & dosage , Biomarkers/blood , Biomarkers/chemistry , Blood Coagulation/drug effects , Blood Coagulation/physiology , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/physiopathology , Case-Control Studies , Chromatography, High Pressure Liquid/methods , Drug Monitoring/methods , Healthy Volunteers , Hemorrhage/blood , Hemorrhage/chemically induced , Hemorrhage/diagnosis , Humans , Liver Neoplasms/blood , Liver Neoplasms/physiopathology , Prothrombin/chemistry , Tandem Mass Spectrometry/methods , Warfarin/administration & dosageABSTRACT
BACKGROUND: Venous thromboembolism (VTE) is the third most common cause of cardiovascular illness and is projected to double in incidence by 2050. It is a spectrum of disease that includes deep venous thrombosis (DVT) and pulmonary embolism (PE). In February 2016, the American College of Chest Physicians provided updated management guidelines for DVT and PE to address some of the unresolved questions from the previous version and to provide recommendations related to newer anticoagulants. CONTENT: Here we review current concepts for screening, diagnosis, thromboprophylaxis, and management of DVT and PE. We also describe the management of VTE in acute, long-term, and extended phases of treatment. Thrombophilia testing is rarely necessary and should be used judiciously; the laboratory can serve an important role in preventing unnecessary testing. The direct oral anticoagulants are as effective as conventional treatment and are preferred agents except in the case of cancer. The initial management of PE should be based on risk stratification including the use of D-dimer testing. Thrombolysis is used in cases of hemodynamically unstable PE and not for low-risk patients who can be treated on an outpatient basis. SUMMARY: This review is intended to provide readers with updated guidelines for screening, testing, prophylaxis, and management from various organizations.
Subject(s)
Anticoagulants/therapeutic use , Clinical Laboratory Techniques/methods , Diagnostic Techniques and Procedures/trends , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , Disease Management , HumansABSTRACT
There are no clear and consistent guidelines on how to utilize DOAC assays, and reports on the use of DOAC levels in clinical practice is limited. The objective of this study was to analyze why DOAC levels are ordered, how the results affect clinical decision-making, and to determine if DOAC assays are utilized appropriately. This was a retrospective chart review study analyzing 150 dabigatran, rivaroxaban, and apixaban levels performed at a single institution. The majority of DOAC assays were ordered in situations or special patient populations where confirming absence or detecting presence of drug may be useful. The most common indication for ordering assays was prior to an invasive procedure. Most DOAC levels were timed appropriately but peak levels were most likely to be incorrectly ordered. Clinical decisions following level results depended on indication for ordering and were most commonly used to determine whether or not to proceed with an invasive procedure. The results of our study suggest while DOAC assays are generally ordered for useful indications, there is still a lack of understanding of when levels should be drawn and how to interpret DOAC assay results.
Subject(s)
Drug Monitoring/methods , Factor Xa Inhibitors/blood , Practice Patterns, Physicians'/standards , Anticoagulants/blood , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Dabigatran/blood , Dabigatran/pharmacology , Dabigatran/therapeutic use , Decision Making , Factor Xa Inhibitors/pharmacology , Factor Xa Inhibitors/therapeutic use , Female , Humans , Male , Pyrazoles/blood , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyridones/blood , Pyridones/pharmacology , Pyridones/therapeutic use , Retrospective Studies , Rivaroxaban/blood , Rivaroxaban/pharmacology , Rivaroxaban/therapeutic use , Surgical Procedures, Operative/methodsABSTRACT
This commentary highlights the article by Kim et al that suggests use of two different next-generation sequencing-based assays for detection of fusion RNAs in patients with acute leukemia.
Subject(s)
Hematologic Neoplasms , RNA , Gene Fusion , High-Throughput Nucleotide Sequencing , Humans , Sequence Analysis, RNA , Translocation, GeneticABSTRACT
Objectives: To compare the accuracy and reliability of phenotypic activated protein C resistance (aPC-R) assays with a genotypic assay for the factor V Leiden F5 p.R506Q (FVL) mutation. Methods: Data were obtained from an electronic data warehouse for FVL testing performed at an academic institution with a large referral laboratory service. In total, 1,596 patients were identified who had undergone both phenotypic aPC-R and genotypic FVL mutation testing. Results: Phenotypic testing showed a high level of sensitivity, specificity, and other biostatistical values compared with genotypic testing. Improvements in technology decreased the amount of equivocal phenotypic results. Conclusions: Phenotypic assays had close to total concordance with genotypic assays over 16 years of testing. Changing ordering practices could result in up to an 80% reduction in testing costs.
Subject(s)
Activated Protein C Resistance/genetics , Factor V/genetics , Activated Protein C Resistance/diagnosis , Activated Protein C Resistance/pathology , Blood Coagulation Tests , Genotype , Humans , Mutation , Phenotype , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Burkitt lymphoma (BL) is a highly aggressive, B cell non-Hodgkin lymphoma (NHL) that is rare outside Africa. We report a case of HIV-associated BL originating in the right maxillary sinus in a 31-year-old Hispanic male living in Washington, USA. We also highlight the diagnostic challenges in arriving at the diagnosis when the patient initially presented with a painless right facial swelling. Rapid diagnosis and treatment are critical because BL is one of the fastest-growing tumors. Treatment involves brief duration of high intensity chemotherapy and central nervous system prophylaxis. It is important for oral and maxillofacial surgeons to recognize this disease and understand the necessary steps to treat this aggressive tumor.
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BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue and other physical and neurocognitive symptoms. Some studies suggest that CFS is accompanied by disruptions in the number and function of various lymphocytes. However, it is not clear which lymphocytes might influence CFS symptoms. PURPOSE: To determine if patient reported fatigue symptoms and physical functioning scores significantly changed across time with lymphocyte counts as evidence of a relation among chronic fatigue symptoms and the immune response. METHODS: The current longitudinal, naturalistic study assessed the cellular expression of three lymphocyte subtypes -- natural killer (NK) cells (CD3-CD16+ and CD3-CD56+) and naïve T cells (CD4+CD45RA+) -- to determine whether changes in lymphocytes at 4 time points across 18 months were associated with clinical outcomes, including CFS symptoms, physical functioning, and vitality, among patients with chronic fatigue.. Latent growth curve models were used to examine the longitudinal relationship between lymphocytes and clinical outcomes. RESULTS: Ninety-three patients with Fukuda-based CFS and seven with non-CFS fatigue provided study data. Results indicated that higher proportions of naïve T cells and lower proportions of NK cells were associated with worse physical functioning, whereas higher proportions of NK cells (CD3-CD16+) and lower proportions of naïve T cells were associated with fewer CFS symptoms. CONCLUSION: These findings suggest that lymphocytes are modestly related to clinical outcomes over time.
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OBJECTIVES: To describe the use of molecular diagnostic techniques for patients with hemoglobin disorders. METHODS: A clinical scenario is presented in which molecular diagnosis is important for genetic counseling. Globin disorders, techniques for their diagnosis, and the role of molecular genetic testing in managing patients with these disorders are described in detail. RESULTS: Hemoglobin disorders, including thalassemias and hemoglobinopathies, are among the commonest genetic diseases, and the clinical laboratory is essential for the diagnosis of patients with these abnormalities. Most disorders can be diagnosed with protein-based techniques such as electrophoresis and chromatography. Since severe syndromes can result due to inheritance of combinations of globin genetic disorders, genetic counseling is important to prevent adverse outcomes. Protein-based methods cannot always detect potentially serious thalassemia disorders; in particular, α-thalassemia may be masked in the presence of ß-thalassemia. Deletional forms of ß-thalassemia are also sometimes difficult to diagnose definitively with standard methods. CONCLUSIONS: Molecular genetic testing serves an important role in identifying individuals carrying thalassemia traits that can cause adverse outcomes in offspring. Furthermore, prenatal genetic testing can identify fetuses with severe globin phenotypes.