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1.
Blood ; 140(12): 1335-1344, 2022 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-35797471

RESUMEN

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.


Asunto(s)
Púrpura Trombocitopénica Trombótica , Proteína ADAMTS13 , Corticoesteroides , Humanos , Púrpura Trombocitopénica Trombótica/terapia , Recurrencia , Rituximab/uso terapéutico
2.
J Natl Compr Canc Netw ; 22(7): 483-506, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-39236759

RESUMEN

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.


Asunto(s)
Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiología , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/terapia , Tromboembolia Venosa/prevención & control , Neoplasias/complicaciones , Neoplasias/terapia , Neoplasias/diagnóstico , Oncología Médica/normas , Oncología Médica/métodos , Anticoagulantes/uso terapéutico , Manejo de la Enfermedad
3.
Am J Hematol ; 98(8): 1265-1276, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37350302

RESUMEN

Obstructive sleep apnea (OSA) causes intermittent hypoxia during sleep. Hypoxia predictably initiates an increase in the blood hemoglobin concentration (Hb); yet in our analysis of 527 patients with OSA, >98% did not have an elevated Hb. To understand why patients with OSA do not develop secondary erythrocytosis due to intermittent hypoxia, we first hypothesized that erythrocytosis occurs in these patients, but is masked by a concomitant increase in plasma volume. However, we excluded that explanation by finding that the red cell mass was normal (measured by radionuclide labeling of erythrocytes and carbon monoxide inhalation). We next studied 45 patients with OSA before and after applying continuous positive airway pressure (CPAP). We found accelerated erythropoiesis in these patients (increased erythropoietin and reticulocytosis), but it was offset by neocytolysis (lysis of erythrocytes newly generated in hypoxia upon return to normoxia). Parameters of neocytolysis included increased reactive oxygen species from expanded reticulocytes' mitochondria. The antioxidant catalase was also downregulated in these cells from hypoxia-stimulated microRNA-21. In addition, inflammation-induced hepcidin limited iron availability for erythropoiesis. After CPAP, some of these intermediaries diminished but Hb did not change. We conclude that in OSA, the absence of significant increase in red cell mass is integral to the pathogenesis, and results from hemolysis via neocytolysis combined with inflammation-mediated suppression of erythropoiesis.


Asunto(s)
Policitemia , Apnea Obstructiva del Sueño , Humanos , Especies Reactivas de Oxígeno , Policitemia/etiología , Hepcidinas , Hipoxia , Apnea Obstructiva del Sueño/complicaciones , Inflamación
4.
Cancer ; 128(12): 2348-2357, 2022 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-35363373

RESUMEN

BACKGROUND: Patients with lymphoma have an increased risk of venous thromboembolism (VTE). The authors examined the risk of VTE and subsequent health care utilization in elderly patients with diffuse large B cell lymphoma (DLBCL). METHODS: A total of 5537 DLBCL patients ≥66 years old enrolled in Medicare from the Surveillance, Epidemiology, and End Results registry and a noncancer control group of Medicare beneficiaries (n = 5537) were identified. Cumulative incidence function to examine the risk of VTE 12 months after DLBCL diagnosis was used. Fine and Gray method was used to examine the risk factors associated with VTE risk in multivariable models. Total number of hospitalizations, outpatient visits, and Medicare spending were compared in DLBCL patients with and without VTE. RESULTS: VTE was diagnosed in 8.3% DLBCL patients and 1.5% controls, yielding an 8.6-fold higher risk of VTE in DLBCL in adjusted analysis (95% confidence interval [CI], 6.62-11.20; P < .001). Multivariable regression analysis showed that precancer VTE history was associated with an increased risk of developing VTE after a DLBCL diagnosis (hazard ratio [HR], 5.39; 95% CI, 4.39-6.63), and Asian individuals were associated with a lower risk (HR, 0.54; 95% CI, 0.29-1.00). Patients newly diagnosed with VTE after lymphoma had a 1.7-fold higher rate of hospitalization and a 1.2-fold higher rate of outpatient visits compared to those without, resulting in excess Medicare spending of $22,208 in the first year after DLBCL diagnosis. CONCLUSIONS: Elderly patients with DLBCL have an elevated risk of VTE resulting in excess health care utilization. VTE history before DLBCL was associated with increased risk of post-DLBCL VTE, and Asian individuals were associated with a lower risk of VTE.


Asunto(s)
Linfoma de Células B Grandes Difuso , Tromboembolia Venosa , Anciano , Humanos , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/epidemiología , Linfoma de Células B Grandes Difuso/terapia , Medicare , Aceptación de la Atención de Salud , Factores de Riesgo , Estados Unidos/epidemiología , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/patología
5.
J Stroke Cerebrovasc Dis ; 29(11): 105209, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33066926

RESUMEN

BACKGROUND AND PURPOSE: Testing for thrombophilic disorders is often performed in patients after cryptogenic ischemic stroke in an attempt to identify a hematologic explanation for the event. However, the role of commonly tested thrombophilias in ischemic stroke is poorly defined. There is limited evidence to quantify how these disorders affect ischemic stroke risk and testing practices are highly variable. METHODS: Retrospective evaluation of thrombophilia testing practices and clinical outcomes was performed in hospitalized patients with acute ischemic stroke (n = 1898) at a large academic hospital over a two-year period. Variables assessed included testing components, timing of testing, number of abnormal results, and frequency of change in clinical management prompted by abnormal results. A provider survey was also performed to assess perceptions of current testing practices and provider understanding of testing indications. RESULTS: Thrombophilia testing was performed in 190 (10%) patients admitted for acute ischemic stroke. Of those tested, 137 (72.1%) had at least one abnormal result, but this decreased to 37.4% when elevated factor VIII activity was excluded. An abnormal result prompted initiation of anticoagulation in only 4 patients (2%). The provider survey indicated that all providers (100%) were selecting thrombophilia tests using a pre-existing order set and were interested in additional education on testing indications and interpretation. Comparison to similar studies at other institutions revealed significant variation in testing practices, and a small proportion of patients in which testing prompted a change in management (1-8%). CONCLUSIONS: Thrombophilia testing is frequently obtained in hospitalized patients with acute ischemic stroke, yet testing only changed management in 2% of patients. Efforts to improve provider education and the stewardship of testing are needed to ensure appropriate evaluation and treatment of patients with acute ischemic stroke.


Asunto(s)
Pruebas de Coagulación Sanguínea/tendencias , Coagulación Sanguínea , Isquemia Encefálica/etiología , Hospitalización , Pautas de la Práctica en Medicina/tendencias , Accidente Cerebrovascular/etiología , Trombofilia/diagnóstico , Adulto , Anciano , Anticoagulantes/uso terapéutico , Coagulación Sanguínea/efectos de los fármacos , Isquemia Encefálica/diagnóstico , Toma de Decisiones Clínicas , Femenino , Disparidades en Atención de Salud/tendencias , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico , Trombofilia/sangre , Trombofilia/complicaciones , Trombofilia/tratamiento farmacológico
6.
Biol Blood Marrow Transplant ; 25(11): 2261-2266, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31278995

RESUMEN

Hemostatic complications are commonly encountered in blood or marrow transplantation (BMT) recipients, increasing their morbidity and mortality and are well described in the immediate post-transplantation period. The risk of venous thromboembolism (VTE) in long-term survivors of autologous BMT has not been studied previously. Patients who underwent autologous BMT between January 1, 1974, and December 31, 2010 for a hematologic malignancy, lived 2 years or more after transplantation, and were age ≥18 years were surveyed for long-term outcomes. The median duration of follow-up was 9.8 years (interquartile range, 6.4 to 14.3 years). We analyzed the risk of VTE in 820 autologous BMT recipients who survived for ≥2 years, compared with 644 siblings. BMT survivors were at a 2.6-fold higher risk of VTE compared with siblings (95% confidence interval [CI], 1.6 to 4.4; P =.0004), after adjusting for sociodemographic characteristics. Conditional on surviving for ≥2 years after BMT, the mean cumulative incidence of VTE was 3.9 ± .8% at 5 years and 6.1 ± 1.1% at 10 years. A diagnosis of plasma cell disorder (hazard ratio [HR], 2.37; 95% CI, 1.3 to 4.2; P = .004) and annual household income ≤$50,000 (HR, 2.02; 95% CI, 1.2 to 3.6; P = .015) were associated with increased VTE risk. Our data indicate that autologous BMT survivors are at elevated risk for developing late-occurring VTE. The development of risk prediction models to identify autologous BMT survivors at greatest risk for VTE and thromboprophylaxis may help decrease the morbidity and mortality associated with VTE.


Asunto(s)
Trasplante de Médula Ósea , Trasplante de Células Madre de Sangre Periférica , Tromboembolia Venosa/mortalidad , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Hermanos , Tasa de Supervivencia , Trasplante Autólogo , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control
7.
Cancer ; 125(24): 4498-4508, 2019 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-31469420

RESUMEN

BACKGROUND: Patients with non-Hodgkin lymphoma (NHL) have an increased risk of venous thromboembolism (VTE), particularly when they are receiving treatment. Blood or marrow transplantation (BMT) is recommended for relapsed/refractory NHL, and the risk of VTE after these patients undergo BMT is uncertain. METHODS: Patients with NHL who survived 2 years or longer after BMT were surveyed for long-term health outcomes, including VTE. The median follow-up was 8.1 years (interquartile range, 5.6-12.9 years). The risk of VTE in 734 patients with NHL versus 897 siblings without a history of cancer and the risk factors associated with VTE were analyzed. RESULTS: BMT survivors of NHL were at increased risk for VTE in comparison with siblings (odds ratio for allogeneic BMT survivors, 4.61; P < .0001; odds ratio for autologous BMT survivors, 1.75; P = .035). The cumulative incidence of VTE was 6.3% ± 0.9% at 5 years after BMT and 8.1% ± 1.1% at 10 years after BMT. In allogeneic BMT recipients, an increased body mass index (BMI; hazard ratio [HR] for BMI of 25-30 kg/m2 , 3.52; 95% confidence interval [CI], 1.43-8.64; P = .006; HR for BMI > 30 kg/m2 , 3.44; 95% CI, 1.15-10.23; P = .027) and a history of chronic graft-versus-host disease (HR, 3.33; 95% CI, 1.59-6.97; P = .001) were associated with an increased risk of VTE. Among autologous BMT recipients, a diagnosis of coronary artery disease (HR, 5.94; 95% CI, 1.7-20.71; P = .005) and prior treatment with carmustine (HR, 4.91; 95% CI, 1.66-14.51; P = .004) were associated with increased VTE risk. CONCLUSIONS: Patients with NHL who survive BMT are at risk for developing late occurring VTE, and ongoing vigilance for this complication is required. Future studies assessing the role of thromboprophylaxis in high-risk patients with NHL are needed.


Asunto(s)
Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/epidemiología , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Anciano , Transfusión Sanguínea , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/métodos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Hermanos , Tromboembolia Venosa/prevención & control
8.
Haematologica ; 104(1): 166-175, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30171022

RESUMEN

Immune-mediated thrombotic thrombocytopenic purpura is characterized by severe thrombocytopenia and microangiopathic hemolytic anemia. It is primarily caused by immunoglobin G type autoantibodies against ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. However, reliable markers predictive of patient outcomes are yet to be identified. Seventy-three unique patients with a confirmed diagnosis of immune-mediated thrombotic thrombocytopenic purpura between April 2006 and December 2017 were enrolled from the Univeristy of Alabama at Birmingham Medical Center. Clinical information, laboratory values, and a panel of special biomarkers were collected and/or determined. The results demonstrated that the biomarkers associated with endothelial injury (e.g., von Willebrand factor antigen and collagen-binding activity), acute inflammation (e.g., human neutrophil peptides 1-3 and histone/deoxyribonucleic acid complexes), and activation of the complement alternative pathway (e.g., factors Bb and iC3b) were all significantly increased in patients with acute immune-mediated thrombotic thrombocytopenic purpura compared to those in the healthy controls. Moreover, failure to normalize platelet counts within 7 days or failure to markedly reduce serum lactate dehydrogenase by day 5, low total serum protein or albumin, and high serum troponin levels were also predictive of mortality, as were the prolonged activated partial thromboplastin time, high fibrinogen, and elevated serum lactate dehydrogenase, Bb, and sC5b-9 on admission. These results may help to stratify patients for more intensive management. The findings may also provide a framework for future multicenter studies to identify valuable prognostic markers for immune-mediated thrombotic thrombocytopenic purpura.


Asunto(s)
Autoanticuerpos/sangre , Proteínas Sanguíneas/metabolismo , Púrpura Trombocitopénica Trombótica/sangre , Púrpura Trombocitopénica Trombótica/diagnóstico , Adulto , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
9.
J Natl Compr Canc Netw ; 15(6): 757-760, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28596255

RESUMEN

Pegylated interferon alfa-2a (pegIFNa) is being increasingly used for treatment of myeloproliferative neoplasms; however, its side effects, including autoimmune complications, are not unusual. We report on a 47-year-old woman with polycythemia vera (PV) treated with pegIFNa and in complete hematologic remission who developed thrombotic thrombocytopenic purpura (TTP). To our knowledge, thrombotic microangiopathy has been reported as a side effect of interferon (IFN) use in patients with hepatitis and chronic myeloid leukemia, but not in those with PV. Our patient had a low ADAMTS13 level due to an inhibitor, which normalized after withholding pegIFNa and initiating treatment for TTP with therapeutic plasma exchange and corticosteroids. She experienced refractory TTP, necessitating treatment with rituximab and splenectomy. Postsplenectomy, she developed a high platelet count, warranting the need to restart treatment for PV. However, JAK2V617F allelic burden by real-time PCR was 0.7%, indicating that the increased platelet count was likely secondary to splenectomy. Therefore, we elected to monitor her counts and JAK2V617F allelic burden closely. With this case report, we hope to alert treating physicians that TTP should be considered as a complication of pegIFNa therapy in PV and that prompt discontinuation of the drug with necessary treatment should be instituted to prevent fatal complications.


Asunto(s)
Interferón-alfa/uso terapéutico , Policitemia Vera/complicaciones , Polietilenglicoles/uso terapéutico , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Biomarcadores , Recuento de Células Sanguíneas , Terapia Combinada , Femenino , Humanos , Janus Quinasa 2/genética , Persona de Mediana Edad , Mutación , Policitemia Vera/diagnóstico , Púrpura Trombocitopénica Trombótica/diagnóstico , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento
11.
South Med J ; 109(9): 549-53, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27598359

RESUMEN

Bone marrow necrosis with subsequent embolization of the fat and necrotic tissues into the systemic circulation causing fat embolism syndrome and multiorgan failure is a rare complication of patients with hemoglobinopathies. The exact etiology of this condition is not known. Because it occurs more often in patients with compound heterozygous conditions than in sickle cell disease, some patients are unaware of their predisposition. The initial symptoms are nonspecific, such as back and/or abdominal pain, fever, and fatigue, which may rapidly progress to respiratory failure and severe neurologic compromise. Common laboratory tests reveal anemia without reticulocytosis, thrombocytopenia, leukoerythroblastic picture with immature white cells and nucleated red blood cells, increased lactate dehydrogenase, high ferritin, and, sometimes increased creatinine. The diagnosis can be delayed because of an apparent lack of awareness about bone marrow necrosis with fat embolism syndrome, its rarity, and its similarities with other conditions such as thrombotic thrombocytopenic purpura. Although a bone marrow biopsy is diagnostic, waiting for it delays definitive treatment, which appears to be essential for the recovery of end-organ damage, such as neurologic and pulmonary damage. In our experience, either multiple units of red blood cell transfusion or, preferably, red cell exchange initiated promptly, is lifesaving.


Asunto(s)
Médula Ósea/patología , Embolia Grasa/etiología , Hemoglobinopatías/complicaciones , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/patología , Embolia Grasa/diagnóstico , Embolia Grasa/terapia , Hemoglobinopatías/patología , Humanos , Necrosis
16.
J Thromb Haemost ; 22(7): 1984-1996, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38574862

RESUMEN

BACKGROUND: Coagulopathy and associated bleeding and deep vein thrombosis (DVT) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated. OBJECTIVES: To evaluate the associations between biomarker levels and bleeding and DVT in acute leukemia patients. METHODS: We examined plasma levels of activators, inhibitors, and biomarkers of the coagulation and fibrinolytic pathways in patients aged ≥18 years with newly diagnosed acute leukemia compared with those of normal controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and DVT in acute leukemia patients. The study included 358 patients with acute leukemia (29 with acute promyelocytic leukemia [APL], 253 with non-APL acute myeloid leukemia, and 76 with acute lymphoblastic leukemia) and 30 normal controls. RESULTS: Patients with acute leukemia had higher levels of extracellular vesicle tissue factor (EVTF) activity, phosphatidylserine-positive extracellular vesicles, plasminogen activator inhibitor-1, plasmin-antiplasmin complexes, and cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared with normal controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among acute leukemia patients. There were 41 bleeding and 23 DVT events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (subdistribution hazard ratio, 2.30; 95% CI, 0.99-5.31), whereas high levels of plasminogen activator inhibitor-1 were associated with increased risk of DVT (subdistribution hazard ratio, 3.00; 95% CI, 0.95-9.47) in these patients. CONCLUSION: Our study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and DVT.


Asunto(s)
Biomarcadores , Coagulación Sanguínea , Hemorragia , Leucemia Mieloide Aguda , Tromboembolia Venosa , Humanos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Hemorragia/sangre , Hemorragia/diagnóstico , Tromboembolia Venosa/sangre , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiología , Biomarcadores/sangre , Estudios de Casos y Controles , Anciano , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Factores de Riesgo , Leucemia Promielocítica Aguda/sangre , Leucemia Promielocítica Aguda/complicaciones , Trombosis de la Vena/sangre , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/etiología , Histonas/sangre , Inhibidor 1 de Activador Plasminogénico/sangre , Tromboplastina/metabolismo , Tromboplastina/análisis , Adulto Joven , Fosfatidilserinas/sangre
17.
J Thromb Haemost ; 22(2): 503-515, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37918635

RESUMEN

BACKGROUND: Regulatory organizations recommend assessing hospital-acquired (HA) venous thromboembolism (VTE) risk for medical inpatients. OBJECTIVES: To develop and validate a risk assessment model (RAM) for HA-VTE in medical inpatients using objective and assessable risk factors knowable at admission. METHODS: The development cohort included people admitted to medical services at the University of Vermont Medical Center (Burlington, Vermont) between 2010 and 2019, and the validation cohorts included people admitted to Hennepin County Medical Center (Minneapolis, Minnesota), University of Michigan Medical Center (Ann Arbor, Michigan), and Harris Health Systems (Houston, Texas). Individuals with VTE at admission, aged <18 years, and admitted for <1 midnight were excluded. We used a Bayesian penalized regression technique to select candidate HA-VTE risk factors for final inclusion in the RAM. RESULTS: The development cohort included 60 633 admissions and 227 HA-VTE, and the validation cohorts included 111 269 admissions and 651 HA-VTE. Seven HA-VTE risk factors with t statistics ≥1.5 were included in the RAM: history of VTE, low hemoglobin level, elevated creatinine level, active cancer, hyponatremia, increased red cell distribution width, and malnutrition. The areas under the receiver operating characteristic curve and calibration slope were 0.72 and 1.10, respectively. The areas under the receiver operating characteristic curve and calibration slope were 0.70 and 0.93 at Hennepin County Medical Center, 0.70 and 0.87 at the University of Michigan Medical Center, and 0.71 and 1.00 at Harris Health Systems, respectively. The RAM performed well stratified by age, sex, and race. CONCLUSION: We developed and validated a RAM for HA-VTE in medical inpatients. By quantifying risk, clinicians can determine the potential benefits of measures to reduce HA-VTE.


Asunto(s)
Trombosis , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/complicaciones , Pacientes Internos , Teorema de Bayes , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/epidemiología , Trombosis de la Vena/complicaciones , Trombosis/etiología , Medición de Riesgo/métodos , Factores de Riesgo , Hospitales , Estudios Retrospectivos
18.
Res Pract Thromb Haemost ; 8(3): 102388, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38651093

RESUMEN

Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States. Recent advances in machine learning technology can help analyze large numbers of variables with complex interactions for the development of prediction models. Objectives: To validate the French TMA Reference Score in the United States Thrombotic Microangiopathy (USTMA) iTTP database and subsequently develop a novel mortality prediction tool, the USTMA TTP Mortality Index. Methods: We analyzed variables available at the time of initial presentation, including demographics, symptoms, and laboratory findings. We developed our model using gradient boosting machine, a machine learning ensemble method based on classification trees, implemented in the R package gbm. Results: In our cohort (n = 419), the French score predicted mortality with an area under the receiver operating characteristic curve of 0.63 (95% CI: 0.50-0.77), sensitivity of 0.35, and specificity of 0.84. Our gradient boosting machine model selected 8 variables to predict acute mortality with a cross-validated area under the receiver operating characteristic curve of 0.77 (95% CI: 0.71-0.82). The 2 cutoffs corresponded to sensitivities of 0.64 and 0.50 and specificities of 0.76 and 0.87, respectively. Conclusion: The USTMA Mortality Index was acceptable for predicting mortality due to acute iTTP in the USTMA registry, but not sensitive enough to rule out death. Identifying patients at high risk of iTTP-related mortality may help individualize care and ultimately improve iTTP survival outcomes. Further studies are needed to provide external validation. Our model is one of many recent examples where machine learning models may show promise in clinical prediction tools in healthcare.

19.
Expert Rev Hematol ; 16(11): 861-869, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37767808

RESUMEN

INTRODUCTION: Immune-mediated TTP (iTTP) is a rare condition without pathognomonic signs and symptoms. For this reason, the diagnosis of iTTP may be delayed or even missed, with potentially catastrophic consequences. AREAS COVERED: The authors performed an extensive literature review on the diagnosis of iTTP and its challenges combined with their own experience in a referral center for patients with iTTP. EXPERT OPINION: Although a definitive diagnosis of iTTP depends on the ADAMTS13 activity result, timely testing is rarely available at many centers to which patients present. If less complex tests were to become available, they would decrease the chances of late and/or missed diagnoses of iTTP throughout the world. While clinical scores to estimate the likelihood of iTTP exist, they are not well known, and can be misleading if used in the wrong context. Furthermore, the three scoring systems (PLASMIC, Bentley, and French) only moderately correlate with each other, which further complicates the landscape. The existence of these scores and how they should be used in practice is but one opportunity that can be seized through more robust programs to educate nonspecialist clinicians on how to recognize and treat patients with iTTP.


Asunto(s)
Púrpura Trombocitopénica Trombótica , Humanos , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/terapia , Proteína ADAMTS13
20.
Cancer Med ; 12(7): 8639-8651, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36583503

RESUMEN

BACKGROUND: Cytopenia is associated with cancer through mechanisms including clonal hematopoiesis and chronic inflammation. Cytopenia is more prevalent in Black people but its relationship with racial disparities in cancer mortality is unknown. METHODS: Cytopenia was defined in 19,028 Black and White participants recruited between 2003 and 2007 for the REasons for Geographic and Racial Differences in Stroke cohort, based on age-, sex-, and race-adjusted ranges for blood counts. Cancer death was ascertained from Social Security Death and National Death Indexes. Multivariable Cox models estimated the risk of cancer mortality associated with cytopenia, adjusting for demographics (model1), anemia and cancer risk factors (model2), and socioeconomics (model3). Racial differences in the cytopenia-cancer death association were tested by cross-product interaction terms. RESULTS: Cytopenia was identified in 383 (2%) participants, 250 (65%) White, and 113 (35%) Black people. With median follow-up 11.3 years, 1,224 (6.4%) cancer deaths occurred. Cytopenia was associated with increased risk of cancer mortality in model1 (HR = 1.57, 95%CI 1.15-2.24), model2 (HR = 1.67, 95%CI 1.22-2.30), and model3 (HR = 1.59, 95%CI 1.17-2.17). Participants with cytopenia had twofold increased cumulative incidence of cancer death (13% vs. 6.5%, p < 0.01). Race by cytopenia interaction terms showed higher HR for cancer death in Black compared to White participants: 2.01 versus 1.41 (pinteraction  = 0.016, model1), 2.12 versus 1.45 (pinteraction  = 0.009, model2), and 1.82 versus 1.44 (pinteraction  = 0.04, model3). CONCLUSION: In this large, observational biracial prospective study, cytopenia was a risk factor for cancer death, with stronger association in Black than White people. Though race impacted the association of cytopenia with cancer mortality, cytopenia was not a mediator of the racial disparity in cancer mortality.


Asunto(s)
Anemia , Neoplasias , Humanos , Estados Unidos , Estudios Prospectivos , Factores Raciales , Factores de Riesgo , Blanco
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