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1.
Br J Haematol ; 200(6): 792-801, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36444397

RESUMEN

The diagnostic work-up of patients referred to the haematologist for bleeding evaluation is performed in a stepwise way: bleeding history and results of screening laboratory tests guide further diagnostic evaluation. This can be ineffective, time-consuming and burdensome for patients. To improve this strategy, the initial laboratory investigation can be extended. In a model-based approach, effectiveness and costs of a conventional stepwise versus a newly proposed all-in-one diagnostic approach for bleeding evaluation were evaluated and compared, using data from an observational patient cohort study, including adult patients referred for bleeding evaluation. In the all-in-one approach, specialized platelet function tests, coagulation factors, and fibrinolysis tests were included in the initial investigation. Final diagnosis, hospital resource use and costs and patient burden were compared. A total of 150 patients were included. Compared to the stepwise approach, in the all-in-one approach, 19 additional patients reached a diagnosis and patient burden was lower, but total costs per patient were higher [€359, 95% bootstrapped confidence interval (BCI) 283-518, p = 0.001]. For bleeding evaluation of patients referred to the haematologist, an all-in-one diagnostic approach has a higher diagnostic yield and reduces patient burden, at a higher cost. This raises the question what costs justify the diagnosis of a bleeding disorder and a less burdensome diagnostic strategy.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Trastornos Hemorrágicos , Adulto , Humanos , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos Hemorrágicos/diagnóstico , Hemorragia , Fibrinólisis , Análisis Costo-Beneficio
2.
Br J Haematol ; 196(6): 1388-1400, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35001370

RESUMEN

Patients referred for evaluation of bleeding symptoms occasionally have a prolonged platelet function analyser (PFA) closure time, without evidence for von Willebrand disease or impaired platelet aggregation. The aim of this study was to establish a shear-dependent platelet function defect in these patients. Patients were included based on high bleeding score and prior PFA prolongation. Common tests of von Willebrand factor (VWF) and platelet function and exome sequencing were performed. Microfluidic analysis of shear-dependent collagen-induced whole-blood thrombus formation was performed. In 14 PFA-only patients, compared to healthy volunteers, microfluidic tests showed significantly lower platelet adhesion and thrombus formation parameters. This was accompanied by lower integrin activation, phosphatidylserine exposure and P-selectin expression. Principal components analysis indicated VWF as primary explaining variable of PFA prolongation, whereas conventional platelet aggregation primarily explained the reduced thrombus parameters under shear. In five patients with severe microfluidic abnormalities, conventional platelet aggregation was in the lowest range of normal. No causal variants in Mendelian genes known to cause bleeding or platelet disorders were identified. Multiparameter assessment of whole-blood thrombus formation under shear indicates single or combined effects of low-normal VWF and low-normal platelet aggregation in these patients, suggesting a shear-dependent platelet function defect, not detected by static conventional haemostatic tests.


Asunto(s)
Trombosis , Enfermedades de von Willebrand , Plaquetas/metabolismo , Hemorragia , Hemostasis , Humanos , Agregación Plaquetaria , Pruebas de Función Plaquetaria , Factor de von Willebrand/genética , Factor de von Willebrand/metabolismo
3.
Eur J Haematol ; 108(4): 310-318, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34923665

RESUMEN

BACKGROUND: Intracranial hemorrhage is seen more frequently in acute leukemia patients compared to the general population. Besides leukemia-related risk factors, also risk factors that are present in the general population might contribute to hemorrhagic complications in leukemia patients. Of those, cardiovascular risk factors leading to chronic vascular damage could modulate the occurrence of intracranial hemorrhage in these patients, as during their disease and treatment acute endothelial damage occurs due to factors like thrombocytopenia and inflammation. OBJECTIVES: Our aim was to explore if cardiovascular risk factors can predict intracranial hemorrhage in acute leukemia patients. METHODS: In a case-control study nested in a cohort of acute leukemia patients, including 17 cases with intracranial hemorrhage and 55 matched control patients without intracranial hemorrhage, data on cardiovascular risk factors were collected for all patients. Analyses were performed via conditional logistic regression. RESULTS: Pre-existing hypertension and ischemic heart disease in the medical history were associated with intracranial hemorrhage, with an incidence rate ratio of 12.9 (95% confidence interval [CI] 1.5 to 109.2) and 12.1 (95% CI 1.3 to110.7), respectively. CONCLUSION: Both pre-existing hypertension and ischemic heart disease seem to be strong predictors of an increased risk for intracranial hemorrhage in leukemia patients.


Asunto(s)
Enfermedades Cardiovasculares , Leucemia Mieloide Aguda , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios de Casos y Controles , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/etiología , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/diagnóstico , Factores de Riesgo
4.
Ann Hematol ; 100(1): 261-271, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33067700

RESUMEN

We designed a study to describe the incidence of intracranial hemorrhage according to severity and duration of thrombocytopenia and to quantify the associations of platelet transfusions with intracranial hemorrhage in patients with acute leukemia. In this case-control study nested in a cohort of 859 leukemia patients, cases (n = 17) were patients diagnosed with intracranial hemorrhage who were matched with control patients (n = 55). We documented platelet counts and transfusions for seven days before the intracranial hemorrhage in cases and in a "matched" week for control patients. Three measures of platelet count exposure were assessed in four potentially important time periods before hemorrhage. Among these leukemia patients, we observed the cumulative incidence of intracranial hemorrhage of 3.5%. Low platelet counts were, especially in the three to seven days preceding intracranial hemorrhage, associated with the incidence of intracranial hemorrhage, although with wide confidence intervals. Platelet transfusions during the week preceding the hemorrhage were associated with higher incidences of intracranial hemorrhage; rate ratios (95% confidence interval) for one or two platelet transfusions and for more than two transfusions compared with none were 4.04 (0.73 to 22.27) and 8.91 (1.53 to 51.73) respectively. Thus, among acute leukemia patients, the risk of intracranial hemorrhage was higher among patients with low platelet counts and after receiving more platelet transfusions. Especially, the latter is likely due to clinical factors leading to increased transfusion needs.


Asunto(s)
Hemorragias Intracraneales/epidemiología , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/terapia , Transfusión de Plaquetas/tendencias , Trombocitopenia/epidemiología , Adulto , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Hemorragias Intracraneales/sangre , Hemorragias Intracraneales/diagnóstico , Leucemia Mieloide Aguda/sangre , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Transfusión de Plaquetas/efectos adversos , Trombocitopenia/sangre , Trombocitopenia/diagnóstico , Resultado del Tratamiento
5.
Am J Hematol ; 96(1): 51-59, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32974947

RESUMEN

Acquired hemophilia A (AHA) is a severe auto-immune bleeding disorder. Treatment of AHA is burdensome and optimal management is still unresolved. Therefore a retrospective nationwide multi-center cohort study (1992-2018) was performed to evaluate clinical presentation and treatment efficacy and safety of AHA in the Netherlands. Multivariate logistic and Cox regression analysis was used to study independent associations between patient characteristics and clinical outcomes. A total of 143 patients (median age 73 years; 52.4% male) were included with a median follow-up of 16.8 months (IQR 3.6-41.5 months). First-line immunosuppressive treatment was mostly steroid monotherapy (67.6%), steroids/cyclophosphamide (11.9%) and steroids/rituximab (11.9%), with success rates of 35.2%, 80.0% and 66.7% respectively, P < .05. Eventually 75% of patients achieved complete remission (CR). A high anti-FVIII antibody titer, severe bleeding and steroid monotherapy were associated with lower CR rates. Infections, the most important adverse event, occurred significantly more often with steroid combination therapy compared to steroids alone (38.7% vs 10.6%; P = .001). Overall mortality was 38.2%, mostly due to infections (19.2%) compared to 7.7% fatal bleeds. Advanced age, underlying malignancy and ICU admission were predictors for mortality. This study showed that AHA is characterized by significant disease-related and treatment-related morbidity and mortality. A high anti-FVIII titer, severe bleeding and steroid monotherapy were associated with a lower CR rate. The efficacy of steroid combination therapies however, was overshadowed by higher infection rates and infections represented the most important cause of death. The challenging and delicate balance between treatment effectivity and safety requires ongoing monitoring of AHA and further identification of prognostic markers.


Asunto(s)
Ciclofosfamida/administración & dosificación , Bases de Datos Factuales , Hemofilia A , Rituximab/administración & dosificación , Esteroides/administración & dosificación , Anciano , Autoanticuerpos/sangre , Inhibidores de Factor de Coagulación Sanguínea/sangre , Supervivencia sin Enfermedad , Factor VIII/antagonistas & inhibidores , Factor VIII/metabolismo , Femenino , Estudios de Seguimiento , Hemofilia A/sangre , Hemofilia A/tratamiento farmacológico , Hemofilia A/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Estudios Retrospectivos , Tasa de Supervivencia
6.
Br J Haematol ; 189(1): 171-181, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31730713

RESUMEN

In daily haematological practice, predicting bleeding in thrombocytopenic patients is difficult, and clinicians adhere to transfusion triggers to guide patients through the aplastic phase of chemotherapy. Platelet count is not the only determinant of bleeding and additional mechanisms for impending haemostasis are likely. Beside clot formation, platelets are essential for the maintenance of integrity of vascular beds. We therefore prospectively investigated associations between biomarkers for endothelial damage (urine albumin excretion) and inflammation (C-reactive protein) and bleeding (WHO grading) in 88 patients with 116 on-protocol episodes. We found an increase in grade 2 bleeding with a higher urine albumin/creatinine ratio one day after the measurement [odds ratio (OR) 1·24 for every doubling of the ratio, 95% CI 1·05-1·46, P-value 0·01] and a 29% increase in the odds of grade 2 bleeding for every doubling of serum C-reactive protein (CRP) (95% CI 1·04-1·60, P-value 0·02) after correction for morning platelet count. The 24 h post-transfusion corrected count increment (CCI24 ) showed a significant association with these biomarkers: increasing urine albumin/creatinine ratio and CRP were associated with lower CCI24. We report two inexpensive and easy-to-apply biomarkers that could be useful in designing a prediction model for bleeding risk in thrombocytopenic patients.


Asunto(s)
Albuminuria , Proteína C-Reactiva/metabolismo , Endotelio Vascular/metabolismo , Hemorragia , Trombocitopenia , Adulto , Anciano , Albuminuria/sangre , Albuminuria/terapia , Biomarcadores/sangre , Biomarcadores/orina , Femenino , Hemorragia/sangre , Hemorragia/orina , Humanos , Inflamación/sangre , Inflamación/orina , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Prospectivos , Trombocitopenia/sangre , Trombocitopenia/orina
7.
Blood ; 132(2): 223-231, 2018 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-29773572

RESUMEN

Pathogen inactivation of platelet concentrates reduces the risk for blood-borne infections. However, its effect on platelet function and hemostatic efficacy of transfusion is unclear. We conducted a randomized noninferiority trial comparing the efficacy of pathogen-inactivated platelets using riboflavin and UV B illumination technology (intervention) compared with standard plasma-stored platelets (control) for the prevention of bleeding in patients with hematologic malignancies and thrombocytopenia. The primary outcome parameter was the proportion of transfusion-treatment periods in which the patient had grade 2 or higher bleeding, as defined by World Health Organization criteria. Between November 2010 and April 2016, 469 unique patients were randomized to 567 transfusion-treatment periods (283 in the control arm, 284 in the intervention arm). There was a 3% absolute difference in grade 2 or higher bleeding in the intention-to-treat analysis: 51% of the transfusion-treatment periods in the control arm and 54% in the intervention arm (95% confidence interval [CI], -6 to 11; P = .012 for noninferiority). However, in the per-protocol analysis, the difference in grade 2 or higher bleeding was 8%: 44% in the control arm and 52% in the intervention arm (95% CI -2 to 18; P = .19 for noninferiority). Transfusion increment parameters were ∼50% lower in the intervention arm. There was no difference in the proportion of patients developing HLA class I alloantibodies. In conclusion, the noninferiority criterion for pathogen-inactivated platelets was met in the intention-to-treat analysis. This finding was not demonstrated in the per-protocol analysis. This trial was registered at The Netherlands National Trial Registry as #NTR2106 and at www.clinicaltrials.gov as #NCT02783313.


Asunto(s)
Plaquetas/metabolismo , Hemostasis , Transfusión de Plaquetas , Coagulación Sanguínea , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Estudios Multicéntricos como Asunto , Evaluación del Resultado de la Atención al Paciente , Pruebas de Función Plaquetaria , Transfusión de Plaquetas/efectos adversos , Transfusión de Plaquetas/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto
8.
Haematologica ; 105(4): 1158-1165, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31273090

RESUMEN

Plasma transfusion is indicated for replenishment of coagulative proteins to stop or prevent bleeding. In 2014, the Netherlands switched from using ~300mL fresh frozen plasma (FFP) units to using 200mL Omniplasma, a solvent/detergent treated pooled plasma (SD plasma), units. We evaluated the effect of the introduction of SD plasma on clinical plasma use, associated bleeding, and transfusion reaction incidences. Using diagnostic data from six Dutch hospitals, national blood bank data, and national hemovigilance data for 2011 to 2017, we compared the plasma/red blood cell (RBC) units ratio (f) and the mean number of plasma and RBC units transfused for FFP (~300mL) and SD plasma (200mL) for various patient groups, and calculated odds ratios comparing their associated transfusion reaction risks. Analyzing 13,910 transfusion episodes, the difference (Δf = fSD - fFFP) in mean plasma/RBC ratio (f) was negligible (Δfentire_cohort = 0.01 [95% confidence interval (CI): -0.02 - 0.05]; P=0.48). SD plasma was associated with fewer RBC units transfused per episode in gynecological (difference of mean number of units -1.66 [95% CI: -2.72, -0.61]) and aneurysm (-0.97 [-1.59, -0.35]) patients. SD plasma was further associated with fewer anaphylactic reactions than FFP (odds ratio 0.37 [0.18, 0.77; P<0.01]) while the differences for most transfusion reactions were not statistically significant. SD plasma units, despite being one third smaller in volume than FFP units, are not associated with a higher plasma/RBC ratio. SD plasma is associated with fewer anaphylactic reactions than FFP plasma/RBC units ratio.


Asunto(s)
Plasma , Reacción a la Transfusión , Transfusión de Componentes Sanguíneos/efectos adversos , Detergentes , Transfusión de Eritrocitos , Humanos , Países Bajos/epidemiología , Estudios Retrospectivos , Solventes
9.
Am J Hematol ; 95(10): 1142-1147, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32562285

RESUMEN

Phenotypic characterization of congenital platelet defects (CPDs) could help physicians recognize CPD subtypes and can inform on prognostic implications. We report the analyses of the bleeding phenotype and diagnostic characteristics of a large cohort of adult patients with a confirmed CPD. A total of 96 patients were analyzed and they were classified as Glanzmann thrombasthenia, Bernard-Soulier syndrome, dense granule deficiency, defects in the ADP or thromboxane A2 (TxA2) pathway, isolated thrombocytopenia or complex abnormalities. The median ISTH-BAT bleeding score was nine (IQR 5-13). Heavy menstrual bleeding (HMB) (80%), post-partum hemorrhage (74%), post-operative bleeds (64%) and post-dental extraction bleeds (57%) occurred most frequently. Rare bleeding symptoms were bleeds from the urinary tract (4%) and central nervous system (CNS) bleeds (2%). Domains with a large proportion of severe bleeds were CNS bleeding, HMB and post-dental extraction bleeding. Glanzmann thrombasthenia and female sex were associated with a more severe bleeding phenotype.

10.
Platelets ; 30(1): 81-87, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-29135309

RESUMEN

Light transmission aggregation (LTA) is the gold standard for the diagnosis of platelet function disorders (PFDs), but it is time-consuming and limited to specialized laboratories. Whole-blood impedance aggregometry (Multiplate) and platelet function analyzer (PFA) may be used as rapid screening tools to exclude PFDs. The aim of this study is to assess the diagnostic performance of Multiplate and PFA for PFDs, as detected by LTA.Data from preoperative patients, patients referred to the hematologist for bleeding evaluation, and patients with a diagnosed bleeding disorder were used. PFDs were defined as ≥2 abnormal LTA curves. Diagnostic performance of Multiplate and PFA for detecting PFDs was expressed as sensitivity and specificity. The ability of Multiplate agonists and PFA kits to detect corresponding LTA curve abnormalities was expressed as area under the receiver operating characteristic curve. Prevalence of PFDs was 16/335 (4.8%) in preoperative patients, 10/54 (18.5%) in referred patients, and 3/25 (12%) in patients with a diagnosed bleeding disorder. In preoperative and referred patients, the sensitivity of Multiplate and PFA for detecting mild PFDs varied between 0% and 40% and AUCs for detecting corresponding LTA curve abnormalities were close to 0.50. In patients with a diagnosed bleeding disorder, both assays could detect Glanzmann thrombasthenia (GT) with sensitivity of 100% and AUCs of 0.70-1.00. Multiplate and PFA cannot discriminate between preoperative and referred patients with and without mild PFDs, meaning that they cannot be used as screening tests to rule out mild PFDs in these populations. Both Multiplate and PFA can detect GT in previously diagnosed patients.


Asunto(s)
Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/diagnóstico , Plaquetas/metabolismo , Adulto , Anciano , Trastornos de las Plaquetas Sanguíneas/terapia , Plaquetas/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria , Pruebas de Función Plaquetaria , Reproducibilidad de los Resultados
11.
Haematologica ; 103(9): 1557-1567, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29880611

RESUMEN

Severe thrombocytopenia (≤50×109 platelets/L) due to hematological malignancy and intensive chemotherapy is associated with an increased risk of clinically significant bleeding. Since the bleeding risk is not linked to the platelet count only, other hemostatic factors must be involved. We studied platelet function in 77 patients with acute leukemia, multiple myeloma or malignant lymphoma, who experienced chemotherapy-induced thrombocytopenia. Platelets from all patients - independent of disease or treatment type - were to a variable extent compromised in Ca2+ flux, integrin a ß activation and P-selectin expression when stimulated with a panelIIbof3 agonists. The patients' platelets were also impaired in spreading on fibrinogen. Whereas the Ca2+ store content was unaffected, the patients' platelets showed ongoing phosphatidylserine exposure, which was not due to apoptotic caspase activity. Interestingly, mitochondrial function was markedly reduced in platelets from a representative subset of patients, as evidenced by a low mitochondrial membrane potential (P<0.001) and low oxygen consumption (P<0.05), while the mitochondrial content was normal. Moreover, the mitochondrial impairments coincided with elevated levels of reactive oxygen species (Spearman's rho=-0.459, P=0.012). Markedly, the impairment of platelet function only appeared after two days of chemotherapy, suggesting origination in the megakaryocytes. In patients with bone marrow recovery, platelet function improved. In conclusion, our findings disclose defective receptor signaling related to impaired mitochondrial bioenergetics, independent of apoptosis, in platelets from cancer patients treated with chemotherapy, explaining the low hemostatic potential of these patients.


Asunto(s)
Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias/complicaciones , Trombocitopenia/etiología , Trombocitopenia/metabolismo , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de los fármacos , Biomarcadores , Coagulación Sanguínea/efectos de los fármacos , Señalización del Calcio/efectos de los fármacos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Activación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Recuento de Plaquetas , Pruebas de Función Plaquetaria , Índice de Severidad de la Enfermedad , Trombocitopenia/sangre , Trombocitopenia/diagnóstico
12.
Transfusion ; 57(9): 2096-2103, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28653425

RESUMEN

BACKGROUND: Extension of storage time of platelet (PLT) concentrates may result in an increased risk of bacteremia, directly via transfusion of contaminated products or indirectly via transfusion-related immunomodulation. We aimed to quantify the association of storage time of PLT concentrates and all-cause bacteremia in hematologic patients. STUDY DESIGN AND METHODS: We established a cohort of hematologic patients who received a PLT transfusion between 2005 and 2015. Cases were defined as patients with a bacteremia the day after transfusion and matched to as many controls as possible. A conditional logistic regression was performed, stratified by storage medium. RESULTS: Among 3514 patients receiving 36,032 PLT concentrates stored in plasma, 613 cases of bacteremia were found. The relative risk of all-cause bacteremia the day after transfusion was 0.80 (95% confidence interval [CI], 0.58-1.12) for PLT concentrates stored 3 to 4 days and 0.67 (95% CI, 0.49-0.92) for at least 5 days, compared to no more than 2 days. Among 1527 patients receiving 11,822 PLT concentrates stored in PLT additive solution, 182 cases of bacteremia were found. The relative risk of all-cause bacteremia was 1.14 (95% CI, 0.70-1.84) for PLT concentrates stored for 3 to 4 days and 1.19 (95% CI, 0.70-2.01) for at least 5 days, compared to not more than 2 days. CONCLUSION: Storage time of PLT concentrates was not associated with increased occurrence of all-cause bacteremia the day after transfusion. If anything, fewer cases of bacteremia occurred with increasing storage time of PLT concentrates in plasma. These bacteremias are not directly caused by transfusion of a contaminated product and the underlying mechanism warrants further research.


Asunto(s)
Bacteriemia/etiología , Plaquetas/microbiología , Conservación de la Sangre , Transfusión de Plaquetas/efectos adversos , Humanos , Factores de Tiempo
13.
Haematologica ; 101(4): 427-36, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26721892

RESUMEN

Coated platelets, formed by collagen and thrombin activation, have been characterized in different ways: i) by the formation of a protein coat of α-granular proteins; ii) by exposure of procoagulant phosphatidylserine; or iii) by high fibrinogen binding. Yet, their functional role has remained unclear. Here we used a novel transglutaminase probe, Rhod-A14, to identify a subpopulation of platelets with a cross-linked protein coat, and compared this with other platelet subpopulations using a panel of functional assays. Platelet stimulation with convulxin/thrombin resulted in initial integrin α(IIb)ß3 activation, the appearance of a platelet population with high fibrinogen binding, (independently of active integrins, but dependent on the presence of thrombin) followed by phosphatidylserine exposure and binding of coagulation factors Va and Xa. A subpopulation of phosphatidylserine-exposing platelets bound Rhod-A14 both in suspension and in thrombi generated on a collagen surface. In suspension, high fibrinogen and Rhod-A14 binding were antagonized by combined inhibition of transglutaminase activity and integrin α(IIb)ß3 Markedly, in thrombi from mice deficient in transglutaminase factor XIII, platelet-driven fibrin formation and Rhod-A14 binding were abolished by blockage of integrin α(IIb)ß3. Vice versa, star-like fibrin formation from platelets of a patient with deficiency in α(IIb)ß3(Glanzmann thrombasthenia) was abolished upon blockage of transglutaminase activity. We conclude that coated platelets, with initial α(IIb)ß3 activation and high fibrinogen binding, form a subpopulation of phosphatidylserine-exposing platelets, and function in platelet-dependent star-like fibrin fiber formation via transglutaminase factor XIII and integrin α(IIb)ß3.


Asunto(s)
Plaquetas/metabolismo , Factor XIII/metabolismo , Fibrina/metabolismo , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/metabolismo , Trombastenia/sangre , Animales , Coagulación Sanguínea , Plaquetas/efectos de los fármacos , Plaquetas/patología , Venenos de Crotálidos/farmacología , Factor Va/química , Factor Va/metabolismo , Factor XIII/química , Factor Xa/química , Factor Xa/metabolismo , Fibrina/química , Fibrinógeno/química , Fibrinógeno/metabolismo , Humanos , Lectinas Tipo C , Ratones , Ratones Noqueados , Sondas Moleculares/química , Fosfatidilserinas/química , Fosfatidilserinas/metabolismo , Activación Plaquetaria/efectos de los fármacos , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/química , Cultivo Primario de Células , Unión Proteica , Trombastenia/patología , Trombina/farmacología
15.
Transfusion ; 55(5): 1021-7, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25641128

RESUMEN

BACKGROUND: Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) is approved for the use of stem cell collection in patients who fail to mobilize on G-CSF. In 2009 the Stem Cell Working Party of the Dutch-Belgian Cooperative Trial group for Hematology Oncology (HOVON) composed a guideline for the use of plerixafor. According to this guideline it is recommended to add plerixafor to G-CSF in patients with circulating CD34+ cell counts of fewer than 20 × 10(6) /L on 2 consecutive days accompanied by increasing white blood cells. STUDY DESIGN AND METHODS: In this analysis we evaluated retrospectively the outcome of the use of this guideline in the Netherlands. In total 111 patients received plerixafor with a median one administration (range, one to four administrations). Of these patients 55.8% had non-Hodgkin lymphoma, 31.5% multiple myeloma, 8.1% Hodgkin lymphoma, and 4.5% nonhematologic malignancies. RESULTS: In 63.9% patients sufficient numbers of CD34+ cells were collected. In patients with multiple myeloma more successful mobilizations with plerixafor were observed compared to patients with non-Hodgkin lymphoma (71.4% vs. 61.3%). In patients with circulating CD34+ cell counts of at least 2.0 × 10(6) /L before administration of plerixafor a successful mobilization was achieved in 76.5%, and in the patients with very low (0-1 × 10(6) /L) circulating CD34+ cell counts the success rate was 44.2%. CONCLUSION: Application of the HOVON guideline on the just-in-time administration of plerixafor is effective for mobilization of hematopoietic stem cells in the majority of patients. Stem cell yield in patients with non-Hodgkin lymphoma was lower compared to patients with multiple myeloma. Also patients with very low circulating CD34+ cells before addition of plerixafor might benefit from this approach.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Compuestos Heterocíclicos/uso terapéutico , Adulto , Anciano , Antígenos CD34/metabolismo , Bencilaminas , Ciclamas , Movilización de Célula Madre Hematopoyética , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Linfoma no Hodgkin/metabolismo , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/metabolismo , Países Bajos , Estudios Retrospectivos
18.
Eur J Haematol ; 93(2): 150-6, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24660761

RESUMEN

OBJECTIVES: A period of thrombocytopenia is common after stem cell transplantation (SCT). To prevent serious bleeding complications, prophylactic platelet transfusions are administered. Previous studies have shown that a rise in immature platelets precedes recovery of platelet count. Our aim was to define a cutoff value for immature platelets predicting thrombopoietic recovery within 2 d. METHODS: Hematological parameters were measured on the Sysmex XN hemocytometer. We calculated reference change values (RCV) for platelets in eight healthy individuals as marker for platelet recovery. To define a cutoff value, we performed ROC analysis using data from 16 autologous SCT patients. RESULTS: RCV for platelet concentration was 14.1%. Platelet recovery was observed 13 (median; range 9-31) days after SCT. Increase in immature platelet fraction (IPF) before platelet recovery was seen in all autologous SCT patients. Optimal cutoff IPF was found to be 5.3% for platelet recovery within 2 d (specificity 0.98, sensitivity 0.47, positive predictive value 0.93). CONCLUSIONS: We identified an optimal cutoff value for IPF 5.3% to predict platelet recovery after autologous SCT within 2 d. Implementing this cutoff value in transfusion strategy may reduce the number of prophylactic platelet transfusions.


Asunto(s)
Plaquetas/citología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Transfusión de Plaquetas , Trombocitopenia/terapia , Adulto , Anciano , Automatización de Laboratorios , Diferenciación Celular , Femenino , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Curva ROC , Valores de Referencia , Trombocitopenia/etiología , Trombocitopenia/patología , Factores de Tiempo , Trasplante Autólogo
19.
J Cardiothorac Vasc Anesth ; 28(2): 210-6, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24630470

RESUMEN

OBJECTIVES: In the present study, the authors have investigated whether rotational thromboelastometry (ROTEM) could predict thrombocytopenia and hypofibrinogenemia in cardiac surgery using the clot amplitude after 5 minutes (A5). Another parameter, PLTEM, in which the contribution of fibrinogen is eliminated by subtracting a fibrin-specific ROTEM test (FIBTEM) from an extrinsically-activated ROTEM test (EXTEM), was investigated. Furthermore, the turnaround time of ROTEM was compared to conventional laboratory tests. DESIGN: Prospective cohort study. SETTING: Single academic medical center. PARTICIPANTS: Ninety-seven patients undergoing cardiac surgery between July 2011 until August 2012. INTERVENTIONS: The correlations between EXTEM/FIBTEM A5, A10, and maximal clot formation (MCF), EXTEM/PLTEM (A5/A10, and MCF) and platelet count, and FIBTEM (A5/A10, and MCF) and fibrinogen were evaluated using the Pearson's correlation coefficient and receiver-operating characteristic curves. Turnaround times of ROTEM tests and conventional laboratory tests were assessed in the central laboratory. MEASUREMENTS AND MAIN RESULTS: EXTEM A5 and FIBTEM A5 showed an excellent correlation with A10 (R:0.99/1.00) and MCF (R:0.97/0.99). The correlation between EXTEM A5 and platelet count (R:0.74) was comparable with the correlation of A10 (R:0.73) and MCF (R:0.70) with platelet count. FIBTEM A5 predicted fibrinogen levels (R:0.87) as well as A10 (R:0.86) and MCF (R:0.87). PLTEM A5 (R:0.85) correlated better with platelet count than EXTEM A5 (R:0.74; p = 0.04) and showed significantly better area under the curve values than EXTEM for predicting thrombocytopenia (A5 p = 0.012, A10 p = 0.019). Turnaround time for ROTEM tests, 12 minutes, was comparable with emergency requests for platelet count, 13 minutes, and shorter than emergency requests for fibrinogen levels, 37 minutes. CONCLUSIONS: Implementation of PLTEM and FIBTEM A5 in ROTEM-guided transfusion protocols may improve transfusion management.


Asunto(s)
Afibrinogenemia/diagnóstico , Procedimientos Quirúrgicos Cardíacos/métodos , Tromboelastografía/métodos , Trombocitopenia/diagnóstico , Anciano , Área Bajo la Curva , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Transfusión Sanguínea/métodos , Estudios de Cohortes , Femenino , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Trombocitopenia/sangre
20.
Eur J Clin Nutr ; 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127840

RESUMEN

BACKGROUND/OBJECTIVES: Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) often receive medical nutrition therapy (MNT) during intensive remission-induction treatment. Since little is known about changes in nutritional status, specifically body composition, in this patient population, these changes and their associations with physical and clinical outcomes were assessed. SUBJECTS/METHODS: In this multicenter prospective observational study, newly diagnosed AML/MDS patients who received intensive remission-induction chemotherapy, routine dietary counseling by a dietician and MNT immediately upon inadequate nutritional intake, were included. At treatment initiation and discharge, nutritional status, including Patient-Generated Subjective Global Assessment (PG-SGA)-scores and body composition, physical outcomes and fatigue were assessed. Associations of nutritional status/body composition with physical outcomes, fatigue, fever duration, number of complications, time to neutrophil engraftment and hospital length of stay (LOS) (collected from medical records) were examined using multiple regression analysis. RESULTS: In >91% of the 126 AML/MDS patients included, nutritional intake was adequate, with 61% receiving MNT. Nevertheless, body weight decreased significantly (p < 0.001) and mainly consisted of a loss of muscle/fat-free mass (FFM) (p < 0.001), while fat mass (FM) remained unchanged (p-value range = 0.71-0.77). Body weight and waist circumference showed significant negative associations with fever duration and/or number of complications. Significant positive associations were found between mid-upper arm muscle circumference (MUAMC) and physical functioning and between PG-SGA-scores and fatigue. Body weight and MUAMC were also negatively associated with LOS. CONCLUSION: Despite MNT in AML/MDS patients undergoing intensive chemotherapy, muscle/FFM decreased while FM remained unchanged. Maintenance of nutritional status was associated with improved physical and clinical outcomes.

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