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COVID-19 , Complejo GPIb-IX de Glicoproteína Plaquetaria , Trombina , Humanos , COVID-19/complicaciones , COVID-19/inmunología , COVID-19/fisiopatología , Trombina/análisis , Trombina/inmunología , Complejo GPIb-IX de Glicoproteína Plaquetaria/inmunología , Trastornos de las Plaquetas Sanguíneas/etiología , Trastornos de las Plaquetas Sanguíneas/inmunología , Trastornos de las Plaquetas Sanguíneas/fisiopatologíaRESUMEN
Extracorporeal circulation (ECC) is frequently used in intensive care patients with impaired lung or cardiac function. Despite being a life-saving therapeutic option, ECC is associated with increased risk for both bleeding and thrombosis. The management of bleeding and thromboembolic events in ECC patients is still challenging partly due to the lack of information on the pathophysiological changes in hemostasis and platelet function during the procedure. Using a combination of an ex vivo model for shear stress and a sensitive and easy-to-use laboratory method, we analyzed platelet responsiveness during ECC. After shear stress simulation in an ex vivo closed-loop ECC model, we found a significantly decreased response of α-granules after activation with adenosine diphosphate and thrombin receptor activating peptide (TRAP-6) and CD63 expression after activation with TRAP-6. Mepacrine uptake was also significantly reduced in the ex vivo shear stress model.In the same line, platelets from patients under ECC with venovenous systems and venoarterial systems showed impaired CD62P degranulation after stimulation with ADP and TRAP-6 compared with healthy control on day 1, 6, and 10 after implantation of ECC. However, no correlation between platelet degranulation and the occurrence of bleeding or thromboembolic events was observed.The used whole blood flow cytometry with immediate fixation after drawing introduces a sensitive and easy-to-use method to determine platelet activation status and our data confirm that increased shear stress conditions under ECC can cause impaired degranulation of platelet.
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Trastornos de las Plaquetas Sanguíneas , Plaquetas , Humanos , Estudios Prospectivos , Plaquetas/metabolismo , Activación Plaquetaria , Trastornos de las Plaquetas Sanguíneas/etiología , Circulación Extracorporea/efectos adversos , Circulación Extracorporea/métodos , Adenosina Difosfato/metabolismoRESUMEN
INTRODUCTION: Sticky platelet syndrome is a less known platelet function disorder with a familiar occurrence and likely genetic background. Clinically, it is characterized by an increased risk of venous and arterial thromboembolic events and obstetric placenta-mediated complications. The increased aggregation after low-dose ADP and/or epinephrine is its distinctive laboratory feature. Though described for almost 40 years, several issues regarding its etiology, involved pathomechanisms, genetic background, optimal diagnostic and treatment approach remain controversial. AREAS COVERED: The work aims to summarize published studies, the actual definition of the syndrome, and point out its drawbacks. A literature search on Medline, Embase, and archives from EHA congresses was performed (terms: 'sticky platelet syndrome' - 'platelet hyperreactivity' - 'platelet hyperaggregability'). The authors added in their unpublished data. The introductory overview of the present understanding is followed by the discussion of the pathophysiologic, diagnostic, and therapeutic problems. EXPERT OPINION: Despite the growing evidence provided by case reports and series, the lack of robust studies limits the decision-making on diagnostics and management. The diagnostic issues, particularly the standardization of light transmission aggregometry, represent the crucial problem for the broader acceptance of the syndrome.
PLAIN LANGUAGE SUMMARY Sticky platelet syndrome is aplatelet function disorder. It is associated with an increased risk of venous thromboembolism, arterial thrombosis, and obstetric placenta-mediated complications. Increased aggregation after low-dose ADP and/or epinephrine is the defining laboratory feature. Furthermore, afew studies report the familiar occurrence with possible genetic background. Several issues regarding the syndrome remain controversial: its exact etiology, genetics, optimal diagnostic, and treatment approach. These uncertainties provide ground for debate of the syndrome as aunique clinical entity. The review has two goals. Firstly, it summarizes the published studies and the actual definition of the syndrome. Secondly, it tries to point out the open pathophysiologic, diagnostic, and therapeutic problems.
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Trastornos de las Plaquetas Sanguíneas , Agregación Plaquetaria , Trastornos de las Plaquetas Sanguíneas/etiología , Trastornos de las Plaquetas Sanguíneas/genética , Plaquetas , Femenino , Humanos , Embarazo , SíndromeRESUMEN
BACKGROUND: Rapid platelet function testing is frequently used to determine platelet function in patients with traumatic intracranial hemorrhage (tICH). Accuracy and clinical significance of decreased platelet response detected by these tests is not well understood. We sought to determine whether VerifyNow and whole blood aggregometry (WBA) can detect poor platelet response and to elucidate its clinical significance for tICH patients. METHODS: We prospectively enrolled patients with isolated tICH between 2018 and 2020. Demographics, medical history, injury characteristics, and patient outcomes were recorded. Platelet function was determined by VerifyNow and WBA testing at the time of arrival to the trauma bay and 6 hours later. RESULTS: A total of 221 patients were enrolled, including 111 patients on no antiplatelet medication, 78 on aspirin, 6 on clopidogrel, and 26 on aspirin and clopidogrel. In the trauma bay, 29.7% and 67.7% of patients on no antiplatelet medication had poor platelet response on VerifyNow and WBA, respectively. Among patients on aspirin, 72.2% and 82.2% had platelet dysfunction on VerifyNow and WBA. Among patients on clopidogrel, 67.9% and 88.9% had platelet dysfunction on VerifyNow and WBA. Patients with nonresponsive platelets had similar in-hospital mortality (3 [3.0%] vs. 6 [6.3%], p = 0.324), tICH progression (26 [27.1%] vs. 24 [26.1%], p = 0.877), intensive care unit admission rates (34 [34.3%] vs. 38 [40.0%), p = 0.415), and length of stay (3 [interquartile range, 2-8] vs. 3.2 [interquartile range, 2-7], p = 0.818) to those with responsive platelets. Platelet transfusion did not improve platelet response or patient outcomes. CONCLUSION: Rapid platelet function testing detects a highly prevalent poor platelet response among patients with tICH, irrespective of antiplatelet medication use. VerifyNow correlated fairly with whole blood aggregometry among patients with tICH and platelet responsiveness detectable by these tests did not correlate with clinical outcomes. In addition, our results suggest that platelet transfusion may not improve clinical outcomes in patients with tICH. LEVEL OF EVIDENCE: Diagnostic tests, level II.
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Trastornos de las Plaquetas Sanguíneas , Lesiones Traumáticas del Encéfalo , Hemorragia Intracraneal Traumática , Inhibidores de Agregación Plaquetaria , Pruebas de Función Plaquetaria/métodos , Transfusión de Plaquetas , Anciano , Trastornos de las Plaquetas Sanguíneas/diagnóstico , Trastornos de las Plaquetas Sanguíneas/etiología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/epidemiología , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Hemorragia Intracraneal Traumática/sangre , Hemorragia Intracraneal Traumática/complicaciones , Hemorragia Intracraneal Traumática/mortalidad , Hemorragia Intracraneal Traumática/terapia , Tiempo de Internación , Masculino , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/clasificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Transfusión de Plaquetas/métodos , Transfusión de Plaquetas/estadística & datos numéricos , Centros Traumatológicos/estadística & datos numéricos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Congenital platelet disorders (CPDs) are rare bleeding disorders that are associated with mucocutaneous bleeds. However, data on vaginal bleeding in women with CPDs are scarce. A set of generic and bleeding-specific questionnaires were used to evaluate the prevalence of vaginal bleeding, its impact on quality of life (QoL) and sexual functioning and the consequences for pregnancy, miscarriage and delivery in a cohort of women who were referred for diagnostic evaluation for CPDs. A total of 78 women included in the study were either diagnosed with a CPD (n = 35) or were clinically suspected of a CPD (n = 43). Heavy menstrual bleeding (HMB) was reported by a large proportion of women, which mainly started at menarche. In all, 76% of women received any kind of HMB treatment, often leading to surgical prodecures. HMB was shown to have a high impact on QoL, which improved upon treatment. Even though women reported that vaginal bleeding affects sexuality, this topic is not frequently discussed with physicians. Heavy blood loss frequently occurred after miscarriage/delivery, often requiring treatment. Women with (suspected) CPDs frequently encounter HMB, negatively impacting daily life and sexual functioning. Together with peripartum bleeding, these data highlight the burden of vaginal bleeding in CPDs and importance of adequate treatment.
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Trastornos de las Plaquetas Sanguíneas/complicaciones , Trastornos de las Plaquetas Sanguíneas/epidemiología , Hemorragia Uterina/epidemiología , Hemorragia Uterina/etiología , Adulto , Edad de Inicio , Trastornos de las Plaquetas Sanguíneas/etiología , Costo de Enfermedad , Estudios Transversales , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Menorragia , Persona de Mediana Edad , Países Bajos/epidemiología , Prevalencia , Vigilancia en Salud Pública , Calidad de Vida , Encuestas y Cuestionarios , Resultado del Tratamiento , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/terapiaRESUMEN
BACKGROUND: Pre-injury anti-platelet use has been associated with increased risk of progression of traumatic intracranial hemorrhage (TICH) and worse outcomes. VerifyNow® assays assess platelet inhibition due to aspirin/clopidogrel. This study assesses the outcomes of patients with TICH and platelet dysfunction treated with desmopressin and/or platelets. METHODS: We performed a retrospective chart review of patients with mild TICH at a level 1 trauma center 1/1/2013-6/1/2016. Patients with documented platelet dysfunction who received desmopressin and/or platelets were compared to those who were untreated. Primary outcomes were progression of TICH and neurologic outcomes at discharge. RESULTS: Of 565 patients with a mild TICH, 200 patients had evidence of platelet dysfunction (a positive VerifyNow® assay). Patients had similar baseline demographics, injury characteristics, and rate of TICH progression; but patients who received desmopressin and/or platelets had worse Glasgow Outcomes Score at discharge. CONCLUSION: Treatment of patients with mild TICH and platelet dysfunction with desmopressin and/or platelets did not affect TICH progression but correlated with worse neurologic status at discharge.
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Trastornos de las Plaquetas Sanguíneas/terapia , Hemostáticos/administración & dosificación , Hemorragia Intracraneal Traumática/terapia , Inhibidores de Agregación Plaquetaria/efectos adversos , Transfusión de Plaquetas/efectos adversos , Anciano , Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/diagnóstico , Trastornos de las Plaquetas Sanguíneas/etiología , Desamino Arginina Vasopresina/administración & dosificación , Desamino Arginina Vasopresina/efectos adversos , Progresión de la Enfermedad , Femenino , Hemostáticos/efectos adversos , Humanos , Hemorragia Intracraneal Traumática/sangre , Hemorragia Intracraneal Traumática/complicaciones , Masculino , Persona de Mediana Edad , Transfusión de Plaquetas/estadística & datos numéricos , Estudios Retrospectivos , Centros Traumatológicos/estadística & datos numéricos , Resultado del TratamientoRESUMEN
To reveal if coagulopathies relate to the course of COVID-19, we examined 255 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about » of cases were associated with high levels of C-reactive protein and antiphospholipid antibodies, which impeded coagulation in vitro. Contraction of blood clots was hindered in about ½ of patients, especially in severe and fatal cases, and correlated directly with prothrombotic parameters. A decrease in platelet contractility was due to moderate thrombocytopenia in combination with platelet dysfunction. Clots with impaired contraction were porous, had a low content of compressed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin, suggesting that the uncompacted intravital clots are more obstructive but patients could also be prone to bleeding. The absence of consumption coagulopathy suggests the predominance of local and/or regional microthrombosis rather than disseminated intravascular coagulation. The results obtained (i) confirm the importance of hemostatic disorders in COVID-19 and their relation to systemic inflammation; (ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction; (iii) substantiate the active prophylaxis of thrombotic complications in COVID-19.
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Trastornos de la Coagulación Sanguínea/etiología , Trastornos de las Plaquetas Sanguíneas/etiología , COVID-19/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Plaquetas/ultraestructura , Femenino , Humanos , Inflamación/etiología , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Trombocitopenia/etiología , Resultado del Tratamiento , Adulto Joven , Tratamiento Farmacológico de COVID-19RESUMEN
INTRODUCTION: Patients with renal failure are at increased risk of both bleeding and thrombosis. Further descriptions of laboratory investigations in these patients are required. METHODS: Investigation of 24 patients with chronic kidney disease (CKD) stages IV-V with light transmission aggregometry, platelet secretion assays and platelet nucleotide analysis. Patients were in a nonbleeding state and not on antiplatelet medication. Results were compared with our local reference range used within the clinical haematology service. RESULTS: Of the 24 patients, two had decreased responses to arachidonic acid, adenosine diphosphate, collagen, thrombin receptor activator peptide-6 and one had decreased responses to high dose ristocetin, and one had increased response to low dose ristocetin. 11 and 13 out of 24 had abnormal platelet secretion release to collagen and thrombin, respectively. Platelet nucleotide analysis in patients was normal with the exception of a reduction in ADP content in one patient and ATP/ADP ratio in one patient. CONCLUSIONS: In our collection of patients with CKD investigated for platelet function in the nonbleeding state, they generally had normal light transmission aggregometry and nucleotide analysis but around 50% had decreased platelet secretion assays. These results could be important in determining the significance of platelet function tests in patients with bleeding symptoms and renal failure. Further characterization of platelet function tests in future will help characterize haemostasis in renal failure further.
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Coagulación Sanguínea , Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/etiología , Fallo Renal Crónico/complicaciones , Biomarcadores/sangre , Pruebas de Coagulación Sanguínea , Trastornos de las Plaquetas Sanguíneas/diagnóstico , Plaquetas/metabolismo , Hemorragia/sangre , Hemorragia/diagnóstico , Hemorragia/etiología , Humanos , Fallo Renal Crónico/diagnóstico , Agregación Plaquetaria , Pruebas de Función Plaquetaria , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Studies of thrombin generation (TG) with platelet-rich plasma (PRP) and platelet-poor plasma (PPP) have provided insights on bleeding disorders. We studied TG for a cohort with commonly encountered platelet function disorders (PFD). METHODS: Participants included 40 controls and 31 with PFD due to: nonsyndromic dense granule (DG) deficiency (PFD-DGD, n = 9), RUNX1 haploinsufficiency (n = 6) and aggregation defects from other, uncharacterized causes (n = 16). TG was tested with PRP and PPP samples. As DG store ADP and polyphosphate that enhance platelet-dependent TG, PFD-DGD PRP TG was tested for correction with ADP, polyphosphate and combined additives. Tissue factor pathway inhibitor (TFPI), platelet factor V (FV), and platelet TFPI and ANO6 transcript levels were also evaluated. Findings were tested for associations with TG endpoints and bleeding. RESULTS: PFD samples had impaired PRP TG, but also impaired PPP TG, with strong associations between their PRP and PPP TG endpoints (P ≤ .005). PFD-DGD PRP TG endpoints showed associations to PPP TG endpoints but not to DG counts, and were improved, but not fully corrected, by adding polyphosphate and agonists. PFD participants had increased plasma TFPI and reduced platelet TFPI (P ≤ .02) but normal levels of platelet FV, and platelet TFPI and ANO6 transcripts levels. PFD plasma TFPI levels showed significant association to several PPP TG endpoints (P ≤ .04). Several PFD PRP TG endpoints showed significant associations to bleeding symptoms, including wound healing problems and prolonged bleeding from minor cuts (P ≤ .04). CONCLUSION: TG is impaired in commonly encountered PFD, with their PRP TG findings showing interesting associations to symptoms.
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Biomarcadores , Coagulación Sanguínea , Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/etiología , Susceptibilidad a Enfermedades , Trombina/biosíntesis , Pruebas de Coagulación Sanguínea , Trastornos de las Plaquetas Sanguíneas/diagnóstico , Manejo de la Enfermedad , Humanos , Fenotipo , Plasma Rico en Plaquetas , PronósticoRESUMEN
Introduction: Patients with severe COVID-19 infections have coagulation abnormalities indicative of a hypercoagulable state, with thromboembolic complications and increased mortality. Platelets are recognized as mediators of inflammation, releasing proinflammatory and prothrombotic factors, and are hyperactivated in COVID-19 infected patients. Activated platelets have also been reported in type 2 diabetes (T2D) patients, putting these patients at higher risk for thromboembolic complications of COVID-19 infection. Methods: A case-control study of T2D (n=33) and control subjects (n=30) who underwent a hyperinsulinemic clamp to induce normoglycemia in T2D subjects: T2D: baseline glucose 7.5 ± 0.3mmol/l (135.1 ± 5.4mg/dl), reduced to 4.5 ± 0.07mmol/l (81 ± 1.2mg/dl) with 1-hour clamp; Controls: maintained at 5.1 ± 0.1mmol/l (91.9 ± 1.8mg/dl). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was used to determine a panel of platelet proteins. Results: Prothrombotic platelet proteins were elevated in T2D versus controls: platelet factor 4 (PF4, p<0.05); platelet glycoprotein VI (PGVI p<0.05); P-selectin (p<0.01) and plasminogen activator inhibitor I (PAI-1, p<0.01). In addition, the antithrombotic platelet-related proteins, plasmin (p<0.05) and heparin cofactor II (HCFII, p<0.05), were increased in T2D. Normalization of glucose in the T2D cohort had no effect on platelet protein levels. Conclusion: T2D patients have platelet hyperactivation, placing them at higher risk for thromboembolic events. When infected with COVID-19, this risk may be compounded, and their propensity for a more severe COVID-19 disease course increased. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03102801, identifier NCT03102801.
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Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/etiología , Plaquetas/química , Proteínas Sanguíneas/análisis , COVID-19/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemia/sangre , Hipoglucemia/complicaciones , Anciano , COVID-19/complicaciones , Estudios de Casos y Controles , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Activación Plaquetaria , Tromboembolia/sangre , Tromboembolia/etiologíaRESUMEN
The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in excessive inflammation and respiratory disease, with cytokine storm and acute respiratory distress syndrome implicated in the most severe cases. Thrombotic complications are a major cause of morbidity and mortality in patients with COVID-19. Patients with pre-existing cardiovascular disease and/or traditional cardiovascular risk factors, including obesity, diabetes mellitus, hypertension and advanced age, are at the highest risk of death from COVID-19. In this Review, we summarize new lines of evidence that point to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and describe the mechanisms that might account for the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19. We highlight the distinct contributions of coagulopathy, thrombocytopathy and endotheliopathy to the pathogenesis of COVID-19 and discuss potential therapeutic strategies in the management of patients with COVD-19. Harnessing the expertise of the biomedical and clinical communities is imperative to expand the available therapeutics beyond anticoagulants and to target both thrombocytopathy and endotheliopathy. Only with such collaborative efforts can we better prepare for further waves and for future coronavirus-related pandemics.
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Trastornos de la Coagulación Sanguínea/sangre , Trastornos de las Plaquetas Sanguíneas/sangre , COVID-19/sangre , Endotelio Vascular/fisiopatología , Inflamación/sangre , Trombosis/sangre , Administración por Inhalación , Anticoagulantes/uso terapéutico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/fisiopatología , Trastornos de las Plaquetas Sanguíneas/tratamiento farmacológico , Trastornos de las Plaquetas Sanguíneas/etiología , Trastornos de las Plaquetas Sanguíneas/fisiopatología , COVID-19/complicaciones , COVID-19/fisiopatología , Factores Relajantes Endotelio-Dependientes/uso terapéutico , Epoprostenol/uso terapéutico , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Iloprost/uso terapéutico , Inflamación/etiología , Inflamación/fisiopatología , Óxido Nítrico/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Trombosis/etiología , Trombosis/inmunología , Microangiopatías Trombóticas/sangre , Microangiopatías Trombóticas/tratamiento farmacológico , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/fisiopatología , Enfermedades Vasculares/sangre , Enfermedades Vasculares/tratamiento farmacológico , Enfermedades Vasculares/etiología , Enfermedades Vasculares/fisiopatología , Vasodilatadores/uso terapéutico , Tromboembolia Venosa/sangre , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/fisiopatología , Tratamiento Farmacológico de COVID-19RESUMEN
AIMS: This study was aimed at investigating the prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer (EOC) patients in Lagos, Nigeria. METHODS: This was a retrospective cohort study involving the review of the clinical record of 72 patients with histologically confirmed EOC who were managed at the Lagos University Teaching Hospital, Lagos, Nigeria over a 7-year period from January 2010 to December 2016. Information on the sociodemographic data and platelet counts at diagnosis of EOC were retrieved from the patients' medical records. Descriptive statistics were then computed for all baseline patients' characteristics. Survival analyses were carried out using the Kaplan-Meier estimates. Multivariate analysis of these data was performed with the Cox proportional hazards model. RESULTS: This study revealed that the prevalence of pretreatment thrombocytosis was 41.7% among the women with EOC. Fifty-three (73.6%) of the women had the advanced-stage disease (FIGO stage III-IV) while 52 (72.2%) had high-grade disease (II-III). The majority (66.7%) of the women had a serous histological type of EOC while 76.4% had documented recurrence. Pretreatment thrombocytosis was significantly associated with the women's parity (P = 0.009), serum carbohydrate antigen 125 levels (P = 0.018), median progression-free survival (PFS) (P < 0.001), 3-year median overall survival (OS) (P < 0.001), type of primary treatment (P = 0.002), extent of cytoreduction (P < 0.001), presence of ascites (P = 0.002), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.008), and histological type (P = 0.011). Pretreatment thrombocytosis was negatively associated with PFS (hazard ratio [HR] = 0.25; 95% CI 0.83, 0.75; P = 0.014) and 3-year OS (HR = 0.03; 95% CI 0.03, 0.27; P = 0.002). CONCLUSIONS: The study suggests that pretreatment thrombocytosis may be a useful predictor of survivals in EOC patients.
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Trastornos de las Plaquetas Sanguíneas/etiología , Carcinoma Epitelial de Ovario/mortalidad , Neoplasias Ováricas/mortalidad , Trombocitosis/epidemiología , Adulto , Anciano , Antígenos de Carbohidratos Asociados a Tumores/sangre , Carcinoma Epitelial de Ovario/sangre , Carcinoma Epitelial de Ovario/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Nigeria/epidemiología , Neoplasias Ováricas/sangre , Neoplasias Ováricas/patología , Recuento de Plaquetas , Periodo Preoperatorio , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Trombocitosis/sangreRESUMEN
OBJECTIVE: Piperacillin/tazobactam (TZP ) is commonly used against multi-resistant nosocomial Pseudomonas infections. While TZP-induced thrombocytopenia is a well-known and easily diagnosed complication, we herein present an unusual case of spontaneous TZP-induced bleeding caused by platelet dysfunction. CASE SUMMARY: A 73-year-old-man experienced severe pulmonary hemorrhage and bloody diarrhea during the treatment with TZP for Pseudomonas aeruginosa ventilator-associated pneumonia. While both platelet count and coagulation tests were normal, platelet functional test revealed severely impaired ADP-dependent platelet aggregation. CONCLUSION: Platelet dysfunction is a little-known mechanism of TZP-induced bleeding. This is the second reported case of TZP-related bleeding that has been attributed to platelet dysfunction, and the first case report that has not been associated with surgery. While thrombocytopenia is easily recognized, this form of TZP-induced bleeding can be detected only by platelet functional tests.
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Trastornos de las Plaquetas Sanguíneas/etiología , Piperacilina/efectos adversos , Anciano , Antibacterianos/efectos adversos , Infección Hospitalaria/tratamiento farmacológico , Humanos , Combinación Piperacilina y Tazobactam , Neumonía Asociada al Ventilador/tratamiento farmacológicoRESUMEN
ANTECEDENTES Y OBJETIVO: La β-talasemia mayor (β-TM) se define como una enfermedad hereditaria relacionada con las células rojas sanguíneas. En los pacientes adultos, los eventos trombóticos se asocian con la talasemia. Así, el objetivo de esta investigación fue examinar algunos de los parámetros hemostáticos, incluyendo la antitrombina III (AT-III), la proteína C (PRC) y la proteína S (PRS), en pacientes β-TM. MÉTODOS: Se seleccionó a 30pacientes β-TM remitidos para un ingreso de seguimiento de rutina en la clínica de talasemia del Centro Especial de Enfermedades Kerman, junto con otros 30 sujetos sanos. Tras el registro y 3 semanas después de la última transfusión, se recogieron especímenes de sangre periférica, y se midió la concentración plasmática de AT-III, PRC y PRS. RESULTADOS: Hemos observado que la concentración de inhibidores naturales de la coagulación (PRC y PRS) estaba ligeramente disminuida en los pacientes β-TM (p < 0,05), mientras que el nivel plasmático de AT-III no era muy diferente en los pacientes β-TM cuando se los comparaba con los sujetos sanos. CONCLUSIÓN: Conforme a los hallazgos obtenidos en el presente trabajo, podríamos considerar los cambios significativos en las PRC, PRS y AT-III, que se observan en pacientes β-TM multitransfundidos, como factores de riesgo críticos para el desarrollo de eventos tromboembólicos futuros a lo largo de su vida
BACKGROUND AND AIM: The β-thalassemia major (β-TM) is defined as a hereditary red blood cell-related disease. Thrombotic events are associated with thalassemia in adult patients. Thus, the present investigation was aimed to examine some hemostatic parameters, including anti thrombin-III (AT-III), protein-C (PRC) and protein-S (PRS) in β-TM patients. METHODS: Thirty B-TM patients who referred for routine follow-up admission to the thalassemia clinic of Kerman Special Disease Center alongside with 30 healthy subjects were selected and enrolled in the present study. Further registration, the peripheral blood specimens were collected after 3 weeks of last transfusion and then the plasma concentrations of AT-III, PRC and PRS were measured in them. RESULTS: We have observed that the concentrations of natural coagulation inhibitors (PRC and PRS) were significantly attenuated in β-TM patients (P<0.05), while the plasma level of AT-III was not remarkably differed in β-TM patients in compare to healthy subjects. CONCLUSION: According to the findings of present work, significant changes in the PRC, PRS and AT-III which could be observed in multi transfused β-TM patients may attribute as critical risk factors for the development of upcoming thromboembolic events in their future life
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Humanos , Masculino , Femenino , Niño , Adolescente , Adulto Joven , Talasemia beta/complicaciones , Tromboembolia/etiología , Trastornos de las Plaquetas Sanguíneas/etiología , Trastornos de las Plaquetas Sanguíneas/sangre , Tromboembolia/sangre , Activación Plaquetaria , Antitrombina III/análisis , Proteína C/análisis , Proteína S/análisisRESUMEN
The aim of this study was to examine the impact of the nonphysiological shear stress (NPSS) on platelet hemostatic function relevant to thrombosis and bleeding in mechanically assisted circulation. Fresh human blood was circulated for four hours in in vitro circulatory flow loops with a CentriMag blood pump operated under a flow rate of 4.5 L/min against three pressure heads (70 mm Hg, 150 mm Hg, and 350 mm Hg) at 2100, 2800, and 4000 rpm, respectively. Hourly blood samples from the CentriMag pump-assisted circulation loops were collected and analyzed for glycoprotein (GP) IIb/IIIa activation and receptor shedding of GPVI and GPIbα on the platelet surface with flow cytometry. Adhesion of platelets to fibrinogen, collagen, and von Willebrand factor (VWF) of the collected blood samples was quantified with fluorescent microscopy. In parallel, mechanical shear stress fields within the CentriMag pump operated under the three conditions were assessed by computational fluid dynamics (CFD) analysis. The experimental results showed that levels of platelet GPIIb/IIIa activation and platelet receptor shedding (GPVI and GPIbα) in the blood increased with increasing the circulation time. The levels of platelet activation and loss of platelet receptors GPVI and GPIbα were consistently higher with higher pressure heads at each increasing hour in the CentriMag pump-assisted circulation. The platelet adhesion on fibrinogen increased with increasing the circulation time for all three CentriMag operating conditions and was correlated well with the level of platelet activation. In contrast, the platelet adhesion on collagen and VWF decreased with increasing the circulation time under all the three conditions and was correlated well with the loss of the receptors GPVI and GPIbα on the platelet surface, respectively. The CFD results showed that levels of shear stresses inside the CentriMag pump under all three operating conditions exceeded the maximum level of shear stress in the normal physiological circulation and were strongly dependent on the pump operating condition. The level of platelet activation and loss of key platelet adhesion receptors (GPVI and GPIbα) were correlated with the level of NPSS generated by the CentriMag pump, respectively. In summary, the level of NPSS associated with pump operating condition is a critical determinant of platelet dysfunction in mechanically assisted circulation.
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Trastornos de las Plaquetas Sanguíneas/etiología , Corazón Auxiliar/efectos adversos , Trastornos Hemostáticos/etiología , Activación Plaquetaria , Trombosis , Adulto , Femenino , Humanos , Hidrodinámica , Masculino , Estrés Mecánico , Adulto JovenRESUMEN
BACKGROUND: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients. METHODS: Blood samples were prospectively collected from level 1 trauma patients at initial presentation, assayed for force of and time to contraction and compared with thrombelastography. Blood from healthy subjects was assayed to establish a reference range. Results from trauma patients were compared with healthy controls and trauma patients that died. RESULTS: The study includes one hundred trauma patients with mean age 45 y, 74% were male, and median injury severity score of 14 ± 12. Patients that survived (n = 90) demonstrated significantly elevated platelet contraction force compared with healthy controls (n = 12) (6390 ± 2340 versus 4790 ± 470 µN, P = 0.043) and trauma patients that died (n = 10) (6390 ± 2340 versus 2860 ± 1830 µN, P = 0.0001). Elapsed time to start of platelet contraction was faster in trauma patients that survived compared with healthy controls (660 ± 467 versus 1130 ± 140 s, P = 0.0022) and those that died (660 ± 470 versus 1460 ± 1340 s, P < 0.0001). CONCLUSIONS: In contrast with all existing platelet function tests reported in the literature, which report platelet dysfunction in trauma patients, contractile force demonstrates hyperfunction in surviving trauma patients and dysfunction in nonsurvivors. Platelet contraction reflects platelet metabolic reserve and thus may be a potential biomarker for survival after trauma. Contractile force warrants further investigation to predict mortality in severely injured trauma patients.
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Trastornos de las Plaquetas Sanguíneas/diagnóstico , Plaquetas/fisiología , Heridas y Lesiones/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Coagulación Sanguínea/fisiología , Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/etiología , Trastornos de las Plaquetas Sanguíneas/fisiopatología , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Pruebas de Función Plaquetaria/métodos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Curva ROC , Tromboelastografía , Heridas y Lesiones/sangre , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Platelet dysfunction (PD) is an independent predictor of mortality in patients with severe traumatic brain injury (sTBI). Platelet transfusions (PLTs) have been shown to be an effective treatment strategy to reverse platelet inhibition. Their use is contingent on availability and may be associated with increased cost and transfusion-related complications, making desmopressin (DDAVP) attractive. We hypothesized that DDAVP would correct PD similarly to PLTs in patients with sTBI. METHODS: This retrospective study evaluated all blunt trauma patients admitted to an urban, level 1 trauma center from July 2015 to October 2016 with sTBI (defined as head abbreviated injury scale [AIS] ≥3) and PD (defined as adenosine diphosphate [ADP] inhibition ≥60% on thromboelastography) and subsequently received treatment. Per our institutional practice, patients with sTBI and PD are transfused one unit of apheresis platelets to reverse inhibition. During a platelet shortage, we interchanged DDAVP for the initial treatment. Patients were classified as receiving DDAVP or PLT based on the initial treatment. RESULTS: A total of 57 patients were included (DDAVP, n = 23; PLT, n = 34). Patients who received DDAVP were more severely injured (injury severity score, 29 vs. 23; p = 0.045), but there was no difference in head AIS (4 vs. 4, p = 0.16). There was no difference between the two groups in admission platelet count (244 ± 68 × 10/µL vs. 265 ± 66 × 10/µL, p = 0.24) or other coagulation parameters such as prothrombin time, partial thromboplastin time, or international normalized ratio. Before treatment, both groups had similar ADP inhibition as measured by thromboelastography (ADP, 86% vs. 89%, p = 0.34). After treatment, both the DDAVP and PLT groups had similar correction of platelet ADP inhibition (p = 0.28). CONCLUSION: In patients with severe traumatic brain injury and PD, DDAVP may be an alternative to PLTs to correct PD. LEVEL OF EVIDENCE: Therapeutic, level IV.
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Trastornos de las Plaquetas Sanguíneas/terapia , Lesiones Traumáticas del Encéfalo/terapia , Desamino Arginina Vasopresina/administración & dosificación , Traumatismos Cerrados de la Cabeza/terapia , Hemostáticos/administración & dosificación , Transfusión de Plaquetas/estadística & datos numéricos , Escala Resumida de Traumatismos , Adulto , Trastornos de las Plaquetas Sanguíneas/sangre , Trastornos de las Plaquetas Sanguíneas/diagnóstico , Trastornos de las Plaquetas Sanguíneas/etiología , Plaquetas/efectos de los fármacos , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/etiología , Femenino , Traumatismos Cerrados de la Cabeza/sangre , Traumatismos Cerrados de la Cabeza/complicaciones , Traumatismos Cerrados de la Cabeza/diagnóstico , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tromboelastografía , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Platelet dysfunction associated with isolated traumatic brain injury (TBI) can be measured using thromboelastography-platelet mapping (TEG-PM). We hypothesized that platelet dysfunction can be detected after blunt TBI, and the degree of dysfunction is associated with increased TBI severity and in-hospital mortality. METHODS: This was a retrospective review of adult trauma patients admitted to a single level 1 trauma center from August 2013 to March 2015 who suffered isolated severe blunt TBI. Subjects were included if they received a TEG-PM within 24â¯h from injury, and excluded if on preinjury antiplatelet medications. RESULTS: 119 subjects were analyzed. Severe TBI subjects (AIS-head 5) had ADPi 18.4 points higher than moderate TBI subjects (AIS-head 3) (pâ¯=â¯0.001). Platelet dysfunction was not associated with TBI progression. ADPi significantly predicted mortality (OR 1.033; 95% CI 1.005-1.061, pâ¯=â¯0.02). CONCLUSION: Platelet dysfunction occurs immediately after isolated blunt TBI, is more pronounced with increasing TBI severity, and is associated with higher odds of in-hospital mortality. Further investigation is needed to determine whether this is a marker of disease severity or a therapeutic target.
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Trastornos de las Plaquetas Sanguíneas/etiología , Lesiones Traumáticas del Encéfalo/complicaciones , Tromboelastografía , Heridas no Penetrantes/complicaciones , Trastornos de las Plaquetas Sanguíneas/mortalidad , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Centros Traumatológicos , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/mortalidadRESUMEN
: Primary myelofibrosis (PMF) is a clonal hematopoietic stem cell disorder characterized by fibrosis of the marrow cavity, marked megakaryocyte atypia and progressive cytopenias. Although thrombosis predominates, bleeding is the primary manifestation in up to 20% of patients and may be life-threatening. In this report, we document restoration of megakaryocyte and platelet structure and function in PMF after allogeneic hematopoietic cell transplantation (HCT). A 59-year-old man presented with recurrent episodes of postoperative bleeding preceding a diagnosis of primary myelofibrosis (PMF). Platelet aggregation and secretion studies showed abnormal responses to all agonists tested (epinephrine, ADP, arachidonic acid, U46619, collagen, ristocetin) despite the presence of thrombocytosis. After an allogeneic HCT, platelet morphology and function studies were all normal. The pathophysiology of platelet dysfunction in myeloid neoplasia is not well understood but, as highlighted in our report, restoration of platelet function by HCT supports a clonal process involving an early hematopoietic progenitor cell.