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The standard of care for patients with acute promyelocytic leukaemia (APL) relapsing after front-line treatment with arsenic trioxide (ATO)-based regimens remains to be defined. A total of 67 patients who relapsed after receiving ATO-based up-front therapy and were also salvaged using an ATO-based regimen were evaluated. The median (range) age of patients was 28 (4-54) years. While 63/67 (94%) achieved a second molecular remission (MR) after salvage therapy, three (4·5%) died during salvage therapy. An autologous stem cell transplant (auto-SCT) was offered to all patients who achieved MR, 35/63 (55·6%) opted for auto-SCT the rest were administered an ATO + all-trans retinoic acid maintenance regimen. The mean (SD) 5-year Kaplan-Meier estimate of overall survival and event-free survival of those who received auto-SCT versus those who did not was 90·3 (5·3)% versus 58·6 (10·4)% (P = 0·004), and 87·1 (6·0)% versus 47·7 (10·3)% (P = 0·001) respectively. On multivariate analysis, failure to consolidate MR with an auto-SCT was associated with a significantly increased risk of relapse [hazard ratio (HR) 4·91, 95% confidence interval (CI) 1·56-15·41; P = 0·006]. MR induction with ATO-based regimens followed by an auto-SCT in children and young adults with relapsed APL who were treated with front-line ATO-based regimens was associated with excellent long-term survival.
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Antineoplásicos/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Gerenciamento Clínico , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia de Salvação , Resultado do Tratamento , Adulto JovemRESUMO
In this work, we present a new method-Thrombodynamics-4D-for the assessment of both plasma and platelet contributions to clotting. Thrombodynamics-4D potentially allows for the determination of plasma or platelet disorders and the effects of various drugs on plasma clotting or on platelet procoagulant function. In this assay, clot formation in platelet-rich plasma or platelet-free plasma supplemented with phospholipids is activated with tissue factor immobilized on a surface. Spatial fibrin clot growth and thrombin concentration dynamics are registered by measuring light scattering of the fibrin clot and fluorescence of the product formed by cleavage of the synthetic fluorogenic substrate by thrombin, respectively. Here, we describe the preanalytical requirements, measurement methodology and calculation principles of assay parameters. Preanalytical and analytical variability and reference ranges of the assay are given. Additionally, we show some clinical examples, which determine the effect of anticoagulants, measure clotting dysfunction in patients with platelet or coagulation disorders and evaluate the effect of surgery.
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Testes de Coagulação Sanguínea/métodos , Coagulação Sanguínea/fisiologia , Fibrina/metabolismo , Fosfolipídeos/metabolismo , Trombina/metabolismo , HumanosRESUMO
In a developing country like India, with limited resources and access to healthcare facilities, dealing with massive hemorrhage is a major challenge. This challenge gets compounded by pre-existing anemia, hemostatic disorders, and logistic issues of timely transfer of such patients from peripheral hospitals to centers with adequate resources and management expertise. Despite the awareness amongst healthcare providers regarding management modalities of bleeding patients, no uniform Patient Blood Management (PBM) or perioperative bleeding management protocols have been implemented in India, yet. In light of this, an interdisciplinary expert group came together, comprising of experts working in transfusion medicine, hematology, obstetrics, anesthesiology and intensive care, to review current practices in management of bleeding in Indian healthcare institutions and evaluating the feasibility of implementing uniform PBM guidelines. The specific intent was to perform a gap analysis between the ideal and the current status in terms of practices and resources. The expert group identified interdisciplinary education in PBM and bleeding management, bleeding history, viscoelastic and platelet function testing, and the implementation of validated, setting-specific bleeding management protocols (algorithms) as important tools in PBM and perioperative bleeding management. Here, trauma, major surgery, postpartum hemorrhage, cardiac and liver surgery are the most common clinical settings associated with massive blood loss. Accordingly, PBM should be implemented as a multidisciplinary and practically applicable concept in India in a timely manner in order to optimize the use the precious resource blood and to increase patients' safety.
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Arsenic trioxide (ATO)-based regimens are the standard of care for treating acute promyelocytic leukaemia (APL) and have replaced chemotherapy-based approaches. However, the cost of "patented" ATO is prohibitive because of patent rights. "Generic" ATO has been used in a few countries, but its implications for health resource utilization (HRU) and cost of treatment are unknown. We hypothesized that treating APL patients using generic ATO (APL-ATO) will be cost effective compared to the chemotherapy-based regimen (APL-CT). In a single-centre retrospective study, we used a bottom-up costing method to compare the direct medical cost of treatment and HRU between APL-ATO and APL-CT. These costs and the survival and relapse probabilities were imputed in a three-state Markov decision model to estimate the cost effectiveness of APL-ATO compared to APL-CT. The mean cost of treatment for APL-ATO (n = 30, $8500 ± 2078) was significantly less than for APL-CT (n = 30, $22 600 ± 5528) (P < 0·001). APL-ATO reduced hospitalization, antibiotic and antifungal usage (P < 0·001). In the Markov model, five-year treatment costs were significantly lower for APL-ATO ($11 131) than for APL-CT ($17 926) (P < 0·001). Treatment cost and health resource utilization were significantly lower for generic ATO-treated APL patients compared to the chemotherapy-based regimen.
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Antineoplásicos/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Análise Custo-Benefício/métodos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/economia , Adulto , Antineoplásicos/farmacologia , Trióxido de Arsênio/farmacologia , Humanos , Estudos RetrospectivosRESUMO
INTRODUCTION: Factor replacement therapy in treatment of haemophilia A is complicated by the production of neutralising antibodies known as inhibitors. The formation of inhibitors is multifactorial being associated with both genetic and environmental factors. AIM: To document the prevalence of inhibitors in severe haemophilia in the community where most patients receive only infrequent episodic replacement therapy and evaluate the factors which could be contributing to it. METHODS: Community based camps were conducted in different parts of the country. Patients were assessed through a structured questionnaire and blood samples were obtained for laboratory evaluation of inhibitors and defined immunological parameters. RESULTS: Inhibitors were present in 87/447 (19.5%) of the evaluated patients. High-titre inhibitor (>5 Bethesda Units [BU]) was identified in 31 (35.6%) patients. HLA DRB1-13-positive cases (RR = 2.04; 95% CI 1.06-3.911; P = 0.033) had an increased risk of inhibitor formation which was retained in the high-titre subset. A decreased risk of inhibitor formation was noted with heterozygous IL4-590 C/T allele (RR = 0.22; 95% CI 0.108-0.442: P = 0.000). There were no significant correlations between any of the evaluated environmental factors and the development of inhibitors in this study. CONCLUSION: The overall prevalence of inhibitors in patients with severe haemophilia A is similar to that reported among patients receiving regular replacement therapy. The data from this study, limited by its retrospective and cross-sectional study design, would suggest that genetic rather than environmental are more likely to impact the development of inhibitors.
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Fator VIII/antagonistas & inibidores , Hemofilia A/patologia , Isoanticorpos/sangue , Adolescente , Adulto , Idoso , Alelos , Criança , Pré-Escolar , Haplótipos , Hemofilia A/epidemiologia , Humanos , Índia/epidemiologia , Interleucina-4/genética , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Polimorfismo de Nucleotídeo Único , Prevalência , Tempo de Protrombina , Adulto JovemRESUMO
Blood coagulation is a delicately regulated space- and time-dependent process that leads to the formation of fibrin clots preventing blood loss upon vascular injury. The sensitivity of the coagulation network was previously investigated without accounting for transport processes. To investigate its sensitivity to coagulation factor deficiencies in a spatial reaction-diffusion system, we combined an in vitro experimental design with a computational systems biology model. Clot formation in platelet-free plasma supplemented with phospholipids was activated with identical amounts of tissue factor (TF) either homogeneously distributed (concentration 5 pM, homogeneous model) or immobilized on the surface (surface density 100 pmole/m2, spatially heterogeneous model). Fibrin clot growth and thrombin concentration dynamic in space were observed using video microscopy in plasma of healthy donors or patients with deficiencies in factors (F) II, FV, FVII, FVIII, FIX, FX, or FXI. In the spatially heterogeneous model, near-activator thrombin generation was decreased in FV-, FVII-, and FX-deficient plasma. In the homogeneous model, clotting was not registered in these samples. The simulation and experiment data showed that the coagulation threshold depended on the TF concentration. Our data indicate that the velocity of spatial clot propagation correlates linearly with the concentration of thrombin at the clot wave front but not with the overall thrombin wave amplitude. Spatial clot growth in normal plasma at early stages was neither reaction nor diffusion limited but became diffusion limited later. In contrast, clot growth was always diffusion limited in FV-, FVII-, and FX-deficient plasma and reaction limited in FVIII-, FIX-, and FXI-deficient plasma. We conclude that robustness of the spatially heterogeneous coagulation system was achieved because of the combination of 1) a local high TF surface density that overcomes activation thresholds, 2) diffusion control being shared between different active factors, and 3) an early saturated stimulus-response dependence of fibrin clot formation by thrombin.
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Coagulação Sanguínea , Fibrina/metabolismo , Modelos Biológicos , Trombina/metabolismo , Fatores de Coagulação Sanguínea/metabolismo , Difusão , Humanos , CinéticaRESUMO
BACKGROUND:: The diagnosis of sepsis is challenging in the absence of a gold standard test. Recent studies have explored the role of neutrophil and monocyte volume, conductivity, and scatter (VCS), derived from automated hematology analyzers, in diagnosing sepsis. We assessed the diagnostic accuracy of VCS parameters in critically ill patients with sepsis. METHODOLOGY:: In this prospective study, VCS parameters, procalcitonin, and C-reactive protein (CRP) were assessed in patients with proven sepsis (cases) and 2 control groups (intensive care unit [ICU] patients without sepsis and healthy blood donors). The diagnostic property of each test was explored by calculating sensitivity, specificity, negative and positive predictive values, and area under the curve (AUC). RESULTS:: The study included 65 patients with sepsis, 58 nonseptic ICU controls, and 98 blood donors. Procalcitonin and CRP were not significantly different ( P > .06) between patients with sepsis and nonseptic patients. Mean (95% confidence interval [CI]) neutrophil volume (MNV) was significantly higher ( P < .001) in patients with sepsis (165.5; 95%CI 161.6-169.4) than in nonseptic (157.3; 95%CI 154.6-160.1) patients and donors (148.9; 95%CI 147.9-150). A similar pattern was seen with mean monocyte volume (MMoV). Neutrophil and monocyte conductivity and scatter parameters were variably associated. The AUC was highest for MMoV (0.74) and lowest for CRP (0.62). Among all parameters, MNV and MMoV had the highest specificity of 85% and 80%, respectively. CONCLUSION:: In critically ill patients with suspected sepsis, VCS parameters may help strengthen the diagnostic probability of sepsis. Future studies may explore the role of serial monitoring of VCS to track response to antimicrobial therapy.
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Técnicas Citológicas , Monócitos/citologia , Neutrófilos/citologia , Sepse/diagnóstico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Estudos Prospectivos , Sensibilidade e Especificidade , Sepse/sangue , Adulto JovemRESUMO
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders related to hematopoietic stem and progenitor cell dysfunction. Several studies have shown the role of the bone marrow microenvironment in regulating hematopoietic stem, and progenitor function and their individual abnormalities have been associated with disease pathogenesis. In this study, we simultaneously evaluated hematopoietic stem cells (HSC), hematopoietic stem progenitor cells (HSPCs) and different stromal elements in a cohort of patients with MDS-refractory cytopenia with multilineage dysplasia (RCMD). Karyotyping of these patients revealed variable chromosomal abnormalities in 73.33% of patients. Long-term HSC and lineage-negative CD34+CD38- cells were reduced while among the HPCs, there was an expansion of common myeloid progenitor and loss of granulocyte-monocyte progenitors. Interestingly, loss of HSCs was accompanied by aberrant frequencies of endothelial (ECs) (CD31+CD45-CD71-) and mesenchymal stem cells (MSCs) (CD31-CD45-71-) and its subsets associated with HSC niche. We further demonstrate down-regulation of HSC maintenance genes such as Cxcl12, VEGF in mesenchymal cells and a parallel upregulation in endothelial cells. Altogether we report for the first time quantitative and qualitative de novo changes in hematopoietic stem and its associated niche in a cohort of MDS-RCMD patients. These findings further reinforce the role of different components of the bone marrow microenvironment in MDS pathogenesis and emphasize the need for comprehensive simultaneous evaluation of all niche elements in such studies.
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Células-Tronco Hematopoéticas/patologia , Síndromes Mielodisplásicas/patologia , Nicho de Células-Tronco , Medula Óssea/patologia , Linhagem da Célula , Aberrações Cromossômicas , Células Endoteliais/patologia , Humanos , Células-Tronco Mesenquimais/patologia , Células Progenitoras Mieloides/patologia , Células Estromais/patologiaRESUMO
BACKGROUND: Low-volume plasma exchange (PLEX) and low-dose steroid improve survival in severe alcoholic hepatitis. We aimed to compare one-year survival of very severe alcoholic hepatitis (VSAH) patients treated with centrifugal PLEX (cPLEX), membrane PLEX (mPLEX) or standard medical treatment (SMT). METHODS: We retrospectively analyzed survival in consecutive VSAH patients treated at our department from November 2017 to September 2021. PLEX patients received low-volume PLEX along with low-dose steroid (tab. prednisolone 10 mg or 20 mg daily). To adjust for baseline differences between the three treatment (cPLEX, mPLEX or SMT) groups, propensity score (PS) matching was done. Acute-on-chronic liver failure (ACLF) was defined as per European Association for the Study of the Liver (EASL). The primary study outcome was one-year transplant-free survival of PS-matched VSAH patients treated with cPLEX compared to SMT. RESULTS: Of 101 PLEX-eligible VSAH patients, 30 patients were treated with cPLEX, 21 with mPLEX and 50 with SMT. On comparing 30 PS-matched patients each in the cPLEX group vs. the SMT group, transplant-free survival in the cPLEX group was 86.7% at one month, 70% at three months and 52.4% at one year and in the SMT group was 33.3% at one month, 23.3% at three months and 16.7% at one year with hazard ratio (HR [95% CI]) in favor of the cPLEX group (0.29 [0.15-0.56], p < 0.001). Total 21 patients each (PS-matched) in cPLEX and mPLEX groups were compared and one-year survival was better with cPLEX (0.33 [0.16-0.69], p = 0.001). The sub-group analysis of VSAH (PS-matched cohort) patients with ACLF also showed better survival with cPLEX compared to SMT (0.38 [0.17-0.83], p = 0.003) and compared to mPLEX (0.43 [0.17-0.95], p = 0.03). CONCLUSION: Better one-year transplant-free survival was noted among PS-matched VSAH patients treated with cPLEX (and low-dose steroid) compared to SMT (without steroid).
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Evidence on agreement of point-of-care (POC) INR testing with laboratory testing in APS patients on oral anticoagulation (OAC), is scarce. This study assessed agreement of paired PT INR testing by a POC device vs. conventional platform-based laboratory test, in APS patients on OAC using a pre-determined definition of agreement. Simultaneous paired PT INR estimation in 92 APS patients was carried out, during October 2020-September 2021. POC INR was performed on capillary blood (pin prick) using the qLabs® PT-INR hand-held device, while laboratory INR estimation was performed using citrated blood (venepuncture) on STA-R Max Analyzer® using STA-NeoPTimal thromboplastin reagent®. Concordance was defined no greater than ± 30% (as per international standards ISO 17593:2007 guidelines) for each paired INR estimation. Agreement between the two was defined as ≥ 90% of paired INR measurements being concordant. 211 paired estimations were performed, within which 190 (90%) were concordant. Good correlation was seen between the 2 methods of INR estimation on Bland Altman plot analysis with an Intra-class correlation coefficient (95% CI) of 0.91(0.882, 0.932). Lab INR range > 4 (P = 0.001) was a significant predictor of higher variability between both methods of INR estimation. Lupus anti-coagulant, other anti-phospholipid antibodies (APL) or triple APL positivity did not result in any statistically significant variation in paired measurements. This study demonstrated good correlation between POC INR measurement and Lab INR estimation and agreement was ascertained between the 2 methods in APS patients on OAC.
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BACKGROUND: Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. OBJECTIVES: We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). METHODS: Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8 h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12 reaction units (PRUs) 1 h after the medication loading dose was also determined. RESULTS: The PRU and percentage inhibition median (interquartile range) at 1 h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p = 0.990, p = 0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p < 0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p = 0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. CONCLUSIONS: The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.
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Síndrome Coronariana Aguda , Plaquetas , Humanos , Ticagrelor/uso terapêutico , Clopidogrel/uso terapêutico , Síndrome Coronariana Aguda/tratamento farmacológico , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico , Adenosina/farmacologia , Adenosina/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Resultado do Tratamento , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Antagonistas do Receptor Purinérgico P2Y/uso terapêuticoRESUMO
OBJECTIVE: Non-cirrhotic intrahepatic portal hypertension (NCIPH), a portal microangiopathy affecting small portal vein radicles, is a disease of Indian sub-continent. NCIPH appears to be a complex disease with interactions between inherited and acquired factors, though the exact pathophysiological mechanism is unknown. We aimed at investigating the genetic variants that might contribute to susceptibility to NCIPH. METHODS: In this case-control study, we analyzed genes associated with microangiopathy-VWF-ADAMTS13 (von Willebrand factor and its cleavase enzyme - a disintegrin and matrix metalloprotease with thrombospondin type-1 motifs member 13) and alternative complement system vitamin B12 metabolism and with familial NCIPH. RESULT: Eighty-four Indian patients with liver biopsy-proven NCIPH (cases) and 103 healthy controls (matched for residential region of India) were included in the study. Targeted next-generation sequencing (NGS) panel, comprising 11 genes of interest, was done on 54 cases. Genotyping of selected variants was performed in 84 cases and 103 healthy controls. We identified variants in MBL2, CD46 and VWF genes either associated or predisposing to NCIPH. We also identified a single case with a novel compound heterozygous mutation in MBL2 gene, possibly contributing to development of NCIPH. CONCLUSION: In this first of a kind comprehensive gene panel study, multiple variants of significance have been noted, especially in ADAMTS13-VWF and complement pathways in NCIPH patients in India. Functional significance of these variants needs to be further studied.
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Activated platelets provide phospholipid surface and secrete coagulation factors, enhancing blood clotting. We investigated the role of platelets in the regulation of blood coagulation spatial dynamics. We activated blood clotting with tissue factor-bearing (TF) surface in platelet-rich plasma (PRP) or platelet-free plasma (PFP). When blood coagulation was initiated by high TF density, clot growth rate (V) in PRP (2 × 105/µL platelets) was only 15 % greater than in PFP. Spatial distribution of thrombin in PRP had a peak-like shape in the area of the fibrin clot edge, while in PFP thrombin was distributed in the shape of descending plateau. Platelet inhibition with prostaglandin E1 or cytochalasin D made spatial thrombin distribution look like in the case of PFP. Inhibition of blood coagulation by natural endogenous inhibitor heparin was diminished in PRP, while the effect of the exogenous or artificial inhibitors (rivaroxaban, nitrophorin, hirudin) remained undisturbed in the presence of platelets. Ten times decrease of the TF surface density greatly depressed blood coagulation in PFP. In PRP only clotting initiation phase was, while the propagation phase remained intact. Coagulation factor deficiency greatly reduced amount of thrombin and decreased V in PFP rather than in PPR. Thus, platelets were redundant for clotting in normal plasma under physiological conditions but provided robustness of the coagulation system to the changes in initial conditions.
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Plasma Rico em Plaquetas , Trombose , Humanos , Trombina/farmacologia , Coagulação Sanguínea , Plaquetas/fisiologia , Fatores de Coagulação Sanguínea , TromboplastinaRESUMO
BACKGROUND: Coated-platelets are sub-population of platelets "coated" with highly procoagulant proteins and phosphatidylserine that sustains thrombin generation. They are produced upon dual agonist stimulation by collagen and thrombin. This study was conducted to assess if there was any difference in the levels of coated-platelets in patients with primary intracranial hemorrhage (PICH) and ischemic stroke due to large artery atherosclerosis (LAA) as compared to healthy controls, and to see if coated-platelet levels had any influence on the hemorrhagic transformation (HT) of ischemic stroke. METHODS: Coated-platelet levels were determined by flow cytometry using fluorescently tagged Annexin V antibody to identify phosphatidylserine exposed on the surface of platelets activated by dual agonists (convulxin and thrombin) in cross-sectional cohort of 75 patients with stroke and 34 controls. RESULTS: Patients with PICH (n = 35) had significantly lower coated-platelets than the controls (adjusted mean ± SE, 21.0 ± 1.9% vs. 36.1 ± 1.7%, p < 0.001), while patients with LAA (n = 30) had significantly higher coated-platelets than controls (adjusted mean ± SE, 51.9 ± 1.5% vs. 36.1 ± 1.7%, p < 0.001). Patients with subsequent HT of ischemic stroke (n = 10) had significantly lower coated-platelet levels at admission compared to those without HT (adjusted mean ± SE, 18.1 ± 2.6% vs. 51.9 ± 1.5%, p < 0.001). CONCLUSIONS: Coated-platelet levels are significantly different in patients with hemorrhagic and ischemic stroke as compared with controls. Lower levels of coated-platelets measured by flow cytometry may be earliest predictor of subsequent HT in patients with ischemic stroke even before the radiological changes suggestive of HT are visualized.
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AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Biomarcadores/metabolismo , Plaquetas/metabolismo , Estudos Transversais , Citometria de Fluxo , Humanos , AVC Isquêmico/diagnóstico , Fenótipo , Fosfatidilserinas/metabolismo , Ativação Plaquetária , Acidente Vascular Cerebral/diagnóstico , Trombina/metabolismo , Trombose/metabolismoRESUMO
BACKGROUND AND AIM: The dietary profiles of patients with type 2 diabetes mellitus (T2DM) from Southern India have been infrequently studied. We aimed to study the differences in dietary intake of macro and micronutrients in elderly patients of Type 2 diabetes mellitus (T2DM), with and without foot ulcers. METHODS: Elderly patients with T2DM and foot ulcers (n = 79; mean age: 60.6 years) and those without foot ulcers (n = 59; mean age: 55.0 years) were studied. Biochemical evaluation for measures of glycemia, lipids and albumin were done and staging of foot ulcers was done using Wagner's scale. A 24-hour dietary recall was administered to quantify the mean daily intake (MDI) of macro, micronutrients and trace elements from portion sizes of food items consumed and compared to the recommended dietary allowance (RDA) for Indians aged 55 years and above. RESULTS: In patients with T2DM and foot ulcers, the MDI of carbohydrates, fats and phosphorus were significantly higher whereas the MDI of proteins and micronutrients namely zinc, folic acid, iron and carotene were lower than the RDA. Elderly patients with nephropathy and longer duration of T2DM have higher odds of developing foot ulcers, when compared to patients without foot ulcers. CONCLUSION: Elderly patients with T2DM and foot ulcers were deficient in dietary intake of proteins and micronutrients inclusive of carotene, folic acid, zinc, and Iron. Clinical care, regular monitoring of dietary intake and appropriate correction of nutritional deficiencies will aid in the management of diabetic foot ulcers.
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Diabetes Mellitus Tipo 2 , Pé Diabético , Idoso , Diabetes Mellitus Tipo 2/complicações , Ingestão de Alimentos , Humanos , Micronutrientes , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Background: Alcohol-related acute on chronic liver failure (A-ACLF) patients have high short-term mortality and are poor candidates for steroid therapy. Plasma exchange (PLEX) improves survival in ACLF patients. We analyzed our experience with low volume PLEX (50% of plasma volume exchanged per session) and low dose steroids to treat A-ACLF patients. Methods: We retrospectively compared the efficacy of low volume PLEX and low-dose steroids with standard medical treatment (SMT) in A-ACLF patients treated at our center between November 2017 to June 2019. The primary study outcome was one-year survival. Results: Twenty-one A-ACLF patients in PLEX group [age 40 (29-56) years, median (range); MELD score 31 (29-46)] and 29 A-ACLF patients in SMT group [age 41.5 (28-63) years, MELD score 37 (21-48)] were studied. All 50 study patients had severe alcoholic hepatitis [mDF 84.7 (50-389)]. PLEX group patients had 3 (1-7) PLEX sessions with 1.5 (1.4-1.6) liters of plasma exchanged per session and oral Prednisolone 20 mg daily, tapered over 1 month. Kaplan Meier analysis showed better survival over 1 year in the PLEX group compared to the SMT group (P = 0.03). There was renal dysfunction in 10 patients in the PLEX group, which normalized in six patients after PLEX. Conclusion: In this preliminary report, compared to SMT, low volume PLEX and low dose steroid improved survival over one year in A-ACLF patients with severe alcoholic hepatitis. In patients with renal dysfunction, 60% showed improvement in renal function with PLEX. Studies with a larger number of patients are needed to validate these results.
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CONTEXT: Hemophilia A is classified as mild, moderate, and severe based on Factor VIII levels (FVIII). Clot-based assays only detect initiation of thrombin generation, hence FVIII levels may not accurately predict the bleeding risk in all hemophilia patients. The entire process of thrombin generation as measured by global hemostasis tests like activated partial thromboplastin time clot waveform analysis (APTT CWA) and thrombin generation test (TGT) may reflect the actual bleeding phenotype. AIMS: To assess the utility of TGT and CWA as a screening tool to identify bleeders and to evaluate the bleeding phenotype in Hemophilia A. SETTINGS AND DESIGN: Prospective, observational study of 147 consecutive patients referred for coagulation workup. SUBJECTS AND METHODS: Bleeding assessment tool was used to identify bleeders. Patients were classified as severe and nonsevere bleeders based on clinical criteria. TGT was performed by calibrated automated thrombogram, CWA by photo-optical coagulometer and factor levels by one stage clot-based assays. STATISTICAL ANALYSIS USED: The Kruskal-Wallis test with post-hoc analysis was done to examine the difference in CWA/TGT parameters amongst hemophilia classified by FVIII levels. Receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic accuracy of CWA and TGT in discriminating between clinically severe vs nonsevere bleeders. RESULTS: Using ROC derived cut-offs of min1, min2 and peak height of thrombin (PH), the sensitivity (min1:91.67%, min2:91.67%, PH: 97.22%, FVIII: 86.11%) and specificity (min1:100%, min2:100%, PH: 90.91%, FVIII: 90.91%) of CWA/TGT was superior to FVIII to distinguish between clinically severe vs nonsevere bleeders. Phenotypic heterogeneity of bleeding severity was identified in our study population. Clinical severity correlated with CWA/TGT parameters instead of FVIII levels. CONCLUSIONS: CWA and TGT are more effective tools than conventional factor assays to identify clinically severe bleeders and tailor prophylaxis as per bleeding phenotype.
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Hemorragia/metabolismo , Tempo de Tromboplastina Parcial/normas , Fenótipo , Trombina/análise , Trombose , Testes de Coagulação Sanguínea/normas , Hemofilia A/diagnóstico , Hemorragia/classificação , Humanos , Tempo de Tromboplastina Parcial/métodos , Estudos Prospectivos , Curva ROC , Trombina/metabolismoRESUMO
INTRODUCTION: We previously showed that patients with chronic kidney disease (CKD) Stage G4-5 have normal bleeding times. This made us question whether hemodialysis (HD) initiation was really necessary solely to improve platelet function. METHODS: In this prospective observational study, two 5 ml citrated blood samples and one 2 ml EDTA blood sample were collected from incident HD patients fulfilling inclusion criteria prior to HD initiation (baseline sample) and after three sessions of short duration, low flow, counter-current HD. In each instance, one sample was used to perform Collagen adenosine diphosphate closure time (CADPCT) using the Platelet function analyzer (PFA 200, normal range 68-142 seconds) and the second for light transmission aggregometry (LTA) with ADP as agonist (normal ≥50%). RESULTS: This study included 20 patients between October 2017 and February 2019. Overall, and in the subgroup with normal baseline CADPCT or LTA, there was no statistically significant improvement after HD. However, of the 30% of patients who had an abnormal baseline CADPCT, 50% attained a normal value after three HD sessions, and the overall reduction in CADPCT in this group was statistically significant (P = 0.02). Of those with a baseline normal CADPCT, 21% developed abnormal prolongation post HD. CONCLUSION: HD for the sole purpose of improving platelet function is only of benefit in the subgroup of patients with an abnormal CADPCT at baseline, with close to 50% normalizing their platelet function after three sessions of low flow, short duration, counter-current HD.
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BACKGROUND: Coagulation abnormalities are not infrequent in sepsis. It is unclear if abnormalities in thromboelastogram (TEG) are associated with mortality in patients with severe sepsis without overt bleeding. MATERIALS AND METHODS: In this prospective study, patients were categorised as those with normal coagulation, hypercoagulable or hypercoagulable state based on admission TEG parameters (R time, K time, Maximum amplitude (MA), α angle). Their association with mortality was explored using Fisher's exact and Mann-Whitney U test as appropriate. RESULTS: The study cohort (n = 87; 49 male) with median (IQR) age 51 (42-60) years and admission SOFA score 8 (6-11) included scrub typhus (24.1%), pneumonia (22.6%) and urosepsis (10.3%). Non-invasive and invasive ventilation and vasopressors were required in 28.1%, 68.9% and 74%, respectively. Mortality was 24.1%. Based on R time, K time and α angle, 3.5% to 9.3% had a hypercoagulable state and 26.7 to 29.9% were hypocoagulable. Prolonged R time (p = 0.04) and reduced alpha angle (p = 0.01) in patients with hypocoagulable state was associated with mortality. K time, α angle and MA were significantly different in patients requiring transfusion (p < 0.001). CONCLUSION: A subset of patients with severe sepsis without overt bleeding are hypocoagulable. Hypocoagulability is associated with mortality and need for transfusion.