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Introduction: Hospital-acquired venous thromboembolism (VTE) is a major cause of preventable deaths. Incidence of VTE and adequacy of thromboprophylaxis have rarely been reported in low-resourced countries. The aim of this study was to estimate the incidence of VTE and to evaluate the adequacy of thromboprophylaxis in acutely-ill medical hospitalized patients., Methods: The PROFMiG is a prospective cohort study conducted in Brazil. We consecutively enrolled adult (> 18 years) acutely-ill hospitalized medical patients at admission. Risk assessment for VTE was evaluated by the IMPROVE7 (International Medical Prevention Registry on Venous Thromboembolism). Outcomes were death and VTE events during hospital stay up to 90 days after discharge. All VTE and death events were adjudicated. We also evaluated pulmonary embolism-related death and adequacy of thromboprophylaxis. VTE incidence was estimated by competing risk methods., Results: A total of 2380 participants was included. Median age was 70 years, 56.1 % women, median length of hospital stay was 10 days. A total of 2052 (86.3 %) patients were classified as low-risk for VTE, 30 (1.3 %) patients had objectively confirmed VTE, and 1449 (60.8 %) received inadequate thromboprophylaxis. The overall mortality rate was 14.0 %. Cumulative incidence of VTE was 2.0 % (95 % confidence interval 0.9 %-3.8 %) at 130 days after admission when considering death as competing risk., Conclusion: The cumulative incidence of VTE in this cohort corroborates with that reported in high-resourced countries. Despite recommendation, thromboprophylaxis was mostly inadequate. We suggest the adoption of competing risk analysis to estimate the cumulative incidence of VTE in hospitalized patients., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the conceptualization of the study, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Up to about 60% of venous thromboembolic events in a community are associated with hospitalization, and most can be prevented by appropriate thromboprophylaxis. Several randomized clinical trials and guidelines have addressed the issue of thromboprophylaxis in hospitalized patients and recommended strategies to assess patients' risk and thromboprophylaxis. Simple and validated risk assessment models are available to assist physicians in selecting patients who are at high risk for VTE, in whom thromboprophylaxis should be used. However, some concepts employed are imprecise or not appropriately defined. Indeed, there has been wide variation in the onset, duration, and adequacy of thromboprophylaxis, as well as in the definition of some risk factors. In this article, we highlight these issues and the unmet definitions in thromboprophylaxis in hospitalized patients mainly by addressing selected randomized clinical trials and guidelines., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objectives: To analyze the inter-observer reliability of risk for venous thromboembolism (VTE) in a population of adult acutely-ill medical patients., Methods: In this prospective cohort study, we collected risk factors and risk classification for VTE using RAM IMPROVE7. Kappa statistics was used to evaluate inter-observer reliability between lead clinicians and trained researchers. We evaluated occurrence of VTE in patients with mismatched classification., Results: We included 2,380 patients, median age 70 years (interquartile range [IQR], 58-79), 56.2% female. Adjusted Kappa for VTE risk factors ranged from substantial (0.64, 95% confidence interval [CI], 0.61-0.67) for "immobilization", to almost perfect (0.98; 95% CI 0.97-0.99) for "thrombophilia"; risk classification was 0.64 (95% CI 0.60-0.67). Divergent risk classification occurred in 434 patients (18.2%) of whom seven (1.6%) developed VTE., Conclusion: Despite substantial to almost perfect reliability between observers for risk factors and risk classification, lead clinicians tended to underestimate the risk for VTE.

Background: Intravenous thrombolysis (IVT) for lacunar stroke (LS) is debated, as the underlying pathophysiological mechanism may not be thrombogenic., Aims: To investigate outcomes after IVT in LS in the SITS International Stroke Thrombolysis Register and perform a meta-analysis., Methods: LS was identified by both baseline NIHSS-subscores and discharge ICD-10 codes, and contrasted by IVT to non-IVT treated. IVT patients were predominantly from Europe, non-IVT patients predominantly from South America and Asia. Outcome measurements were functional independence (modified Rankin Scale [mRS] score ≤2), excellent outcome (mRS ≤ 1), and mortality at three months. Matched-control comparisons of symptomatic intracerebral hemorrhage (SICH) between IVT-treated LS and IVT-treated non-LS patients were performed. Additionally, we performed a meta-analysis., Results: Median age for IVT-treated LS patients ( n  = 4610) was 66 years vs. 64 years and NIHSS score was 6 vs. 3, compared to non-IVT-treated LS ( n  = 1221). Univariate outcomes did not differ; however, IVT-treated LS patients had higher adjusted odds ratios (aOR) for functional independence (aOR = 1.65, 95% CI = 1.28-2.13) but similar mortality at three months (aOR = 0.57, 0.29-1.13) than non-IVT-LS. Propensity-score matched analysis showed that IVT-treated LS patients had a 7.1% higher chance of functional independency than non-IVT LS patients ( p  < 0.001). IVT-treated LS patients had lower odds for SICH (aOR = 0.33, 0.19-0.58 per SITS, aOR = 0.40, 0.27-0.57 per ECASS-2) than matched non-LS controls, which was mirrored in the meta-analysis., Conclusions: Our adjusted results show that IVT treatment in LS patients was associated with better functional outcome than non-IVT-treated LS and less SICH than IVT-treated non-LS patients.

Background and Purpose: Standardized registries may provide valuable data to further improve stroke care. Our aim was to obtain updated information about characteristics of stroke patients and management of stroke across the Ibero-American countries, using a common in-hospital registry (Safe Implementation of Treatments in Stroke–Sociedad Iberoamericana de Enfermedades Cerebrovasculares) as a basis for further quality improvement., Methods: Data for this study were entered into the Safe Implementation of Treatments in Stroke registry from September 2009 to December 2013 by 58 centers in 14 countries. Data included demographics, risk factors, onset-to-door time, National Institutes of Health Stroke Scale score, stroke subtype, ischemic stroke etiology, treatments, 3-month mortality, and modified Rankin Scale score. Time to treatment was also recorded for patients treated with thrombolysis., Results: Five thousand four hundred one patients were registered; median age, 65 years; 46% women; 3915 (72.5%) ischemic strokes; 686 (13.7%) hemorrhagic strokes; 213 (4.3%) subarachnoid hemorrhages; 414 (8.3%) transient ischemic attacks; and 31 (0.6%) cerebral vein thrombosis. The most prevalent risk factors were hypertension (71.3%), dyslipidemia (35.2%), and diabetes mellitus (23.6%). Atrial fibrillation was present in 15.1%. Three hundred one ischemic strokes were treated with intravenous thrombolysis (IVT; 7.7%). Patients undergoing IVT were more severely affected (median baseline National Institutes of Health Stroke Scale score, 11 versus 6). The rate of symptomatic intracerebral hemorrhages after IVT was 5.7%. At 3 months, 60.3% of IVT-treated patients and 59.1% of untreated patients were independent (modified Rankin Scale score, 0–2). Mortality was 11.4% in treated and 12.8% in untreated patients., Conclusions: Safe Implementation of Treatments in Stroke–Sociedad Iberoamericana de Enfermedades Cerebrovasculares is the largest registry of a general stroke population and the first study to evaluate the level of IVT use in Ibero-America. It provides valuable information that may help to improve the quality of stroke care in the Ibero-American region., (© 2019 American Heart Association, Inc.)

Venous thrombosis (VT) is a preventable cause of death in hospitalized patients. The main strategy to decrease VT incidence is timely thromboprophylaxis in at-risk patients. We sought to evaluate the reliability of risk assessment model (RAM) data, the incremental usefulness of additional variables and the modelling of an adjusted score (the NAVAL score). We used the RAM proposed by Caprini for initial assessment. A 5 % systematic sample of data was independently reviewed for reliability. We evaluated the incremental usefulness of six variables for VT during the score modelling by logistic regression. We then assessed the NAVAL score for calibration, reclassification and discrimination performances. We observed 11,091 patients with 37 (0.3 %) VT events. Using the Caprini RAM, high-risk and moderate-risk patients were respectively associated with a 17.4 (95 % confidence interval [CI] 6.1-49.9) and 4.2 (95 % CI 1.6-11.0) increased VT risk compared with low-risk patients. Four independent variables were selected for the NAVAL score: "Age", "Admission clinic", "History of previous VT event" and "History of thrombophilia". The area under the receiver-operating-characteristic curve for the NAVAL score was 0.72 (95 % CI 0.63-0.81). The Net Reclassification Index (NRI) for the NAVAL score compared with the Caprini RAM was -0.1 (95 % CI -0.3 to 0.1; p = 0.28). We conclude that the NAVAL score is a simplified tool for the stratification of VT risk in hospitalized patients. With only four variables, it demonstrated good performance and discrimination, but requires external validation before clinical application. We also confirm that the Caprini RAM can effectively stratify VT risk in hospitalized patients in our population.

Background: Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available., Objectives: To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives., Search Methods: Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions., Selection Criteria: We selected studies including healthy women taking COC with VT as outcome., Data Collection and Analysis: The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies., Main Results: 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk., Authors' Conclusions: All combined oral contraceptives investigated in this analysis were associated with an increased risk of venous thrombosis. The effect size depended both on the progestogen used and the dose of ethinylestradiol. Risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate and drospirenone were similar, and about 50-80% higher than with levonorgestrel. The combined oral contraceptive with the lowest possible dose of ethinylestradiol and good compliance should be prescribed-that is, 30 μg ethinylestradiol with levonorgestrel.

The aim of the study was to evaluate patient characteristics associated with pharmacologic thromboprophylaxis (PTP) use/nonuse in a general tertiary hospital cohort. Eligible patients were classified according to venous thromboembolism (VTE) risk category by trained nurses. Either standard or low-molecular weight heparin was recommended to intermediate or high-risk VTE patients. Adopting the recommended PTP was at the physician's discretion. At discharge, PTP use was recorded. PTP was recommended to 10,016 patients, of whom 2165 (21.6%) received the recommended thromboprophylaxis. In the multivariate logistic regression, PTP use/nonuse remained independently associated with female sex [odds ratio (OR) 0.75; 95% confidence interval (CI) 0.68-0.84], age (OR 1.04; 95% CI 1.03-1.04), being admitted to the Gynecology-Obstetrics (OR 0.31; 95% CI 0.25-0.39) or surgery (OR 1.26; 95% CI 1.12-1.42), thrombophilia (OR 5.15; 95% CI 2.04-12.98), previous VTE event (OR 2.98; 95% CI 1.78-4.98), diabetes (OR 1.84; 95% CI 1.61-2.10), acute myocardial infarction (OR 5.87; 95% CI 4.81-7.17), and admission to a major orthopedic surgery (OR 3.03; 95% CI 1.98-4.64). PTP in this hospital population was grossly underused. Eight independent variables predicted use/nonuse of PTP. Targeting variables related to the use and nonuse of PTP is important to direct the application of thromboprophylaxis.

Pulmonary embolism is a serious and potentially fatal disorder. Pulmonary embolism risk stratification may allow early hospital discharge and outpatient treatment for low-risk patients. Also, it may prevent death by early medical intervention in high-risk groups. We evaluated objectively confirmed pulmonary embolism in 126 patients by multidetector computed tomographic pulmonary angiography at a single center from January 2008 to January 2010. The Pulmonary Severity Embolism Index (PESI), the right ventricle (RV) to left ventricle (LV) diameter (RV/LV) ratio and the vascular obstruction index (VOI) were derived from data extracted from electronic hospital records and image database. A total of six out of 96 patients (6.3%) died during follow-up. There was an association between PESI and mortality (P-value < 0.001 χ² test). PESI class I-II had a 100% negative predictive value for death in 90 days. No association was found between the RV/LV ratio, the VOI and mortality (P-value > 0.05 χ² test). Also, no association was found between the RV/LV ratio and the VOI and PESI (P-value > 0.05 χ² test). PESI is an accurate tool for pulmonary embolism prognostic stratification. It safely discriminates low-risk from high-risk patients regarding death outcome. We were unable to demonstrate an association between image scores and mortality.

Introduction: Tissue factor (TF) is the main physiological initiator of blood coagulation; it is membrane-bound on monocytes (mTF) and free in plasma (pTF). Abnormal expression of TF by monocytes has been implicated in various diseases. We therefore quantified monocytes expressing TF and pTF levels in patients with lower-limb deep venous thrombosis (DVT)., Materials and Methods: DVT was confirmed by Duplex Scan. Blood mTF levels under resting condition (baseline), after incubation without (unstimulated) and with (stimulated) lipopolysaccharide (LPS), and total mTF levels were determined by flow cytometry using two analytical methods (Histogram and Quadrant-Statistics). Plasma TF levels were measured using an enzyme-linked immunoabsorbent assay (ELISA). Results were compared with age-matched controls., Results: Histogram analysis in patients with DVT showed significantly elevated mTF levels for baseline, unstimulated and total mTF over controls. For Quadrant-Statistics, DVT patients also showed significantly raised baseline, unstimulated, stimulated and total mTF. Similarly, pTF levels were significantly raised in subjects with DVT compared to controls. Baseline mTF levels correlated with pTF levels by Histogram and Quadrant-Statistics analysis. Using the relative operating characteristic (ROC) curve, baseline mTF and pTF assays displayed sensitivity and specificity in detecting DVT. Quadrant-Statistics baseline mTF and pTF gave the best discrimination., Conclusions: The TF assays used in this study showed acceptable sensitivity and specificity and are cost-effective and practical. Therefore, they should be considered in patients with, or at risk of, DVT.

Background: Mutations in factor V (factor V Leiden-G1691A) and prothrombin (G20210A) genes are important risk factors for thrombophilia due to their high incidence in patients with thromboembolic events, especially among the young. However, it is not clear if levels of hypercoagulability markers are significantly altered in asymptomatic young carriers of factor V Leiden or prothrombin G20210A., Methods: Hemostatic status of 32 asymptomatic young individuals carrying these mutations and of 18 normal control individuals was investigated through the determination of plasma thrombomodulin (TM), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and D-dimer., Results: No significant differences were observed in these hemostatic markers when comparing groups of individuals carrying mutations and the control group., Conclusion: Analysis of these results leads to the conclusion that the presence of these mutations, in the absence of acquired risk factors, does not constantly predispose these young carriers to a state of hypercoagulability.

A Brazilian National Registry was established in 1999 to investigate the incidence of risk factors for venous thromboembolism (VTE) in hospitalized medical and surgical patients and to investigate the use of thromboprophylaxis in these populations. A 4-year pilot study confirmed the feasibility and value of a registry project in this region, showing a dramatic increase in the use of low-molecular-weight heparin (LMWH) over the study period, associated with a sixfold reduction in the incidence of symptomatic VTE. Data on more than 27,000 patients from the Brazilian Registry have revealed that almost 25% of high-risk patients and 45% of those at moderate risk currently receive no thromboprophylaxis. Among the high-risk patients-in whom general measures alone are not considered appropriate prophylaxis-42% of patients did not receive pharmacological prophylaxis with either LMWH or unfractionated heparin. The Brazilian Registry highlights the need to raise awareness of VTE risk factors and recommended prophylactic regimens in Latin America.

Analysis of bone marrow slides from 1,386 patients entered into the Medical Research Council's 8th and 9th trials in Acute Myeloid Leukaemia confirmed that features associated with differentiation in blast cells, in particular increasing Sudan Black (SB) positivity, were the most important morphological features for predicting remission achievement (P = 0.002) and hence survival (P less than 0.0001). SB positivity was also weakly predictive of remission duration (P = 0.05). A low complement of maturing granulocytes was associated with early induction death and a high percentage of blasts with shorter remissions. The few patients with acute promyelocytic leukaemia (FAB M3) had a high haemorrhagic death rate during induction and a low relapse rate. Apart from this, lineage involvement was not predictive of outcome. Multiple lineage leukaemias, in particular those with megakaryocytic and/or erythroid involvement, which had been reported previously to have a poor prognosis, did not have any worse remission rates in this series. When more than one cell line was involved, no combination with particularly good or poor prognosis could be identified. Multivariate analysis suggested that percentage SB positivity was adequate on its own to divide granulocytic leukaemias into poorly differentiated (less than 50% SB +ve) and well-differentiated groups (50% or more SB +ve) without the need for further measurements. This simple and reproducible test was strongly predictive of resistant disease but not of induction deaths. It was of considerably greater prognostic value--and was less open to inter-observer disagreement--than the FAB criteria which are usually used to classify granulocytic lineage leukaemias into the M1 and M2 subgroups. It is proposed that greater than or equal to 50% of blasts with SB positivity should replace blasts greater than 10% of maturing myeloid cells for this sub-categorization between M1 and M2.

Six hundred and nineteen patients with de novo acute myeloid leukaemia, entered into the Medical Research Council's eighth trial of therapy have been studied. All patients were treated with the same remission induction regimen. Pretreatment variables comprising age, clinical status, haematological status and a detailed marrow cytology and cytochemistry score have been analysed. Poorer remission rates have been found in older patients, in those with lower Karnofsky scores and in patients with a platelet count of less than 25 X 10(9)/l. Leukaemias showing evidence of cytoplasmic maturation along the granulocyte and monocyte lines, as evidenced by granules, Auer rods, a high percentage of Sudan black positive blast cells and morphological and cytochemical abnormalities of neutrophils were associated with a higher remission rate. Marrow eosinophilia was a good prognostic feature. Nuclear features of immaturity, i.e. increasing numbers and prominence of nucleoli were associated with a low remission rate. Abnormalities of the erythroid series, notably Periodic acid-Schiff positivity which was present in 133 cases (22% of the total), was associated with a low remission rate. Patient age and pretreatment Karnofsky score were the most useful predictors of treatment outcome.

The outcome of treatment with standard first line therapy of 66 patients with acute myeloid leukaemia (AML) secondary to preceding chemotherapy (Group 1), a myelodysplastic state (Group 2) or a myeloproliferative disorder (Group 3) was analysed in relation to the preceding disorder, the cytogenetic pattern where available, and the cytology and cytochemistry of blood and bone marrow. The complete remission (CR) rate for the secondary AMLs was 36% (24/66), with 24% (16/66) dying in the induction period and 39% (26/66) having resistant disease. The CR rate was 25% (5/20) for Group 1, 42% (15/36) for Group 2, and 40% (4/10) for Group 3. Even after allowance for the generally older age of the secondary AML patients, they still had a significantly poorer CR rate than the de novo AMLs (P = 0.0004). The lower CR rate was chiefly due to resistant disease. Despite this, overall survival was not significantly worse for the secondary AML patients (P = 0.15). For the 36% that achieved remission, remission duration appeared similar to that of de novo cases. Of 62 cases with adequate cytology, 38 (61%) had evidence of erythroid and/or megakaryocytic dysplasia with a CR rate of 32% (12/38). The CR rate of these multineage leukaemias was not significantly different from that of the 24 (39%) who showed granulocyte/monocyte precursor involvement only, 42% (10) of whom achieved CR. The presence of features of differentiation within blast cells such as Auer rods or sudanophilia (greater than 50% positive blasts) was associated with a higher remission rate 47% (18/38) than that of poorly differentiated cases 17% (3/18) (P = 0.04) and thus appeared to be a more important determinant of CR achievement than was lineage involvement. Cases with a normal karyotype had a 33% (7/21) CR rate, while those with chromosomal abnormalities had a 37% (9/24) CR rate. Only 12 of the 45 cases with adequate cytogenetic analysis showed deletions or monosomies involving chromosomes 5 or 7, and seven of these were in Group 1.