Excessive prolongation of prothrombin time among patients treated with warfarin and admitted to the emergency room

INTRODUCTION: Patients treated with warfarin are uncommonly admitted with excessive prolongation of international normalized ratio (INR) of prothrombin time (PT) to the emergency room (ER). Here we wanted to evaluate the reasons behind this prolongation, clinical and laboratory parameters, course and outcome of these patients. PATIENTS AND METHODS: Consecutive patients admitted to the ER with prolonged PT-INR>6 under warfarin treatment and who gave sufficient information regarding history of warfarin treatment, were followed prospectively. Patients or care-givers were asked about warfarin treatment, PT monitoring, current and new medications especially antibiotics and diet. Clinical and laboratory parameters, course and outcome were also documented. Age and gender matched patients with therapeutic INR level were used as a control group. RESULTS: 75 patients finished the study. The median INR level among the patients was 8.5 and a range of 6.1-59.5. The median duration of warfarin treatment was 12 months among the patients vs. 36 in the control group, p<0.001 and family physician was the sole decider on warfarin dose in 71 patients vs. 49 in the control group, p<0.100. 19 patients adhered to balanced diet vs. 34 in the control group, p=0.01. Dose increment of warfarin was the most common definite cause of prolonged PT followed by adding new medication especially amiodarone and recently started warfarin. Significantly more patients had evidence of bleeding than the control group but no difference in mean hemoglobin level or number of patients transfused with packed cells. No difference in the number of patients hospitalized or duration of hospitalization, but 5 in-hospital fatalities in the patients' group vs. none in the control group. CONCLUSION: Excessive PT prolongation is mainly due to warfarin dose increment, adding new medication especially amiodarone and recently started warfarin. It is significantly more associated with bleeding and higher in-hospital mortality.     

Patients admitted to the emergency room with symptoms indicative of acute myocardial infarction

All 7157 patients (55% men) admitted to the emergency room with chest pain or other symptoms indicative of acute myocardial infarction during a period of 21 months were registered consecutively. Chest pain was reported by 93% of the patients. On the basis of history, clinical examination, and electrocardiogram in the emergency room, all patients were prospectively classified in one of four categories: (i) obvious infarction (4% of all patients); (ii) strongly suspected infarction (20%); (iii) vague suspicion of infarction (35%); and (iv) no suspected infarction (41%). In patients with no suspected infarction (n = 2910), musculoskeletal (26%), obscure (21%) and psychogenic origins (16%) of the symptoms occurred most frequently. We conclude that few of the patients had an obvious infarction on admission, and that a musculoskeletal origin of the symptoms occurred most frequently in patients with no suspected infarction.     

Autoantibodies to platelet glycoproteins in patients with disease-related immune thrombocytopenia

Although increased platelet destruction and elevated platelet-associated IgG have been shown in patients with lymphomas and various autoimmune diseases, such as systemic lupus erythematosus (SLE), there have been few studies evaluating autoantibodies against platelet-specific antigens. We evaluated 24 patients retrospectively with disease-related thrombocytopenia (12 with lymphoproliferative diseases and 12 with various autoimmune disorders) using a recently reported antigen-specific assay. Autoantibodies against platelet GPIIb/IIIa or GPIb/IX were noted in 15 of the 24 patients (10 of 12 with autoimmune disease and five of 12 with lymphoproliferative disorders). Platelet-associated autoantibodies were present in 60% and plasma autoantibodies in 33%. Anti-GPIIb/IIIa autoantibodies were much more common than those against GPIb/IX. In one patient each with thrombocytopenia and either SLE or myasthenia gravis, absorption of plasma with platelets completely removed the anti-GPIIb/IIIa autoantibodies, but did not affect the level of anti-cochlear autoantibody involved with immune-mediated hearing loss in the SLE patient or the anti-acetylcholine receptor autoantibody in the myasthenic patient. These findings show that, in some cases of disease-related immune thrombocytopenia, autoantibodies against GPIIb/IIIa or GPIb/IX can be detected similar to those seen in chronic ITP. As shown in two patients with multiple autoimmune manifestations, the various autoantibodies have diverse specificities and do not crossreact.     

Procoagulant profile in patients with immune thrombocytopenia

Despite their low platelet count some immune thrombocytopenia (ITP) patients seldom bleed, indicating the presence of factors to compensate thrombocytopenia. Moreover, ITP patients may have an increased risk for thrombosis. These facts suggest the presence of procoagulant mechanisms that have not been clarified yet. The aim of this study was to identify these possible factors. Moreover, the utility of rotational thromboelastometry (ROTEM^®) to test haemostasis in these patients was also evaluated. Patients with ITP presented a procoagulant profile due to an increased amount of platelet‐ and red cell‐microparticles, an increased resistance to protein C and the formation of a clot more resistant to fibrinolysis due to augmented levels of plasminogen activator inhibitor‐1, which might reflect an endothelial damage/activation in ITP patients. Despite increased maximum clot firmness and reduced lysis, ROTEM^® profiles showed a prolonged clotting time that might rely on the presence of anti‐platelet antibodies as suggested by the increased lagtime in thrombin generation test caused by plasma from ITP patients on platelets from healthy controls. These results indicate the need to individualize therapeutic treatment for ITP patients, considering their procoagulant profile and the presence of concomitant risk factors. Moreover, ROTEM^® appeared to be useful for evaluating haemostasis in ITP patients.     

Autoantibodies to thrombopoietin and the thrombopoietin receptor in patients with immune thrombocytopenia

Autoantibodies to thrombopoietin (TPO, also termed THPO) or the TPO receptor (cMpl, also termed MPL) could play a pathological role in immune thrombocytopenia (ITP). In this study, we tested for autoantibodies against TPO, cMpl, or the TPO/cMpl complex in ITP and other thrombocytopenic disorders. Using an inhibition step with excess TPO in fluid‐phase to improve binding specificity, the prevalence of anti‐TPO autoantibodies was: active ITP: 9/32 (28%); remission ITP: 0/14 (0%); non‐immune thrombocytopenias: 1/10 (10%); and healthy controls: 1/11 (9%). Similarly, using an inhibition step with excess cMpl, the prevalence of specific anti‐cMpl autoantibodies was: active ITP: 7/32 (22%); remission ITP: 1/14 (7%); non‐immune thrombocytopenias: 3/10 (30%); and healthy controls: 0/11 (0%). Two active ITP patients had autoantibodies against the TPO/cMpl complex, but not against TPO or cMpl alone. Anti‐TPO or anti‐cMpl autoantibodies were found in 44% of ITP patients, and in 40% of patients with other thrombocytopenic disorders. These autoantibodies did not correlate with ITP disease severity or number of ITP treatments received; however, in this cohort, 3 patients failed to respond to TPO receptor agonist medications, and of those, 2 had anti‐TPO autoantibodies. This suggests that anti‐TPO and anti‐cMpl autoantibodies are associated with thrombocytopenia, and may be clinically relevant in a subset of ITP patients.     

Cardiac or pulmonary dyspnea in patients admitted to the emergency department

A simple and quick way of discrimination between cardiac and pulmonary causes of dyspnea is essential in patients admitted to the emergency department. We aimed to assess the utility of easily applicable diagnostic tools in the differential diagnosis of cardiac and pulmonary causes of dyspnea in patients presenting with shortness of breath. Clinical and radiologic evaluation, peak expiratory flow (PEF), PaO2, PaCO2 measurements were performed in 94 patients admitted to the emergency room with dyspnea. All the patients were hospitalized for accurate diagnosis and later were categorized into cardiac and pulmonary dyspnea groups. PEF, %PEF (percent of predicted PEF), dyspnea differentiation index (DDI = PEF x PaO2/1000), %DDI (%PEF x PaO2/1000), PaO2 and PaCO2 measurements were compared between the two groups. When cardiac and pulmonary dyspnea groups were compared, considering 1.6 as the cut-off value for DDI, measurements above this value imply cardiac pathology with 76.7% sensitivity and 67.2% specificity. The sensitivity and specificity for cardiac dyspnea calculated according to the cut-off values were 96.7% and 40.6% for %DDI; 86.7% and 60.9% for PEF; 86.7% and 54.7% for %PEF; 66.7 and 68.7 for PaO2. Also for pulmonary dyspnea, sensitivity and specificity values for PaCO2 were 50% and 93%. We conclude that DDI, %DDI, PEF, %PEF, PaO2 and PaCO2 are simple and easily applicable tools for differential diagnosis of cardiac and pulmonary dyspnea. Adjunctive utility of these tests in the emergency department with clinical and radiologic evaluation contributes to this discrimination.     

A prospective registry of emergency department patients admitted with infection

Background  

Patients with infections account for a significant proportion of Emergency Department (ED) workload, with many hospital patients admitted with severe sepsis initially investigated and resuscitated in the ED. The aim of this registry is to systematically collect quality observational clinical and microbiological data regarding emergency patients admitted with infection, in order to explore in detail the microbiological profile of these patients, and to provide the foundation for a significant programme of prospective observational studies and further clinical research.     

Fatigue in adult patients with primary immune thrombocytopenia

Background: Patients with primary immune thrombocytopenia (ITP) commonly describe symptoms of fatigue. However, hematologists rarely consider fatigue a manifestation of ITP. Objectives: To document the prevalence of fatigue among patients with ITP and to determine the patient characteristics that are associated with fatigue. Methods: Using a cross‐sectional design, we surveyed 1871 members of the UK ITP Support Association [585 (31%) responded], and 93 patients enrolled in the Oklahoma (US) ITP Registry [68 (73%) responded] with questions about their ITP and with validated symptom assessment scales for fatigue, daytime sleepiness, and orthostatic symptoms. Results: The prevalence of fatigue among both UK (39%) and US (22%) patients was significantly greater than expected compared with normal subjects (P < 0.0001 and P < 0.0001 respectively). In univariate analysis of the combined cohorts, fatigue was associated with a platelet count <100 000/μL, treatment with steroids, bleeding symptoms, presence of other medical conditions, daytime sleepiness, and orthostatic symptoms. Fatigue was not associated with age, gender, duration of ITP, or splenectomy status. Multivariate analysis of the combined cohorts was stratified for the presence or absence of bleeding symptoms. Among 107 patients with bleeding symptoms, fatigue was independently associated with a platelet count <100 000/μL and female gender. Among 491 patients without bleeding symptoms, fatigue was independently associated with a platelet count <30 000/μL, presence of other medical conditions, daytime sleepiness, and orthostatic symptoms. Conclusions: Fatigue is a common symptom among patients with ITP. These data provide the basis for future studies to define the clinical importance of fatigue in ITP.     

Treatment of immune thrombocytopenia during pregnancy with thrombopoietin receptor agonists

The introduction of thrombopoietin receptor agonists (TPO-RAs) led to a paradigm shift in the management of immune thrombocytopenia (ITP). However, TPO-RAs are not approved for use during pregnancy due to the absence of evidence and concerns for possible effects on the fetus due to their expected transplacental transfer. This comprehensive review examines the safety and efficacy of TPO-RA in 45 pregnancies of women with ITP (romiplostim n = 22; eltrombopag n = 21; both in the same pregnancy n = 2). Mothers experienced failure of the median of three treatment lines during pregnancy prior to TPO-RA administration. A platelet response (>30 × 10⁹/L) was seen in 86.7% of cases (including a complete response >100 × 10⁹/L in 66.7%) and was similar between eltrombopag and romiplostim (87.0% and 83.3%, p = 0.99). The maternal safety profile was favourable, with no thromboembolic events encountered. Neonatal thrombocytopenia was noted in one third of cases, with one case of ICH grade 3, and neonatal thrombocytosis was observed in three cases. No other neonatal adverse events attributable to TPO-RAs were seen. This review suggests that the use of TPO-RA during pregnancy is associated with a high response rate and appears safe. Nevertheless, TPO-RA should not be routinely used in pregnancy and should be avoided in the first trimester until further evidence is accumulated.     

Performance of whole-blood interferon-gamma release assay in patients admitted to the emergency department with pulmonary infiltrates

Background  

This study was conducted to evaluate the performance of a whole-blood interferon-gamma release assay in inpatients who were admitted to the emergency department (ED) with pulmonary infiltrates who required a differential diagnosis with pulmonary tuberculosis (TB).     

Respiratory viral infections and effects of meteorological parameters and air pollution in adults with respiratory symptoms admitted to the emergency room

Background

Respiratory viral infections (RVIs) are the most common causes of respiratory infections. The prevalence of respiratory viruses in adults is underestimated. Meteorological variations and air pollution are likely to play a role in these infections.

Objectives

The objectives of this study were to determine the number of emergency visits for influenza-like illness (ILI) and severe acute respiratory infection (SARI) and to evaluate the association between ILI/SARI, RVI prevalence, and meteorological factors/air pollution, in the city of Porto Alegre, Brazil, from November 2008 to October 2010.

Methods

Eleven thousand nine hundred and fifty-three hospitalizations (adults and children) for respiratory symptoms were correlated with meteorological parameters and air pollutants. In a subset of adults, nasopharyngeal aspirates were collected and analyzed through IFI test. The data were analyzed using time-series analysis.

Results

Influenza-like illness and SARI were diagnosed in 3698 (30·9%) and 2063 (17·7%) patients, respectively. Thirty-seven (9·0%) samples were positive by IFI and 93 of 410 (22·7%) were IFI and/or PCR positive. In a multivariate logistic regression model, IFI positivity was statistically associated with absolute humidity, use of air conditioning, and presence of mold in home. Sunshine duration was significantly associated with the frequency of ILI cases. For SARI cases, the variables mean temperature, sunshine duration, relative humidity, and mean concentration of pollutants were singnificant.

Conclusions

At least 22% of infections in adult patients admitted to ER with respiratory complaints were caused by RVI. The correlations among meteorological variables, air pollution, ILI/SARI cases, and respiratory viruses demonstrated the relevance of climate factors as significant underlying contributors to the prevalence of RVI.     

Clinical analysis of patients with tuberculosis admitted on an emergency cases

A retrospective study was made of 75 patients with tuberculosis and tuberculous pleurisy who received medical care in our hospital from 2002 through 2006. Of the 75 patients, 9 were admitted as tertiary emergency cases, and 12 patients were admitted by ambulance as secondary emergency cases. We studied the reason for their emergency medical admission, and the process of diagnosing 21 patients as tuberculosis. In some cases, the reasons for emergency admission were cardiorespiratory arrest, loss of consciousness, and injury resulting from a traffic accident, not common symptoms of tuberculosis such as dyspnea, hemoptysis and bloody sputum. Chest radiographic findings of most patients showed tuberculosis, and other cases were likely to be diagnosed as tuberculosis from their medical history or back-ground such as being homeless, previous tuberculosis, and receiving for therapy of tuberculosis. It was not so difficult to diagnose our cases as tuberculosis, nevertheless we may have an unconscious patient with normal chest radiograph. These data suggest that any patients visiting the emergency room may possibly have tuberculosis even if they are without respiratory symptoms.     

Humoral response to mRNA-based COVID-19 vaccine in patients with immune thrombocytopenia

Data for COVID-19 vaccine response in patients with immune thrombocytopenia (ITP) are very limited. In a study of 28 patients with ITP, anti-severe acute respiratory syndrome coronavirus 2 spike antibody titres were measured after vaccination. The seroconversion rate for ITP patients was 91.3%, comparable to that in healthy controls (HCs). However, the antibody titre in ITP patients was significantly lower than that in HCs and declined with ageing. Furthermore, the antibody titre in ITP patients who received a minimum prednisolone dose of at least 5 mg/day at any time-point at or after initial vaccination was lower than that in other patients.