Platelet transfusion in adults: An update.

Many patients worldwide receive platelet components (PCs) through the transfusion of diverse types of blood components. PC transfusions are essential for the treatment of central thrombocytopenia of diverse causes, and such treatment is beneficial in patients at risk of severe bleeding. PC transfusions account for almost 10% of all the blood components supplied by blood services, but they are associated with about 3.25 times as many severe reactions (attributable to transfusion) than red blood cell transfusions after stringent in-process leukoreduction to less than 106 residual cells per blood component. PCs are not homogeneous, due to the considerable differences between donors. Furthermore, the modes of PC collection and preparation, the safety precautions taken to limit either the most common (allergic-type reactions and febrile non-hemolytic reactions) or the most severe (bacterial contamination, pulmonary lesions) adverse reactions, and storage and conservation methods can all result in so-called PC "storage lesions". Some storage lesions affect PC quality, with implications for patient outcome. Good transfusion practices should result in higher levels of platelet recovery and efficacy, and lower complication rates. These practices include a matching of tissue ABH antigens whenever possible, and of platelet HLA (and, to a lesser extent, HPA) antigens in immunization situations. This review provides an overview of all the available information relating to platelet transfusion, from donor and donation to bedside transfusion, and considers the impact of the measures applied to increase transfusion efficacy while improving safety and preventing transfusion inefficacy and refractoriness. It also considers alternatives to platelet component (PC) transfusion.

Intention to get vaccinations against COVID-19 in French healthcare workers during the first pandemic wave: a cross-sectional survey.

BACKGROUND: Healthcare workers (HCWs) are at the frontline of the COVID-19 pandemic and identified as a priority target group for COVID-19 vaccines. We aimed to determine COVID-19 vaccine acceptance rate in HCWs in France. METHODS: We conducted an anonymous survey from 26th March to 2nd July 2020. The primary endpoint was the intention to get vaccinated against COVID-19 if a vaccine was available. RESULTS: Two-thousand and forty-seven HCWs answered the survey; women accounted for 74% of respondents. Among respondents, 1.554 (76.9%, 95% confidence interval 75.1-78.9) would accept a COVID-19 vaccine. Older age, male gender, fear about COVID-19, individual perceived risk and flu vaccination during previous season were associated with hypothetical COVID-19 vaccine acceptance. Nurses and assistant nurses were less prone to accept vaccination against COVID-19 than physicians. Vaccine hesitancy was associated with a decrease in COVID-19 vaccine acceptance. Flu vaccine rate was 57.3% during the previous season, and 54.6% of the respondents had the intention to get a flu vaccine during the next season. CONCLUSIONS: Intention to get vaccinated against COVID-19 reached 75% in HCWs with discrepancies between occupational categories. COVID-19 pandemic had no positive effect on flu vaccine acceptance rate.

Nanofibrillar networks enable universal assembly of superstructured particle constructs.

Superstructured colloidal materials exploit the synergies between components to develop new or enhanced functions. Cohesion is a primary requirement for scaling up these assemblies into bulk materials, and it has only been fulfilled in case-specific bases. Here, we demonstrate that the topology of nanonetworks formed from cellulose nanofibrils (CNFs) enables robust superstructuring with virtually any particle. An intermixed network of fibrils with particles increases the toughness of the assemblies by up to three orders of magnitude compared, for instance, to sintering. Supramolecular cohesion is transferred from the fibrils to the constructs following a power law, with a constant decay factor for particle sizes from 230 nm to 40 µm. Our findings are applicable to other nanofiber dimensions via a rationalization of the morphological aspects of both particles and nanofibers. CNF-based cohesion will move developments of functional colloids from laboratory-scale toward their implementation in large-scale nanomanufacturing of bulk materials.

Bleeding risk of terminally ill patients hospitalized in palliative care units: the RHESO study.

Essentials Bleeding incidence as hemorrhagic risk factors are unknown in palliative care inpatients. We conducted a multicenter observational study (22 Palliative Care Units, 1199 patients). At three months, the cumulative incidence of clinically relevant bleeding was 9.8%. Cancer, recent bleeding, thromboprophylaxis and antiplatelet therapy were independent risk factors. SUMMARY: Background The value of primary thromboprophylaxis in patients admitted to palliative care units is debatable. Moreover, the risk of bleeding in these patients is unknown. Objectives Our primary aim was to assess the bleeding risk of patients in a real-world practice setting of hospital palliative care. Our secondary aim was to determine the incidence of symptomatic deep vein thrombosis and to identify risk factors for bleeding. Patients/Methods In this prospective, observational study in 22 French palliative care units, 1199 patients (median age, 71 years; male, 45.5%), admitted for the first time to a palliative care unit for advanced cancer or pulmonary, cardiac or neurologic disease were included. The primary outcome was adjudicated clinically relevant bleeding (i.e. a composite of major and clinically relevant non-major bleeding) at 3 months. The secondary outcome was symptomatic deep vein thrombosis. Results The most common reason for palliative care was cancer (90.7%). By 3 months, 1087 patients (91.3%) had died and 116 patients had presented at least one episode of clinically relevant bleeding (fatal in 23 patients). Taking into account the competing risk of death, the cumulative incidence of clinically relevant bleeding was 9.8% (95% confidence interval [CI], 8.3-11.6). Deep vein thrombosis occurred in six patients (cumulative incidence, 0.5%; 95% CI, 0.2-1.1). Cancer, recent bleeding, antithrombotic prophylaxis and antiplatelet therapy were independently associated with clinically relevant bleeding at 3 months. Conclusions Decisions regarding the use of thromboprophylaxis in palliative care patients should take into account the high risk of bleeding in these patients.

A Hospice and Palliative Care Bed Dedicated to Patients Admitted to the Emergency Department for End-of-Life Care.

A hospice and palliative care (PC) bed was created in 2006, located within a quiet area of our intensive care unit, in order to admit terminally ill patients sent to the emergency department (ED) for end-of-life care. We retrospectively analyze the records of the 342 terminally ill patients sent to the ED from 2007 to 2011. Among them, 176 (51.5%) were admitted to our hospice and PC bed, where 114 died. Besides, 99 (28.9%) of them died on stretchers in the ED. Our intervention led to a significant decrease in the number of terminally ill patients dying on stretchers in the ED. It also allowed both patients and families to have access to a more suitable environment.

Poor anticoagulant response to tissue factor pathway inhibitor in patients with venous thrombosis.

Tissue factor pathway inhibitor (TFPI) is of major importance in regulating the coagulation triggering effects of tissue factor. An association between TFPI deficiency and thrombosis has still not been clearly demonstrated. We evaluated the anticoagulant activity of exogenous TFPI added either to the plasma of patients with venous thrombosis (n = 118) or to the plasma of healthy controls similar in terms of mean age and sex ratio (n = 107). A poor anticoagulant response to TFPI, defined as TFPI resistance, was observed in 4.7% of controls and in 11.0% of patients. TFPI resistance was associated with an almost threefold increase in the risk of thrombosis and could therefore represent a novel hemostatic risk factor for venous thrombosis.

Priming effect of adrenic acid (22:4(n-6)) on tissue factor activity expressed by thrombin-stimulated endothelial cells.

Tissue factor (TF) which initiates clotting process can be expressed by stimulated endothelial cells (EC). TF is an apolipoprotein requiring an association with phospholipids (PL) in order to become active. Also PL constitute an important storage pool of polyunsaturated fatty acids (PUFAs) in EC which can be modulated by diet or cell medium supplementation. In order to test the effect of such manipulation upon TF activity, we have pre-enriched human EC cultures with different fatty acids of nutritional interest. TF was evaluated after 4 h of thrombin stimulation by using a chromogenic method. Without additional stimulating agents, these acids have no effect on the basal level of TF. Eicosapentaenoic and docosapentaenoic acids appeared to be ineffective at the stimulated TF level. Only adrenic acid (22:4(n-6)) has been found to significantly enhance TF activity of thrombin-stimulated endothelial cells. Other TF inducers were also tested after 22:4(n-6) enrichment. An increase tendency of TF expression was found only with tumor necrosis factor, whereas interleukin-1 beta, lipopolysaccharide and especially phorbol myristate acetate stimulations were not significantly modified. The priming effect of adrenic acid on thrombin stimulated TF expression might involve alterations of signal transduction pathways rather than modifications of apolipoprotein III environment. Adrenic acid, which is a prostacyclin inhibitor, appears to be potential prothrombotic agent.

Evaluation of D-dimer ELISA test in elderly patients with suspected pulmonary embolism.

STUDY OBJECTIVE: To determine the clinical usefulness of D-dimer ELISA test in elderly patients with clinically suspected pulmonary embolism (PE). DESIGN: Prospective cohort study. PATIENTS: Ninety-six consecutive outpatients older than 70 years with a duration of symptoms shorter than one week and without metastatic cancer or recent surgery, trauma, infection, stroke, myocardial infarction, deep vein thrombosis (DVT) or PE, or treatment with curative doses of heparin or oral anticoagulant. INTERVENTION: All patients underwent at least ventilation/perfusion scan and bilateral ultrasonic duplex scan and a blood sample collection within 24 hours of admission. When necessary a pulmonary angiography and/or a bilateral venography were also performed. Patients were classified as follows: (1) PE-positive: positive angiography or high probability V/Q scan and deep vein thrombosis (proven either by venography or by ultrasonic duplex scan) or non high probability V/Q scan and either DVT (proven at presentation by venography or by ultrasonic duplex scan) or symptomatic thromboembolic event within 3 months of follow-up; or (2) PE-negative; normal V/Q scan or normal angiography or non high probability V/Q scan and either negative ultrasonic duplex scan or normal venography and low clinical probability and absence of symptomatic thromboembolism within 3 months of follow-up. D-dimer measurements were performed using both a conventional and a single semi-quantitative ELISA test (Asserachrom D-di, Instant I.A.D-dimer). RESULTS: Using a cutoff value of 500 ng/ml, the conventional ELISA D-dimer test showed a sensitivity and a negative predictive value of 100% with poor specificity and positive predictive value of 14.3% and 45.5% respectively. The new rapid semi-quantitative D-dimer test displays worse results with sensitivity, negative predictive value, specificity and positive predictive value of 92.3%, 82.4%, 25% and 46% respectively. CONCLUSION: In a geriatric population, conventional ELISA D-dimer is a good marker to exclude PE but, due to the comorbid conditions, only a few patients presented with D-dimer values less than 500 ng/ml.

Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials.

BACKGROUND: The prevention of venous thromboembolic disease is less studied in medical patients than in surgery. METHODS: We performed a meta-analysis of randomised trials studying prophylactic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in internal medicine, excluding acute myocardial infarction or ischaemic stroke. Deep-vein thrombosis (DVT) systematically detected at the end of the treatment period, clinical pulmonary embolism (PE), death and major bleeding were recorded. RESULTS: Seven trials comparing a prophylactic heparin treatment to a control (15,095 patients) were selected. A significant decrease in DVT and in clinical PE were observed with heparins as compared to control (risk reductions = 56% and 58% respectively, p <0.001 in both cases), without significant difference in the incidence of major bleedings or deaths. Nine trials comparing LMWH to UFH (4,669 patients) were also included. No significant effect was observed on either DVT, clinical PE or mortality. However LMWH reduced by 52% the risk of major haemorrhage (p = 0.049). CONCLUSIONS: This meta-analysis, based on the pooling of data available for several heparins, shows that heparins are beneficial in the prevention of venous thromboembolism in internal medicine.

Prevalence of factor V Leiden in patients with myocardial infarction and normal coronary angiography.

Factor V Leiden is associated with an increased risk of venous thrombosis and myocardial infarction in young women, but not in men in this latter case. The aim of this study was to evaluate the prevalence of this mutation in patients with myocardial infarction but normal coronary angiography. We compared 3 groups of patients: one group consisted of 107 patients with premature myocardial infarction but no significant coronary artery stenosis; another group of 244 patients with myocardial infarction and significant coronary artery stenosis; a third group of 400 healthy controls. Factor V Leiden was found in 13 patients (12.1%) who had a myocardial infarction without significant coronary artery stenosis, 11 patients (4.5%) who had a myocardial infarction with significant coronary artery stenosis (p = 0.01) and in 20 controls (5%) (p = 0.01). Odds ratio associated with factor V Leiden were respectively 2.93 (CI95: 1.18-7.31 ) and 2.63 (CI95: 1.19-5.78) when we compared myocardial infarction patients without significant coronary artery stenosis to controls or to patients with significant coronary artery stenosis. In myocardial infarction patients without significant coronary artery stenosis, prevalence of factor V Leiden is significantly higher than in controls. This new finding supports the hypothesis that thrombosis plays a key role in this selected situation.

Acute thrombosis of a vena cava filter with a clot above the filter. Successful treatment with low-dose urokinase.

Inferior vena cava thrombosis is a major complication after filter placement. The thrombus can propagate through the filter leading to a high risk of pulmonary embolism. We report such a case in a patient with a Günther filter, successfully treated with urokinase, and we discuss the efficacy and the safety of thrombolytic therapy in such situations.

Efficacy and safety of danaparoid sodium (ORG 10172) in critically ill patients with heparin-associated thrombocytopenia.

OBJECTIVE: To evaluate the effectiveness and the safety of danaparoid sodium in the treatment of critically ill patients with standard unfractionated heparin-induced thrombocytopenia (HIT) or low-molecular-weight HIT. SETTING: University hospital. PATIENTS AND METHODS: Retrospective analysis of 42 consecutive critically ill patients who were admitted for HIT between October 1992 and February 1997 and were treated either with therapeutic or prophylactic doses of danaparoid sodium. RESULTS: Among the 26 patients treated with therapeutic doses, neither new thrombotic complications nor thrombosis extension was clinically suspected. Two deaths were directly related to lower limb acute arterial thrombosis associated with HIT. Two major hemorrhagic complications were observed when aspirin in addition to danaparoid sodium was administered. When danaparoid sodium was used in prophylactic doses (20 courses of treatment) to prevent either postsurgical or medical thrombotic complications, no thrombotic event was observed. No death related to HIT or danaparoid sodium treatment was observed. One aggravation of a postsurgical cerebral lesion was observed. During danaparoid sodium treatment, a persistence or a recurrence of thrombocytopenia was observed in 6.5% of patients without thrombotic complications. CONCLUSION: Danaparoid sodium appears to be an efficient and safe treatment in critically ill patients with HIT. The concomitant use of aspirin in addition to danaparoid sodium seems to represent an important additional hemorrhagic risk that should be avoided in patient management.

Circadian dynamics of coagulation and chronopathology of cardiovascular and cerebrovascular events. Future therapeutic implications for the treatment of these disorders?

Arterial thromboembolic disorders are the leading cause of death in most of the advanced nations. The study of epidemiologic relationship of these disorders to biological rhythms may lead to a better understanding and perhaps a better treatment. Chronoepidemiologic studies demonstrated a morning peak for arterial thromboembolic disorders (cerebral and myocardial infarctions) and sudden cardiac deaths. These variations might be explained partially by circadian variations in hemostasis. Indeed chronophysiologic studies have shown that hemostatic variables follow circadian rhythms. The level of platelet aggregation and that of blood coagulation have been found to be increased in the morning whereas fibrinolytic activity is lower at this time of the day. The facts suggest a chronotherapeutic approach in thromboembolic disorders.

Death of terminally ill patients on a stretcher in the emergency department: a French speciality?

OBJECTIVES: To determine the frequency, modalities of admission and management of terminally ill patients who died on a stretcher in an emergency department (ED). DESIGN AND SETTING: Retrospective study in an ED of a university hospital. METHODS: Current place of residence, modalities of admission in ED, mortality probability scores and type of management were extracted for each patient in the terminal stage of chronic disease who died on a stretcher in our ED during a 3year period. RESULTS: Of 159 deaths observed in the ED, 56 (35%) concerned terminally ill patients. The illness was a malignancy in 22 cases, a neurological disease in 22 cases and a cardiopulmonary disease in 12 cases. Most of the patients were referred by their regular doctor. Seventy-two percent of the malignancy patients were living at home, 55% of the neurological patients came from nursing facilities and 58% of the cardio-respiratory patients came from the hospital. In 73%, 83% and 23% of the patients with malignancy, cardiopulmonary and neurological diseases, respectively, admission was related to the evolution of the chronic disease. Severity of illness on admission was similar whatever the disease. Request for compassionate end-of-life care was expressed in only 12.5%. At the ED, 91% of patients with neurological diseases received palliative support care. Supportive therapy was undertaken in one third of patients with malignancy or cardiopulmonary disease. CONCLUSION: An ED may be used as a place for dying for some terminally ill patients. This could be related to the legal opposition to withdrawal or withholding of life-support therapies as well as the absence of guidelines from scientific bodies.

Serum and ascitic procalcitonin levels in cirrhotic patients with spontaneous bacterial peritonitis: diagnostic value and relationship to pro-inflammatory cytokines.

OBJECTIVE: To assess the potential role of procalcitonin and pro-inflammatory cytokines, TNF-alpha, and IL-6, in the diagnosis of spontaneous bacterial peritonitis (SBP). DESIGN: Prospective study. SETTING: The emergency unit of a teaching hospital. PATIENTS: We included 21 patients with SBP and 40 patients with sterile ascitic fluid. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the diagnosis of SBP, the best markers were serum levels of procalcitonin with a cut-off value of 0.75 ng/ml, a sensitivity of 95%, a specificity of 98%, and ascitic fluid levels of IL-6 with a cut-off value of 5,000 ng/ml, a sensitivity of 100%, and a specificity of 88%. C-reactive protein and serum polymorphonuclear count have low sensitivity/specificity at 62/92% and 57/90%, respectively. From 21 patients with SBP, ascitic fluid to serum ratio of TNF-alpha and IL-6 was greater than to 2 in all cases with a mean at 6.2 +/- 6.5 and 34 +/- 31, respectively. By contrast, this ratio for procalcitonin was less than 1 in all cases with a mean at 0.31 +/- 0.25. We found no correlation between procalcitonin levels and cytokine levels in either ascitic fluid or serum. CONCLUSIONS: Serum procalcitonin level may become a useful marker for the diagnosis of SBP in cirrhotic patients. The low ratio of ascitic fluid to serum procalcitonin supports the hypothesis that procalcitonin is not produced intraperitoneally.

Prevalence of factor V Leiden (APCR) and other inherited thrombophilias in young patients with myocardial infarction and normal coronary arteries.

OBJECTIVE: To investigate the role of activated protein C resistance (APCR, factor V Leiden) in coronary artery thrombosis. METHODS: The prevalence of APCR and of congenital deficiencies of antithrombin III, protein C, protein S, plasminogen, and factor XII was investigated in adult patients under 45 years of age with acute myocardial infarction. The results were compared with those of a group of 53 age and sex matched control subjects. RESULTS: Among 75 patients under the age of 45 years who were admitted from November 1994 to April 1996 for acute myocardial infarction, 22 (29.3%) had normal coronary arteriography (group I) and 53 (70.7%) had significant coronary artery disease (group II). Inherited thrombophilia was more often found in group I (4/22, 18.2%) than in group II (4/53, 7.5%) but the difference was not significant (F test: p = 0.22). The prevalence of APCR was 9.1% (2/22) in group I, 3.8% (2/53) in group 2 (p = 0.57), and 3.8% (2/53) in the normal control group (p = 0.57). CONCLUSIONS: The prevalence of congenital thrombophilias, including APCR, does not seem to be increased in young patients with myocardial infarction and normal coronary angiograms, compared with young patients with coronary atherosclerosis and with normal control subjects. However, the statistical power of the study is too low to detect a significant difference and these results are published to allow a meta-analysis of this problem in the future.

Effects of long travels in sitting position in elderly volunteers on biological markers of coagulation activation and fibrinolysis.

OBJECTIVE: To evaluate whether long travel in sitting position is associated with an increase of coagulation activation and/or a decrease of fibrinolytic activity. DESIGN: Comparison of blood coagulation and fibrinolysis parameters before and after two pleasure trips by bus organized in winter period (600 km in 8 hours) and in summer period (1200 km in 16 hours). SUBJECTS: 31 and 23 healthy elder volunteers for the winter and the summer trip respectively. Nine other elder volunteers were selected as a control group for the winter study. MAIN OUTCOME MEASURES: prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III (TAT), D-dimers (D-D), factor VII activated, plasminogen activator inhibitor (PAI), tissue-type plasminogen activator (t-PA), plasma albumin. RESULTS: A significant difference before and after the travel was only observed for TAT in the summer period. However all values of TAT were in the normal range. No volunteer presented with thromboembolic disease during the month following the travel. CONCLUSION: In the condition of our study, long travel in sitting position does not lead to an enhanced procoagulant state for elderly with varicose veins. These results suggest that there is no biological support to propose heparin prophylactic therapy for the elderly with varicose veins wishing to travel by bus.

Thrombotic thrombocytopenic purpura: MR findings.

Neurologic manifestations occur in over 90% of patients with thrombotic thrombocytopenic purpura. Neuropathologically, thrombi produce occlusion of terminal arterioles and capillaries resulting in diffuse small infarcts. In the great majority of surviving patients, brain CT does not disclose any abnormalities. The authors report a case of thrombotic thrombocytopenic purpura in which brain MR examination showed multiple punctate lesions in the white matter.

Pharmacokinetic and pharmacodynamic variations of acenocoumarol orally administrated either once or twice daily in patients with deep venous thrombosis.

The literature suggests that variations in anticoagulant effect occur when acenocoumarol is administrated in a daily dose. We assessed the anticoagulant effects of acenocoumarol with INR, factors VII and X and protein C in 12 randomly selected hospitalised patients with deep-vein thrombosis, six of them receiving a daily dose of acenocoumarol, the other six receiving twice daily doses. When the drug effect had been at a steady-state for at least 72 h, five blood samples were drawn per patient over a period of 24 h. No nycthemeral significant variations were noted for INR, factor X and protein C in the two groups (P > 0.10). Nycthemeral significant variation in factor VII when acenocoumarol was administered once daily was noted (P = 0.02), but the clinical relevance of factor VII variation at steady-state is uncertain. In spite of the short pharmacokinetic half-life of acenocoumarol, a stable nycthemeral pharmacodynamic activity was observed after once daily administration; twice-daily administration of acenocoumarol does not appear to be justified.