Health effects of reduced occupational sedentary behaviour in type 2 diabetes using a mobile health intervention: a study protocol for a 12-month randomized controlled trial-the ROSEBUD study.

BACKGROUND: Short-term trials conducted in adults with type 2 diabetes mellitus (T2DM) showed that reducing sedentary behaviour by performing regular short bouts of light-intensity physical activity enhances health. Moreover, support for reducing sedentary behaviour may be provided at a low cost via mobile health technology (mHealth). There are a wide range of mHealth solutions available including SMS text message reminders and activity trackers that monitor the physical activity level and notify the user of prolonged sitting periods. The aim of this study is to evaluate the effects of a mHealth intervention on sedentary behaviour and physical activity and the associated changes in health in adults with T2DM. METHODS: A dual-arm, 12-month, randomized controlled trial (RCT) will be conducted within a nationwide Swedish collaboration for diabetes research in primary health care. Individuals with T2DM (n = 142) and mainly sedentary work will be recruited across primary health care centres in five regions in Sweden. Participants will be randomized (1:1) into two groups. A mHealth intervention group who will receive an activity tracker wristband (Garmin Vivofit4), regular SMS text message reminders, and counselling with a diabetes specialist nurse, or a comparator group who will receive counselling with a diabetes specialist nurse only. The primary outcomes are device-measured total sitting time and total number of steps (activPAL3). The secondary outcomes are fatigue, health-related quality of life and musculoskeletal problems (self-reported questionnaires), number of sick leave days (diaries), diabetes medications (clinical record review) and cardiometabolic biomarkers including waist circumference, mean blood pressure, HbA1c, HDL-cholesterol and triglycerides. DISCUSSION: Successful interventions to increase physical activity among those with T2DM have been costly and long-term effectiveness remains uncertain. The use of mHealth technologies such as activity trackers and SMS text reminders may increase awareness of prolonged sedentary behaviour and encourage increase in regular physical activity. mHealth may, therefore, provide a valuable and novel tool to improve health outcomes and clinical management in those with T2DM. This 12-month RCT will evaluate longer-term effects of a mHealth intervention suitable for real-world primary health care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04219800 . Registered on 7 January 2020.

Red blood cell transfusion in southern Finland from 2011 to 2016: a quality audit.

OBJECTIVES: The current trends in RBC use and pre- and post-transfusion Hb levels were analysed to improve practice and to provide international comparison. BACKGROUND: Indications for RBC transfusion have changed with growing scientific evidence. The lowest acceptable haemoglobin (Hb) level has decreased, and transfusing single units instead of pairs has become the new standard. Evidence-based guidelines and patient blood management (PBM) programmes increase clinician awareness of rational RBC use. In Finland, however, no formal PBM programme has been established to date. METHODS: The study was registry-based, retrospective and observational. All RBC transfusions for adult patients from 2011 to 2016 in the southern region of Finland were analysed. RESULTS: RBC usage decreased from 34·9 to 27·5 units per 1000 population (P < 0·001). The percentage of single-unit transfusions increased from 57·9 to 66·7%, and the median pre- and post-transfusion Hb levels decreased from 8·4 to 8·2 g dL-1 (P < 0·001) and 9·9 to 9·6 g dL-1 (P < 0·001), respectively. The proportion of transfusions with pre-transfusion Hb ≥ 9·0 g dL-1 decreased during the study period but remained high, being 29·5% in 2011 and still 25·2% in 2016. CONCLUSIONS: Consumption of RBCs has decreased despite aging population and increasing healthcare performance demands. The results indicate more rational and evidence-based RBC use. Nevertheless, the transfusion rate and pre- and post-transfusion Hb are still sufficiently high to enable more restrictive transfusion practice.

Serial measurements of plasma homocysteine levels in early and late phases of ischemic stroke.

High plasma levels of homocysteine (Hcy) may predispose to ischemic stroke (IS), but results of previous studies have been conflicting. We decided to determine in IS patients whether their Hcy levels are elevated, whether levels vary at different time points following stroke, whether levels are associated with stroke severity, outcome, recurrence, etiology, infarct volume, or risk factors, and whether levels are correlated with hemostatic factors or C-reactive protein values. We measured plasma Hcy levels in 102 consecutive IS patients on admission and at 1 week, 1 month, and 3 months after stroke and once in 102 control subjects. Hemostatic factors were measured in 55 patients. Compared with controls, plasma Hcy levels in patients were significantly lower on admission but not at later time points, with levels increasing by week and remaining at this level for 3 months. Hcy levels showed a positive correlation with age and a negative correlation with Mini-Mental State Examination (MMSE) scores. Plasma Hcy levels inversely correlated with plasminogen activator inhibitor type-1. Decreased Hcy levels on admission may reflect the strength of the acute-phase response rather than a pathogenetic event. The negative correlation between Hcy levels and MMSE scores is more probably age-related than stroke-related.

Development of permanent national register of blood component use utilizing electronic hospital information systems.

BACKGROUND AND OBJECTIVES: We wanted to establish a permanent national database system, which can be utilized to study transfusion recipients and blood use in Finland. MATERIALS AND METHODS: A regularly updated register for permanent use was developed. To study the usability of the database, years 2002 and 2003 were further analysed. Database included all transfused patients in major blood-transfusing hospitals from four university and five central hospital districts managing altogether 63% of Finnish inpatient hospital episodes. RESULTS: Audit of gathered data reveal 96.8% match in adult blood components with Finnish Red Cross, Blood Service sales figures. Model data set includes 59,535 transfused patients (44.3% men and 55.7% women) having received 529,104 blood components. Half of all blood units were transfused in connection with surgical operations. Most of the blood recipients were elderly (51.6% are over 64 years of age). Blood-component use and transfusion-related costs varied widely between hospitals. CONCLUSION: Hospital data managing systems can be useful for creating a population-based database system to monitor and compare transfusion practices. This record provides information about transfusion epidemiology for transfusion professionals, hospital management, and hospital administration.

Serial changes in fibrinolysis and coagulation activation markers in acute and convalescent phase of ischemic stroke.

BACKGROUND: The changes in the activity of a number of plasma markers of coagulation and fibrinolysis have previously been studied in patients with ischemic stroke, with conflicting results. We aimed to find out the changes in the activities of a wide array of markers of the coagulation and the fibrinolytic system of mildly or moderately affected first-ever ischemic stroke patients. METHODS: In a prospective, longitudinal, case-control study, we studied plasma plasminogen activator inhibitor type-1 (PAI-1) activity, tissue-type plasminogen activator antigen (t-PA:Ag), d-dimer, prothrombin fragment 1+2 (F 1+2), and thrombin-antithrombin III complex (TAT) levels in 55 consecutive patients on admission, 1 week, 1 month, and 3 months after an ischemic stroke. Sex- and age-matched controls were studied once. All patients underwent blood sampling at each study time point; comprehensive stroke risk factors were recorded, and the etiology of the ischemic stroke was determined. All patients were contacted 3 years later for possible recurrent ischemic events. RESULTS: PAI-1 activity was increased in the acute phase and at 3 months, D-dimer levels were significantly higher at 1 week and 1 month after stroke, whereas t-PA:Ag, TAT and F 1+2 levels remained stable during the whole study period. CONCLUSIONS: The changes of the fibrinolytic and coagulation system activity in the patients with mild or moderate ischemic stroke appeared minor compared with the results of previous studies, which included more severely ill patients.

A simple automatized audit system for following and managing practices of platelet and plasma transfusions in a neonatal intensive care unit.

During neonatal intensive care, blood components are often used in clinical situations where both their efficacy and safety lack solid justification. A practical system to continuously analyse actual transfusion practices is a prerequisite for improvements of quality in transfusion therapy. We hypothesized that such a system would reveal inappropriate variations in clinical decision making and offer a means for staff education and quality improvement and assurance. The study consisted of three 120-152-day periods (P I, P II and P III) between January 2000 and October 2001 and involved 543 new patient admissions (141 patients with birth weight < 1501 g) and 6227 days of patient care at a single tertiary level NICU. P I was a control with no intervention, P II was after technically introducing the computer system and, the last period, P III was after presenting and discussing the results of P I and P II at a staff meeting. Upon an order of platelet or fresh frozen plasma (FFP) unit from the blood bank, a computer-based audit system compared the last platelet count or prothrombin time [expressed as percentage of normal clotting activity, prothrombin time (PT-%)] to predefined criteria. In the case of exceeding the preset thresholds, the system required additional information and recorded the pretransfusion laboratory values for later analysis. Thirty-two per cent of platelet transfusions were given with pretransfusion platelet count >49 x 10(9) L(-1), and 60% of these transfusions (19% of all platelet transfusions) could not be clinically justified in retrospective chart review. There was no significant change in this practice from P II to P III. FFP transfusions were given with significantly different pretransfusion PT-% values during P II and P III. The proportions of FFP transfusions with pretransfusion PT-% > 49% were 7.8% and 0.9% during P II and P III, respectively (P < 0.0001). In chart review, none of the FFP transfusions with pretransfusion PT-% > 49% could be justified by clinical grounds. Inappropriate transfusions of both platelets and plasma remain a significant challenge for quality assurance of neonatal intensive care. Automated recording of pretransfusion platelet count and prothrombin time reliably identified the poorly justified transfusions and thus offered a practical resource-saving tool for quality assurance of transfusion in the NICU. A significant shift towards more appropriate use of plasma was demonstrated after implementation of the audit system.

Propacetamol augments inhibition of platelet function by diclofenac in volunteers.

BACKGROUND: Acetaminophen (paracetamol) enhances the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is a weak inhibitor of cyclooxygenase (COX), and its combination with an NSAID may augment COX inhibition-related side effects. METHODS: Ten healthy male volunteers (21-30 yr) were given diclofenac 1.1 mg kg(-1) alone, a combination of propacetamol 30 mg kg(-1) (which is hydrolysed to 50% acetaminophen) and diclofenac 1.1 mg kg(-1) or placebo intravenously in a double blind, crossover study. Platelet function was assessed at 5 min, 90 min and 22-24 h by photometric aggregometry, platelet function analyser (PFA-100(TM)) and by measuring the release of thromboxane B(2) (TxB(2)). Analgesia was assessed with the cold pressor test. RESULTS: Platelet aggregation induced with arachidonic acid was fully inhibited by both diclofenac alone and the combination at the end of the 30-min drug infusion. Propacetamol augmented the inhibition by diclofenac at 90 min (P=0.014). At 22-24 h, platelet function had fully recovered. TxB(2) release was inhibited by the combination of propacetamol and diclofenac at 90 min in comparison with diclofenac alone (P=0.027). PFA-100(TM) detected no difference in platelet function between these two groups. No analgesic effect was detected with the cold pressor test. CONCLUSIONS: The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.

Computerized quality assurance of decisions to transfuse blood components to critically ill patients.

BACKGROUND: In critically ill patients optimal transfusion therapy for most clinical settings has not been determined. The objective of this study was to evaluate the impact of a computerized audit on transfusion decisions of red blood cells (RBC), fresh frozen plasma (FFP), and platelets among critically ill patients. METHODS: Two hundred and ninety consecutive patients admitted to nine-bed medical-surgical intensive care unit at a university hospital were included in this prospective study. Prior to the study, the criteria for transfusions of RBCs, FFP and platelets were established. Phase I, the first 3-month period served as a control period. During phase II the fulfilment of these criteria was prospectively monitored by an audit software belonging to the computerized blood request program. If the predefined transfusion criteria were not met the audit software was automatically activated. The last 3-month period, phase III, was to assess if possible effects on transfusion decisions were permanent. RESULTS: The proportion of RBC transfusions administered according to predefined trigger during the study phases I, II, and III were 55.9%, 75.1% and 67.9%, respectively (P < 0.001). The proportion of FFP and platelet transfusions according to a predefined trigger did not differ statistically significantly between the study phases. Logistic multiple regression analysis revealed an independent effect of the audit phase on the decision to transfuse RBCs and FFP. CONCLUSIONS: The data suggests that a computerized prospective transfusion audit has impact on the realisation of predefined transfusion decisions.

Fresh frozen plasma reduces thrombin formation in newborn infants.

BACKGROUND: Newborn infants undergoing intensive care are at risk of bleeding and thrombotic complications. Fresh frozen plasma (FFP) is used in hope of preventing these complications, despite poorly defined effects on the coagulation system and lack of proven clinical efficacy. OBJECTIVES AND METHODS: We prospectively evaluated coagulopathy and the effect of standardized amount of FFP transfusion (10 mL kg-1 + 4 mL in 2 h) on various coagulation markers in 33 newborn infants during the first 24 h of intensive care. RESULTS: Increased levels of prothrombin fragment F1+2, thrombin-antithrombin complexes (TAT), and d-dimer were found prior to the transfusion in 97%, 81%, and 100% of the patients, respectively. FFP transfusion was associated with a decrease in F1+2 level in 26/32 (81%) of the patients. The extent of F1+2 decrease correlated with the pretransfusion F1+2 level (R = 0.65, P < 0.0001). The patient series was divided into two groups according to increasing pretransfusional F1+2 level: Group 1 (preFFP F1+2 > or = 2.35 nm, n = 16), Group 2 (F1+2 <2.35 nm, n = 16). In Group 1, F1+2 decreased on average 1.58 nm (P < 0.01) from the baseline during FFP transfusion but no significant change in the level of F1+2 during the transfusion was observed in Group 2. Pretransfusional levels of individual factors or prothrombin time (PT) did not correlate with the FFP-associated decrease in F1+2 level. CONCLUSIONS: In the patients with the highest pretransfusional thrombin formation, FFP had an acute thrombin-reducing effect. Pretransfusion thrombin generation markers, rather than PT or individual pro- and anticoagulants, may be helpful in identifying the patient who will have measurable coagulational effects induced by FFP.

Natural anticoagulants (antithrombin III, protein C, and protein S) in patients with mild to moderate ischemic stroke.

BACKGROUND AND PURPOSE: The role of the natural anticoagulants, antithrombin III (AT III), protein C (PC), and protein S (PS), in patients with mild to moderate ischemic stroke remains uncertain. We aimed to find out whether their levels in peripheral blood correlated with the severity of neurological deficit or can predict clinical outcome and recurrence. METHODS: We studied AT III, PC, and free PS levels in 55 consecutive patients likely to survive the study period on admission, 1 week, 1 month and 3 months after a first-ever ischemic stroke. Sex- and age-matched controls were studied once. All patients underwent a full neurological examination and blood sampling at each study time point; comprehensive stroke risk factors were recorded, and the etiology of the ischemic stroke was determined. All patients were contacted 3 years later for possible recurrent ischemic events. RESULTS: AT III level was found to be significantly lower at all time points after stroke; PC level was significantly increased on admission and normal at subsequent measurements, and PS level was normal on admission but significantly decreased later. The levels of the natural anticoagulants did not correlate with the etiology of stroke, any stroke risk factor, or neurological scores, except that the AT III level on admission showed significant correlation with stroke severity and disability at 3 months. Natural anticoagulant levels did not predict recurrence of ischemic stroke. CONCLUSIONS: The measurements of the level of AT III, PC, or PS did not deliver useful information for management of patients with mild or moderate ischemic stroke, expect that AT III level on admission might predict outcome.

Advances in cardiac surgical transfusion practices during the 1990s in a Finnish university hospital.

BACKGROUND AND OBJECTIVES: Recent transfusion practices in coronary artery bypass (CABG) operations in a Finnish university hospital were evaluated, utilizing the data stored automatically in hospital registers. MATERIALS AND METHODS: The register-based transfusion data on all 2363 CABG patients operated on during a 2.5-year period, from 1997 to 1999, were analysed and compared with a review of surgical transfusion practices in Finland from 1993 to 1994. RESULTS: The rate of allogeneic transfusion showed a decrease from 76% in 1993-94 to 48% in the time-period January to June 1999, and the mean number of donor exposures decreased from 3.3 to 2.0 units per patient. The mean blood product purchase costs per patient almost halved from 1993-94 to 1997-99. CONCLUSION: Hospital registers provide a good means for prompt evaluation and reporting of large-scale transfusion data. Since 1993, transfusion rates and costs in CABG operations have decreased markedly. Further development of transfusion registers is warranted.

Variability in platelet responses to collagen--comparison between whole blood perfusions, traditional platelet function tests and PFA-100.

The purpose of this study was to determine if the results obtained in platelet function tests and whole blood perfusions are associated with those in platelet function analyser (PFA)-100. We used collagen type I monomers and fibrils to analyse the distinct roles of glycoprotein (GP) Ia/IIa and other collagen receptors in flowing blood under a high shear rate (1600/s) and in aggregation studies. Also, anticoagulation [citrate vs. D-phenylalanyl-1-prolyl-1 arginine chloromethyl ketone (PPACK)] was varied to enhance the functions of GP Ia/IIa, since it has been shown that the cation-poor environment of citrated blood impairs GP Ia/IIa-dependent platelet recruitment. Large interindividual variability (45-fold) was detected in deposition of platelets in whole blood perfusions over collagen monomers, whereas this variation was only fourfold in fibrils. In PFA, this variation was reduced to 2.5-fold. However, platelet deposition on monomers is associated with epinephrine-enhanced PFA (r=-.49, P<.03), whereas platelet deposition on fibrils is correlated with adenosine diphosphate (ADP)-enhanced PFA (r=-.47, P<.05), suggesting a distinct synergism between epinephrine and monomers (GP Ia/IIa) as well as ADP with fibrils (other collagen receptors). Donors with 807 C/C polymorphism of GP Ia (n=14) had longer lag phase in aggregation experiments compared with C/T (n=7) both by monomers and fibrils (P<.04), but these polymorphisms with their mild impact on GP Ia/IIa activity did not markedly differ in other tests. In conclusion, the results obtained in perfusion studies and PFA experiments correlated, but PFA fails to reveal the large-scale variability related to collagen-induced platelet responses.

Transfusion practice in Helsinki University Central Hospital: an analysis of diagnosis-related groups (DRG).

Transfusion data combined with data automatically recorded in hospital databases provides an outstanding tool for blood utilization reporting. When the reporting is performed with an online analytical processing (OLAP) tool, real time reporting can be provided to blood subscribers. When this data is combined with a common patient classification system, Diagnosis-Related Groups (DRG), it is possible to produce statistical results, that are similar in different institutions and may provide a means for international transfusion bench-marking and cost comparison. We use a DRG classification to describe the transfusion practice in Helsinki University Central Hospital. The key indicators include the percentage of transfused patients, the number of transfused units and costs in different DRG groups, as well as transfusion rates per DRG weighted treatment episodes. Ninety-three per cent of all transfusions could be classified into different DRGs. The largest blood-using DRG group was acute adult leukaemia (DRG 473), which accounted for 10.4% of all transfusion costs. The 13 largest blood consuming DRGs accounted for half the total costs in 1998. Currently, there is a lack of an internationally accepted standardized way to report institutional or national transfusion practices. DRG-based transfusion reporting might serve as a means for transfusion benchmarking and thus aid studies of variations in transfusion practice.

Effects of alcohol and the evening meal on shear-induced platelet aggregation and urinary excretion of prostanoids.

Moderate regular alcohol intake has been found to be associated with a decreased risk for coronary heart disease and stroke. We investigated the effects of acute intake of red wine (60 g ethanol) and a standard dinner under controlled conditions on haemostatic factors. Shear-induced platelet aggregation (SIPA) decreased after the intake of alcohol irrespective of whether the subjects were fasting or not, and also after the intake of food. The intake of alcohol inhibited the postprandial increase of von Willebrand factor multimers. Plasma levels of plasminogen activator inhibitor 1 activity (PAI-1) and serum triglycerides were increased by alcohol. Excretion of the platelet thromboxane A(2) metabolites 11-dehydrothromboxane B(2) and 2,3-dinorthromboxane B(2), as well as the endothelial prostacyclin metabolite 2, 3-dinor-6-ketoprostaglandin F(1)alpha, into urine was not influenced by either alcohol or food. We conclude that eating a dinner together with red wine has no untoward effect on SIPA and that the decrease of SIPA is not specific for alcohol.

The effect of acute ingestion of a large dose of alcohol on the hemostatic system and its circadian variation.

BACKGROUND AND PURPOSE: Heavy binge drinking may trigger the onset of embolic stroke and acute myocardial infarction, but the underlying mechanisms are unclear. The effects of binge drinking on the hemostatic system and its circadian variation have not been investigated. We investigated the effects of an acute intake of a large dose of alcohol (1.5 g/kg). METHODS: Twelve healthy, nonsmoking men participated in sessions where they were served ethanol in fruit juice or served fruit juice alone and, lying in a supine position, were followed up for 12 to 24 hours. The treatments were randomized and separated from each other by a 1-week washout period. Blood and urine were collected for hemostatic measurements. RESULTS: The urinary excretion of the platelet thromboxane A(2) metabolite 2, 3-dinor-thromboxane B(2) was significantly (P<0.05) greater during the night after an evening intake of alcohol than during the control night. A smaller increase was observed during the daytime after an intake of alcohol in the morning. The effects on the endothelial prostacyclin metabolite 2,3-dinor-6-ketoprostaglandin F(1alpha) excretion were negligible. A 7-fold increase in plasminogen activator inhibitor 1 activity was observed after both morning (P<0. 05) and evening (P<0.01) intakes of alcohol. CONCLUSIONS: This is the first study to suggest that acute ingestion of a relatively large but tolerable dose of alcohol transiently enhances thromboxane-mediated platelet activation. The observations also demonstrate alcohol-induced changes in the normal circadian periodicity of the hemostatic system in subjects not accustomed to consumption of alcohol.

Comparison of hypotensive epidural anaesthesia and spinal anaesthesia on blood loss and coagulation during and after total hip arthroplasty.

BACKGROUND: Hypotensive epidural anaesthesia (HEA) is a technique for reducing peroperative blood loss by significantly lowering mean arterial pressure (MAP). METHODS: Thirty patients scheduled for primary total hip arthroplasty were given HEA (n=15) or spinal anaesthesia (SPA) (n= 15) with bupivacaine in random order. The dose of bupivacaine was titrated to provide epidural blockade up to T1-T4 and spinal blockade at least to T10. Intravenous adrenaline infusion was adjusted to achieve a MAP of about 50-60 mmHg in the HEA group. During SPA MAP was maintained above 70 mmHg with ephedrine, as needed. RESULTS: Intraoperative blood loss (median and 25th and 75th percentiles) was 400 ml (163-575) in the HEA group and 900 ml (663-1,100) in the SPA group (P<0.05). At 3 h postoperatively cumulative blood loss was still smaller in the HEA group (600 ml versus 1,100 ml, P<0.05). The cumulative number of transfused packed red cell concentrate (PRC) units was smaller in the HEA group than in the SPA group during surgery and postoperatively. Prothrombin time value was smaller in the SPA than in the HEA group (69% versus 79%, P<0.05) at 3 h postoperatively. D-dimer concentrations increased more in the SPA group at the end of the surgery and 3 h postoperatively (P<0.05). CONCLUSIONS: HEA resulted in reduced blood loss due to hypotension and reduced number of transfused PRC units during total hip arthroplasty. Based on lower prothrombin time value and higher D-dimer concentrations in the SPA group, the coagulation system might be better preserved during HEA than SPA.

Relation of inflammation to vascular function in patients with coronary heart disease.

Endothelium plays a pivotal role in the regulation of vascular relaxation. Inflammation may in turn induce endothelial dysfunction and thus increase the risk of atherothrombosis. We investigated 31 men with angiographically verified coronary heart disease, aged 57. 7+/-5.3 years, in regard to endothelium-dependent, acetylcholine-induced, and to endothelium-independent, sodium nitroprusside-induced vasodilatation in the forearm vasculature by strain-gauge plethysmography. Logistic regression analysis served to determine the relation between forearm vascular function and the inflammatory factors measured, concentration of C-reactive protein, subtypes of peripheral blood T-lymphocytes, and other factors potentially affecting endothelial function (lipoprotein and glucose levels). Concentration of C-reactive protein was an independent determinant of endothelium-dependent vascular function (P<0.001 for low dose acetylcholine, P=0.01 for high dose acetylcholine). Other determinants of endothelium-dependent vascular dysfunction were CD8-lymphocytes expressing ICAM-1 (P=0.001), antibodies to oxidized low-density lipoprotein (P<0.001), and body weight (P=0.007). The present data showed an association between inflammatory risk factors linked to atherothrombosis and endothelial dysfunction in coronary heart disease patients. It is possible that endothelial dysfunction in coronary heart disease patients is related to the chronic inflammation or infection coexisting with atherosclerosis.

Platelet dysfunction after intravenous ketorolac or propacetamol.

BACKGROUND: Paracetamol is a weak cyclo-oxygenase inhibitor in vitro. A recent study in children has shown that high doses of paracetamol are effective and safe. We studied the effect of propacetamol on haemostasis in adult volunteers. METHODS: Ten volunteers were investigated in a double-blind, randomized, crossover study. They received propacetamol 60 mg kg(-1) or ketorolac 0.4 mg kg(-1) in saline i.v. (30 min) in two different sessions. Platelet function was evaluated before the test infusion (S-0), two (S-2) and 24 h (S-24) after the start of the infusion. Coagulation parameters (PT, APTT, factor V and VII activities) were measured at S-0, S-24 and 48 h (S-48). RESULTS: One of the volunteers had no secondary platelet aggregation in S-0 and was excluded from the final analysis. Two hours (S-2) after propacetamol and ketorolac administration the adrenaline (0.9 microg ml(-1) and 9.0 microg ml(-1)) induced maximal platelet aggregation was decreased compared with S-0. At S-2 platelet aggregation was inhibited more after ketorolac than after propacetamol. At 24 h after ketorolac, but not after propacetamol, there was still a decrease in the adrenaline-induced maximal platelet aggregation. Propacetamol did not affect adenosine diphosphate (ADP)-induced maximal platelet aggregation, whereas ketorolac decreased 3 and 6 microM ADP-induced maximal platelet aggregation at S-2 and S-24. However, 2 h after both ketorolac and propacetamol, thromboxane B2 (TxB2) concentration decreased in platelet rich plasma after 5 min aggregation induced by 8 microM ADP. Coagulation was unaffected. CONCLUSION: Propacetamol 60 mg kg(-1) i.v. causes reversible platelet dysfunction demonstrated by a decrease in maximal platelet aggregation and TxB2 concentration. After 0.4 mg kg(-1) ketorolac i.v. platelet aggregation and TxB2 formation are inhibited more in comparison with propacetamol, and platelet dysfunction is still seen after 24 h.

Plasminogen activator inhibitor-1 in patients with ischemic stroke.

Low fibrinolytic activity may increase the risk of thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of the fibrinolytic system. We examined the PAI-1 levels in patients with ischemic stroke. Plasma levels of PAI-1 were measured using enzyme-linked immunosorbent assay (ELISA) in 55 consecutive patients (age 60.2 +/- 11.4, 40 males and 15 females) with ischemic stroke. The PAI-1 assessments as well as neurological examinations using validated stroke scales were conducted at admission and 1 week, 1 month, and 3 months after stroke. Sex- and age-matched controls (+/- 4 years) underwent plasma PAI-1 measurement once. Etiology of the stroke was classified using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. All pertinent stroke risk factors were recorded. All patients were contacted 3 years after stroke for recurrent vascular thrombotic disease. The plasma PAI-1 levels were 17.2 +/- 7.8 IU at admission, 11.2 +/- 9.2 IU at 1 week, 14.4 +/- 7.9 IU at 1 month, and 17.8 +/- 7.8 IU at 3 months among patients and 11.8 +/- 9.5 IU among controls (p values are < .002, .7, .12, and < .0005, respectively). As a rule, the neurological scores did not show a correlation to the PAI-1 levels. Presence of diabetes, hypertension, obesity, smoking, anticoagulant treatment, and sleep apnea did not affect the PAI-1 levels at any time point. Females had slightly higher PAI-1 levels. Age was a strong determinant for PAI-1 levels being higher in younger patients at every sampling time point (p values .02, .02, .02, and .03 respectively). The etiology of the ischemic stroke did not have an impact on PAI-1 levels. In 16 patients recurrent thrombosis had occurred. The high PAI-1 levels at admittance may reflect either an acute phase response or a chronic state. Normalized levels at 1 week and 1 month may be due to hospital diet, antithrombotic medication, weight loss, active physical therapy, and better care for diabetes. PAI-1 levels at 3 months after stroke did not predict recurrent thrombosis.