[Venous thromboembolism prophylaxis in medical patients at Sahlgrenska University Hospital]. / Medicinpatienter behöver bättre trombosprofylax - 12 procent av patienter med hög risk för venös tromboembolism fick profylax ­ den internationella siffran är 40­60 procent.

Venous thromboembolism prophylaxis in medical patients at Sahlgrenska University Hospital A hospitalized medical patient with risk factors has a 5-15 % risk of venous thromboembolism (VTE). Nonetheless thromboprophylaxis is largely underused. Our aim was to establish the proportion of high risk patients at Sahlgrenska University Hospital receiving thromboprophylaxis and to examine the 3-month incidence of VTE and bleeding. 198 patients were included and risk-stratified according to American College of Chest Physician guidelines. 12 % of high risk patients without and 26 % with increased bleeding risk received pharmacological thromboprophylaxis, as did 8 % of the patients without increased risk of VTE. VTE events occurred in 4.5 % of high risk patients, none received prophylaxis. Bleeding occurred in 5.8 % of those with increased bleeding risk. There is a need to improve thromboprophylaxis use to enhance patient safety and quality of care, for instance by issuing local guidelines.

Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays.

Dabigatran is an oral, reversible thrombin inhibitor that has shown promising results in large clinical trials. Laboratory monitoring is not needed but the effects on common coagulation assays are incompletely known. Dabigatran was added to plasma from healthy subjects in the concentration range 0-1,000 µg/l and analysed using several reagents for activated thromboplastin time (APTT), prothrombin time (PT), fibrinogen, antithrombin, and activated protein C resistance. Typical trough concentrations are about 50 µg/l, peak concentrations 100-300 µg/l. At 100 µg/l all APTT-results were prolonged. The concentration required to double APTT ranged between 227 and 286 µg/l, the responses for all five reagents were similar. PT-reagents were much less affected with almost no samples above INR 1.2 at 100 µg/l. The effect was sample dilution dependent with PT Quick type more sensitive than PT Owren type methods. If a patient on dabigatran has prolonged APTT, >90 seconds, and Quick PT INR>2 or Owren PT INR>1.5 over-dosing or accumulation of dabigatran should be considered. Two of four fibrinogen reagents underestimated the fibrinogen concentration considerably at expected peak concentration. Methods based on inhibition of thrombin over-estimated the antithrombin concentration, but not Xa-based. The APC-resistance methods over-estimated the APC-ratio, which may lead to miss-classification of factor V Leiden patients as being normal. Different coagulation assays, and even different reagents within an assay group, display variable effects at therapeutic concentrations of dabigatran. Some of these assay variations are of clinical importance, thus knowledge is needed for a correct interpretation of results.

Risk of clinically relevant bleeding in warfarin-treated patients--influence of SSRI treatment.

PURPOSE: To investigate the risk of clinically relevant bleeding in warfarin-treated patients with or without concomitant treatment with selective serotonin reuptake inhibitors (SSRIs). METHODS: A cohort study was performed in patients treated with warfarin due to atrial fibrillation. Exposed patients were defined as patients treated with SSRI at any time between January 1999 and September 2005 (n = 117). Unexposed patients without SSRI-treatment were randomly selected and matched for age and sex (1:1). The primary endpoint was hospital admission due to bleeding during the same time period. RESULTS: Bleeding occurred in 17 exposed patients (totally 23 bleedings) and in two unexposed patients (totally two bleedings) (p = 0.0003). A total of 11 bleedings occurred during treatment with the combination of warfarin and SSRI, and 14 during treatment with warfarin only. The total incidences of bleedings per 1000 treatment years were 51.4 (25.7-92.0) and 23.9 (13.1-40.1), respectively, and the unadjusted incidence rate ratio (IRR) 2.15 (0.88-5.11). Cox regression analysis including first bleedings revealed an adjusted hazard ratio of 3.49 (1.37-8.91) for bleeding during treatment with a combination of SSRI and warfarin compared with treatment with warfarin only. Initiation of SSRI therapy was not associated with a change in dose of warfarin or with a change in international normalized ratio (INR) (p = 0.48 and p = 0.31, respectively). CONCLUSION: Addition of SSRI to warfarin-treated patients may be associated with an increased risk of clinically relevant bleeding. The effect seems not to be associated with a direct influence of SSRI on the anti-coagulant activity of warfarin.

Menorrhagia and minor bleeding symptoms in women on oral anticoagulation.

BACKGROUND: Oral anticoagulation (OA) is a common treatment with a known risk of fatal or major bleeding, but also minor bleeding symptoms and menorrhagia can cause substantial discomfort and necessitate medical or surgical interventions. The extent of these side effects is however not previously reported. The objective of this study is to assess the frequency of minor bleeding symptoms and menorrhagia attributed to OA treatment. METHODS: Ninety fertile women between 15 and 49 years-of-age on OA treatment completed an inquiry at the anticoagulation clinics of Malmö, Lund and Gothenburg, Sweden. RESULTS: The frequency of minor bleeding symptoms was significantly increased during OA treatment (P < 0.05) except for hematuria. The incidence of bleeding after tooth extraction (>3 h) increased from 3.0 to 45.2%, easy bruising 17.8-75.6%, epistaxis 11.1-23.6%, gingival bleeding 22.2-48.3% and hematuria 10.0-15.6% (Table 1). Hematemesis was reported in 5.6% prior to as compared to 14.4% during OA treatment, blood in the feces in 8.9 and 18.9%, respectively. Mean duration of menses increased from 5.6 to 6.1 days (P < 0.01) and reported menorrhagia from 44.2 to 70.8% (P < 0.001). Eighteen percent were treated for menorrhagia before and 29.9% during OA treatment (P < 0.01). CONCLUSIONS: OA treatment is known to confer increased risk of fatal or major bleeding. This study shows that fertile women on OA also experience significantly increased minor bleeding symptoms including menorrhagia that may considerably impair quality of life.

Experimental exposure to wood-smoke particles in healthy humans: effects on markers of inflammation, coagulation, and lipid peroxidation.

Particulate air pollution is known to increase cardiovascular morbidity and mortality. Proposed mechanisms underlying this increase include effects on inflammation, coagulation factors, and oxidative stress, which could increase the risk of coronary events and atherosclerosis. The aim of this study was to examine whether short-term exposure to wood smoke affects markers of inflammation, blood hemostasis, and lipid peroxidation in healthy humans. Thirteen subjects were exposed to wood smoke and clean air in a chamber during two 4-h sessions, 1 wk apart. The mass concentrations of fine particles at wood smoke exposure were 240-280 mug/m3, and number concentrations were 95,000-180,000/cm3. About half of the particles were ultrafine (< 100 nm). Blood and urine samples were taken before and after the experiment. Exposure to wood smoke increased the levels of serum amyloid A, a cardiovascular risk factor, as well as factor VIII in plasma and the factor VIII/von Willebrand factor ratio, indicating a slight effect on the balance of coagulation factors. Moreover, there was an increased urinary excretion of free 8-iso-prostaglandin2alpha, a major F2-isoprostane, though this was based on nine subjects only, indicating a temporary increase in free radical-mediated lipid peroxidation. Thus, wood-smoke particles at levels that can be found in smoky indoor environments seem to affect inflammation, coagulation, and possibly lipid peroxidation. These factors may be involved in the mechanisms whereby particulate air pollution affects cardiovascular morbidity and mortality. The exposure setup could be used to establish which particle characteristics are critical for the effects.

An instrument for measuring health-related quality of life in patients with Deep Venous Thrombosis (DVT): development and validation of Deep Venous Thrombosis Quality of Life (DVTQOL) questionnaire.

BACKGROUND: Few studies have evaluated patient-reported outcomes in connection with a primary event of deep venous thrombosis, partly due to a lack of disease-specific measures. The aim here was to develop a disease-specific health-related quality of life (HRQL) measure, the deep venous thrombosis quality of life questionnaire (DVTQOL), for patients with recent exposition and treatment of proximal deep venous thrombosis. METHODS: A total of 121 consecutive outpatients (50 % males; mean age 61.2 +/- 14 years) treated with warfarin (Waran) for symptomatic proximal deep venous thrombosis were included in the study. Patients completed the SF-36, EQ-5D and the pilot version of the DVTQOL. RESULTS: Items having: high ceiling and floor effect, items with lower factor loadings than 0.50 and items loading in several factors were removed from the pilot version of DVTQOL. In addition, overlapping and redundant items identified by the Rasch analysis were excluded. The final DVTQOL questionnaire consists of 29 items composing six dimensions depicting problems with: emotional distress; symptoms (e.g. pain, swollen ankles, cramp, bruising); limitation in physical activity; hassle with coagulation monitoring; sleep disturbance; and dietary problems. The internal consistency reliability was high (alpha value ranged from 0.79 to 0.93). The relevant domains of the SF-36 and EQ-5D significantly correlated with DVTQOL, thereby confirming its construct validity. CONCLUSIONS: The DVTQOL is a short and user-friendly instrument with good reliability and validity. Its test-retest reliability and responsiveness to change in clinical trials, however, must be explored.

Local INR calibration of the Owren type prothrombin assay greatly improves the intra- and interlaboratory variation. A three-year follow-up from the Swedish national external quality assessment scheme.

In 1999, a simplified procedure for calibration of the Owren prothrombin time (Owren PT) assay was introduced by a working group of the organisation for national quality assurance in laboratory medicine in Sweden. The new protocol allowed local calibration by means of only two lyophilised national plasma calibrators and expression of results as an international normalized ratio (INR). This is our report of a three-year follow-up involving the analysis of data from all laboratories, in hospitals (n=88 in 2002) and primary health care units (n=246 in 2002) that perform the Owren PT assay in Sweden. The interlaboratory variation was significantly improved after the introduction of the new calibration procedure. For the larger hospital-based laboratories, the mean coefficient of variation (CV) was reduced from 7.9% to 5.2% (p<0.0001) when analysing test materials with INR range 2-4. In the higher INR range (>4), the CV was reduced even further, from 10.4% to 6.8% (p<0.0001). The corresponding results from smaller laboratories in the primary health care units showed a similar decrease in CV from 8.2% to 5.7% in the INR range 2-4 (p<0.0001). At the INR range >4, the CV was reduced from 9.5% to 7.8%. The intralaboratory variation was also improved for both types of laboratory categories. This study shows an improved precision, with CV less than 6% at the therapeutic INR range, for both hospital-based laboratories and smaller laboratories in the primary health care system. The results indicate that the Owren PT assay is well suited for local INR calibration employing only two calibrant plasmas in a simplified procedure.

Home treatment of deep vein thrombosis. An out-patient treatment model with once-daily injection of low-molecular-weight heparin (tinzaparin) in 555 patients.

During a 22-month period, 555 consecutive patients at seven hospitals in the western part of Sweden with an acute deep vein thrombosis (DVT) not involving the iliac vein and not having pulmonary embolism were included in a study testing the efficacy of implementing out-patient treatment. For all patients with a confirmed diagnosis of acute DVT, a folder was used that contained two checklists with detailed instructions for further treatment, one for the doctor and one for the nurse, an information pamphlet for the patient and prepared prescriptions for low-molecular-weight heparin (LMWH) tinzaparin (Innohep) of 175 anti-Xa IU/kg body weight subcutaneously once daily and warfarin. Patients not requiring hospitalisation, according to strict guidelines, were then eligible for treatment as out-patients. Prior to release from the emergency department for home treatment, a nurse provided detailed information to the patient and administered the first tinzaparin injection. In 194 (35.0%) out of 555 patients, the DVT was localised only in the lower leg not reaching the popliteal vein. Factors predisposing to venous thromboembolism were identified in 35.0% of the patients. 332 (59.8%) out of the 555 patients studied did not require hospitalisation and were therefore treated as out-patients. 140 of these patients (42.2%) injected themselves, the injection was given by a relative in 63 (19.0%) patients and by the community nurse in 129 (38.9%). Six (1.8%) patients reported a worsening of the DVT condition during the LMWH treatment period. No major bleedings were observed during the injection treatment period. Except for local minor skin bleedings at the injection site, only 3 (0.9%) patients reported minor bleedings during the injection treatment period. Recurrences of venous thromboembolism during the first 2 months were reported in 9 patients (2.7%) out of 332 patients who were sent home from the emergency department. Five (2.2%) patients out of the 223 who were admitted to the hospital had an increased tendency to bleeding. Twelve patients (5.4%) were hospitalised because of a pronounced local status, 26 (11.7%) were senile, social factors were the reason for hospitalisation in 76 (34.1%) and lack of time of the physician in 39 (17.5%) of the patients. A pharmacoeconomic analysis found a cost reduction of 69% with the present model for home treatment compared with traditional in-hospital treatment of DVT patients. We conclude that tinzaparin can be safely used at home by patients with DVT below the inguinal region and that the model used in the present study is cost-effective.

[Less variation in laboratory results after the introduction of INR. Differences between hospital laboratories and laboratories within primary health care are levelled out]. / Mer samstämmiga laboratorieresultat efter övergången till INR. Skillnaderna mellan sjukhus- och primärvårdslaboratorier utjämnade.

In 1999 a new and simplified procedure for calibration of the Owren prothrombin time (Owren PT) assay was introduced in Sweden by the national external quality assessment scheme (Equalis). The new protocol allowed local calibration by means of lyophilised national plasma calibrators and expression of results as an international normalised ratio (INR). A two-year follow-up involving analysis of data from all laboratories that have returned results to Equalis is reported. There was a significant reduction in both between-laboratory and within-laboratory variation after the introduction of the new calibration procedure. For the larger hospital laboratories analysing external controls with INR > 2, the mean coefficient of variation (CV) was reduced from 9.1% to 5.6% (P < 0.0001). The corresponding results from smaller laboratories in the primary health care units showed a similar decrease in CV from 8.8% to 6.3% (P < 0.0001). This study shows that the Owren PT assay is well suited for INR calibration employing calibrant plasmas.