Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis

Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb <100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb≥120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12±1.2 g/l vs 4±0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P<0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18±1.1 g/l vs 7±1.1 g/l, P<0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenous efforts should have been made to control the disease itself. Received: 21 February 1997 / Accepted: 21 April 1997     

Substance use-related outpatient consultations in specialized health care: an underestimated entity

Background To study the occurrence and documentation of substance use related outpatient visits in specialized health care.
Methods The diagnosis recorded in retrospective discharge data in Tampere University Hospital for 6 years was compared with the prospective data gathered from separately completed forms added during an 8-week period to every outpatient's discharge data. In this form, the relation of substance use and the actual reason for the consultation were specifically elicited.
Results On the basis of diagnoses, retrospectively, 0.4% (6,666 of 1,555,898) of outpatient visits were caused by substance use. In the prospective part of the study, 5.6% of visits (1,401/25,014) were related to substance use. Retrospective study demonstrated 2% prevalence of substance use, whereas prospective study showed 36% substance use–related visits at the emergency room. According to the retrospective discharge data, alcohol-related organ damages were the major reason for substance use–related outpatient visits. In the prospective study, the proportion of acute traumas was most prevalent.
Conclusions Our study indicates that substance use–related visits often remain undetected in specialized health care. Substance use–related visits were underdocumented/undetected in the emergency room. Using a simple separate form could dramatically increase the detection of substance use–related visits.     

Acute sinusitis: Finnish clinical practice guidelines

These clinical practice guidelines aim at providing assistance mainly to primary health care physicians for the diagnosis and management of acute sinusitis. Despite the huge impact of upper respiratory infections, criteria for diagnoses are often vague, and physicians are often uncertain of their diagnoses. This is not surprising, as the sole definition of acute sinusitis is somewhat confusing, not to mention the existing discrepancies between treatments, even among specialists. The Finnish Society of Otorhinolaryngology has set up a committee to evaluate existing data on acute sinusitis and to formulate these guidelines. The committee comprised Finnish experts in adult and paediatric otorhinolaryngology, clinical microbiology, radiology, paediatrics, and epidemiology. Recommendations given are based on the principles of evidence-based medicine, with the level of evidence presented.     

Predictors of New Airway Obstruction – An 11 Year’s Population-Based Follow-Up Study

In the present study we aimed to investigate the incidence and predictors of spirometry based airway obstruction in a representative population-based sample. Altogether 3,863 subjects, 1,651 males and 2,212 females aged ≥30 years had normal spirometry in year 2000. Fifty-three percent of them were never and 23% current smokers. A re-spirometry was performed 11 years later. Several characteristics, such as level of education, use of alcohol, physical activity, diet using Alternate healthy eating (AHEI) index, body mass index, circumwaist, sensitive C reactive protein (CRP) and cotinine of the laboratory values and co-morbidities including asthma, allergic rhinitis, sleep apnoea and chronic bronchitis, as potential risk factors for airway obstruction were evaluated. Using forced expiratory volume in one second/ forced vital capacity below the lower limit of normal, we observed 124 new cases of airway obstruction showing a cumulative 11-year incidence of 3.2% and corresponding to an incidence rate of 5.6/1,000 per year (PY). The incidence rate was higher in men than in women (6.3/1,000 PY vs. 5.0/1,000 PY, respectively). The strongest risk factors were current smoking (Odds ratio [OR] 2.5) and previously diagnosed asthma (OR 2.1). Sensitive CRP associated with the increased risk and high AHEI index with the decreased risk of airway obstruction. Using the similar study approach our findings on the incidence of airway obstruction are in line with the previously published figures in Europe. We were able to confirm the recent findings on the protective effect of healthy diet.