Blood coagulation in Prediabetes clusters-impact on all-cause mortality in individuals undergoing coronary angiography.

BACKGROUND: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. METHODS: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. RESULTS: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. CONCLUSIONS: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies.

Gender-Associated Variation in DOAC Levels.

BACKGROUND: Direct oral anticoagulants (DOAC) such as Xa inhibitors rivaroxaban (riva) and apixaban (apix) are increasingly replacing Vitamin K antagonists in prophylaxis and treatment of venous thromboembolism (VTE). Measurements of DOAC plasma levels may be necessary in certain clinical conditions to determine the further dosage. Making decisions is made more difficult by the fact that the peak and trough plasma levels are subject to strong inter-individual fluctuations with overlapping reference ranges. We wanted to find out whether the peak and trough levels can be narrowed if they are determined based on age and gender. METHODS: Therefore, we collected data on peak and trough anti-Xa concentrations in patients treated with either rivaroxaban (n = 93) or apixaban (n = 51) in one center. After exclusion of blood samples of uncertain oral intake, 83 samples for rivaroxaban and 49 samples for apixaban remained for further analysis. Differences between male (riva n = 42, apix n = 28) and female (riva n = 41 and apix n = 21) as well as young (≤ 60 years, riva n = 44, apix n = 23) and elder (> 60 years) patients (riva n = 39 and apix n = 26) were analyzed by Student`s t-test and retrospective regression. RESULTS: We found no differences in age and gender for the apix peak levels. But women had significantly higher riva peak concentrations than men (308.8 ± 178.1 ng/mL versus 206.4 ± 80 ng/mL, p = 0.013). Patients older than 60 years had significantly higher riva peak levels than those younger than 60 (293.7 ± 126.7 ng/mL versus 211.7 ± 158.4 ng/mL, p = 1.29 x 10-8). CONCLUSIONS: In search of narrowing standard peak and trough levels in patients' sera we found significant differ-ences between patients below and above sixty years of age. Gender-associated differences were found in rivaroxa-ban levels possibly explaining DOAC associated hypermenorrhea. In conclusion, gender and age should be included in the determination of peak blood concentration references.

Thrombophilia Testing - a Systematic Review.

BACKGROUND: Thrombophilia testing is controversial, not least because of its high cost. Because comprehensive valid testing requires standardized blood collection close by the specialized laboratory, and interpretation of findings together with clinical data, often only part of the necessary laboratory analyses can be performed in remote central laboratories. Restrictive indications for testing, as have been recommended by previous reviews on the topic, have been based on incomplete analytics, studies with small case numbers, or short observation periods, and on an inappropriate, simple risk stratification for venous thromboembolism (VTE), further subdivided into provoked and unprovoked events. METHODS: The authors reviewed four electronic databases for all peer-reviewed and in-press articles about thrombophilia, VTE, obstetric complications, and arterial thrombosis. After confirmation for relevance to the topic, 201 articles were accepted for inclusion in this article. This review summarizes the studies relevant to the evaluation of thrombophilic conditions, and their combination with each other and with clinical risk factors, to stratify individual risk for thromboembolism and obstetric complications. RESULTS: Thrombophilia testing requires highly skilled personnel for laboratory analysis and interpretation. Clinical conditions that influence the results as well as special preanalytical, analytical, and postanalytical aspects must be considered if valid results are to be obtained. Tests involved include the natural anticoagulants antithrombin, protein C, and protein S; the procoagulants fibrinogen (dysfibrinogen), prothrombin (mutation G20210A), factor V (Leiden mutation), factor VIII/von Willebrand factor/blood group ABO, factor IX, and factor XI; the anti-phospholipid antibodies to detect an antiphospholipid syndrome and potentially additional uncertain thrombophilic conditions. The risks of thrombophilic conditions and clinical risk factors for VTE are cumulative or even supra-additive. Scores from thrombophilic conditions and other genetic and nongenetic risk factors permit estimation of risk for first and recurrent VTE. Therapeutic strategies can be derived from this risk stratification. CONCLUSIONS: Thrombophilia testing is indicated when the results have potential to influence the type and duration of treatment. Indications include certain patients after VTE; or patients without previous VTE but with positive family history regarding VTE or thrombophilia before major surgery, pregnancy, combined oral contraceptives, or hormone replacement therapy. Whether or not thrombophilia is present should help determine anticoagulation, hormonal contraception, or hormone replacement.

Platelet Reactivity and Cardiovascular Mortality Risk in the LURIC Study.

BACKGROUND: The clinical and prognostic implications of platelet reactivity (PR) testing in a P2Y12-inhibitor naïve population are poorly understood. OBJECTIVES: This explorative study aims to assess the role of PR and explore factors that may modify elevated mortality risk in patients with altered PR. METHODS: Platelet ADP-induced CD62P and CD63 expression were measured by flow-cytometry in 1520 patients who were referred for coronary angiography in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC). RESULTS: High- and Low-platelet reactivity to ADP were strong predictors of cardiovascular and all-cause mortality and risk equivalent to the presence of coronary artery disease. (High platelet reactivity 1.4 [95% CI 1.1-1.9]; Low platelet reactivity: 1.4 [95% CI 1.0-2.0]). Relative weight analysis indicated glucose control (HbA1c), renal function ([eGFR]), inflammation (high-sensitive C-reactive protein [hsCRP]) and antiplatelet therapy by Aspirin as consistent mortality risk modifiers in patients with Low- and High-platelet reactivity. Pre-specified stratification of patients by risk modifiers HbA1c (<7.0%), eGFR (>60 mL/min/1.73 m2) and CRP (<3 mg/L) was associated with a lower mortality risk, however irrespective of platelet reactivity. Aspirin treatment was associated with reduced mortality in patients with high platelet reactivity only (p for interaction: 0.02 for CV-death [<0.01 for all-cause mortality]. CONCLUSIONS: Cardiovascular mortality risk in patients with High- and Low platelet reactivity is equivalent to the presence of coronary artery disease. Targeted glucose control, improved kidney function and lower inflammation are associated with reduced mortality risk, however independent of platelet reactivity. In contrast, only in patients with High-platelet reactivity was Aspirin treatment associated with lower mortality.

Microsurgical Breast Reconstruction in Patients with Disorders of Hemostasis: Perioperative Risks and Management.

BACKGROUND: Surgical and technological advances have resulted in the widespread adoption of microsurgical breast reconstruction. Many comorbidities that potentially might impair vasculature and wound healing are no longer considered contraindications for these procedures. However, some uncertainty still prevails regarding the perioperative management of patients with disorders of hemostasis. METHODS: The authors combined a literature review with a retrospective chart review of patients with disorders of hemostasis who had undergone microsurgical breast reconstruction at the senior author's (J.F.) center between 2015 to 2020. Several disorders associated with thrombotic and/or hemorrhagic complications were identified, and a standardized risk assessment and management strategy was developed in cooperation with a hematologist. RESULTS: Overall, 10 studies were identified comprising 29 patients who had a defined disorder of hemostasis and underwent microsurgical breast reconstruction. Seventeen microsurgical breast reconstructions were performed on 11 patients at the senior author's (J.F.) center. High factor VIII levels, heterozygous factor V Leiden, and heterozygous prothrombin mutation G20210A were the most common genetic or mixed genetic/acquired thrombophilic conditions. As expected, hereditary antithrombin, protein C, or protein S deficiencies were rare. Among hemorrhagic disorders, thrombocytopenia, platelet dysfunction, and von Willebrand disease or low von Willebrand factor levels were those factors most frequently associated with increased perioperative bleeding. CONCLUSIONS: Patients should be screened for elevated risk of thrombosis or bleeding before undergoing microsurgical breast reconstruction, and positive screening should prompt a complete hematologic evaluation. Interdisciplinary management of these disorders with a hematologist is essential to minimize risks and to obtain optimal reconstructive results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Immune Status and Mortality in Smokers, Ex-smokers, and Never-Smokers: The Ludwigshafen Risk and Cardiovascular Health Study.

INTRODUCTION: Elevated leukocyte counts are associated with cardiovascular disease. Smoking induces inflammation and alters levels of leukocyte subtypes. AIMS AND METHODS: Our aim was to investigate the effect of smoking on circulating immune cells and their association with mortality. Lymphocyte subtypes were identified by flow cytometry of fluorescent-labeled cells. We analyzed the association of leukocytes with mortality using Cox regression and assessed their effect on risk prediction based on principle components (PCs) using area under the receiver operating characteristic curve and net-reclassification in 2173 participants from the Ludwigshafen Risk and Cardiovascular Health Study, a prospective case-control study in patients who underwent coronary angiography. RESULTS: The numbers of T cells, monocytes, and neutrophils were higher and natural killer cells were lower in smokers compared with never-smokers. In never-smokers, lymphocyte counts were inversely associated with mortality while a positive association was observed for neutrophils. The neutrophil-to-lymphocyte ratio (NLR) had the strongest association in never-smokers with a hazard ratio (95% confidence interval) of 1.43 (1.26-1.61). No associations were found in smokers. Adding the first five PCs or the NLR to a risk prediction model based on conventional risk factors did not improve risk prediction in smokers, but significantly increased the area under the curve from 0.777 to 0.801 and 0.791, respectively, in never-smokers. CONCLUSIONS: Lymphocyte counts were inversely associated with mortality in never-smokers but not in active smokers. Markers of innate immunity, namely total neutrophils and CD11b+/CD18+ and CD31+/CD40- granulocytes, were directly associated with mortality. Adding markers of immune function like PCs or the NLR to basic risk models improved risk prediction in never-smokers only. IMPLICATIONS: Total leukocyte counts were higher in active smokers as compared to never-smokers due to elevated counts of neutrophils and monocytes but declined in ex-smokers with increasing time since quitting. In the never-smokers but not in smokers, lymphocyte counts were inversely associated with mortality while there was a direct association with neutrophils, even after adjustment for conventional cardiovascular risk factors. Adding markers of immune function to basic risk models improved risk prediction in never-smokers only. Our data indicate that smoking status has an important impact on the ability of leukocyte counts to predict long-term cardiovascular outcomes.

Comparison of platelet function tests for the in vitro quality assessment of platelet concentrates produced under real-life conditions.

Platelet quality in different platelet concentrates (PCs) has been the subject of several studies. Nonetheless, there is a lack of robust data on the correlation and agreement among platelet function tests as a prerequisite for the association of PC functionality in vitro with platelet function in vivo post PC transfusion. The purpose of our study was to correlate a larger panel of platelet function assays in PCs and to assess whether the methods agree sufficiently and can be used interchangeably. Twelve apheresis platelet concentrates in plasma (APC), 16 pooled platelet concentrates in plasma (PPC), and 12 PPC in T-sol (PPCA) were examined on days 1 and 4 after production. PCs were tested for platelet count, light transmission aggregation (LTA) induced by ADP, collagen, or TRAP; platelet ATP release induced by collagen; and spontaneous and ADP and TRAP-induced increase in CD62P and PAC1 expression measured by flow cytometry. All tests were performed in undiluted platelet-rich plasma, recalcified and mixed with an inhibitor of factor Xa and thrombin. Most platelet function parameters correlated significantly with each other, but agreement among methods was insufficient. A proper inverse correlation was observed between ADP-induced LTA and spontaneous platelet activation assessed by CD62P expression (r = -0.61, p < 0.0001). Spontaneous CD62P correlated also significantly with spontaneous PAC1 (r = 0.69, p < 0.0001) and inversely with TRAP-induced CD62P expression (r = -0.86, p < 0.0001). We found significant correlations among all flow cytometric assays measuring platelet CD62P and PAC1 expression induced by ADP or TRAP. Subsequent Bland Altman analysis revealed insufficient agreement between methods. With one exception (collagen-induced LTA compared with TRAP-induced LTA, percentage error = 16%) the limits of agreement expressed as percentage error exceeded the chosen acceptable difference of 30%. In APC, platelet count was 41% and 44% higher, respectively, than in PPC and PPCA (p < 0.0001). Spontaneous CD62P and PAC1 expression were significantly greater, and ADP-induced aggregation and agonist-induced increase in CD62P and PAC1 were significantly lower in PPCA compared to APC and PPC on day 4 of storage. ADP and TRAP-induced CD62P and PAC1 activatability fell significantly during storage between day 1 and day 4 in APC and PPCA, but not in PPC. In conclusion, different platelet function tests capture different aspects of platelet function and do not correlate and agree sufficiently to be used interchangeably.

Platelet activation by ADP is increased in selected patients with anterior ischemic optic neuropathy or retinal vein occlusion.

To investigate whether adenosine diphosphate (ADP)-induced platelet hyperaggregability is associated with nonarteritic anterior ischemic optic neuropathy (NAION) or retinal vein occlusion (RVO). We retrospectively reviewed thrombophilia screening data of patients with NAION or RVO without a history of arterial hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette abuse. Patients with a positive family history for thromboembolism were not excluded. Platelet aggregation (area under the curve, AUC) after induction of 0.5, 1.0, and 2.0 µmol of ADP was estimated in 25 NAION and RVO patients and compared with 25 healthy controls. We observed significantly greater platelet aggregation post 0.5 (P = 0.002) and 1.0 (P = 0.008) µmol of ADP among NAION and RVO patients compared with healthy controls. Platelet hyperaggregability was significantly more prevalent in patients than in controls (56% vs. 8%; P = 0.0006). Our results suggest that in NAION and RVO patients without a history of arterial hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette abuse, platelets are significantly hyperreactive after induction of very low concentrations of ADP when compared with healthy individuals. This hyperreactivity is particularly evident in patients with a family history of thromboembolism.

Prothrombin polymorphism A19911G, factor V HR2 haplotype A4070G, and plasminogen activator-inhibitor-1 polymorphism 4G/5G and the risk of retinal vein occlusion.

BACKGROUND: Thus far, no data has become available to evaluate systematically the prevalences of prothrombin polymorphism A19911G (PT A19911G), factor V HR2 haplotype A4070G (FV A4070G), or plasminogen activator-inhibitor-1 polymorphism 4G/5G (PAI-1 4G/5G) in patients who develop retinal vein occlusion (RVO) without cardiovascular risk factors. MATERIALS AND METHODS: We retrospectively evaluated comprehensive thrombophilia data from 42 preselected RVO patients without cardiovascular risk factors. The prevalences of different gene mutations and polymorphisms including factor V Leiden mutation G1691A (FVL), FV A4070G, prothrombin mutation G20210A, PT A19911G, and PAI-1 4G/5G were compared with 241 healthy controls matched for age and sex. RESULTS: A total of 20 patients (47.7%) were found to carry thrombophilic gene polymorphisms including FVL, FV A4070G, and homozygous PT A19911G compared with 72 of 241 controls (29.9%; p = 0.03). Subgroup analysis of patients with a significant personal or family history of thromboembolism revealed a high prevalence of FVL, FV A4070G, and homozygous PT A19911G (p = 0.005). FV A4070G was found to be significantly associated with at least two other heterozygous or one homozygous gene polymorphisms (p = 0.02). Multivariate analysis revealed the presence of FVL (p = 0.0017) and homozygous PT A19911G (p = 0.03) polymorphism as independent risk factors for the development of RVO. CONCLUSIONS: Our results indicate that in selected RVO patients screening for thrombophilic gene polymorphisms including FVL, FV A4070G and homozygous PT G19911A may be helpful in a high percentage of cases. Our findings suggest that hereditary thrombophilia associated with RVO is more likely to be multigenic than caused by any single risk factor.

Selective Thrombophilia Screening in Young Patients with Retinal Artery Occlusion.

PURPOSE: To investigate the prevalence of various thrombophilic disorders among young patients with retinal artery occlusion (RAO). PROCEDURES: We retrospectively reviewed thrombophilia screening data of young patients ≤60 years of age with RAO and healthy controls matched for gender and age. RESULTS: Thrombophilia screening data of 25 young patients and 62 healthy controls were analyzed. Mean patient age by the time of the RAO was 43.3 ± 10.8 years. Overall, thrombophilic defects were found to be present in 17 patients (68%) compared with 11 of 62 controls (17.7%; p < 0.0001). Multivariate logistic regression analysis confirmed a statistically significant association between the development of RAO and increased levels of lipoprotein(a) (odds ratio: 9.48; p = 0.001) and factor VIII (odds ratio: 6.41; p = 0.024). There was a strong association between the presence of thrombophilic disorders and a personal or family history of thromboembolism (p = 0.01). CONCLUSIONS: Our results indicate that screening for thrombophilic disorders among selected young patients with RAO yields positive results in a high percentage of cases.

The impact of whole blood processing and freezing conditions on the quality of therapeutic plasma prepared from whole blood.

BACKGROUND: The quality of whole blood (WB)-derived plasma preparations has been the subject of several studies, but there has been a lack of robust, comparative data for the different methods of processing and freezing. STUDY DESIGN AND METHODS: Six WB-derived plasma units were pooled and split (n = 16) and frozen within either 8 or 24 hours after WB collection, stored at 4°C or at room temperature (RT), and then frozen either slowly at -20°C or rapidly to below -30°C. Plasma units were tested for fibrinogen, Factor (F)V, FVII, FVIII, FXI, and von Willebrand factor (VWF), protein C (PC), protein S (PS) activity and free PS, prothrombin time, and partial thromboplastin time. RESULTS: FVIII was reduced by 9% to 19% after having been stored for 24 hours irrespective of storage temperature. Slow freezing (SF) reduced FVIII by 17% to 25% compared to rapid freezing (RF) to below -30°C. Storage temperature, but not 24-hour storage, decreased PS activity by 20% to 28%. PS activity was 8% to 17% lower in plasma units frozen slowly compared to RF. Storage and freezing had no influence on free PS. SF caused small losses of FVII and FXI activity. CONCLUSION: Twenty-four-hour hold at RT and SF both reduce FVIII levels below 70 U/dL in many plasma units. PS activity is affected substantially by storage temperature and SF, but free PS is not. With regard to plasma quality, freezing to below -30°C within 1 hour is superior to SF at -20°C.

Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function.

Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen+ ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin+ UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p < 0.05) and an impaired platelet aggregation response to ADP (p < 0.05). These results suggest that Intercept treatment may induce platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established.

Preoperative hemostasis and its association with bleeding and blood component transfusion requirements in cardiopulmonary bypass surgery.

BACKGROUND: Variables of hemostasis before surgery might indicate an elevated risk of bleeding. We determined hemostasis tests and standardized bleeding history and their association with bleeding and transfusion requirements in cardiopulmonary bypass (CPB) surgery. STUDY DESIGN AND METHODS: In a prospective trial, variables from 104 patients were associated with postsurgical bleeding and with red blood cells (RBCs) and platelet concentrate (PC) transfusions. Variables included standardized bleeding history, prothrombin time (PT), fibrinogen, fibrin monomers, Factor VIII, von Willebrand factor (VWF), multiple electrode aggregation (MEA), and the day of aspirin or thienopyridine withdrawal before operation. RESULTS: Multiple linear regression revealed bleeding history score, ADP-induced MEA, CPB time, and hemoglobin (Hb) independently associated with postoperative bleeding and bleeding history, arachidonic acid (AA)-induced MEA, CPB time, and PT associated with RBC transfusions. The logistic regression model for the outcome of bleeding within 24 hours after operation indicated ADP-induced MEA, the day of aspirin withdrawal before operation, and CPB time as predictors. AA-induced MEA, CPB time, Hb, and PT were predictors of RBCs transfusion. ADP-induced MEA, the day of aspirin withdrawal, PT, and VWF were associated with PC transfusion. CONCLUSIONS: A standardized bleeding history may help to identify patients undergoing CPB surgery whose risk of bleeding is elevated. ADP-induced MEA appears to predict postoperative bleeding and PC transfusion requirements, while AA-induced MEA and preoperative Hb indicate the need for RBCs. The time of aspirin withdrawal before surgery influences perioperative blood loss and PC transfusion.

The Use of Solvent/Detergent Treatment in Pathogen Reduction of Plasma.

The solvent/detergent (SD) process used for plasma can safely inactivate all lipid-enveloped viruses. The introduction of a specific prion-binding ligand gel in combination with SD treatment, time-reduced from 4 to 1-1.5 h, still ensures efficient virus kill, reduces abnormal prion protein by >5 log steps, and preserves levels of plasmin inhibitor at close to the reference range. Infections with known non-enveloped viruses such as HAV or parvovirus B19 are prevented by ensuring low virus loads in the starting plasma units, dilution through pooling of single plasma units, and neutralization of immune antibodies already present in the initial plasma pools. The major advantages of SD plasma over fresh frozen plasma and the other pathogen-inactivated plasmas are its extreme safety with respect to transfusion-related acute lung injury and the significantly lower likelihood of provoking allergic reactions. Both advantages are best interpreted as results of the dilution effect of pooling. No fewer than 18 clinical studies covering all indications for plasma, and extensive clinical experience have shown that reduced levels of coagulation factors and inhibitors as a result of SD treatment do not impair significantly the clinical efficacy or tolerance of plasma. Properly standardized clotting factor and inhibitor potencies and low batch-to-batch variations when compared with single-donor plasma units makes SD plasma more suitable for standardized treatment.

[Advanced Nursing Practice in daily nursing care: practice development of an acute geriatric Advanced Nursing Practice team]. / Advanced Nursing Practice (ANP) im direkten Pflegealltag: Die pflegerische Praxisentwicklung eines akutgeriatrischen ANP-Teams.

In 2000, the Institute of Nursing Science in Basel started with a clinically oriented Master programme in Advanced Nursing Practice (ANP). The nursing expertise achieved with this degree includes enhanced skills and know-how in a specialised area. Together with their nurse colleagues, the clinically, scientifically, and practice-orientated Advanced Practice Nurses (APNs) support and develop nursing practice in Switzerland further, especially for chronically ill and geriatric patients. It is estimated that 25 % of older adults aged 80-years and older experience at least one hospitalisation per year. Beside the acute diagnosis, they suffer from several chronic illnesses. These highly complex and fragile patients need to be cared for by nurses with enhanced practice skills in gerontology. At the acute geriatric ward of the University Hospital Basel a practice development project is ongoing under the guidance of an APN to support person-oriented, geriatric care. The practice development project is led by the principles of action research. The circular process of "look-think-act" facilitates the critical examination of nursing practice. First results show shorter length of hospital stay for patients and improved job-satisfaction and self-efficacy for nurses. This article shortly reveals the history of ANP and highlights the development, implementation, and first results of the practice development project.

Sources of variation in factor VIII, von Willebrand factor and fibrinogen measurements: implications for detecting deficiencies and increased plasma levels.

OBJECTIVES: Differences in pre-analytical and assay conditions, inappropriate reference ranges, or inflammation may have the potential to impair clinical decisions based on measurements of factor VIII (FVIII), von Willebrand factor (VWF) and fibrinogen (Fg). This study examined the impact on FVIII, VWF and Fg in plasma of freezing and thawing, different citrate anticoagulant concentrations, and inflammation, as determined by high-sensitivity C-reactive protein (hsCRP). MATERIALS AND METHODS: FVIII was determined prior to freezing and after thawing using a one-stage clotting assay (FVIII:C), an amidolytic assay (FVIII:AM) and an enzyme immunoassay (FVIII:Ag). Samples were anticoagulated with 106 or 129 mmol/L of citrate. FVIII, VWF and Fg were quantified in 300 individuals to establish reference ranges and to investigate associations with hsCRP. RESULTS: Freezing and thawing reduced FVIII:C and FVIII:AM markedly. FVIII coagulant activities were not significantly different between samples anticoagulated with 106 or 129 mmol/L of citrate, respectively. FVIII, VWF and Fg were significantly associated with hsCRP. FVIII:C was greater than FVIII:AM and FVIII:Ag in all experiments, indicating that the presence of activated FVIII may lead to overestimation of FVIII:C. CONCLUSIONS: Standardized freezing and thawing of plasma samples appears to be indispensable if reliable FVIII results are to be obtained. Because inflammation can potentially mask deficiency states or mimic an increased risk of thrombosis, FVIII, VWF and Fg determinations should be supplemented by measurements of hsCRP.