Ambulatory screening and decontamination to prevent Staphylococcus aureus complications in patients undergoing elective surgery (STAUfrei): study protocol for a controlled intervention study.

BACKGROUND: Surgical site infections (SSI) are the most common health care associated infections in German acute hospitals and can result in prolonged hospital stays, increased use of antibiotics and utilisation of care. Staphylococcus aureus bacteria (methicillin-resistant S Aureus (MRSA) and methicillin-susceptible S Aureus (MSSA)) are amongst the most prominent causes of SSI. While up to 90% of documented S Aureus colonization is already detectable prior to hospital admission, the majority of hygiene measures in Germany is focused on the hospital setting. It is hypothesized that early detection and decontamination of S Aureus colonization in primary care can prevent health care associated infections and reduce the number of S Aureus isolates in the hospital setting. METHODS: This study is a controlled interventional study (N = 13,260) with a pre-post comparison. The intersectoral intervention (over 2 years) will encompass the following elements: ambulatory detection and decontamination of MRSA and MSSA prior to elective surgery combined with a structured follow-up care. Patients from the control group will be screened in the hospital setting, in accordance with the standard operating procedure (SOP) in routine care. The primary endpoint is the reduction of MRSA and MSSA colonization upon hospital admission. Secondary endpoints are complication rate (SSI), length of stay, recolonization of patients (3 and 6 months after release), patient and provider satisfaction, patient compliance and cost development. DISCUSSION: In case of positive results, the chance of a widespread uptake and implementation in routine care are considered high. The active involvement of primary care providers in the implementation of screening and decontamination as well as follow-up care is a unique feature of this study. The positive resonance of primary care providers during the recruitment phase highlights the relevance of the topic to the participating actors. These efforts are coupled with patient education and specifically trained medical staff, promising a sustained impact. The STAUfrei care pathway can homogenize current practices in routine care and provide a template for further intersectoral cooperation. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00016615. Registered on April 1st, 2019.

Prophylactic Anticoagulation With Intermediate-Dose Certoparin in Vascular-Risk Pregnancies-The PACER-VARP Registry.

The management of pregnant women at increased risk of thromboembolic/other vascular events is still a matter of debate. In a single-center, retrospective, observational trial, we analyzed the safety and efficacy of prophylactic anticoagulation with certoparin in pregnant women at intermediate- or high-risk by EThIG criteria of thromboembolic/other vascular events. Subcutaneous certoparin 8,000 IU once daily was administered immediately after pregnancy confirmation and continued for 6 weeks postpartum. We investigated 74 pregnancies (49 women; mean age 31.8 years; weight 77.3 kg). Most prevalent risk factors were factor V Leiden mutation (40.5%), thrombogenic factor II mutation (12.2%) and protein S deficiency (8.1%). In 76 control pregnancies prior to registry inclusion/without anticoagulation there were 14 cases [18.4%] of venous thromboembolism (between week 7 gestation and week 8 postpartum); 63.2% pregnancies resulted in abortion (median week 8.6 gestation). With certoparin anticoagulation, thromboembolism was 1.4%, exclusively non-major bleeding was 4.1% and abortion was 10.8%. One case of pre-eclampsia necessitating obstetric intervention occurred. Prophylactic anticoagulation with intermediate-dose certoparin throughout pregnancies at increased venous vascular risk was safe and effective.

Plasmatic coagulation and fibrinolytic system alterations in PNH: relation to clone size.

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized pathophysiologically by intravascular lysis of blood cells and clinically by thromboembolic events, often atypical in localization. In this study, we examined the plasmatic coagulation system of PNH patients to investigate a potential relation between coagulation alterations and disease intensity (PNH clone size). We found evidence for both an increase in procoagulant and in fibrinolytic activity, resulting in increased fibrin generation and turnover. Whereas a positive association of the procoagulant potential with PNH clone size was notable, fibrinolytic activity showed an inverse association with clone size. As a possible cause, a growing impairment of fibrinolytic activation and/or an increasing displacement of fibrinolytic activity is assumed. These mechanisms are most likely caused by the detachment of the glycosyl-phosphatidyl-inositol-anchored urokinase plasminogen activator receptor from cell surfaces, causing a progressive resistance to fibrinolytic stimuli, together with a probable shift of the fibrinolytic potential from cell surfaces to soluble, circulating complexes, resulting in a cellular fibrinolysis-steal phenomenon. Together, these processes are accused of mediating an increased thrombophilic risk in PNH. As hereditary prothrombogenic defects were found more frequently in patients suffering ischaemic complications, genetic thrombophilia seems to confer an additional thromboembolic risk in PNH, and should therefore be screened for.

Acquired thrombophilia in pregnancy: essential thrombocythemia.

The management of pregnant patients with essential thrombocythemia (ET) is a difficult problem. The clinical course of ET is mainly determined by thromboembolic complications. Pregnancy itself is a physiological hypercoagulable state. When ET affects women during pregnancy, an adverse outcome caused by thrombotic complications is a matter of concern. We reviewed 155 pregnancies in 86 women with ET. The success rate (baby alive) was 59%. First-trimester abortion was the most frequent complication and occurred in 31% of pregnancies. Placental infarction caused by thrombosis seemed to be the most consistent pathologic event. Maternal thrombotic or hemorrhagic complications were rare but were more common than those seen in normal pregnancy. Pregnancy itself does not appear to affect adversely the natural course and prognosis of ET. A meta-analysis revealed a significant benefit for aspirin in comparison to no treatment. If cytoreductive therapy becomes necessary, interferon alpha appears to be the drug of choice. The value of heparin prophylaxis has not been established but may have a role in selected cases.

The platelet function defect of paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired stem cell disorder, characterised by an abnormal susceptibility of red blood cells to complement induced lysis, resulting in repeated episodes of intravascular haemolysis and haemoglobinuria, thromboembolic events at atypical locations and, to a much lesser extent, bleeding complications. Platelet function is assumed to be abnormal, however, a defect has not yet been characterised and underlying mechanisms remain elusive. To explore these issues, we investigated platelet function in PNH patients using assays for clot formation under low and high shear force (thrombelastography and PFA100 device), adhesion to glass beads in native whole blood (Hellem method), aggregometry using various agonists (Born method), and flow cytometric assays for baseline and agonist-induced surface expression density of alpha-granule (CD62P) and lysosomal granule proteins (CD63), ligand binding to surface receptors (thrombospondin), and expression density of activation-induced neoepitopes of the fibrinogen receptor complex (PAC-1). Platelet PNH clone size determined by CD55 and CD59 labelling was compared to the clone sizes of granulocytes, monocytes, erythrocytes, and reticulocytes. A profound reduction of platelet reactivity was observed in PNH patients for all "global function" assays (clot formation, adhesion, aggregation). Platelet hyporeactivity was confirmed using flow cytometric assays. Whereas baseline levels of flow cytometrically determined platelet activation markers did not differ significantly between controls and PNH patients, agonist-induced values of all markers were distinctly reduced in the PNH group. Moreover, significantly reduced white blood cell counts (3.1/nl vs. 5.9/nl), haemoglobin values (9.5 vs. 14.3/g per dl), and platelet counts (136 vs. 219/nl) delineate profound tricytopenia in PNH patients. The fraction of particular cell types lacking the surface expression of GPI-anchored glycoproteins is referred to as the respective PNH clone; median PNH clone sizes of cells with short life spans (reticulocytes, platelets, granulocytes) was 50-80% of total cell populations compared to 20% of red blood cells. The results of our laboratory investigations show, that in PNH, reduced platelet counts coincide with reduced platelet reactivity. The foremost clinical complication in PNH, however, is venous thromboembolism, very probably induced by an activated and dysregulated plasmatic coagulation system. From these seemingly contradictory findings we infer, that part of the platelet hyporeactivity is probably due to reactive downregulation of platelet function in response to chronic hyperstimulation. The overall result is thought to be an unsteady balance, associated with thromboembolism in a larger proportion of patients, and with bleeding in a smaller proportion.