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Hamburg, Germany

Panzer S.,Medical University of Vienna | Eslam R.B.,Medical University of Vienna | Schneller A.,Medical University of Vienna | Kaider A.,Medical University of Vienna | And 5 more authors.
Thrombosis and Haemostasis | Year: 2010

Severe aortic stenosis is associated with a haemostatic abnormality that resembles acquired von Willebrand syndrome type 2. It is assumed that high shear conditions render large von Willebrand factor (VWF) multimers accessible to cleavage by ADAMTS-13. However, whether loss of these large multimers affects platelet function by impairing adhesion, aggregate formation, or both has not been evaluated in clinical studies. We prospectively enrolled 47 patients with severe aortic stenosis, and studied them prior to aortic valve surgery and at a median of six months after valve replacement. We investigated levels of large VWF multimers, platelet function under high shear conditions, and residual response to suboptimal concentrations of ADP to express P-selectin. As expected, there was a significant reduction of VWF large multimers before surgery that resolved thereafter in most patients (p<0.0001). The closure time of the ADP cartridge of the PFA-100 was also corrected in most patients after the operation (p<0.0001). We used the cone and plate(let) analyser Impact-R to differentiate between adhesion and aggregation. Both adhesion (p=0.03) and ADP-inducible platelet aggregation (p=0.002) improved considerably after valve replacement. Consequently, ADP-inducible expression of P-selectin was higher after valve replacement (p=0.001). We conclude that reduced levels of large VWF multimers associated with aortic stenosis lead to impairment of both adhesion and, especially, ADP-inducible platelet aggregation. © Schattauer 2010.

Fuchs T.,University of Mannheim | Hahn M.,University of Mannheim | Riabov V.,University of Heidelberg | Yin S.,University of Heidelberg | And 7 more authors.
Immunobiology | Year: 2015

Recent evidence indicates the presence of macrophage subpopulations that express the TCRαβ in two major inflammatory diseases, tuberculosis and atherosclerosis. Inflammation is also a well-established attribute of cancer progression and macrophages are one of the major immune cells that infiltrate tumors. Here, we demonstrate that the macrophage-TCRαβ is expressed in the tumor microenvironment of human and murine malignancies. We identify TCRαβ+ macrophages in each case of four randomly selected distinct human tumor entities. In human tumor tissues, the TCRαβ expressed by macrophages in the tumor microenvironment is a combinatorial and individual-specific immune receptor. Furthermore, we routinely find TCRαβ+ macrophage subpopulations in experimental tumors (TS/A, mammary adenocarcinoma) which we induced both in normal mice and mice deficient in the macrophage receptor stabilin-1. Expression of the combinatorial murine tumor macrophage TCRαβ is individual-specific and independent of stabilin-1. These results demonstrate that TCRαβ expression is a characteristic feature of macrophages in the tumor microenvironment and identify an as yet unrecognized flexible element in the macrophage-based host response to tumors. © 2015 Elsevier GmbH.

Meyer A.L.,University of Leipzig | Malehsa D.,Hannover Medical School | Budde U.,AescuLabor Hamburg | Bara C.,Hannover Medical School | And 2 more authors.
JACC: Heart Failure | Year: 2014

Objectives: The aim of this study was to determine whether differences in continuous flow left ventricular assist devices (LVADs) may lead to differences in the von Willebrand profile and the occurrence of bleeding and thromboembolic events. Background: The HeartMate II (Thoratec Corp., Pleasanton, California) and HeartWare Ventricular Assist Device (HVAD) (HeartWare, Inc., Framingham, Massachusetts) systems are the most frequently implanted LVADs worldwide. In all patients with an axial-flow HeartMate II, acquired von Willebrand syndrome (AvWS) due to the loss of large molecular weight multimers was found. The large molecular weight multimers of the von Willebrand factor (vWF) play a key role in primary hemostasis through interactions with platelets. Methods: This was a retrospective study of the vWF profile and incidence of bleeding and thromboembolic events in 102 patients receiving the HeartMate II (n= 51) and HVAD (n= 51). Between January 2003 and December 2010, vWF testing was performed in 102 of 175 consecutive patients after LVAD implantation. Results: AvWS was found in all patients, demonstrated by a decrease in the high molecular weight multimers of vWF to 30±14% in HeartMate II patients and 34 ± 13% in patients with an HVAD. Significant predictors of vWF antigen included age (p= 0.011), number of days on the device (p= 0.035), C-reactive protein (p< 0.001), and blood group (p= 0.007). Bleeding and thromboembolic event rates were similar. However, lower fractions of vWF antigen and high molecular weight multimers did not correlate with the rate of bleeding complications or thromboembolic events. Conclusions: AvWS developed in all patients after centrifugal or axial flow pump implantation. Different patterns of AvWS wereseen between the devices as well as individually. However, the complication rates after implantation were similar. © 2014 American College of Cardiology Foundation.

Fuchs T.,University of Mannheim | Puellmann K.,AescuLabor Hamburg | Emmert A.,University of Gottingen | Fleig J.,Mannheim University of Applied Sciences | And 7 more authors.
Biochemical and Biophysical Research Communications | Year: 2015

Recent evidence indicates constitutive expression of a recombinatorial TCRαβ immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCRβ repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCRαβ+ macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag-/- mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCRαβ bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCRαβ repertoires that are characterized by a striking usage of the Vβ22 and Vβ16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCRαβ signatures. Our results implicate the macrophage-TCRαβ combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease. © 2014 Elsevier Inc. All rights reserved.

Nebe T.,Institute For Transfusionsmedizin | Bentzien F.,Universitatsklinikum Hamburg Eppendorf | Bruegel M.,Klinische Chemie und Molekulare Diagnostik Universitatsklinikum Leipzig | Fiedler G.M.,Klinische Chemie und Molekulare Diagnostik Universitatsklinikum Leipzig | And 7 more authors.
LaboratoriumsMedizin | Year: 2011

The analysis of blood cell count including differential, is the most frequent laboratory test and has still essential diagnostic value in the diagnosis of primary or secondary diseases of the hematopoietic system. The interpretation is based on a comparison with age matched reference intervals, despite the fact that a comparison with the patients own preceding values allows a more precise statement. In the present study, blood counts and differential were performed in 1158 healthy males and females with an age ranging from 16 to 75 years were investigated using current hematology systems. The donors were examined by personnel physicians and those examining blood donors in transfusion medicine and in addition were asked via standardized questionnaire. The study resulted in reference ranges for the complete blood count, the differential blood count and reticulocytes. For several analytes, age-, gender- or analyzerspecific reference ranges were obtained. We found an age dependent decrease of the erythrocyte concentration and an increase for MCH and MCV as well as for basophils. These findings could be important for the dignosis of diseases of the elderly like myeloproliferative diseases (MPN) and myelodysplasias (MDS). Gender specific changes could be shown for the hemoglobulin-, the erythrocyte- and reticulocyte concentration, as well as for hematocrit and MCHC, being reduced in females. On the other hand, females showed significant higher levels for platelets and leukocytes, based on an increase of neutrophils and lymphocytes. The leukocytosis of smokers was confirmed for neutrophils and lymphocytes but lower than one could expect from recent studies. A multicentric study shows a broader distribution compared to unicentric data but this probably better reflects the reality and improves the applicability of the reference ranges. © 2011 by Walter de Gruyter.

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