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Institute
- Institut fĂŒr Immunologie u. Transfusionsmedizin - Abteilung Transfusionsmedizin (29) (remove)
Ziel dieser Arbeit war es, die Auswirkungen des demographischen Wandels auf die
Blutversorgung in Mecklenburg-Vorpommern (MV) zu analysieren. Dabei sollten
Grundlagen fĂŒr die Entwicklung von gesundheitspolitischen Strategien geschaffen
werden, um einem Defizit in der Versorgung entgegenwirken zu können.
Durch eine prospektive Longitudinalstudie mit Daten zu allen Vollblutspendern und
EmpfÀngern von Erythrozytenkonzentraten (EK) in MV in den Jahren 2005, 2010 und
2015 wird die Versorgungskette vollstÀndig abgebildet. Derartige Informationen liegen
zum jetzigen Zeitpunkt fĂŒr kein anderes Bundesland vor.
Es konnte gezeigt werden, dass die demographischen VerÀnderungen durch eine
Abnahme der Spenderzahlen zu einem ausgeprĂ€gten RĂŒckgang der Vollblutspenden
gefĂŒhrt haben (-18,0%). Dies wird verstĂ€rkt durch einen RĂŒckgang der Spendebereitschaft
um -10,6% insbesondere bei den <30-JĂ€hrigen. Gleichzeitig konnte trotz
alternder Bevölkerung auch der Blutbedarf dank des medizinischen Fortschritts um
13,5% reduziert werden. Dennoch deckten bereits im Jahr 2015 die gewonnenen
Blutspenden nur noch knapp den Blutbedarf der Patienten. Die durchgefĂŒhrten Vorausberechnungen
fĂŒr 2030 lassen erwarten, dass es mit einem Defizit von circa
18.000 EK zu erheblichen Versorgungsproblemen im Bundesland kommen wird,
wenn Spendebereitschaft und Transfusionsbedarf auf dem Niveau von 2015 verbleiben.
Die demographische Situation Mecklenburg-Vorpommerns ist denen der westlichen
BundeslÀnder Deutschlands circa 10 Jahre voraus. Damit nimmt Mecklenburg-
Vorpommern als Modellregion eine Vorreiterrolle bezĂŒglich der BewĂ€ltigung der
damit einhergehenden Herausforderungen fĂŒr die Blutversorgung ein. Um den Blutbedarf
der Patienten langfristig und ĂŒberregional decken zu können, wird in Zukunft
eine noch engere interdisziplinÀre Kooperation von Blutspendediensten, KrankenhÀusern
und Gesundheitspolitik sowohl auf Landes- als auch Bundesebene notwendig
sein.
Thrombozyten reagieren auf Infektionen, unter anderem auf die mit dem Humanen Immundefizienz-Virus (HIV). Dabei zeigt sich eine erhöhte Rate an kardiovaskulĂ€ren und thrombotischen Ereignissen. Die medikamentöse Therapie hemmt unter anderem die reverse Transkriptase der HI-Viren. Allerdings wirken diese Arzneimittel auch auf die humanen Thrombozyten. Diese besitzen eine endogene reverse Transkriptase. Eine solche ist in den BlutplĂ€ttchen in Form von Long Interspersed Nuclear Element 1 (LINE-1) RibonukleinsĂ€ure (RNA) als Grundlage fĂŒr die Translation vorhanden. Auch die entsprechenden Proteine sind als Open Reading Frame 1 (ORF1) und Open Reading Frame 2 (ORF2) - Proteine nachweisbar. Diese kodieren unter anderem fĂŒr eine Endonuklease, Chaperone und reverse Transkriptase. Letztgenannte ist in den BlutplĂ€ttchen auch aktiv. Folglich sind humane Thrombozyten in der Lage RNA in DesoxyribonukleinsĂ€ure (DNA) umzuschreiben. Dem Dogma der Molekularbiologie folgend, besitzen Zellen ohne Nucleus keine DNA. Auf Grund des Vorhandenseins einer endogenen reversen Transkriptase in humanen Thrombozyten konnte erstmals DNA in Form von Gewebsthromboplastin und Urokinase-Typ Plasminogen Aktivator Rezeptor (uPAR) nachgewiesen werden.
Background
Signs of an inflammatory process have been described in major depression.
Methods
In a double-blind, randomized study of celecoxib or placebo add-on to reboxetine in 40 depressed patients, celecoxib treatment has beneficial effects. In order to evaluate the tryptophan/kynurenine metabolism and to identify predictors for remission, tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QUIN) were estimated in the serum of 32 patients before and after treatment and in a group of 20 healthy controls.
Results
KYN levels were significantly lower in patients (pâ=â0.008), and the QUIN/KYN ratios were significantly higher (pâ=â0.028). At baseline, the higher KYN/TRP ratio was predictive for remission during celecoxib add-on treatment (pâ=â0.04) as well as for remission in the overall patient group (pâ=â0.01). In the placebo group, remitters showed a higher KYNA/QUIN ratio (pâ=â0.032). In the overall group, remitters showed lower KYNA/KYN (pâ=â0.035) and QUIN/KYN (pâ=â0.011) ratios. The lower the formation of downstream metabolites, especially QUIN, the better the treatment outcome.
Conclusion
The high KYN/TRP ratio predicted remission after treatment with celecoxib in this small sample of depressed patients. Eventually, the KYN/TRP ratio might be a marker for those patients, which benefit from an additional anti-inflammatory treatment.
Background: We assessed the effect of the uniform donor questionnaire (UDQ) on deferral rates in first-time and repeat donors. We focused on the introduced question about unprotected sexual contact with a new partner. Another goal was a stratified comparison of the deferral rates of the donor questionnaire (DQ) and UDQ. Methods: Data on donors and deferrals using the DQ and UDQ were collected at four blood establishments. The comparison included a 2-year period by questionnaire version. For the comparison of the questionnaires, an adjusted multinomial logistic regression was performed. Results: The analysis included 260,848 donations. First-time (FTD) and repeat donations (RD) showed higher deferral rates with the UDQ (FTD +5.4%, RD +1.4%). Deferral due to a new partner was 3.0% in first-time and 0.4% in repeat donors. The majority of these occurred in the youngest age groups. The most frequent deferral criterion was âdisease' (5.1%). Conclusion: The regression revealed stronger predictors for deferral than the questionnaire version. Especially younger age carried a higher and independent risk for deferral. The additional deferrals of mainly young first-time donors due to a new sexual partner may identify those donors with potential heterosexual risk behavior who would otherwise not be identified.
Background: Patients with mucin-producing adenocarcinoma have an increased risk for venous and arterial thrombosis. When these patients present with thrombocytopenia, disseminated intravascular coagulopathy (DIC) is often the underlying cause. Case Report: We report 2 patients who were admitted due to bleeding symptoms of unknown cause, in whom further workup revealed adenocarcinoma-induced DIC. Conclusion: In elderly patients presenting with signs of DIC, such as reduced fibrinogen levels, elevated prothrombin time, elevated D-dimer, and thrombocytopenia, without any obvious reason (e.g., sepsis), adenocarcinoma-associated coagulopathy should be considered as the underlying cause. Paradoxically, in these patients bleeding symptoms improve when the patient is sufficiently anti-coagulated with low molecular weight heparin. Treatment of the underlying disease is of central importance in controlling acute or chronic DIC associated with malignant diseases and chemotherapy should be started as soon as possible.
Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 ”g/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT<sub>4</sub> levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT<sub>4</sub>, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.
Background: Securing future blood supply is a major issue of transfusion safety. In this prospective 10-year longitudinal study we enrolled all blood donation services and hospitals of the federal state Mecklenburg-Western Pomerania. Methods and Results: From 2005 to 2015 (time period with major demographic effects), whole blood donation numbers declined by 18%. In male donors this paralleled the demographic change, while donation rates of females declined 12.4% more than expected from demography. In parallel, red cell transfusion rates/1,000 population decreased from 2005 to 2015 from 56 to 51 (-8.4%), primarily due to less transfusions in patients >60 years. However, the transfusion demand declined much less than blood donation numbers: -13.5% versus -18%, and the population >65 years (highest transfusion demand) will further increase. The key question is whether the decline in transfusion demand observed over the previous years will further continue, hereby compensating for reduced blood donation numbers due to the demographic change. The population structure of Mecklenburg-Western Pomerania reflects all Eastern German federal states, while the Western German federal states will reach similar ratios of age groups 18-64 years / â„65 years about 10 years later. Conclusions: Regular monitoring of age- and sex-specific donation and transfusion data is urgently required to allow transfusion services strategic planning for securing future blood supply.
Background: The phenomena of co-incidence of transfusion-induced allo- and autoantibodies, blockage and/or loss of red blood cell (RBC) antigens are conspicuous and may result in confusion and misdiagnosis. Case Report: A 67-year-old female was transferred to the intensive care unit due to hemolysis which developed 2 days following transfusion of three Rh(D)-negative RBC units in the presence of strongly reactive autoantibodies. Standard serological testing and genotyping were performed. Upon arrival, the patient was typed as Ccddee. Her hemolysis was decompensated, and an immediate blood transfusion was required. In addition, direct and indirect antiglobulin tests (DAT and IAT) as well as the eluate were strongly positive. Emergency transfusion of Rh(D)-negative RBCs resulted in increased hemolysis and renal failure. An exhaustive testing revealed anti-D, anti-c, CCddee phenotype and CCD.ee genotype. Three units of cryopreserved CCddee RBCs were transfused, and the patient's condition immediately improved. The discrepancy between Rh-D phenotyping and genotyping was likely caused by masking of the D-epitopes by the autoantibodies. In fact, further enquiry revealed that the patient had been phenotyped as Rh(D)-positive 6 months ago and had been transfused at that time following hip surgery. Conclusion: The phenomena of transfusion-induced autoantibodies, masked alloantibodies, antigen blockage and/or loss are rare but important features which should be considered in patients presenting with autoimmune hemolytic anemia and/or hemolytic transfusion reactions.
Platelets transfusion is a safe process, but during or after the process, the recipient may experience an adverse reaction and occasionally a serious adverse reaction (SAR). In this review, we focus on the inflammatory potential of platelet components (PCs) and their involvement in SARs. Recent evidence has highlighted a central role for platelets in the host inflammatory and immune responses. Blood platelets are involved in inflammation and various other aspects of innate immunity through the release of a plethora of immunomodulatory cytokines, chemokines, and associated molecules, collectively termed biological response modifiers that behave like ligands for endothelial and leukocyte receptors and for platelets themselves. The involvement of PCs in SARsâparticularly on a critically ill patientâs contextâcould be related, at least in part, to the inflammatory functions of platelets, acquired during storage lesions. Moreover, we focus on causal link between platelet activation and immune-mediated disorders (transfusion-associated immunomodulation, platelets, polyanions, and bacterial defense and alloimmunization). This is linked to the plateletsâ propensity to be activated even in the absence of deliberate stimuli and to the occurrence of time-dependent storage lesions.
Der Bedarf an Blutprodukten ist in den letzten Jahren gestiegen, wĂ€hrend der Kreis der möglichen Blutspender bei alternder Bevölkerung abgenommen hat und weiter abnehmen wird. Blutspende-Einrichtungen betreiben viel Aufwand, Blutspender zu gewinnen und als Dauerspender zu binden. FrĂŒhere Studien zeigten, dass ein Drittel der Dauerspender ein positives âWell-beingâ nach der Spende erfahren und dies als Grund fĂŒr regelmĂ€Ăige Blutspenden angeben. In dieser Studie wurde ntersucht, ob ein âWell-beingâ auch bereits bei Erstspender ausgeprĂ€gt ist und ob dies einen Einfluss auf das RĂŒckkehrverhalten von Erstspendern hat. ZusĂ€tzlich sollte gezeigt werden, dass die Studie als Intervention einen Einfluss auf das RĂŒckkehrverhalten bei Erstspendern hat. Ăber drei aufeinander folgende Monate wurden 235 Erstspender in die Studie eingeschlossen und entweder in die Fragebogengruppe oder in die Kontrollgruppe randomisiert. Bei allen Studienteilnehmern wurde zwölf Monate nach der initialen Spende deren RĂŒckkehrverhalten ausgewertet. Die Teilnehmer der Fragebogengruppe sollten zusĂ€tzlich zu sieben verschiedenen Zeitpunkten, verteilt ĂŒber acht Wochen, den âMultidimensionalen Befindlichkeitsfragebogenâ ausfĂŒllen. An Hand der Ergebnisse des MDBF sollte der Verlauf des âWell-beingâ aufgezeigt werden. Folgende Ergebnisse wurden erhoben: Erstspender scheinen keine gröĂeren VerĂ€nderungen des âWell-beingsâ nach ihrer ersten Blutspende zu erfahren. Des Weiteren beeinflusste das âWell-beingâ nicht das RĂŒckkehrverhalten der Erstspender. Die durchgefĂŒhrten Interventionen fĂŒhrten zu einer erhöhten Wiederkehrrate der mĂ€nnlichen Erstspender, nicht jedoch der weiblichen Erstspender. Um eine praktikable Schlussfolgerung aus den Ergebnissen dieser Studie ziehen zu können, sollten zukĂŒnftige Studien den hier in der Wiederkehrrate aufgetretenen Geschlechterunterschied spezifischer untersuchen. Interessant wĂ€re vor allem, welche der durchgefĂŒhrten Interventionen oder eine Kombination aus diesen zu der gesteigerten Wiederkehrrate mĂ€nnlicher Erstspender gefĂŒhrt hat. Mit Hilfe weiterfĂŒhrender Ergebnisse wĂ€re es dann möglich, gezielt Interventionen zu betreiben, die effizient die Spendefrequenz der Blutspender erhöht.
