[How Much Blood and What Components does the Patient need Intra- and Perioperatively?]. / Wie viel Blut und welche seiner Bestandteile benötigt der Mensch intra- und perioperativ? - neue wichtige Aspekte für den Allgemein-(Viszeral-)Chirurgen aus der Transfusionsmedizin und Hämostaseologie.

By the optimised availability of less expensive and safe red cell packs and other blood products over the last 20 years, numerous surgical interventions have become possible without any demand for comments on the precise need. However, a number of publications indicates that blood transfusion may also induce disadvantageous effects on the postoperative course by immunomodulation, which requires a rather restrictive indication for transfusion. Furthermore, demographic development leads to a decrease in that portion of the population with the potential for blood donation accompanied simultaneously by an increase of the percentage of older patients with more need of blood products during medical treatment. This makes blood-sparing measures necessary. In addition, costs for red cell packs have increased, in particular, for the generally compatible blood group 0 - an extra amount for rhesus negative blood. The present narrative review highlights, therefore, important news from the clinical transfusion medicine, immunohaematology and haemostaseology and their impact on daily transfusion practice. In this context, "blood management" is considered as one of the very effective blood-sparing measures, which focusses especially i) on the substitution of iron in case of depressed preoperative haemoglobin as well as ii) to elucidate disorders of coagulation by structured medical history and, subsequently, to balance possible need by a specific plan for substitution. Simultaneously, prospective studies are initiated to investigate how far the transfusion trigger of a patient can be lowered down to a still appropriate level. As far as consolidated findings are already available, they are described with regard to the single blood components and taking into account the cross-sectional guidelines of the "Bundesärztekammer" (Federal Physicians Chamber). Finally, initial evidence is provided characterising patient- and blood donor-specific, blood group-dependent features of a reasonable haemotherapy.

Treatment of severe autoimmune blistering skin diseases with combination of protein A immunoadsorption and rituximab: a protocol without initial high dose or pulse steroid medication.

BACKGROUND: Skin blistering diseases due to autoantibodies are typically treated with high dose systemic corticosteroids and other conventional immunosuppressants. However, in severe cases, this treatment may not be sufficient to achieve disease control or contraindicated because of comorbidity. METHODS: We describe 15 patients (pts.) with such diseases: 6 pts. with pemphigus vulgaris, 3 pts. with bullous pemphigoid, 3 pts. with mucous membrane pemphigoid (MMP), one being anti-laminin-332-MMP (AL332-MMP), 2 pts. with pemphigus foliaceus and 1 pt. with epidermolysis bullosa acquisita (EBA). Patients were treated with a combination of protein A immunoadsorption (PAIA, 3-21 treatments) and rituximab (3-6 treatments) in addition to low dose conventional immunosuppression. RESULTS: All patients showed rapid clinical improvement starting within the first 4 weeks and decline of circulating autoantibody levels. Complete/partial remission was 88%/12% in pemphigus and 71%/29% in subepidermal blistering diseases. Overall relapse rate was 13% with an average follow-up of 22 months. In the AL332-MMP pt. the PAIA/rituximab treatment was stopped because of an oesophagus cancer considered as the paraneoplastic cause of the skin disease. CONCLUSION: Combined treatment with PAIA and rituximab showed rapid and long-lasting response, thereby allowing substantial reduction of dosage of concomitant immunosuppressive medication. We hereby confirm data from other investigators that PAIA/rituximab treatment is a promising therapeutical modality for pemphigus, pemphigoids and EBA, characterized by a favourable ratio of beneficial efficacy and minimized long-term adverse effects.

Detection of a new HLA-B*15 allele, HLA-B*15:238, in a voluntary stem cell donor.

The newly detected HLA-B*15:238 is distinguished from HLA-B*15:52 by a single-nucleotide exchange at position 527 where T is replaced by A.

[Acquired von Willebrand's disease type 2A following arteriovenous fistula for haemodialysis?]. / Erworbenes von-Willebrand-Syndrom Typ 2A als Begleiterscheinung eines Dialyseshunts?

Acquired von Willebrand's disease (aVWD) is considered to be an underestimated cause of unexplained bleeding. Adsorption of von Willebrand factor (VWF) to tumour cells or hydroxyethyl starch and elimination of VWF by autoantibodies as well as shear stress-induced mechanical alteration of VWF with concomitant cleavage by enzymes may lead to an acquired deficiency of VWF and a bleeding disorder. We report a 39-year-old woman who developed spontaneous bleeding five years after surgical creation of an arteriovenous fistula (AVF) for haemodialysis treatment. AVWD type 2A was diagnosed after successful renal transplantation. One year after surgical closure of the AVF, the aVWD could not be verified again. Thus, the aVWD may have developed because of altered blood flow and shear stress inside the arteriovenous fistula.

[New cross-sectional guidelines of the German Medical Association for hemotherapy with fresh frozen plasma. Evidence-based recommendations for risk-benefit assessment]. / Neue (Querschnitt-)Leitlinien der Bundesärztekammer für die Hämotherapie mit gefrorenem Frischplasma. Evidenzbasierte Empfehlungen für die Risiko-Nutzen-Abwägung.

Some new blood products and plasma derivatives have extended the possibilities in hemotherapy to such an extent that the therapeutic and evidence-based therapy options can only really be managed with the aid of guidelines. Four approved plasma preparations are available in Germany: fresh frozen plasma, lyophilized plasma, solvent-detergent (SD) pool plasma and methylene blue-light-treated plasma. Evidence of the clinical efficacy of plasma is mainly based on uncontrolled observational studies, case reports or expert opinion. Plasma is indicated for complex coagulopathy associated with manifest or imminent bleeding, particularly with massive transfusion, disseminated intravascular coagulation and liver disease. With the exception of emergency situations when clotting assay results are not available in time, a clinically relevant coagulopathy must be verified before plasma is administered. The rapid infusion of at least 10 ml of plasma per kg body weight is required to significantly increase the respective clotting factor or inhibitor levels. Prothrombin complex concentrates (PPSB) should be preferred to plasma for the rapid reversal of oral anticoagulation. Side effects of plasma are rare but have to be considered.

McLeod syndrome: a distinct form of neuroacanthocytosis. Report of two cases and literature review with emphasis on neuromuscular manifestations.

McLeod syndrome was originally described on the basis of a specific blood group phenotype with weak expression of Kell antigens. This erythrocyte abnormality also causes acanthocytosis. The haematological findings are associated with abnormalities in other organ systems, including neuromuscular manifestations. A 51-year-old patient was followed up for 11 years. He presented with persistent muscle creatine kinase elevation and progressive heart disease and later developed a slowly progressive neuropathy and choreic movements. His younger brother presented with grand mal seizures, involuntary movements and high muscle creatine kinase when aged 43 years. Clinical myopathy was absent in both, yet muscle biopsy showed mild myopathic changes. The presence of a motor axonopathy was supported by electrophysiological findings. One brother also showed sensory axonopathy. The movement disorder suggested accompanying basal ganglia dysfunction. Earlier reports of McLeod syndrome are reviewed with respect to neuromuscular involvement. Absence of the Kx membrane protein seems to be the cause of this multi-system disorder.

Influence of blood transfusion on recurrence, survival and postoperative infections of laryngeal cancer.

Clinical and experimental studies indicate, that blood transfusion can modify the recipient's immune system. While beneficial to renal allograft survival, these immunomodulating effects may, however, prove detrimental to cancer patients. Recently, an adverse relationship between blood transfusion and cancer recurrence was reported in colon, lung, breast, kidney and gastric cancer. Moreover, a higher postoperative infection rate was observed when blood units were administered intraoperatively. We retrospectively reviewed the records of 174 patients with squamous cell carcinoma of the larynx undergoing curative resection between 1979 and 1985. One hundred and forty-one patients received blood transfusions, 33 did not. Recurrence rate (16.7%) was significantly related to clinical stage (p = 0.008) and lymph node status (p = 0.000); cumulative survival time depended significantly on clinical stage (p = 0.003), lymph node status (p = 0.004) and tumor size (p = 0.017). In contrast, when corrected for these baseline prognostic factors, no significant correlation could be detected between blood transfusion and cancer relapse. Also, survival time did not depend on blood transfusions. No correlation could be found between postoperative infection rate and intraoperative application of blood transfusion (p = 0.694). The present study does not support the hypothesis that blood transfusion adversely affects the prognosis of patients with laryngeal cancer. It indicates, that risk factors other than blood transfusion have a greater influence on recurrence and survival time.

[Blood, blood components and plasma derivatives. Guideline-based implementation]. / Blut, Blutkomponenten und Plasmaderivate. Leitliniengerechter Einsatz.

The transfusion act authorized the German Medical Association to provide "guidelines for therapy with blood components and plasma derivatives" by a working party for the critical use of blood products to help to protect patients from avoidable risks. Responsible and carefully considered use of blood products is mandatory, particularly because obtaining them requires the willingness of numerous volunteers to donate blood. The individual recommendations were evaluated by evidence-based criteria and for many medical interventions so that they will serve to provide comprehensive operational procedures for transfusion personnel in clinics.

Use of capillary blood count parameters in adults.

BACKGROUND AND OBJECTIVES: Capillary samples can provide blood for cell counts in haematologic patients and blood donors. However, some accept only values from venous blood. This study compares capillary and venous blood counts to verify the hypothesis that they are equivalent. MATERIALS AND METHODS: We analysed 463 capillary (fingerstick) and venous blood samples from 428 adults of both sexes (71% haematologic patients, 29% potential blood and apheresis donors). Both samples were taken at the same time from each subject. Haemoglobin (Hb), haematocrit (Hct), white blood cells (WBC), platelets, red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC) were measured using a haematology analyser (Advia 120, Bayer). RESULTS: Capillary Hb, Hct, WBC, RBC, MCV and MCH were all significantly higher than the venous values [+0.2 mmol/l (+0.3 g/dl), +0.02 l/l (+2%), +0.2 x 10(9)/l, +0.1 x 10(12)/l, +3.1 fl and +0.01 fmol, respectively], whereas the capillary MCHC was lower (-0.6 mmol/l). There was no difference in platelets (-1 x 10(9)/l). Capillary Hb and Hct values were higher in patients with anaemia and polycythaemia, respectively. However, no significant differences occurred in severe thrombocytopenia. CONCLUSION: In adult haematologic patients, however, only the differences in Hb and Hct values may be of clinical relevance. For potential blood and apheresis donors, Hb and platelet screening are equivalent with either capillary and venous blood using a haematology analyser.

[Use of fresh frozen plasma in surgery with special reference to autologous fresh frozen plasma]. / Einsatz von FFP im operativen Bereich unter besonderer Berücksichtigung des Eigen-FFP.

The use of FFP has increased dramatically in the last few years. In the majority of cases FFP is transfused in order to provide coagulation factors. Many physicians expect to get "better" blood parameters from concomitant FFP and red blood cell (RBC) transfusions. To avoid the risk of diseases transmitted by homologous blood predeposited autologous blood is useful for elective surgical patients. Intraoperative autotransfusion by blood salvage using a Cell Saver only provides autologous RBC without plasma, so predeposited autologous plasma seems to be a necessary supplement. However, according to the literature most patients receiving RBC units do not require concomitant FFP. Guidelines for the use of FFP based on controlled clinical trials are necessary.

[The need for thorough infection screening in donors of autologous blood]. / Die Notwendigkeit zur gründlichen Untersuchung auf Infektionskrankheiten von Spendern vor der Eigenblutspende.

To avoid the risk of diseases transmitted by homologous blood, predeposited autologous blood is useful for elective surgical patients. World-wide, there is disagreement over whether complete donor testing should or should not be done on autologous collections. There are a variety of testing concerns which have evolved into reasons for testing all autologous units for the presence of infections disease markers. One of the reasons is the risk of giving the wrong (untested) blood to the wrong patient and transmitting HIV (and thus AIDS) or viral hepatitis. Another stated concern is the risk of creating additional problems in the laboratory by treating some units differently than other units. The argument continues that without this testing, blood bank and hospital personnel may be unnecessarily exposed to blood that has the potential to cause illness. Another justification for testing is given when the blood bank participates in crossover (transfusing blood to recipients other than the autologous donor/patient).

[Leukocyte depletion of blood products. Indications and technical implementation]. / Leukozytendepletion von Blutprodukten. Indikationen und technische Durchführung.

Leukocytes contaminating donated blood are considered to be responsible for many of the side effects associated with blood transfusions. These include HLA sensitization and its sequelae, as also graft versus host reaction, transmission of CMV. The present article summarizes the indications for leukocyte depletion and its technical execution.

Possibility to improve preservation of whole blood by leukocyte-depletion before storage.

In order to evaluate the influence of leukocytes in whole blood on the standard blood bank conditions for storage, we compared several parameters of red cells, leukocytes and platelets in leukocyte-rich and leukocyte-poor whole blood over a storage period of 5 weeks. The leukocyte-depleted units were prepared by filtration with a leukocyte trapping filter (Sepacell R500A). Our data indicate improved storage conditions, made evident by significantly lower cell damage: smaller increases of elastase, beta-thromboglobulin and lactate dehydrogenase in leukocyte-depleted blood. This improvement was achieved in a simple two-bag system using only filtration, without addition of rejuvenating solutions. In addition, this procedure allows greater flexibility in the use of filtrated blood for transfusions.

[Strong and weak histocompatibility antigens and immune response]. / Starke und schwache Histokompatibilitätsantigene und Immunantwort.

In blood samples of 88 healthy donors various red cell, HLA-A, -B, -Cw and -Dr antigens were determined by standard methods. Lymphocyte reactivity was measured by 3H-thymidine uptake into DNA of lymphoblastic cells stimulated by 14 different mitogens and antigens. Cluster analysis confirmed by t test and F test defined 3 distinct clusters of lymphocyte reactivity. Cluster 1 in 70% [relative risk (r.r.) 109, p < 0.001] and cluster 3 in 92% (r.r. 33, p < 0.01) showed significantly different cumulations of 3 or more increased characteristic red cell and HLA antigens. Our data suggest that the patterns of both red cell and HLA antigens play a major role in defining immunoreactivity.

Transforming growth factor beta is increased in plasma of patients with hematologic malignancies after transfusion of platelet concentrates.

BACKGROUND: Transforming growth factor beta 1 (TGF-beta 1) acts as a potent inhibitor of bone marrow proliferation. High concentrations were found in human platelets, which release this cytokine during storage. STUDY DESIGN AND METHODS: TGF-beta 1 levels during a storage period of 5 days were compared in the plasma of platelet concentrates prepared by apheresis or by the buffy coat method. In addition, TGF-beta 1 plasma levels were monitored in patients with hematologic malignancies before and after transfusion. RESULTS: TGF-beta 1 levels in the supernatant of platelet concentrates were found to be 55 times higher than those in the plasma of healthy volunteer donors. During storage, an additional increase was observed. Accordingly, the transfusion of platelet concentrates resulted in a significant increase of plasma TGF-beta 1 levels in patients with hematologic malignancies (before transfusion: 2.2 +/- 0.5 ng/mL; after transfusion: 2.9 +/- 0.6 ng/mL), and these higher levels persisted for at least 4 hours. CONCLUSION: Because TGF-beta 1 reduces the clonogenic capacity of hematopoetic progenitor cells, a myelosuppressive effect of platelet transfusions is suggested.

[Morphologic and functional changes in thrombocytes after deep freezing with DMSO]. / Morphologische und funktionelle Veränderungen von Thrombozyten nach Tieffrierung mit DMSO.

BACKGROUND: During the past decade much work has been carried out towards establishing the optimum method for cryopreservation of platelets. Among the various cryoprotectants dimethyl sulfoxide (DMSO) has been shown to be the most effective. This report describes ultrastructural and functional changes of platelets during the deep-freezing process with DMSO. MATERIALS AND METHODS: Single-donor platelet concentrates were cryopreserved in liquid nitrogen by use of DMSO. Before, during and after the freezing process samples were taken for analysis of ultrastructure and platelet function. RESULTS: While after isolation and addition of DMSO a normal ultrastructure of platelets could be observed, clear signs of beginning cell necrosis were detected after thawing and resuspension in autologous plasma. Fibrinogen-binding capacity and platelet aggregation were significantly diminished. CONCLUSIONS: Although cryopreserved platelets are characterized by hemostatic effects in vivo, it seems conceivable that these effects could be improved by further development of platelet-freezing techniques.

[Quality control of stored platelet concentrates by means of flow cytometry]. / Qualitätskontrolle gelagerter Thrombozytenkonzentrate mittels Durchflusszytometrie.

Storage of single-donor platelets is currently limited to 5 days. During this period, however, numerous morphologic and biochemical changes have been observed. The present study describes increased binding of anti-GMP 140 to stored single-donor platelet concentrates; this reveals a progressive activation process. In contrast, when stored platelets are stimulated with ADP, GMP 140, expression is reduced indicating a diminished release reaction. Additionally, the GP IIb/IIIa receptor complex and its fibrinogen-induced binding site (LIBS1) are reduced by storage time, demonstrating a diminished fibrinogen binding. Further experiments have to clarify whether these changes observed in vitro translate into a reduced hemostatic capacity after transfusion in vivo.