[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.

[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.

[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.

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.

Platelet concentrates derived from buffy coat and apheresis: biochemical and functional differences.

Today, platelet concentrates are generally produced from whole blood by differential centrifugation (buffy coat-derived platelet concentrates--PCs) or by plateletpheresis (apheresis-derived platelet concentrates--APCs). As PCs are characterized by a lower number of platelets than APCs, four to six PCs are customarily combined in order to obtain an equivalent dose. In the 1970s and 1980s, the use of PCs exceeded that of APCs by far; in contrast, since the beginning of the 1990s, APCs comprise more than half of all transfused platelets. However, the selection of PCs or APCs for transfusion to thrombocytopenic patients is still a matter of debate. The present paper compares biochemical and functional properties of both platelet preparations in vitro. Besides plasma parameters (e.g. platelet factor 4 (PF4), P-selectin, C3a-desarginin, plasma coagulation factors), platelet function was analysed by aggregometry and the PFA 100 system. APCs are characterized by a better preservation of ADP and collagen-induced platelet aggregation, and shorter closure times of the PFA 100 test system during storage. The improved primary in vitro haemostatic capacity of APCs is presumed to be owing to a lower cellular activation rate in these preparations. This hypothesis is supported by the higher plasma concentrations of PF4, beta-thromboglobulin and P-selectin found in PCs compared with APCs. The concentrations of C3a-desarginin in PCs exceed those in APCs by far. Additionally, thrombin generation is higher in PCs than in APCs. These data suggest that APCs are characterized by a superior haemostatic capacity over PCs in vitro. However, in vivo studies should be performed to confirm these findings in the patients' circulation also.

[Postoperative haemorrhagia in a girl with congenital factor XI deficiency - successful treatment with desmopressin (DDAVP, Minirin(R))]. / Postoperative Blutung bei einem Mädchen mit angeborenem Faktor-XI-Mangel - erfolgreiche Therapie mit Desmopressin (DDAVP, Minirin(R)).

UNLABELLED: The rare factor XI deficiency is associated with different profuse bleeding without correlation to the severity of reduction of factor XI. Accordingly, traumata or surgical procedures may cause unexpected excessive bleeding in asymptomatic patients. After surgery of a nine-year-old girl with factor XI deficiency (8 per cent) profuse bleeding occurred which could only be stopped after infusion of desmopressin. After administration the factor XI activity was increased to 31 per cent, the factor VIII even to 290 per cent over the normal range. We suppose that the favorable clinical effectiveness is not only related to the increasing factor XI activity but also to the elevation of the factor VIII/von-Willebrand-complex. CONCLUSION: It is recommended to give desmopressin as firstline therapy of bleeding by factor XI deficiency since the only effective alternative such as substitution of factor XI by transfusion of fresh frozen plasma is associated with the risk of transmission of virus infections.

Standardization of the PFA-100(R) platelet function test in 105 mmol/l buffered citrate: effect of gender, smoking, and oral contraceptives.

The PFA-100(R) (PFA) diagnostic system for the detection of platelet dysfunction was evaluated to determine reference ranges in a normal population. The PFA determines the primary haemostasis capacity (PHC) of anticoagulated whole blood, expressed by the system's closure time (CT). In this study the CT reference ranges were determined for blood samples collected in 105 mmol/l (3.2%) buffered citrate and the effect of gender, smoking, and use of oral contraceptives on reference ranges was assessed. Each of the 309 healthy blood donors from five blood centres was confirmed to have normal platelet function before inclusion in the study. Blood samples were tested in duplicate with both the collagen/epinephrine (Col/Epi) and collagen/ADP (Col/ADP) test cartridges. PFA reference ranges (90% central intervals of measured closure times) for both cartridge types were similar for all groups. Subgroup analysis showed that neither gender nor oral contraceptive usage had any effect on PHC. The 95% cut-off value for the Col/Epi CT was slightly higher for smokers than for non-smokers, an effect more pronounced in female than in male donors. However, the small difference did not justify establishment of specific reference ranges for smokers. Data from all included subjects were pooled to calculate the CT reference ranges for blood samples collected in 105 mmol/l buffered citrate (Col/Epi 82-150 s; Col/ADP 62-100 s). Normal levels of fibrinogen, as well as normal platelet counts and normal haematocrit levels, appeared not to influence the PHC. Because slight but significant differences of the reference ranges were observed between some of the participating sites, in-house confirmation of these reference range guidelines is recommended.

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.

Influence of antibiotics on posttransfusion platelet increment.

BACKGROUND: Fever has been identified as a major cause of platelet refractoriness. However, it is regularly attended by the administration of antibiotics, and thus it cannot be determined whether fever, the administration of antibiotics, or both are responsible for the reduced platelet increment. The present study was undertaken to discern the effect of body temperature and antibiotics on transfusion success. STUDY DESIGN AND METHODS: Single-donor platelet transfusions (n = 400) were monitored retrospectively. Besides other influencing factors (e.g., spleen size, number of previous transfusions, diagnosis, bone marrow transplantation), body temperature and the administration of antibiotics were documented from the patients' records. To distinguish the effects of fever and antibiotics, a general mixed model of variance was used for analysis. RESULTS: Besides the well-known factors of splenomegaly, hepatomegaly, bone marrow transplantation, and pretransfusion storage time, both body temperature and antibiotics independently reduced the corrected count increment. Among the various antibiotics, amphotericin B, ciprofloxacin, and vancomycin had the greatest influence. CONCLUSION: The administration of antibiotics has a negative effect on the corrected count increment, independent of the presence of fever. Besides amphotericin B, which has previously been shown to influence the corrected count increment, vancomycin and ciprofloxacin reduce it significantly. Because these antibiotics are widely used in patients with bone marrow failure, these observations should be proven by further prospective in vivo and in vitro studies.

[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.

[Cryopreservation of erythrocytes: detailed quality control]. / Tiefkühlkonservierung von Erythrozyten: Detaillierte Qualitätskontrolle.

It has been well established that cryopreservation of red cells with glycerol is a suitable method for long-time storage. Therefore, many data for quality control have been published. Most measurements, however, are restricted to the final product. Less information is available about the particular steps of cryopreservation. The present paper describes in detail the results of quality control measurements during the procedure. Although the final product meets the demand of the WHO for cryopreserved red cells, it could be demonstrated that erythrocytes are remarkably damaged by the deep-freezing process. Further experiments seem to be necessary in order to improve the details of the deep-freezing procedure.

[Post-transfusion rise in thrombocytes: observations in a hematologic-oncologic patient sample]. / Der posttransfusionelle Thrombozytenanstieg: Beobachtungen an einem hämatologisch-onkologischen Patientengut.

OBJECTIVE: Aim of the present analysis was the evaluation of clinical conditions and product-specific parameters influencing posttransfusion platelet increment. DESIGN: 400 single-donor platelet transfusions were analyzed for patient- and concentrate-specific factors influencing posttransfusion platelet increment. Statistical analysis was performed by the General Mixed Model Analysis of Variance. SETTING: Department of hematology and oncology at a university hospital. PATIENTS: 46 patients (24 male, 22 female; age 17-80 years). INTERVENTIONS: Single-donor platelet transfusions. RESULTS: As demonstrated earlier, splenomegaly, body temperature, and bone marrow transplantation could be proven as factors reducing posttransfusion platelet increment. In addition, hepatomegaly and application of antibiotics had negative effects on platelet increment. Among the product-specific parameters leukocyte contamination and pretransfusion storage time reduced transfusion success significantly. CONCLUSIONS: Clinical factors influencing posttransfusion platelet increment can hardly be controlled. In contrast, concentrate-specific parameters can be influenced by preparation technique and storage procedure. Therefore, high value should be set on low leukocyte contamination and short pretransfusion storage time of platelet concentrates.