[Effects of atypical employment on difficulties in falling asleep and maintaining sleep - gender differences in the lidA study]. / Ein- und Durchschlafstörungen in Abhängigkeit von atypischen Beschäftigungsformen - Geschlechterunterschiede in der lidA-Studie.

BACKGROUND AND AIM: Due to the increasing flexibilisation of the European labour market, new forms of atypical work organisation have been arising. Atypical employment may cause negative health effects similar to unemployment. Considering the health-promoting relevance of sleep for work productivity, we investigate if different forms of atypical employment are associated with difficulties falling and maintaining asleep among middle-aged male and female employees. METHODS: Data were retrieved from the 1(st) wave of the lidA study, a nation-wide survey among employees in Germany in 2011. According to the Integrated Employment Biography (IEB) of the Institute of Employment Research (IAB), participants were born in 1959 or 1965 and subject to mandatory social insurance contributions on 31.12.11. Our analysis is based on 4 544 participants. Using logistic regression models separately for men and women, difficulties falling and maintaining asleep were modelled to depend on years mostly spent in full-time, part-time, in marginal employment or in unemployment during the period from 1999-2010 as well as on years in the current position, fixed-term employment contract, organisational restructuring and dismissals at time of the survey in 2011. RESULTS: Women (9%) were more affected by difficulties falling and maintaining asleep than men (5%). Among women, past years mostly spent in full-time, part-time, marginal employment or in unemployment were not associated with sleep disturbances. Men who had mostly worked part-time or unemployment were more likely to report difficulties falling and maintaining asleep. Likewise, in men a fixed-term contract was linked with a higher risk of sleep disturbances. In women, witnessed dismissal in the working environment was a significant influencing factor. CONCLUSION: Atypical employment can be related to difficulties falling and maintaining asleep. In future research gender-specific reasons for atypical employment as well as adverse working conditions should be taken into account. Changes between different forms of atypical employment as well as cumulative measures of these employment exposures in employees' biographies should be included in future studies.

Complexity of gap junctions between horizontal cells of the carp retina.

In the vertebrate retina, horizontal cells (HCs) reveal homologous coupling by gap junctions (gj), which are thought to consist of different connexins (Cx). However, recent studies in mouse, rabbit and zebrafish retina indicate that individual HCs express more than one connexin. To provide further insights into the composition of gj connecting HCs and to determine whether HCs express multiple connexins, we examined the molecular identity and distribution of gj between HCs of the carp retina. We have cloned four carp connexins designated Cx49.5, Cx55.5, Cx52.6 and Cx53.8 with a close relationship to connexins previously reported in HCs of mouse, rabbit and zebrafish, respectively. Using in situ hybridization, Cx49.5 expression was detected in different subpopulations of retinal neurons including HCs, whereas the Cx52.6 transcript was localized exclusively in HCs. Using specific antibodies, Cx55.5 and Cx53.8 were detected on dendrites of all four HC subtypes and axon terminals. Immunoelectron microscopy confirmed the presence of Cx55.5 and Cx53.8 in gap junctions between these processes and Cx55.5 was additionally observed in HC dendrites invaginating cone pedicles, suggesting its participation in the modulation of photoreceptor output in the carp retina. Furthermore, using single-cell RT-PCR, all four connexins were detected in different subtypes of HCs, suggesting overlapping expression patterns. Thus, the composition of gj mediating homologous coupling between subtypes of carp HCs appears to be more complex than expected. Moreover, BLAST searches of the preliminary carp genome, using novel sequences as query, suggest that most of the analyzed connexin genes are duplicated in carp.

Perspectives of paid whole and plasma donation.

Although payment of blood donors is rejected by the WHO, the FDA, the EU, and the Red Cross (RC), in Germany, monetary compensation of expenses is permitted not only for plasmapheresis but also for whole blood donation. The structure and organisation of the institutions ensuring the blood supply in Germany and the pertaining aspects of blood safety will be discussed. Data reported to the health authorities show that the frequency of transfusion-transmitted infection markers in the German donor population is low and that only very few infections have been transmitted through blood. This is underlined by a detailed analysis of the paid donor population of a small university blood service (UBS). The analysis documents a very stable and reliable cohort of predominantly repeat donors. Unpaid RC donors of blood units transfused to patients at the university hospital of Marburg showed a sixteen-times higher sero-conversion rate than those of the UBS (p < 0.0001). However, in a survey, 77% of the paid donors denied continuation of blood donation in the event of payment being stopped. Therefore non-remuneration would result in acute blood supply shortages. Since increased blood shortages are to be expected anyway in the near future, all measures improving the supply of safe blood, including monetary compensation, should be objectively discussed without prejudice.

In vitro bleeding test--a simple method for the detection of aspirin effects on platelet function.

We investigated platelet function of 21 healthy blood donors before, 4 hrs and 1 to 7 days after a single oral dose of 0.02 (n = 3), 0.05 (n = 3), 0.1 (n = 3), 0.5 (n = 2) and 1.0 g (n = 10) aspirin. Three additional donors received 0.02 g aspirin/day for 5 days. A new and simple in vitro bleeding test (Thrombostat) using whole blood was far more sensitive than all other tests for platelet function (subaquatic bleeding time, thrombelastrogram, resonance-thrombogram, platelet adherence, spreading and aggregation). With this method using 2mM CaCl2 as additional agent all donors showed significantly increased in vitro bleeding volumes, for at least 2 days after ingestion of 0.1 to 1 g aspirin. In the majority of cases the aspirin effect could be detected even after 5-6 days. In 2 of 3 donors even 0.05 g aspirin was detectable. There was already a definite effect seen after 2 days in all 3 cases when 0.02 g was ingested daily. The new in vitro bleeding test should be suitable for the control of low dose aspirin prophylaxis of arterial thromboembolic disorders.

Arginine inhibits hemostasis activation.

BACKGROUND: The diagnosis and the therapy of in vivo hemostasis activation is of great clinical importance. Artefactual changes of the hemostasis (i.e., coagulation or fibrinolysis) in vitro have to be prevented. Usual in vitro anticoagulation by sodium citrate does not fully inhibit coagulation--or fibrinolysis--activation. Therefore, there is need for a simple physiologic inhibitor of hemostasis activation both in diagnosis and therapy of hemostasis activation. METHODS: Whole blood clotting time (WBCT), prothrombin time (PT), activated partial thromboplastin time (APTT), in vitro bleeding test closure time (IVBT-CT), and whole blood aggregometry (WBA) were determined in normal human blood or plasma, supplemented with increasing concentrations of L-arginine or guanidine. RESULTS: Arginine in concentrations of 5-100 mM inhibited the WBCT, PT, APTT, IVBT-CT, and WBA. Arginine (50 mM) resulted in a two-fold prolongation of WBCT, PT, or IVBT-CT (the anti-epinephrine action is superior to the anti-ADP action), a four-fold prolongation of APTT or a 60% inhibition of WBA. CONCLUSION: L-Arginine (or guanidine) inhibited the activation of hemostasis. Arginine might be used as hemostasis stabilizer both in the diagnosis and therapy of hemostasis activation. The usage of arginine as an in vitro hemostasis inhibitor might be indicated in the diagnosis of hemostasis activation, as occurring in pharmacological thrombolysis or disseminated intravascular coagulation (DIC). The storage of blood or blood products might be improved by arginine stabilization. The amino acid (and nitric oxide precursor) L-arginine could be an interesting new pharmacologic agent to inhibit a pathologic hemostasis activation.

Singlet oxygen (1O(2)) disrupts platelet aggregates.

INTRODUCTION: Important mediators of activated polymorphonuclear leukocytes (PMN) are the oxidants HOCl and chloramine, which generate the nonradical photon-emitting oxidant singlet oxygen (1O(2)). Since 1O(2) inhibits platelet aggregation, we became interested in a possible oxidant mediated reversibility of platelet aggregation. METHODS: Chloramine T (CT) is a stable 1O(2) generator that mimics the natural chloramine N-chloro-taurine. Platelet-rich plasma (PRP) was incubated with CT 0-8 min after addition of the aggregation agonist (10 microM adenosine-5'-diphosphate, ADP, or 5 microg/ml collagen) and the aggregation was monitored. Platelet function was also analyzed by the platelet function analyzer, PFA-100. Fifty microliters of 200 micromol/l ADP was added to 400 microl PRP. After 1 min at 37 degrees C, 50 microl of 0 or 30 mmol/l CT was added, and after an incubation for 3 min at 37 degrees C, 50 microl of 25% glutaraldehyde was added. The samples were analyzed in a transmission microscope at x3000 and x7000 magnification. RESULTS: Chloramines inhibit platelet function in PRP: about 1 mM CT suppresses 50% of the aggregatory capacity of thrombocytes in normal PRP (effective dose 50%, ED(50)=1 mM chloramine), which is identical to the ED(50) for CT in whole blood. The ADP- or collagen-induced platelet aggregation can be reversed by addition of CT: up to 2 min after the addition of ADP as the aggregation inducer, the aggregation is reversible to more than 70% by addition of a 1O(2) release-inducer (3 mM CT). In contrast, addition of CT 8 min after the addition of ADP results only in about 50% reversal of platelet aggregation. The electron microscopic images of platelets before ADP, after incubation for 4 min at 20 micromol/l ADP, after incubation for 1 min at 20 micromol/l ADP, and a further incubation for 3 min at 3 mmol/l CT demonstrate an ADP-dependent formation of platelet aggregates, which are disrupted by 1O(2) into the single platelets; a phenomenon comparable to the decomposition of a puzzle or the continental drift of the major earth plates. The morphology of oxidized and unoxidized platelets is similar. CONCLUSION: This study demonstrates that 1O(2) inhibits and reverses platelet aggregation. The physiologic signal action and the direct anticoagulant action of 1O(2) might be a new principle for pharmacologic intervention in atherothrombosis.

Singlet oxygen ((1)O2) inactivates plasmatic free and complexed alpha2-macroglobulin.

alpha2-macroglobulin (alpha2M) is a broad-spectrum proteinase inhibitor and one of the major plasma proteins in humans. Activated phagocytes (especially granulocytes) generate large amounts of oxidants of the HOCI- and chloramine-type that release the mild nonradical, excited (light-emitting) oxidant singlet oxygen ((1)O2). These oxidants have been shown to inactivate several specific serine protease inhibitors in human blood [e.g., alpha1-antitrypsin or alpha2-antiplasmin (plasmin inhibitor)]. The studies reported here demonstrate that nonradical oxidants also inactivate plasmatic alpha2M. The effective dose for 50% inactivation (ED50) of plasmatic alpha2M is similar to that for plasmatic alpha2-antiplasmin. Chloramines are about 1,000-fold more effective than hydrogen peroxide (ED50)=0.75 micromol chloramine T/50 microl plasma). Serine protease-serine protease inhibitor complexes are resistant to oxidants. In contrast, here it is shown that alpha2-macroglobulin, even after binding to serine proteases is sensitive to oxidation, the captured protease is released from the protease/alpha2M complex. This is the first time that oxidative inactivation of a complexed (i.e., bound to a target protease) human protease inhibitor has be shown. The (1)O2 inhibitors methionine, cysteine, cystine, or ascorbate-in contrast to the oxy-radical scavengers mannitol, superoxide dismutase, or catalase-antagonize the chloramine/NaOCl-mediated inactivation of both uncomplexed and complexed alpha2M. Thus, the oxidant involved here is of nonradicalic nature and has reaction characteristics of (1)O2. For the inhibitory function, critical oxidizable methionines or the internal thiol-ester might be targets for (1)O2. Consequently, alpha2M can also be considered a carrier for proteases, since the alpha2M-complexed proteases regain full activity in an oxidative environment. In local areas of inflammation or thrombolysis, activated phagocytes could create microenvironments of uncontrolled protease activity by generation of (1)O2.

A simple screening assay for certain fibrinolysis parameters (FIPA).

Hemostasis, the system of generation and degradation of thrombi, consists of coagulation and fibrinolysis. Whereas global assays to study coagulation have existed for many years, there has been no simple, rapid, and economic routine test for the plasmatic fibrinolysis parameters plasminogen activator inhibitor-1, alpha2-antiplasmin, plasminogen, and aprotinin. Here a fast functional global assay for these plasmatic fibrinolytic parameters is presented. However, the present assay is not sensitive to physiological concentrations of prourokinase or tissue-type plasminogen activator. The following assay conditions have been found to be optimal: 50 microL of citrated plasma is incubated with 50 microL of 10 IU urinary-type plasminogen activator (urokinase)/mL, 1.1 mmol/L tranexamic acid, 1% polygelin, 0.1% Triton X-100, phosphate-buffered saline, pH 7.4, for 20 min at 37 degrees C (plasmin generation phase). Then 50 microL of 3 mmol/L HD-Nva-CHA-Lys-pNA, 1.05 mol/L KCl is added, and deltaA (405 nm)/10 min (37 degrees C) is determined, by using a microtiterplate reader (plasmin detection phase). The results are calibrated against pooled normal plasma (100% plasmatic fibrinolytic parameters activity). The intra- and interassay coefficients of variation have been found to be less than 5%. The detection limit (sensitivity) of the functional fibrinolysis assay is 5 % of the normal plasmatic fibrinolysis parameters activity. The normal plasmatic fibrinolysis parameters activity is 100%, sigma = 25%. The plasmatic fibrinolysis parameters activity correlates negatively (r = -0.684) with the plasminogen activator inhibitor-1 activity of patient samples. The plasmatic fibrinolysis parameters assay is a simple, rapid, and economic functional test for several clinical relevant fibrinolysis parameters.

Singlet oxygen inhibits agonist-induced P-selectin expression and formation of platelet aggregates.

Major mediators of activated polymorphonuclear leukocytes (PMN) are the oxidants HOCl and chloramine, which are a source for the nonradical photon-emitting oxidant singlet oxygen (1O2). We were interested in a possible platelet-modulating activity of 1O2. As a stable 1O2 source we chose the mild oxidant chloramine T (CT), which mimics the natural chloramine N-chloro-taurine. Freshly drawn native whole blood from donors (n = 5) was incubated at 0 to 3 mM CT for 1 minute at 37 degrees C. Then saline. 10 microM adenosine diphosphate (ADP), 5 microg/mL collagen, or 6.25 microM thrombin receptor activator peptide (TRAP) were added and the mixtures were allowed to incubate for 3 minutes at 37 degrees C. Aliquots of activated blood were fixed in 1% para-formaldehyde. After removal of the fixative, platelets were labeled with anti-CD61-FITC and anti-CD62P-PE antibodies and analyzed by flow cytometry. An oxidant concentration-dependent decrease in the expression of P-selectin appeared (at 3 mM CT to 39, 23, and 20% of the 100% saline control level for ADP, collagen, and TRAP, respectively). There was also an oxidant concentration-dependent decrease in the formation of platelet aggregates (at 3 mM CT to 8, 12, and 13% of the 100% saline control level for ADP, collagen, and TRAP, respectively; the 50% effective dose was 1.0 to 1.5 mM chloramine). In ADP- and TRAP-stimulated platelets, an oxidant-mediated increase in platelet fragments appeared (at 3 mM CT: three- to fourfold of the initial value). The addition to the blood of 30 mM of the oxyradical scavenger mannitol in contrast to excess methionine did not antagonize these oxidative modulations of platelet activation. The results were confirmed using equimolar concentrations of NaOCI and N-chloro-taurine. This study shows that 1O2 inhibits platelets, decreasing the expression of CD62P and the formation of platelet aggregates. Activated PMN might modulate hemostasis, shifting it into an antithrombotic state. The physiologic signal action and the direct anticoagulant action of 1O2 (released by chloramines such as vancomycin) might be a new principle for pharmacologic intervention in atherothrombosis.

German multicenter studies on plateletpheresis from healthy donors. German Hemapheresis Study Group.

It is reported on two German Multicenter Plateletpheresis Studies with the Fresenius AS 104 cell separator accompanied by a Multicenter Counting Study. 15 centers participated, a total of 1884 separations were evaluated. It could be shown that multicenter studies help to give a more objective opinion about a cell separator and the separation protocol used if it is possible to improve the counting methods and to eliminate individual center effects by an accompanying Multicenter Counting Study. The AS 104 proved to be a good cell separator for platelet collection regarding platelet yields (3.1 x 11" from 3.5 I citrated blood), separation efficiency (about 45%), yield prediction (SD = not equal to 15%) and leukocyte contamination (median WBC 47 x 10(6)).

[Immunization against blood group antigens by allogeneic bone transplantation]. / Immunisierung gegen Blutgruppenantigene durch allogene Knochentransplantation.

33 bone allotransplants (cryopreserved) of AB0- and Rh-incompatible (donor-recipient) patients were performed to evaluate the question which AB0 Rh-incompatibility leads to immunization of the bone transplant recipient. Several different antibodies were tested pre- and postoperatively in the recipient. Regarding the Rh-system no immunization was demonstrable; however, a significant increase of antibody leads was found regarding the AB0-system. Thus, in bone bank techniques AB0 compatibility is important for allogeneic bone transplantation in young women. Otherwise, there is a risk for the development of MHN in case of pregnancy. Blood group-typing is not necessary in other patient groups. Although no Rh-antibodies were demonstrable, a similar mechanism can be postulated for the Rh-system. We, thus, conclude that in allogeneic bone tx in young women the Rh-system has to be taken into consideration.

Characterization of immune system alterations following preoperative autologous blood donation for elective hip replacement surgery.

Preoperative autologous blood donation (PABD) has been shown to decrease natural killer (NK) cell function in cancer patients, raising concerns about an increased cancer recurrence risk owing to PABD. It is unclear whether PABD leads to other immunomodulatory effects that might affect more short-term risks like postoperative infectious complications in surgical patients. Lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells, NK cells) were determined in 86 consecutive patients donating 2 units of autologous whole blood prior to elective hip replacement surgery. In addition, cytokine secretion patterns of monocytes [tumour necrosis factor (TNF)] and lymphocytes [interferon-gamma, interleukin (IL)-2, IL-4, IL-10] upon stimulation were determined in a random subgroup of 58 patients. Analyses were performed immediately before the first donation and on the day prior to operation. Granulocytes increased during PABD by 4.6% (P < 0.01). Lymphocytes decreased by 8.8% (P < 0.01), accompanied by a relative rise in CD4+ T cells by 10.7% (P < 0.01) and in B cells by 10.3% (P < 0.01), and a fall of NK cells by 20.8% (P < 0.01). Stimulated TNF secretion of monocytes was suppressed (-12.3%, P < 0.01). The effect on the reactivity of lymphocytes and the T helper 1 (Th1)/Th2 balance were variable. The observed changes of innate and cellular immunity might influence the risk of perioperative infectious complications.

Platelets do not adsorb HLA class I molecules during storage of pooled platelet concentrates.

The origin of HLA class I molecules on platelets is still under discussion. Adsorption of HLA molecules on platelets using specific experimental conditions has been described. The study presented investigates whether there is a significant elution and adsorption of HLA class I molecules on platelets during storage of pooled random platelet concentrates (PRPC) under routine conditions. Platelet concentrates (PCs) from whole blood were prepared from HLA-A2-positive and HLA-A2-negative donors, pooled and stored under routine conditions. In addition, platelets from HLA-A2-negative donors were pelleted and resuspended in cell-free plasma from HLA-A2-positive donors. HLA-A2-positive PCs (positive control), HLA-A2-negative PCs (negative control) and HLA-A2-negative platelets in plasma from HLA-A2-negative donors were stored simultaneously. Binding of FITC-conjugated monoclonal murine antihuman HLA-A2 antibodies (anti-HLA-A2-mab) was measured during 5-day storage by flow cytometry. An increased binding of anti-HLA-A2-mab during storage was found on HLA-A2-negative platelets (P < 0.005) independently whether they were incubated with cell-free plasma or platelets from HLA-A2-positive donors or autologous HLA-A2-negative cell-free plasma. However, non-specific binding of IgG controls increased equally, whereas anti-HLA-A2-mab binding to platelets from HLA-A2-positive donors did not decrease during storage. This study suggests that there is no significant elution and adsorption of HLA class I antigens of platelets in pooled PCs during storage under the usual conditions for platelet storage. Increased anti-HLA-A2-mab signal was due to non-specific binding. Therefore, HLA class I compatible platelets should maintain their compatibility for an immunized patient when stored in a pool with HLA incompatible platelets and shortened survival after transfusion should not be expected.

[Perioperative blood coagulation therapy and diagnosis]. / Perioperative Gerinnungstherapie und -diagnostik.

The risks and adverse reactions of fresh frozen plasma (FFP) and coagulation components have changed considerably in the last few years because of the spread of HIV on the one hand, and the advances in preparation and sterilisation of the coagulation components on the other hand. Therefore, the indication for FFP and the various coagulation components deserves permanent consideration. FFP is still the therapeutical means of choice for the treatment of acquired (complex) plasmatic coagulation disorders, even though the (still) small risk of virus transmission in Middle Europe has to be taken into account. Coagulation components are primarily indicated in congenital (isolated) plasmatic coagulation disorders. Only in gross or very acute acquired coagulation disorders are coagulation components needed in addition to FFP. The same regimen is recommended for the use of antithrombin III (AT III) concentrates. In cases of acquired antithrombin deficiency, antithrombin III substitution is indicated only when the anticoagulation by heparin alone or in combination with FFP is insufficient or when the heparin dose required might cause an unacceptable bleeding risk, e.g. in simultaneous thrombocytopenia. Then AT III becomes an important therapeutic agent, especially in DIC. In addition, information regarding a rational and economic substitution of FFP and coagulation components is given, and other substitutes are mentioned which could possibly be used with less risk. Finally, the necessity of accurate diagnosing is emphasized. Close cooperation between the physicians in the clinics and in the department of transfusion medicine/hemostaseology reduces unnecessary and inadequate application of coagulation components. This also means an improvement in the patient's therapy.

[Autologous blood donation]. / Eigenblutspende.

Because of the risks and side reactions of homologous blood transfusion autologous blood donation/transfusion is always indicated when it is practicable. Appropriate performance has to be guaranteed. By adequate training of the responsible physicians drawing and storage of autologous blood as whole blood should be general possible. However, separation into buffy coat poor red cell concentrates and fresh frozen plasma (FFP) has clear advantages. Therefore the cooperation with a blood bank or a transfusion service should be intended to which production of blood components is restricted. There is an indication for autologous blood donation in all patients who plan to undergo an elective operation being cardially compensated without "hematogenous" infection and with at least 12 g/dl hemoglobin. The aptitude examination generally may be confined on history, physical examination including blood pressure and blood counting. In a preoperative interval of 2 to 28 days it is possible to reserve 1 to 4 units of whole blood or the same number of red cell concentrates and FFP when the patient has normal haematopoiesis. The greatest problems concern the organization. They are easily to be solved by adequate information of all persons involved and close cooperation between the various physicians sending the patient to the hospital, taking care of him in the clinic and drawing the autologous blood.

Side-effects and technical problems in cytapheresis with cell separators. Results of a retrospective multicenter study.

On the basis of a survey, the acute side-effects and technical problems in a total of 77,525 cytaphereses (IFC 36,530, CFC 40,995) in donors at 39 hemapheresis centers were retrospectively analysed statistically. In general, relevant donor side-effects (0.78%-1.05%) were more rare than the primary donor-independent disturbances (1.65%-2.63%). The donor side-effects predominated merely with the use of the cell separators Haemonetics M30/Belco (1.06% vs. 0.57%). These were mainly circulatory reactions (0.83%), which were generally much more frequent with IFC (0.54%) than with CFC (IBM/Cobe 0.11%, CS-3000 0.19%). Potentially fatal complications were not reported. The frequency of side-effects, disturbances and discontinuations correlated inversely with the separation rate of the individual centers per method. Centers in which two or three methods were applied simultaneously reported a higher frequency of side-effects and disturbances. Hemolysis was only observed with IFC (0.09%), but not with the use of the Haemonetics V50. The greater susceptibility to disturbances of technical/methodological/operational origin essentially results from the more elaborate, but not yet perfected technology, including computer control and monitoring, as well as defects in the production of the much more complicated disposable sets. Thus the highest rate of discontinuations was calculated for the system which is so far the most sophisticated technically (CS-3000, 1.85%). Although the primary donor-independent problems sometimes correlate directly with the manifestation of donor side-effects, the greater technological sophistication of automatically controlled and monitored systems cannot be dispensed with, since only in this way can potentially fatal risks for the donors be largely ruled out.(ABSTRACT TRUNCATED AT 250 WORDS)

[The status of blood coagulation preparations within the scope of modern hemotherapy in surgical patients]. / Stellenwert der Gerinnungspräparate im Rahmen einer modernen Hämotherapie bei chirurgischen Patienten.

The risks and adverse reactions of fresh frozen plasma (FFP) and coagulation components have changed considerably in the last few years because of the spread of HIV on the one hand, and advances in the preparation and sterilization of coagulation components on the other. Therefore, the indication for FFP and the various coagulation components deserves constant consideration; this is the intention of this paper. FFP is still the therapeutic choice for the treatment of acquired (complex) plasmatic coagulation disorders, even though the (still) small risk of virus transmission in Middle Europe has to be taken into account. Coagulation components are primarily indicated in congenital (isolated) plasmatic coagulation disorders. Only in gross or very acute acquired coagulation disorders are coagulation components needed in addition to FFP. The same regimen is recommended for the use of antithrombin III (AT III) concentrates. In cases of acquired antithrombin deficiency, antithrombin III substitution is indicated only when the anticoagulation by heparin alone or in combination with FFP is insufficient or when the heparin doses required might entail an unexceptable bleeding risk, e.g. in simultaneous thrombocytopenia. Then AT III becomes an important therapeutic factor, especially in DIC. In addition, information regarding a rational and economic substitution of FFP and coagulation components is given, and other substitutes are mentioned which could possibly be used with less risk. Finally, the necessity for an adequate diagnostic procedure is emphasized. Close cooperation between the physicians in the clinics and in the department of transfusion medicine/hemostaseology reduces unnecessary and inadequate application of coagulation components. This also means an improvement of the patient's therapy.