Ralf Knels

Thrombelastography Should Be Included in the Algorithm for the Management of Postpartum Hemorrhage

With great interest, we gratefully appreciated the evaluation of an algorithm for life-threatening postpartum hemorrhage by Dr. Goodnough and coworkers [1] in Transfusion recently. However, the transfusion protocol presented neither is evidence-based nor specifically goal-directed towards the leading pathomechanisms of postpartum hemorrhage (PPH) [2, 3]. Our criticism concerns the lacking evidence for the used cutoff values employed in this transfusion protocol for INR, platelet count, and fibrinogen. Fibrinogen levels might better be maintained at a higher level above 200 mg/dl [4] as opposed to 100 mg/dl. Furthermore, we recommend the use of thrombelastography in addition to standard laboratory tests for two reasons: i) There is a higher rate of hyperfibrinolyses in postpartal hemorrhage and only thrombelastography detects this coagulopathy reliably. ii) The delay between blood sampling and test result information is essential for the choice of the right therapy. We do not agree with the authors’ statement that availability of ‘super-stat’ laboratory results (15–30 min) would be superior to thrombelastography [1]. Even though faster than normally obtained, conventional ‘super-stat’ laboratory tests do not allow reliable diagnosis of frequent causes evolving in PPH in a dramatic pace – hyperfibrinolysis, dilution and consumption of coagulation potential [2]. The listed conventional laboratory tests analyze plasma coagulation to the point where clotting starts, but they do not cover fibrin polymerization, interaction with platelets, and fibrinolysis. Measurement of D-dimers have a low test specifity for hyperfibrinolysis [5], whereas multi-channel rotational thrombelastometry (ROTEM®) enables the valid differentiation of hyperfibrinolysis from other influences such as dilution or colloid effects [6, 7]. In addition, thrombelastometry is highly sensitive to fibrinogen deficiency [8]. Although regular ROTEM® results usually are obtained after only 100 s (coagulation time CT), 160 s (clot formation time CFT) and 15 min (clot firmness after 15 min [9], diagnosis of late hyperfibrinolysis may need longer with this method (see also fig. ​fig.1).1). An algorithm based on the solely use of routine laboratory results does not consider the therapeutic option of antifibrinolytic drugs. Fig. 1 a Fulminant hyperfibrinolysis shows an immediate breakdown of the clot within 30 min. b Intermediate hyperfibrinolysis with a breakdown of the clot between 30–60 min. c Late hyperfibrinolysis: clot breakdown after 60 min. Finally, we agree with the authors that for the first minutes of a life-threatening hemorrhage a rigid relationship of red blood cells, plasma, and platelets may be a reasonable advice. However, the adherence to this ratio as designed in their transfusion algorithm will result in an insufficient substitution of both coagulation factors and fibrinogen (the clot substance). The correction of a 60% loss of plasma in a 70 kg parturient during ongoing bleeding aiming at a 80% concentration of coagulation factors requires a volume of 40% × 70 kg = 2,800 ml, equaling 8–10 units. Taking into account the higher average body weight and increased plasma volume of parturients, the needed plasma transfusion volume might increase further. Early use of cryoprecipitate and, if available (as it is in Europe), purified fibrinogen concentrate is recommended to improve efficacy and to avoid massive volume overload. Substitution therapy optimally is guided by thrombelastography (alternative but minor are fibrinogen levels). Other options are the early use of refrigerated or lyophilized plasma as well as the limited use of synthetic colloids [10].

Eurocode International Blood Labeling System enables unique identification of all biological products from human origin in accordance with the European Directive 2004/23/EC

Due to their limited availability and compatibility, biological products must be exchanged between medical institutions. In addition to a number of national systems and agreements which strive to implement a unique identification and classification of blood products, the ISBT 128 was developed in 1994, followed by the Eurocode in 1998. In contrast to other coding systems, these both make use of primary identifiers as stipulated by the document ISO/IEC 15418 of the International Organization for Standardization (ISO), and thus provide a unique international code. Due to their flexible data structures, which make use of secondary identifiers, both systems are able to integrate additional biological products and their producers. Tissue and cells also constitute a comparable risk to the recipient as that of blood products in terms of false labeling and the danger of infection. However, in contrast to blood products, the exchange of tissue and cells is much more intensively pursued at the international level. This fact is recognised by Directives 2004/23/EC and 2006/86/EC of the European Union (EU), which demand a standardized coding system for cells and tissue throughout the EU. The 2008 workshop agreement of the European Committee for Standardization (CEN) was unique identification by means of a Key Code consisting of country code corresponding to ISO 3166-1, as well as competent authority and tissue establishment. As agreed at the meeting of the Working Group on the European Coding System for Human Tissues and Cells of the Health and Consumers Directorate-General of the European Commission (DG SANCO) held on 19 May 2010 in Brussels, this Key Code could also be used with existing coding systems to provide unique identification and allow EU traceability of all materials from one donation event. Today Eurocode already uses country codes according to ISO 3166-1, and thus the proposed Key Code can be integrated into the current Eurocode data structure and does not need to be introduced separately. The Eurocode product classification for all products is based on its own unique coding system, which can be accessed over the internet by all users who are not themselves members of Eurocode. In summary, it can be said that the standardized single coding system for tissues and cells requires only unique sections in the data structure such the Key Code to fulfil the requirements of the EU Directive. Thus, various systems currently in place in different EU member states can continue to operate if the Key Code as suggested by the EU is integrated into them. The classification and description of each product characteristic is currently being discussed by the DG SANCO Working Group on the European Coding System for Human Tissues and Cells. Following intensive scrutiny in light of the stipulations laid out in EU Directives 2004/23/EC and 2006/86/EC as well as the CEN/ISSS workshop agreements, the Germany Federal Ministry for Health and organisations representing German tissue establishments under the responsibility of the German Society of Transfusion Medicine and Immunohematology, Working Party “Tissue preparations” proposed in 2009 that Eurocode be adopted for the donor identification and product coding of tissue and cells in Germany. The technical details for implementation have already been completed and are presented in the current article.

Administration Safety of Blood Products - Lessons Learned from a National Registry for Transfusion and Hemotherapy Practice

Background: Compared to blood component safety, the administration of blood may not be as safe as intended. The German Interdisciplinary Task Force for Clinical Hemotherapy (IAKH) specialized registry for administration errors of blood products was chosen for a detailed analysis of reports. Methods: Voluntarily submitted critical incident reports (n = 138) from 2009 to 2013 were analyzed. Results: Incidents occurred in the operation room (34.1%), in the ICU (25.2%), and in the peripheral ward (18.5%). Procedural steps with errors were administration to the patient (27.2%), indication and blood order (17.1%), patient identification (17.1%), and blood sample withdrawal and tube labeling (18.0%). Bedside testing (BST) of blood groups avoided errors in only 2.6%. Associated factors were routine work conditions (66%), communication error (36%), emergency case (26%), night or weekend team (39%), untrained personnel (19%). Recommendations addressed process and quality (n = 479) as well as structure quality (n = 314). In 189 instances, an IT solution would have helped to avoid the error. Conclusions: The administration process is prone to errors at the patient assessment for the need to transfuse and the application of blood products to patients. BST is only detecting a minority of handling errors. According to the expert recommendations for practice improvement, the potential to improve transfusion safety by a technical solution is considerable.

Contents of Forthcoming Issues · Themenvorschau

Spinal cord chimeras were produced by replacing a small fragment of neural tube of a 2-day-old White Leghorn chicken embryo with a similar fragment from a Japanese quail embryo. The embryo mortality was 61%, and 72% of hatched birds were ‘cripples’ and had to be sacrificed within 5 days after hatching. Forty-nine chimeras, 10.9% of the total number of operated embryos, were alive for more than 3 weeks. For at least 17 days after hatching, all birds behaved like normal chicks, and the grey quail-like feathers were the only manifestations of their chimerism. Initial neurological symptoms of unsteady walking and drooping of the wings were noted in all birds except for 1 that died an accidental death before it became sick. Advanced symptoms characterized by paralysis of the legs forcing the bird to lie on its side were noted in 40 birds. The chimeras could be divided into two groups, each consisting of 24 birds. The short-survival (SS) chimeras of the first group became terminally ill and had to be sacrificed within 3 months. The long-survival (LS) chimeras of the second group showed more protracted disease, in that only 16 of them showed symptoms of the advanced disease, and the majority showed partial or complete recovery. Ten of the LS birds were kept alive for more than 8 months. Furthermore, many LS chimeras lost their grey feathers. The hallmarks of neurohistological manifestations were mononuclear cell infiltrates, demyelinization with preservation of axons and scar formation. These lesions were restricted to the quail fragment of the spinal cord except for 2 birds in which distant cellular infiltrates were observed. Direct immunofluorescence tests for chicken IgG were positive in spinal cords of most SS chimeras but only of some LS chimeras.

Arbobacteria – Pathogens Transmittable by Arthropods

Anaplasma phagocytophilum, marginatum; Bartonella henselae; Borrelia burgdorferi, afzelii, garinii; Coxiella burnetii; Ehrlichia chaffeensis; Francisella tularensis; Rickettsia prowazekii, akari, rickettsii andYersinia pestis are also known as arbobacteria. Diseases caused by these bacteria are basically zoonoses, i.e. diseases transmittable from animals to humans, and have been known as such for about 100 years (table ​(table1).1). A part of the individual pathogens have not been described until the past few decades. Based on molecular biology analyses, R. prowazekii, Ehrlichia and Anaplasma are categorised as Rickettsiales, while Bartonella is categorised as alpha-2-proteobacteria, Coxiella, Rickettsia grylli and F. tularensis as gamma proteobacteria, and Y. pestis as enterobacteria [1]. Table 1 Vectors for arbobacteria Most arbobacteria grow predominantly intracellularly. However, Borrelia bacteria grow intracellularly and extracellularly, and Yersinia mainly extracellularly. The above described arbobacteria, when transmitted by ticks, show seasonal occurrence and a partly changed antigen repertoire in vector and mammal. R. prowazekii is transmitted by lice world-wide throughout the year. The major clinical symptoms such infections have in common include fever, exanthema, headache, and lymph node swelling, partly a pronounced erythema at the site of the sting, and encephalitic disorders. Neutropenia and thrombocytopenia can occur later. Treatment: Doxycycline is the treatment of choice against most of these bacteria, followed by chloramphenicol and cephalosporins. Quinolones are ineffective against R. prowazekii. The treatment of choice against Y. pestis and F. tularensis is streptomycin or gentamycin, and in addition doxycycline or ciprofloxacine. C. burnetii has been dealt with separately [2]. Therefore, this pathogen is not included in the present review, neither are rare tropical and/or pure tropical diseases. The oriental flea (Xenopsylla cheopsis) is considered as the most effective transmitter for Y. pestis. More than 30 other flea species are known which can transmit Y. pestis as intermediary hosts, including Pulex irritans (human flea), which can play a role in human-to-human transmission. The human louse can also be a vector for transmission of Y. pestis [3]. The following section provides for each pathogen information on the general state of knowledge, characteristics of the pathogen, infectious disease, epidemiology, methods of detection and occurrence of the pathogen in the donor population. This is followed by information concerning all pathogens on epidemiology, defence situation, treatment and prevention in recipient populations as well as a summary evaluation.