Juergen Ringwald

Storage of platelets in additive solutions: a multicentre study of the in vitro effects of potassium and magnesium

Background and Objectives  In a preliminary study, the presence of potassium and magnesium in a modified synthetic medium (PAS‐III) was found to have a significant influence on platelet metabolism (using apheresis‐derived, as well as buffy‐coat‐derived platelets) when compared with standard PAS‐III. The differences included reduced glycolysis, as evidenced by lower consumption of glucose and lower production of lactate, but also better preservation of pH and hypotonic shock response reactivity. The results suggested that storage in modified PAS‐III containing 20% plasma was comparable to storage in standard PAS‐III containing 30% plasma. To confirm the preliminary results and to evaluate the effects of different preparation protocols, an international multicentre study, which included 11 different sites, was conducted.

'New' direct oral anticoagulants in the perioperative setting.

Purpose of review Out of the anesthetists perspective, some uncertainties remain with the perioperative management of the so-called NOACs. This review emphasizes on the question of bleeding and thromboembolic risk as well as the management of bleedings and the discontinuing intervals in the context of regional anesthesia. Recent findings Managing patients with NOAC therapy, an interdisciplinary approach and consent with surgeons and specialist in hemostaseology has to be found. For severe and lifethreatening bleeding there are specific antidotes in development; however, until clinical provement is not yet finished the application of four-factor prothrombin complex concentrate may be the most promising approach. Summary NOACs like dabigatran etexilate, rivaroxaban, apixaban and edoxaban are effective alternatives to warfarin in primary and secondary prophylaxis of thromboembolic conditions. In the perioperative setting, some uncertainties and evidence gaps remain in estimating the bleeding risks associated with surgical procedures, emergency trauma and neuroaxial anesthesia. A discontinuation of NOACs should be at least 1 day before elective operation. Renal and liver impairment, older age, or co-medications could afford longer intervals. As no specific reversal agents are yet available for life-threatening bleeding or emergency surgery; nonspecific prohemostatic therapies are mainly recommended. Oral charcoal, application of tranexamic acid or hemodialysis could bring additional benefit depending on the individual NOAC. Practitioners need to be aware that NOACs can interfere in different pathways with the measurement of common hemostasis parameters. Estimating the bleeding risks and reversal strategies requires careful evaluation also in the light of a potential risk of thromboembolic complications. In difference to warfarin, ‘bridging’ concepts are not generally recommended for NOACs.

Blood group A: an overseen risk factor for early-onset ovarian hyperstimulation syndrome?

Ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication, is classified into two distinct forms, early-onset and late-onset OHSS. Few risk factors have been established, but no association with ABO blood group antigens was known. From January 2000 to October 2007, 122 patients with known blood groups and the diagnosis of OHSS were hospitalized. OHSS classification, pregnancies, age and time of in-patient treatment were collated. Two control groups were established. One group comprised 177 patients treated for infertility without developing OHSS (treatment/no OHSS) and known blood groups. A second one consisted of 2289 obstetric and gynaecological patients (O/G). OHSS grade I, II or III was found in 20, 47 and 55 patients, respectively. The pregnancy rate was 50.8% and did not differ among the different OHSS grades. Blood group A was significantly more frequent and blood group O less frequent in patients with early-onset OHSS compared with the two control cohorts (P = 0.009 versus treatment/no OHSS; P = 0.001 versus O/G). The odds ratio for patients with blood group A versus O to develop early-onset OHSS was 2.169 and 2.262, respectively. No increased risk for late-onset OHSS was found. Blood group A may be associated with early-onset OHSS in Caucasians.

Aggregates in platelet concentrates

P. F. van der Meer, L. J. Dumont, M. Lozano, N. Bondar, J. Wong, S. Ismay, J. Pink, W. Nussbaumer, J. Coene, H. B. Feys, V. Compernolle, D. V. Devine, D. Howe, C. K. Lin, J. Sun, J. Ringwald, E. F. Strasser, R. Eckstein, A. Seltsam, P. Perseghin, P. Proserpio, S. Wakamoto, M. Akino, S. Takamoto, K. Tadokoro, D. Teo, P. H. Shu, S. S. Chua, T. Jimenez-Marco, J. Cid, E. Castro, I. Mu~ noz, H. Gulliksson, P. Sandgren, S. Thomas, J. Petrik, K. McColl, H. Kamel, J. Dugger, J. D. Sweeney, J. B. Gorlin, L. J. Sutor, D. Heath & M. H. Sayers.

EDTA plasma is unsuitable for in vivo determinations of platelet-derived angiogenic cytokines.

Recently, Backen et al. (2009) reported on a ‘fit-forpurpose’ validation of SearchLightTM multiplex ELISAs of angiogenesis for clinical trial use. There is a continuously growing interest on bridging platelet-derived growth factors, cytokines and growth factors from other sources and their receptors on the one, and inflammation, atherosclerosis, and cancer on the other hand (Figg and Folkman, 2008). A validated multiplex assay for measurements of these circulating biomarkers of angiogenesis will meet great interest. A part of the reported validation of the SearchLight multiplex ELISA system was the analysis of plasma samples of eight patients suffering from ovarial cancer. Backen et al. (2009) used EDTA plasma samples for measuring several circulating angiogenesis markers including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) BB. The α-granules of platelets (PLTs) contain large amounts of VEGF, PDGFs, and other cytokines. These molecules and all other contents of α-granules are released when PLTs become activated. Therefore, it is important to know that EDTA causes

Intrauterine use of hyperconcentrated platelet concentrates collected with Trima Accel in a case of neonatal alloimmune thrombocytopenia

BACKGROUND: Due to the threat of serious or fatal bleedings, fetuses with neonatal alloimmune thrombocytopenia (NAIT) may need intrauterine platelet (PLT) transfusions. To prevent a volume overload or an ABO minor mismatch, standard PLT concentrates need to be washed to increase the PLT concentration and to reduce the plasma content. Hyperconcentrated single‐donor PLT concentrates (HCPs) are a therapeutic alternative. The first case of NAIT successfully treated with HCPs collected with the Trima Accel (TA; Gambro BCT) is reported.

Measuring the pH of platelet concentrates

1. Sanchez A, Schreiber G, Nass C, et al. The impact of maleto-male sexual experience on risk profiles of blood donors. Transfusion 2005;45:404-13. 2. Brooks JP. The rights of blood recipients should supersede any asserted rights of blood donors. Vox Sang 2004;87: 280-6. 3. American Association of Blood Banks. Statement of the American Association of Blood Banks before the Blood Products Advisory Committee: Donor Deferral Policy Regarding Men Who Have Had Sex with Another Man Even One Time Since 1977; 2000 Sep 14. 4. Blood Products Advisory Committee 67th meeting [monograph on the Internet]. Rockville (MD): U.S. Food and Drug Administration; 2000 Sep 14-15. Available from: http:// www.fda.gov/ohrms/dockets/ac/00/transcripts/3649t1.rtf 5. Germain M, Remis RS, Delage G. The risks and benefits of accepting men who have had sex with men as blood donors. Transfusion 2003;43:25-33.

Plateletpheresis does not cause long-standing platelet-derived growth factor release into the donor blood.

BACKGROUND: Recently, long‐standing elevations of soluble growth factors released from platelets (PLTs) after contact with artificial surfaces during dialysis were described. They could be jointly responsible for the high frequency of death from cardiovascular diseases in dialysis patients. There are no comparable data on the extent and the duration of a growth factor release by plateletpheresis procedures.

von Willebrand factor, clotting factors, and clotting inhibitors in apheresis platelet concentrates

Apheresis platelet concentrates (APCs) are usually stored in citrated plasma at 22°C. The stability of coagulation proteins—von Willebrand factor (vWF), clotting factors (CFs), and their inhibitors—has often been described in association with the storage of thawed plasma. However, fewer data are available regarding changes in APCs.

Effects of immediate or delayed addition of platelet additive solution on the in vitro quality of apheresis platelets.

BACKGROUND: There is little knowledge how different hold times of hyperconcentrated platelet (PLT) suspensions (HPSs) before the addition of platelet additive solution (PAS) might affect PLT quality. We compared the in vitro quality of single‐donor PLT concentrates (SDPs) with immediate or delayed PAS addition and studied the quality of collected concurrent plasma (CP).