Erik A.M. Beckers

Effects of skin disinfection method, deviation bag, and bacterial screening on clinical safety of platelet transfusions in the Netherlands

BACKGROUND:  Bacterial contamination of blood products is a great hazard for development of fatal transfusion reactions. Bacterial screening of platelet concentrates (PC) by aerobic and anaerobic culturing (BacT/ALERT, bioMérieux) was introduced in the Netherlands in October 2001.

Transfusion-related acute lung injury reports in the Netherlands: an observational study

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is a serious, sometimes fatal complication of transfusion, attributed to white blood cell (WBC)‐reactive antibodies present in the blood product. This study investigated incidence and etiology in the Netherlands.

Male‐only fresh‐frozen plasma for transfusion‐related acute lung injury prevention: before‐and‐after comparative cohort study

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is one of the most serious complications of blood transfusion. It can be caused by incompatible white blood cell antibodies in transfused plasma. The objective of this study was to quantify the reduction of TRALI after introduction of male‐only plasma for transfusion as a preventive measure, which took effect in 2007.

Obstetric hemorrhage and coagulation: an update. Thromboelastography, thromboelastometry, and conventional coagulation tests in the diagnosis and prediction of postpartum hemorrhage.

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal morbidity and mortality. In the current treatment of severe PPH, first-line therapy includes transfusion of packed cells and fresh-frozen plasma in addition to uterotonic medical management and surgical interventions. In persistent PPH, tranexamic acid, fibrinogen, and coagulation factors are often administered. Secondary coagulopathy due to PPH or its treatment is often underestimated and therefore remains untreated, potentially causing progression to even more severe PPH. In most cases, medical and transfusion therapy is not based on the actual coagulation state because conventional laboratory test results are usually not available for 45 to 60 minutes. Thromboelastography and rotational thromboelastometry are point-of-care coagulation tests. A good correlation has been shown between thromboelastometric and conventional coagulation tests, and the use of these in massive bleeding in nonobstetric patients is widely practiced and it has been proven to be cost-effective. As with conventional laboratory tests, there is an influence of fluid dilution on coagulation test results, which is more pronounced with colloid fluids. Fibrinogen seems to play a major role in the course of PPH and can be an early predictor of the severity of PPH. The FIBTEM values (in thromboelastometry, reagent specific for the fibrin polymerization process) decline even more rapidly than fibrinogen levels and can be useful for early guidance of interventions. Data on thromboelastography and thromboelastometry in pregnant women are limited, particularly during the peripartum period and in women with PPH, so more research in this field is needed. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After participating in this CME activity, physicians should be better able to manage postpartum hemorrhage and to evaluate the possible uses of thromboelastography and thromboelastometry to treat obstetric hemorrhage.

Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study

IntroductionThe increasing number of reports on the relation between transfusion of stored red blood cells (RBCs) and adverse patient outcome has sparked an intense debate on the benefits and risks of blood transfusions. Meanwhile, the pathophysiological mechanisms underlying this postulated relation remain unclear. The development of hemolysis during storage might contribute to this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO) scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. The objective of this prospective observational pilot study was to establish whether RBC transfusion results in increased circulating fHb levels and plasma NO consumption. In addition, the relation between increased fHb values and circulating haptoglobin, its natural scavenger, was studied.MethodsThirty patients electively received 1 stored packed RBC unit (n = 8) or 2 stored packed RBC units (n = 22). Blood samples were drawn to analyze plasma levels of fHb, haptoglobin, and NO consumption prior to transfusion, and 15, 30, 60 and 120 minutes and 24 hours after transfusion. Differences were compared using Pearsons chi-square test or Fishers exact test for dichotomous variables, or an independent-sample t test or Mann-Whitney U test for continuous data. Continuous, multiple-timepoint data were analyzed using repeated one-way analysis of variance or the Kruskall-Wallis test. Correlations were analyzed using Spearman or Pearson correlation.ResultsStorage duration correlated significantly with fHb concentrations and NO consumption within the storage medium (r = 0.51, P < 0.001 and r = 0.62, P = 0.002). fHb also significantly correlated with NO consumption directly (r = 0.61, P = 0.002). Transfusion of 2 RBC units significantly increased circulating fHb and NO consumption in the recipient (P < 0.001 and P < 0.05, respectively), in contrast to transfusion of 1 stored RBC unit. Storage duration of the blood products did not correlate with changes in fHb and NO consumption in the recipient. In contrast, pre-transfusion recipient plasma haptoglobin levels inversely influenced post-transfusion fHb concentrations.ConclusionThese data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO consumption in the recipient. This finding may contribute to the potential pathophysiological mechanism underlying the much-discussed adverse relation between blood transfusions and patient outcome. This observation may be of particular importance for patients with substantial transfusion requirements.

Rapid and correct prediction of thrombocytopenia and hypofibrinogenemia with rotational thromboelastometry in cardiac surgery.

OBJECTIVES In the present study, the authors have investigated whether rotational thromboelastometry (ROTEM) could predict thrombocytopenia and hypofibrinogenemia in cardiac surgery using the clot amplitude after 5 minutes (A5). Another parameter, PLTEM, in which the contribution of fibrinogen is eliminated by subtracting a fibrin-specific ROTEM test (FIBTEM) from an extrinsically-activated ROTEM test (EXTEM), was investigated. Furthermore, the turnaround time of ROTEM was compared to conventional laboratory tests. DESIGN Prospective cohort study. SETTING Single academic medical center. PARTICIPANTS Ninety-seven patients undergoing cardiac surgery between July 2011 until August 2012. INTERVENTIONS The correlations between EXTEM/FIBTEM A5, A10, and maximal clot formation (MCF), EXTEM/PLTEM (A5/A10, and MCF) and platelet count, and FIBTEM (A5/A10, and MCF) and fibrinogen were evaluated using the Pearsons correlation coefficient and receiver-operating characteristic curves. Turnaround times of ROTEM tests and conventional laboratory tests were assessed in the central laboratory. MEASUREMENTS AND MAIN RESULTS EXTEM A5 and FIBTEM A5 showed an excellent correlation with A10 (R:0.99/1.00) and MCF (R:0.97/0.99). The correlation between EXTEM A5 and platelet count (R:0.74) was comparable with the correlation of A10 (R:0.73) and MCF (R:0.70) with platelet count. FIBTEM A5 predicted fibrinogen levels (R:0.87) as well as A10 (R:0.86) and MCF (R:0.87). PLTEM A5 (R:0.85) correlated better with platelet count than EXTEM A5 (R:0.74; p = 0.04) and showed significantly better area under the curve values than EXTEM for predicting thrombocytopenia (A5 p = 0.012, A10 p = 0.019). Turnaround time for ROTEM tests, 12 minutes, was comparable with emergency requests for platelet count, 13 minutes, and shorter than emergency requests for fibrinogen levels, 37 minutes. CONCLUSIONS Implementation of PLTEM and FIBTEM A5 in ROTEM-guided transfusion protocols may improve transfusion management.

Storage time of blood products and transfusion-related acute lung injury.

BACKGROUND: Besides white blood cell antibodies in plasma‐rich products, another cause of transfusion‐related acute lung injury (TRALI) could be release of biologically active substances during storage of cellular blood products. We aimed to investigate the association of storage time and risk of TRALI for different product types.

Functional characteristics of photochemically treated platelets.

BACKGROUND: A photochemical treatment (PCT) process using the psoralen compound amotosalen HCL (S59) and long wavelength UVA light was developed for inactivation of infectious pathogens and WBCs. In this study the effect of PCT on functional characteristics of the platelets was evaluated in vitro.

Donors with a rare pheno (geno) type

H. W. Reesink, C. P. Engelfriet, H. Schennach, C. Gassner, S. Wendel, R. Fontão-Wendel, M. A. de Brito, P. Sistonen, J. Matilainen, T. Peyrard, B. N. Pham, P. Rouger, P. Y. Le Pennec, W. A. Flegel, I. von Zabern, C. K. Lin, W. C. Tsoi, I. Hoffer, K. Barotine-Toth, S. R. Joshi, K. Vasantha, V. Yahalom, O. Asher, C. Levene, M. A. Villa, N. Revelli, N. Greppi, M. Marconi, Y. Tani, C. C. Folman, M. de Haas, M. M. W. Koopman, E. Beckers, D. S. Gounder, P. Flanagan, L. Wall, E. Aranburu Urtasun, H. Hustinx, C. Niederhauser, E. Massey, A. Gray, M. Needs, G. Daniels, T. Callaghan, C. Flickinger, S. J. Nance & G. M. Meny

Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII

Coated platelets, formed by collagen and thrombin activation, have been characterized in different ways: i) by the formation of a protein coat of α-granular proteins; ii) by exposure of procoagulant phosphatidylserine; or iii) by high fibrinogen binding. Yet, their functional role has remained unclear. Here we used a novel transglutaminase probe, Rhod-A14, to identify a subpopulation of platelets with a cross-linked protein coat, and compared this with other platelet subpopulations using a panel of functional assays. Platelet stimulation with convulxin/thrombin resulted in initial integrin αIIbβ3 activation, the appearance of a platelet population with high fibrinogen binding, (independently of active integrins, but dependent on the presence of thrombin) followed by phosphatidylserine exposure and binding of coagulation factors Va and Xa. A subpopulation of phosphatidylserine-exposing platelets bound Rhod-A14 both in suspension and in thrombi generated on a collagen surface. In suspension, high fibrinogen and Rhod-A14 binding were antagonized by combined inhibition of transglutaminase activity and integrin αIIbβ3. Markedly, in thrombi from mice deficient in transglutaminase factor XIII, platelet-driven fibrin formation and Rhod-A14 binding were abolished by blockage of integrin αIIbβ3. Vice versa, star-like fibrin formation from platelets of a patient with deficiency in αIIbβ3 (Glanzmann thrombasthenia) was abolished upon blockage of transglutaminase activity. We conclude that coated platelets, with initial αIIbβ3 activation and high fibrinogen binding, form a subpopulation of phosphatidylserine-exposing platelets, and function in platelet-dependent star-like fibrin fiber formation via transglutaminase factor XIII and integrin αIIbβ3.