Norbert Lubenow

Very Low Platelet Counts in Post-transfusion Purpura Falsely Diagnosed as Heparin-induced Thrombocytopenia: Report of Four Cases and Review of Literature

Differential diagnosis between post-transfusion purpura (PTP) and heparin-induced thrombocytopenia (HIT) can be difficult in the initial stages of thrombocytopenia, as the early clinical presentations are often similar. Four patients are described who were suspected clinically of suffering from HIT. All four patients had recent blood transfusions and platelet alloantibodies, thus the diagnosis of PTP was made. One lethal gastrointestinal and one retroperitoneal hemorrhage developed in two of the four patients. Unusually, one patient was male and two different platelet alloantibodies were present in his serum; in another patient platelet alloantibodies and HIT-antibodies were detectable. To arrive at the right diagnosis as quickly as possible is vitally important since treatment, which has to be initiated promptly, is very different for the two syndromes. Thus, we suggest that in patients where HIT is suspected, additional information should be sought. If features consistent with PTP (such as a recent blood transfusion or a marked drop in platelet count to below 15 Gpt/L) are present, we recommend parallel testing for platelet alloantibodies to rule out PTP.

Composition of growth factors and cytokines in lysates obtained from fresh versus stored pathogen-inactivated platelet units

BACKGROUNDnPlatelet lysate is a readily available source of growth factors, and other mediators, which has been used in a variety of clinical applications. However, the product remains poorly standardized and the present investigation evaluates the composition of platelet lysate obtained from either fresh or stored pathogen-inactivated platelet units.nnnMATERIALS AND METHODSnPlatelet pooled units (nu2009=u200910) were obtained from healthy blood donors and tested according to standard procedures. All units were pathogen inactivated using amotosalen hydrochloride and UVA exposure. Platelet lysate was subsequently produced at two separate time-points, either from fresh platelet units or after 5 days of storage, by repeated freeze-thaw cycles. The following mediators were determined at each time-point: EGF, FGF-2, VEGF, IGF-1, PDGF-AB/BB, BMP-2, PF4, TGF-β isoform 1, IL-1β, IL-2, IL-6, IL-10, IL-12p70, 1L-17A, TNF-α, and IFN-γ.nnnRESULTSnThe concentration of growth factors and cytokines was affected by time in storage. Notably, TGF-β, PDGF-AB/BB, and PF4 showed an increase of 27.2% (pu2009<u20090.0001), 29.5% (pu2009=u20090.04) and 8.2% (pu2009=u20090.0004), respectively. A decrease was seen in the levels of IGF-1 and FGF-2 with 22% (pu2009=u20090.041) and 11% (pu2009=u20090.01), respectively. Cytokines were present only in very low concentrations and all other growth factors remained stable with time in storage.nnnCONCLUSIONnThe composition of mediators in platelet lysate obtained from pathogen-inactivated platelet units differs when produced from fresh and stored platelet units, respectively. This underscores the need for further standardization and optimization of this important product, which potentially may influence the clinical effects.

Impact of physical activity of individuals and creatine kinase on 99th percentiles of troponin I assays

Determination of cardiac troponin I (cTnI) is one central means for diagnosis of myocardial infarction. Assay performance of three troponin I assays was compared previously in a large reference population detecting sex-differences in the 99th percentile only for the Dimension Vista cTnI assay. The present study examined the underlying effects. Values for cTnI were reused. Creatine kinase (CK) activity was determined in 2358 samples from blood donors. Information on physical activity was evaluated from health questionnaires. Using quantile regression data were analysed to investigate the impact of sex, physical activity, and CK on the 99th percentile of the cTnI assay. We report significant sex-differences for the 99th percentile of cTnI. Physical activity was significantly associated with cTnI values. Strong association of CK activity with cTnI values was detected only in men. Adjustment for CK in quantile regression abolished sex-differences in the 99th percentile. Two other contemporary sensitive cTnI assays were not relevantly affected by physical activity or CK. Sex-differences in the 99th percentile for the Dimension Vista cTnI assay arise from a positive association between cTnI and physical activity and were abrogated when data were adjusted for CK activity. These findings should be taken into account when using this assay.

High-Sensitivity Cardiac Troponin T: Association of Creatine Kinase Catalytic Activity With the 99th Percentile

To the Editor:nnFast diagnosis is the ultimate ambition for precise treatment of patients with acute myocardial infarction. Cardiac troponin (cTn)1 is considered the biomarker most specific for ischemia-related myocardial necrosis. With implementation of high-sensitivity (hs)-cTn assays, which detect cTn in ≥50% of a healthy population and exhibit ≤10% imprecision at the diagnostic cutoff, sex-specific differences have been reported (1). Recently, 3 contemporary sensitive central laboratory cTnI assays were compared in the same large reference population. For one of the assays, sex-dependent differences in the 99th percentile were detected (2). Physical activity and its surrogate marker creatine kinase (CK) activity were identified to have a positive association with cTnI. Importantly, adjustment for physical activity or CK activity abrogated the impact of sex (2).nnHere, the performance of an hs-cTnT assay was evaluated in the same reference population, with consideration of the influences of age, sex, and CK activity on the 99th percentile. Specimens originated from the well-characterized DONOR SHIP cohort collected in 2005 (2). Aliquots were thawed and hs-cTnT was measured by means of the Cobas e411 (Roche Diagnostics) in 2015. CK activity and other parameters were determined immediately after sampling. Aliquots of plasma samples have been stored for 10 …

An evaluation of the mixed pediatric unit for blood loss replacement in pediatric craniofacial surgery

Surgical correction for craniosynostosis is often associated with significant perioperative hemorrhage. We implemented a transfusion strategy with a strict protocol including transfusion triggers, frequent assessment of coagulation tests, and the use of a novel transfusion unit, the mixed pediatric unit.

The 99th percentile and imprecision of point-of-care cardiac troponin I in comparison to central laboratory tests in a large reference population.

OBJECTIVESnDetermination of cardiac troponin (cTn) is central in the emergency department (ED) for the diagnosis of myocardial infarction. In view of adverse effects of long waiting time on patient outcome, implementation of point-of-care-testing (POCT) is suggested if the turn-around-time is longer than 60min. The present study aimed to determine the 99th percentile and imprecision of two POCT in a healthy population measuring cTnI and cTnT and compare these analytical characteristics against three central laboratory test (CLT) for cTnI.nnnDESIGN & METHODSnCTnI and cTnT were determined in parallel by means of the AQT90 FLEX analyzer in about 2250 plasma samples from individuals with known health status. Results were compared to previously determined performance data of three CLT.nnnRESULTSnThe 99th percentile of cTnI in the POCT was determined at 19ng/L, the lowest concentration with an imprecision of 10% was reached at 22ng/L while an imprecision of 20% was reached at 13ng/L. Age, sex, or physical activity did not affect the 99th percentile of cTnI. Compared to CLT the AQT90 cTnI POCT the analytical performance was equivalent. The cTnT POCT could not be assessed due a considerable number of high values and an inadequate imprecision profile.nnnCONCLUSIONnWhile the cTnI POCT showed analytical performance comparable to CLT, the results of the cTnT assay on the same device did not suffice to determine a reliable 99th percentile. The present evaluation supports the usage of the cTnI POCT, but application of the cTnT POCT needs further evaluation.

Analysis of thromboelastography, PT, APTT and fibrinogen in intraosseous and venous samples-an experimental study.

BackgroundLaboratory analysis of coagulation is often important in emergencies. If vascular access is challenging, intraosseous catheterization may be necessary for treatment. We studied the analysis of coagulation parameters in intraosseous aspirate during stable conditions and after major haemorrhage in a porcine model.MethodsTen anesthetized pigs received central venous and intraosseous catheters and samples were taken for analysis of thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen concentration. Analyses were repeated after removal of 50 % of the calculated blood volume and resuscitation with crystalloid. Intraosseous and venous values were compared.ResultsBleeding and resuscitation resulted in haemodilution and hypotension. Median TEG reaction time was shorter in intraosseous than in venous samples before (1.6 vs 4.6 min) and after (1.6 vs 4.7 min) haemodilution. Median maximal amplitude was smaller in intraosseous samples at baseline (68.3 vs 76.4 mm). No major differences were demonstrated for the other TEG parameters. The intraosseous samples often coagulated in vitro, making analysis of PT, APTT and fibrinogen difficult. After haemodilution, TEG maximal amplitude and α-angle, and fibrinogen concentration, were decreased and PT increased.DiscussionThe intraosseous samples were clinically hypercoagulable and the TEG demonstrated a shortened reaction time. The reason for this may hypothetically be found in the composition of the IO aspirate or in the sampling technique. After 50 % haemorrhage and haemodilution, a clinically relevant decrease in fibrinogen concentration and a lower TEG maximal amplitude were observed.ConclusionsAlthough the sample is small, these data indicate that intraosseous samples are hypercoagulable, which may limit their usefulness for coagulation studies. Major haemodilution only moderately affected the studied parameters.