Anemia in Celiac Disease: Multiple Aspects of the Same Coin.

Extraintestinal manifestations of celiac disease (CD) are an integral part of the disease's clinical profile and, frequently, appear as the presenting feature. Given that anemia in CD may be multifactorial, increased awareness is needed on the part of treating physicians, and especially hematologists, to screen for CD. In this study, we highlight anemia as the presenting feature of CD which has remained undiagnosed for several years. In patients with a positive antibody testing or high suspicion of CD, endoscopy with a biopsy of the small intestine is performed, as it is considered the "gold standard" for diagnosing CD. Since most of the manifestations of CD are preventable or treatable with a gluten-free diet, an early diagnosis is vital for the prevention of serious and potentially lethal complications.

Development and validation of a sepsis diagnostic scoring model for neonates with suspected sepsis.

Background: We aimed to develop and validate a diagnostic model for sepsis among neonates evaluated for suspected sepsis, by incorporating thromboelastometry parameters, maternal/neonatal risk factors, clinical signs/symptoms and laboratory results. Methods: This retrospective cohort study included 291 neonates with presumed sepsis, hospitalized in a NICU, from 07/2014 to 07/2021. Laboratory tests were obtained on disease onset and prior to initiating antibiotic therapy. Τhromboelastometry extrinsically activated (EXTEM) assay was performed simultaneously and Tοllner and nSOFA scores were calculated. Sepsis diagnosis was the outcome variable. A 10-fold cross-validation least absolute shrinkage and selection operator logit regression procedure was applied to derive the final multivariable score. Clinical utility was evaluated by decision curve analysis. Results: Gestational age, CRP, considerable skin discoloration, liver enlargement, neutrophil left shift, and EXTEM A10, were identified as the strongest predictors and included in the Neonatal Sepsis Diagnostic (NeoSeD) model. NeoSeD score demonstrated excellent discrimination capacity for sepsis and septic shock with an AUC: 0.918 (95% CI, 0.884-0.952) and 0.974 (95% CI, 0.958-0.989) respectively, which was significantly higher compared to Töllner and nSOFA scores. Conclusions: The NeoSeD score is simple, accurate, practical, and may contribute to a timely diagnosis of sepsis in neonates with suspected sepsis. External validation in multinational cohorts is necessary before clinical application.

Assessment of agreement between EXTEM and NATEM thromboelastometry measurement assays in critically ill neonates.

OBJECTIVES: To investigate the agreement between the EXTEM and NATEM measurements. METHODS: In this retrospective observational study, EXTEM and NATEM analyses were performed on blood samples from 162 ill neonates, providing 324 paired measurements. The agreement between EXTEM and NATEM measurements was evaluated by the nonparametric spearman's rank correlation to assess the correlation between the paired measurements, by the Bland-Altman analysis for the graphical presentation of the agreement, and by the Deming regression model to assess the significance of the agreement. The agreement between the two methods for the detection of bleeding events was determined by kappa statistic. RESULTS: Strong correlations were found between EXTEM and NATEM measurements for A10, MCF. The Bland-Altman plots showed good agreement for A10, MCF, LI60, and alpha angle parameters, while CT showed a nearly linear slope indicating that bias increased with the mean. The highest agreement for bleeding events was found for the A10 parameter (κ = 0.70, p < .001), while the lowest for the CT parameter (κ = 0.36, p = .94). CONCLUSIONS: NATEM parameters that reflect clot firmness and fibrinolytic activity are strongly correlated with the corresponding EXTEM measurements with a good agreement between them, indicating that these two methods could be used interchangeably.

Haemostatic profile of riboflavin-treated apheresis platelet concentrates.

BACKGROUND: The haemostatic activity of platelet concentrates (PCs) treated with pathogen reduction technology (PRT) remains a subject of debate. Our aim was to investigate the effect of Mirasol PRT on the haemostatic properties of PCs stored in plasma. MATERIAL AND METHODS: Untreated and Mirasol-treated platelets stored in plasma and derived from ten split double-dose apheresis PCs were evaluated in vitro on days 1, 3 and 5 post collection for functionality, microparticle procoagulation activity (MPA), endogenous thrombin potential (ETP), and haemostatic profile using rotational thromboelastometry (ROTEM). RESULTS: P-selectin expression was significantly higher in Mirasol-treated platelets compared with untreated counterparts on days 3 and 5 (p=0.003 and p=0.002, respectively). Clot strength, as shown by EXTEM maximum clot firmness (MCF), was significantly lower in the Mirasol-treated platelets at all time points (days 1, 3, 5) than in untreated platelets (p=0.009, p<0.001, p<0.001, respectively). There was a considerable increase in MPA over time (p<0.001) and this was significantly higher in the Mirasol-treated platelets on day 5 (p=0.015). A notable acceleration of decrease in ETP values was observed for Mirasol-treated PCs over time (p<0.001), with significant differences between PRT-treated and untreated PCs on days 3 and 5 (p=0.038 and p=0.019, respectively). Clot strength attenuation was significantly associated with pH reduction (p<0.001, Spearman's rho: 0.84), increased microparticle procoagulant activity (p<0.001, Spearman's rho: -0.75), and with decreased ETP (p<0.032, Spearman's rho: 0.41). DISCUSSION: Increased platelet activation induced by PRT treatment leads to a decrease in in vitro haemostatic capacity as seen by reduced clot strength and thrombin generation capacity over time. The clinical relevance of this needs to be investigated.

The Safety and Efficacy of Tranexamic Acid in Oncology Patients Undergoing Endoprosthetic Reconstruction and a ROTEM-Based Evaluation of Their Hemostatic Profile: A Pilot Study.

BACKGROUND: An endoprosthetic reconstruction in musculoskeletal oncology patients is associated with significant blood loss. The purpose of this study is to evaluate the safety and efficacy of tranexamic acid (TXA) for these patients and to assess any changes in their hemostatic profile using rotational thromboelastometry (ROTEM). METHODS: A retrospective observational study was performed including 61 patients with primary or metastatic bone tumors who underwent surgery. Group A (n = 30) received both intravenous and local TXA whereas Group B (n = 31) was the control group. The primary outcomes were perioperative blood loss and blood unit transfusions and the secondary outcomes included the incidence of thromboembolic complications and a change in blood coagulability as reflected by ROTEM parameters. RESULTS: The median difference in blood loss between the two groups was 548.5 mL, indicating a 29.2% reduction in the 72 h blood loss following TXA administration (p < 0.001). TXA also led to a reduced transfusion of 1 red blood cell (RBC) unit per patient (p < 0.001). The two groups had similar rates of thromboembolic complications (p = 0.99). The antifibrinolytic properties of TXA were confirmed by the significantly higher INTEM, FIBTEM and EXTEM LI60 (p < 0.001, p = 0.005 and p < 0.001, respectively) values in the TXA group. CONCLUSION: Tranexamic acid was associated with a significant reduction in perioperative blood loss and transfusion requirements without a complete shutdown of the fibrinolysis. Larger studies are warranted to assess the frequency of these outcomes in musculoskeletal oncology patients.

Rotational Thromboelastometry Findings Are Associated with Symptomatic Venous Thromboembolic Complications after Hip Fracture Surgery.

BACKGROUND: Venous thromboembolism is a common complication after hip fractures. However, there are no reliable laboratory assays to identify patients at risk for venous thromboembolic (VTE) events after major orthopaedic surgery. QUESTION/PURPOSES: (1) Are rotational thromboelastometry (ROTEM) findings associated with the presence or development of symptomatic VTE after hip fracture surgery? (2) Were any other patient factors associated with the presence or development of symptomatic VTE after hip fracture surgery? (3) Which ROTEM parameters were the most accurate in terms of detecting the association of hypercoagulability with symptomatic VTE? METHODS: This retrospective study was conducted over a 13-month period. In all, 354 patients with femoral neck and peritrochanteric fractures who underwent hip hemiarthoplasty or cephallomedullary nailing were assessed for eligibility. Of those, 99% (349 of 354) were considered eligible for the study, 1% (3 of 354) of patients were excluded due to coagulation disorders, and another 1% (2 of 354) were excluded because they died before the postoperative ROTEM analysis. An additional 4% (13 of 354) of patients were lost before the minimum study follow-up of 3 months, leaving 95% (336 of 354) for analysis. A ROTEM analysis was performed in all patients at the time of their hospital admission, within hours of the injury, and on the second postoperative day. The patients were monitored for the development of symptoms indicative of VTE, and the gold standard tests for diagnosing VTE, such as CT pulmonary angiography or vascular ultrasound, were selectively performed only in symptomatic patients and not routinely in all patients. Therefore, this study evaluates the association of ROTEM with only clinically evident VTE events and not with all VTE events. ROTEM results did not affect the clinical surveillance of the study group and the decision for further work up. To determine whether ROTEM findings were associated with the presence or development of symptomatic VTE, ROTEM parameters were compared between patients with and without symptomatic VTE. To establish whether any other patient factors were associated with the presence or development of symptomatic VTE after hip fracture surgery, clinical parameters and conventional laboratory values were also compared between patients with and without symptomatic VTE. Finally, to determine which ROTEM parameters were the most accurate in terms of detecting the association of hypercoagulability with symptomatic VTE, the area under the curve (AUC) for certain cut off values of ROTEM parameters was calculated. RESULTS: We found several abnormal ROTEM values to be associated with the presence or development of symptomatic VTE. The preoperative maximum clot firmness was higher in patients with clinically evident VTE than in patients without these complications (median [interquartile range] 70 mm [68 to 71] versus 65 mm [61 to 68]; p < 0.001). The preoperative clot formation time was lower in patients with clinically evident VTE than those without clinically evident VTE (median 61 seconds [58 to 65] versus 70 seconds [67 to 74]; p < 0.001), and also the postoperative clot formation time was lower in patients with clinically evident VTE than those without these complications (median 52 seconds [49 to 59] versus 62 seconds [57 to 68]; p < 0.001). Increased BMI was also associated with clinically evident VTE (odds ratio 1.26 [95% confidence interval 1.07 to 1.53]; p < 0.001). We found no differences between patients with and without clinically evident VTE in terms of age, sex, smoking status, comorbidities, and preoperative use of anticoagulants. Lastly, preoperative clot formation time demonstrated the best performance for detecting the association of hypercoagulability with symptomatic VTE (AUC 0.89 [95% CI 0.81 to 0.97]), with 81% (95% CI 48% to 97%) sensitivity and 86% (95% CI 81% to 89%) specificity for clot formation time ≤ 65 seconds. CONCLUSION: ROTEM's performance in this preliminary study was promising in terms of its association with symptomatic VTE. This study extended our earlier work by demonstrating that ROTEM has a high accuracy in detecting the level of hypercoagulability that is associated with symptomatic VTE. However, until its performance is validated in a study that applies a diagnostic gold standard (such as venography, duplex/Doppler, or chest CT) in all patients having ROTEM to confirm its performance, ROTEM should not be used as a regular part of clinical practice. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Seeking Strategies to Optimize Blood Utilization: The Preliminary Experience with Implementing a Patient Blood Management Program in a Greek Tertiary Hospital.

OBJECTIVES: Our aim was to assess blood utilization after implementation of a patient blood management (PBM) program in a Greek tertiary hospital. METHODS: An electronic transfusion request form and a prospective audit of transfusion practice were implemented. After the one-year implementation period, a retrospective review was performed to assess transfusion practice in medical patients. RESULTS: Pre-PBM, a total of 9478 RBC units were transfused (mean: 1.75 units per patient) compared with 9289 transfused units (mean: 1.57 units per patient) post-PBM. Regarding the post-PBM period, the mean hemoglobin (Hb) level of the 3099 medical patients without comorbidities transfused was 7.19 ± 0.79 gr/dL. Among them, 2065 (66.6%) had Hb levels >7.0 gr/dL, while 167 (5.3%) had Hb levels >8.0 gr/dL. In addition, 331 (25.3%) of the transfused patients with comorbidities had Hb >8.0 gr/dL. The Hb transfusion thresholds significantly differed across the clinics (p < 0.001), while 21.8% of all medical non-bleeding patients received more than one RBC unit transfusion. CONCLUSION: A poor adherence with the restrictive transfusion threshold of 7.0 gr/dL was observed. The adoption of a less strict threshold might be a temporary step to allow physicians to become familiar with the program and be informed on the safety and advantages of the restrictive transfusion strategy.

Homozygosity of the TT methylenetetrahydrofolate reductase C677T genotype is an independent long-term predictor of cardiac death in patients with premature myocardial infarction.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is the main genetic modulator of homocysteine. Data suggest a potential association of homozygosity for the TT MTHFR genotype with premature myocardial infarction (MI). We explored whether TT homozygosity is associated with long-term prognosis in patients with premature ST-segment elevation MI (STEMI). METHODS: A total of 265 consecutive patients who had survived their first STEMI ≤35 years of age were followed for a median of 8 years (5-12). Primary endpoints were cardiac death and secondary endpoints were hospitalizations for acute coronary syndrome, myocardial revascularization, arrhythmic event or ischemic stroke. Serum lipids, homocysteine, folate levels were measured at baseline and all patients were also tested for the MTHFR C677T polymorphism. RESULTS: During follow-up 14 patients died (cardiac death) [5.3%] while 84 (31.7%) met the secondary endpoints. In univariate Cox regression analysis TT homozygosity predicted the occurrence of cardiac death (Hazard ratio (HR): 4.071; 95% confidence interval (CI): 1.404-11.809, p = .010) but not the occurrence of secondary endpoints (HR: 0.877; 95% CI: 0.479-1.605, p = .669). TT homozygosity remained an independent predictor of cardiac death after adjustment for conventional risk factors (i.e., sex, diabetes mellitus, hypertension, family history of premature coronary artery disease [CAD]) [HR: 4.350; 95% CI: 1.472-12.856, p = .008]. The association also remained after adjustment for left ventricular ejection fraction or the presence of significant CAD. CONCLUSIONS: Homozygosity for the TT MTHFR is an independent long-term predictor of cardiac death in patients with premature STEMI.

The role of ROTEM variables based on clot elasticity and platelet component in predicting bleeding risk in thrombocytopenic critically ill neonates.

BACKGROUND: Our aim was to investigate the role of thromboelastometry (ROTEM) parameters, including maximum clot elasticity (MCE) and platelet component (PLTEM MCE and PLTEM MCF), in early prediction of bleeding events in thrombocytopenic critically ill neonates. MATERIAL AND METHODS: This single-center, prospective cohort study included 110 consecutive thrombocytopenic neonates with sepsis, suspected sepsis, or hypoxia. On the first day of disease onset, ROTEM EXTEM and FIBTEM assays were performed and the neonatal bleeding assessment tool was used for the evaluation of bleeding events. RESULTS: Most EXTEM and FIBTEM ROTEM parameters significantly differed between neonates with (n = 77) and without bleeding events (n = 33). Neonates with bleeding events had significantly lower PLTEM MCE and PLTEM MCF values compared to those without bleeding events (P < .001). Platelet count was found to be strongly positively correlated with EXTEM A5 (Spearman's rho = 0.61, P < .001) and A10 (rho = 0.64, P < .001). EXTEM A10 demonstrated the best prognostic performance (AUC = 0.853) with an optimal cutoff value (≤37 mm) (sensitivity = 91%, specificity = 76%) for prediction of bleeding events in thrombocytopenic neonates. CONCLUSIONS: EXTEM A5 and EXTEM A10 were found to be strong predictors of hemorrhage, compared to most ROTEM variables quantifying clot elasticity and platelet component in thrombocytopenic critically ill neonates.

The haemostatic profile in critically ill COVID-19 patients receiving therapeutic anticoagulant therapy: An observational study.

Hypercoagulability and thrombosis remain a challenge in severe coronavirus disease 2019 (COVID-19) infections. Our aim is to investigate the hemostatic profile of critically ill COVID-19 patients on therapeutic anticoagulant treatment.Forty one patients were enrolled into the study. We recruited 11 consecutive, COVID-19, patients who received therapeutic anticoagulant treatment on intensive care unit (ICU) admission. Disease severity indexes, biochemical, hematological and haemostatic parameters, endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1) activity and extrinsically activated rotational thromboelastometry assay (EXTEM) were recorded on days 1, 3, 7. We also enrolled 9 ICU non-COVID-19, 21 non-ICU COVID-19 patients and 20 healthy blood donors as control populations.Critically ill COVID-19 patients demonstrated a more hypercoagulable and hypofibrinolytic profile related to those with COVID-19 mild illness, based on EXTEM amplitude at 10 min (A10), maximum clot firmness (MCF) and lysis index at 60 min (LI60) variables (p = 0.020, 0.046 and 0.001, respectively). Similarly, a more hypercoagulable state was detected in COVID-19 ICU patients related to non-COVID-19 ICU patients based on A10 and MCF parameters (p = 0.03 and 0.04, respectively). On the contrary, ETP and EXTEM (clotting time) CT values were similar between patients with severe and mild form of the COVID-19 infection, probably due to anticoagulant treatment given.Critically ill COVID-19 patients showed a hypercoagulable profile despite the therapeutic anticoagulant doses given. Due to the small sample size and the study design, the prognostic role of the hypercoagulability in this clinical setting remains unknown and further research is required in order to be assessed.

The prognostic value of multiple electrode aggregometry and light transmittance aggregometry in stable cardiovascular patients with type 2 diabetes mellitus.

AIM: Limited data are available regarding the clinical relevance of platelet function measurements in stable patients with coronary artery disease (CAD). Our aim is to evaluate the agreement between multiple electrode aggregometry (MEA) and light transmittance aggregometry (LTA) in detecting clopidogrel low responders and their prognostic value in CAD patients with type 2 diabetes mellitus (T2DM) on dual platelet inhibition. METHODS: LTA and MEA were performed in 122 stable cardiovascular patients with T2DM. The upper quartile of patients according to maximum LTA (LTAmax) and MEA measurements were defined as clopidogrel low responders. Agreement between the two methods was evaluated by kappa statistics. We assessed the potential correlation between antiplatelet response and clinical outcome and the optimal cutoff value according to ROC analysis to predict the occurrence of major adverse cardiovascular events (MACE), during 1-year follow-up period. RESULTS: Cohen's kappa coefficients (0.214) indicated fair agreement (70.2%) between LTA and MEA. A total of 25 MACE occurred in 108 patients (23.1%). Patients with MACE had higher LTAmax than those without (57.1 ±â€¯16.5 vs 49.3 ±â€¯18.3, respectively, p = 0.023). MEA measurements were similar between patients with and without MACE (30.1 ±â€¯15.4 vs 30.6 ±â€¯20.8, respectively; p = 0.84). Multiple logistic regression showed LTAmax response as an independent predictor of death from cardiovascular causes (Odds Ratio, adjusted:0.2;0.05-0.81). ROC analysis indicated that LTAmax cutoff of 62.5% best predicted death (AUC = 0.67, sensitivity = 78%, specificity = 61.5%). CONCLUSIONS: The assessment of platelet responsiveness remains highly test-specific. Our results support the prognostic role of LTA, but not MEA testing, for death risk evaluation in stable cardiovascular T2DM patients.

Platelet and coagulation disorders in newly diagnosed patients with pulmonary arterial hypertension.

There is a complex and not fully elucidated association between pulmonary arterial hypertension (PAH) and coagulation disorders. The goal of this study was to evaluate platelet function, coagulation and fibrinolysis in PAH patients at diagnosis, before PAH-specific treatment initiation. We enrolled 20 healthy controls and 30 PAH patients (20 with connective tissue disease (CTD-PAH) and 10 idiopathic (iPAH)). None of the participants was on any antiplatelet or anticoagulation therapy. Blood samples from PAH patients were collected during the initial right heart catheterization. All subjects were assessed with platelet function analyzer-100 (PFA-100), epinephrine (Epi) and ADP-induced light transmission aggregometry (LTA), thromboelastometry (ROTEM) and endogenous thrombin potential (ETP). Our results showed that Epi and ADP-LTA values were significantly lower in newly diagnosed PAH patients compared to controls. Disaggregation was present in 73% of patients, a characteristic not seen in healthy individuals. In ROTEM assay, CT and CFT measurements were significantly higher and a angle lower compared to controls. ETP testing revealed significantly reduced outcomes in AUC, Cmax and Tmax. When CTD-PAH and iPAH patient groups were compared, iPAH ADP-LTA values were significantly decreased compared to CTD-PAH. In conclusion, newly diagnosed PAH patients presented with decreased platelet aggregation, clot propagation and thrombin generation, along with delayed initiation of the coagulation process. These hemostatic deficits could indicate an "exhaustion" of the coagulation process that could be caused by endothelial dysfunction and chronic activation of the procoagulant pathways. Further studies are warranted to confirm these laboratory findings and assess their potential clinical significance.

Comparison between Nageotte and flow cytometric counting of residual leucocytes in freshly prepared leucocyte-reduced red blood cell components.

BACKGROUND: Flow cytometry (FC) and Nageotte hemocytometry represent the most widely accepted methods for counting residual white blood cells (rWBCs) in leucocyte-reduced (LR) blood components. Our aim was to study the agreement between the two methods, under real working blood bank conditions. MATERIALS AND METHODS: 94 freshly produced LR red blood cell (RBC) units were tested for rWBC concentrations by FC and Nageotte. To assess the precision of each method, we calculated the intra-assay coefficients of variation (CV), and followed the Bland-Altman methodology to study the agreement between the two methods. RESULTS: CV was 18.5% and 26.2% for the Nageotte and the FC, respectively. However, the agreement between the duplicate observations, using the binary cut-off threshold of 1 × 106 WBCs per unit to define the results as "pass/fail", was 71.9% for the Nageotte and 93.3% for the FC. Linear regression analysis did not show any correlation (R-squared = 0.01, p = 0.35) between the two methods, while the Bland-Altman analysis for the measuring agreement showed a bias toward a higher Nageotte count of 0.77 × 106 leucocytes per unit (p < 0.001) with the 95% limits of agreement (d ± 2 sd) ranging from -0.40 × 106 to 1.94 × 106 leucocytes per unit. CONCLUSION: The absence of agreement between Nageotte and FC method, with the differences within d ± 2 sd being of high clinical importance, suggests that the two methods cannot be used for clinical purposes interchangeably. The Nageotte seems unsuitable for quality control even with a pass-fail criterion, under real working blood bank conditions.

Oral Contraceptives and HRT Risk of Thrombosis.

Estrogen-containing medication, prescribed either for contraception in women of reproductive age or for prevention of cardiovascular events and osteoporosis as well as for alleviation of symptoms related to menopause, is associated with changes in the hemostatic balance and contributes to increased risk of development of venous thromboembolic complications. This risk is dose and medication dependent, increases with age, congenital and/or acquired predisposition to thrombosis, and mode of administration. This review attempts to summarize the current knowledge regarding the pathophysiology of oral contraceptive (OC) and hormone replacement therapy (HRT) -induced prothrombotic state in women, the risk of thrombosis associated with administration of various commercially available OCs and HRT, the additional risk in women with hereditary or acquired thrombophilia, and the currently available recommendations regarding massive screening of women for thrombophilia prior to initial prescription or continuation of treatment with OCs and HRT preparations.

Characteristics and Long-Term Prognosis of Patients ≤35 Years of Age with ST Segment Elevation Myocardial Infarction and "Normal or Near Normal" Coronary Arteries.

There are scarce data regarding risk factors and prognosis of patients with premature ST segment elevation myocardial infarction (STEMI) and "normal or near normal" coronary arteries (N/NNCAs). We compared the characteristics and long-term prognosis of patients with premature STEMI and N/NNCAs with their counterparts with significant coronary artery disease (CAD). We recruited 330 patients who had STEMI ≤35 years of age and 167 age- and gender-matched controls. All patients underwent coronary angiography. Coronary arteries with no lesions or lesions causing <30% reduction in lumen diameter were defined as N/NNCAs, whereas narrowings causing ≥50% diameter reduction formed the significant CAD group. Lipid profile, homocysteine levels, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism were determined. Sixty patients (18%) had N/NNCAs. Patients with N/NNCAs had lower low-density lipoprotein-cholesterol and higher high-density lipoprotein-cholesterol levels, higher homocysteine levels, and higher prevalence of MTHFR TT genotype (34.6 vs 18%, p = 0.008) compared with patients with significant CAD. After a median follow-up of 8 years, cardiovascular events occurred in 105 (36%) of 291 patients with available follow-up data. Significant CAD was associated with higher risk for recurrent cardiovascular events after adjustment for traditional risk factors (hazard ratio 2.095, 95% confidence interval 1.088 to 3.664, p = 0.022) and additional adjustment for the left ventricular ejection fraction, reperfusion therapy, and persistent smoking (hazard ratio 1.869, 95% confidence interval 1.007 to 3.468, p = 0.041). In conclusion, patients with premature STEMI and N/NNCAs have fewer lipid abnormalities, higher homocysteine levels and prevalence of MTHFR TT genotype, and better long-term prognosis compared with their counterparts with significant CAD.

Prothrombotic genetic risk factors in patients with very early ST-segment elevation myocardial infarction.

The contribution of prothrombotic genetic risk factors in the pathogenesis of premature acute myocardial infarction (MI) is controversial. We examined the prevalence of prothrombotic polymorphisms (G1691A of factor V gene [FV Leiden] and G20210A of prothrombin [FII] gene), deficiencies of natural anticoagulants (protein C, protein S and antithrombin III) and antiphospholipid syndrome (APS) in patients with early ST-segment elevation MI (STEMI). We recruited 255 consecutive patients who had survived a STEMI ≤ 35 years of age (224 men). The control group consisted of 400 healthy individuals matched with cases for age and sex. G20210A polymorphism of FII gene was more frequent in young patients than in controls (7.4 vs. 3.5%, p = 0.023). The odds ratio (OR) for STEMI for carriers versus non-carriers was 2.239 (95% CI 1.102-4.250). The adjusted OR for major cardiovascular risk factors was 2.569 (95% CI 1.086-6.074). The risk was increased by 22-fold (95% CI 9.192-66.517) when G20210A polymorphism was present in combination with smoking. There was no difference in the prevalence of FV Leiden between patients and controls (7.8 vs. 6.5%, p = 0.512). There was only one patient (0.4%) with protein C deficiency and one with APS (0.4%). G20210A polymorphism of FII gene may be associated with increased risk of premature STEMI and the risk increases substantially when smoking is present. The contribution of other prothrombotic disorders such as deficiencies of protein C, protein S and antithrombin III and APS was minimal in this cohort.

Reference ranges of thromboelastometry in healthy full-term and pre-term neonates.

BACKGROUND: Rotational thromboelastometry (ROTEM) is an attractive method for rapid evaluation of hemostasis in neonates. Currently, no reference values exist for ROTEM assays in full-term and pre-term neonates. Our aim was to establish reference ranges for standard extrinsically activated ROTEM assay (EXTEM) in arterial blood samples of healthy full-term and pre-term neonates. METHODS: In the present study, EXTEM assay was performed in 198 full-term (≥37 weeks' gestation) and 84 pre-term infants (<37 weeks' gestation) using peripheral arterial whole blood samples. RESULTS: Median values and reference ranges (2.5th and 97.5th percentiles) for the following main parameters of EXTEM assay were determined in full-term infants: clotting time (seconds), 41 (range, 25.9-78); clot formation time (seconds), 70 (range, 40-165.2); maximum clot firmness (mm), 66 (range, 41-84.1); lysis index at 60 min (LI60, %), 97 (range, 85-100). The only parameter with a statistically significant difference between full-term and pre-term neonates was LI60 (p=0.006). Furthermore, it was inversely correlated with gestational age (p=0.002) and birth weight (p=0.016) in pre-term neonates. CONCLUSIONS: In conclusion, an enhanced fibrinolytic activity in pre-term neonates was noted. For most EXTEM assay parameters, reference ranges obtained from arterial newborn blood samples were comparable with the respective values from studies using cord blood. Modified reagents, small size samples, timing of sampling, and different kind of samples might account for any discrepancies among similar studies. Reference values hereby provided can be used in future studies.

Endothelial Protein C Receptor Gene Variants and Risk of Thrombosis.

Endothelial protein C receptor (EPCR) is a candidate mediator in the pathogenesis of thrombosis, as several data in the literature indicate that polymorphisms such as EPCR 4678G/C and 4600A/G are associated with either protective effect or increased risk of thrombosis, respectively. We investigated the prevalence of these polymorphisms in patients with thrombotic disorders as well as their impact on the risk of thrombosis, the age of first thrombotic episode, and recurrence. The prevalence of the rare EPCR alleles 4600G and 4678C was comparable in patients and controls. However, in a subset analysis, we observed that 4600G allele was more prevalent among patients who developed thrombosis at younger age (<35 years). Moreover, the prevalence of 4678C allele was significantly lower in younger patients compared to older patients. Neither polymorphism seemed to have an impact on recurrence regardless of age. Soluble EPCR levels were elevated in 4600AG patients compared to controls while 4678CC patients presented with lower levels of soluble form of EPCR compared to carriers of at least 1 4678G allele. Our data suggest that either the lack of the protective EPCR 4678C allele or the presence of EPCR 4600G allele may be associated with earlier development of thrombosis.

Current trends in platelet transfusions practice: The role of ABO-RhD and human leukocyte antigen incompatibility.

Platelet transfusions have contributed to the revolutionary modern treatment of hypoproliferative thrombocytopenia. Despite the long-term application of platelet transfusion in therapeutics, all aspects of their optimal use (i.e., in cases of ABO and/or Rh (D incompatibility) have not been definitively determined yet. We reviewed the available data on transfusion practices and outcome in ABO and RhD incompatibility and platelet refractoriness due to anti-human leukocyte antigen (HLA) antibodies. Transfusion of platelets with major ABO-incompatibility is related to reduced posttransfusion platelet (PLT) count increments, compared to ABO-identical and minor, but still are equally effective in preventing clinical bleeding. ABO-minor incompatible transfusions pose the risk of an acute hemolytic reaction of the recipient that is not always related to high anti-A, B donor titers. ABO-identical PLT transfusion seems to be the most effective and safest therapeutic strategy. Exclusive ABO-identical platelet transfusion policy could be feasible, but alternative approaches could facilitate platelet inventory management. Transfusion of platelets from RhD positive donors to RhD negative patients is considered to be effective and safe though is associated with low rate of anti-D alloimmunization due to contaminating red blood cells. The prevention of D alloimmunization is recommended only for women of childbearing age. HLA alloimmunization is a major cause of platelet refractoriness. Managing patients with refractoriness with cross-matched or HLA-matched platelets is the current practice although data are still lacking for the efficacy of this practice in terms of clinical outcome. Leukoreduction contributes to the reduction of both HLA and anti-D alloimmunization.

Circadian pattern of symptoms onset in patients ≤35 years presenting with ST-segment elevation acute myocardial infarction.

BACKGROUND: There are scarce data regarding the circadian pattern of symptoms onset in young patients presenting with acute myocardial infarction (AMI). We explored whether young patients with ST-segment elevation AMI exhibit a circadian variation in symptoms onset. METHODS: We recruited prospectively 256 consecutive patients who had survived their first ST-segment elevation AMI ≤35 years of age. Patients were categorized into 4 groups by 6-h intervals over 24 h. RESULTS: In 49 patients (19.1%) the clinical presentation of AMI was atypical. The symptoms onset was as follows: 00:01 to 06:00, 19.1%, 06:01 to 12:00, 32.4%; 12:01 to 18:00, 28.1%; and 18:01 to 24:00, 20.3%. There was a significant association between the time of day and the likelihood of symptoms onset (Rayleigh test, p<0.001). Between 00:01 and 06:00 the incidence of AMI onset was lower than expected and between 06:01 and 12:00 was higher (p=0.034 and p=0.011, respectively), whereas in the other 6-h period groups no difference was found between expected and observed AMI incidence (p=0.280 and p=0.131). No significant differences were found regarding clinical characteristics, i.e. traditional risk factors, reperfusion treatment of AMI, ejection fraction of left ventricle, time interval from pain onset to hospital arrival, dietary habits and physical activity, among the 6-h period groups. CONCLUSIONS: ST-segment elevation AMI in individuals ≤35 years of age follows a circadian pattern with a morning peak. This information might be useful for the prompt diagnosis and treatment of AMI in very young patients which occurs rarely and frequently with atypical clinical presentation.