Routine utilization of machine perfusion in liver transplantation: Ready for prime time?

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation. Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses, providing the highest available evidence on the protective effect of machine perfusion (MP) over static cold storage in liver transplantation (LT). Based on a protective effect with less complications and improved graft survival, the field has seen a paradigm shift in organ preservation. This editorial focuses on the role of MP in LT and how it could become the new "gold standard". Strong collaborative efforts are needed to explore its effects on long-term outcomes.

Delayed surgery for acute type A aortic dissection: a retrospective review of an alternative surgical strategy in the COVID-19 era.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, medical resources have often been limited to emergency surgeries. This study aimed to evaluate our experience with delayed surgery for acute type A aortic dissections (ATAADs). METHODS: A retrospective study was conducted on 33 patients who underwent surgery for ATAADs between January 2020 and December 2021. The patients were divided into two groups: patients treated within 12 h of arrival (E group; N = 21) and those treated > 12 h after arrival (D group; N = 12) with strict antihypertensive therapy until surgery. RESULTS: The plasma fibrinogen levels on arrival were lower in the D group than in the E group (174.3 ± 109.1 vs 293.4 ± 165.4, p = 0.038). The time to surgery from symptom onset was longer in the D group than in the E group (4 ± 1 h vs. 86 ± 108 h, p < 0.001). There was one case (3%) of mortality and seven cases (21%) of cerebral infarctions in the E group. There was no significant difference in the intraoperative data and quantity of blood transfused between the two groups. CONCLUSION: Thus, delayed surgery for ATAAD with appropriate preoperative management may be an alternative surgical strategy in the COVID-19 era.

Exploring coagulation parameters as predictive biomarkers of Plasmodium infection: A comprehensive analysis of coagulation parameters.

BACKGROUND: Malaria affects the intravascular environment, leading to abnormal coagulation activation, prolonged prothrombin time, and activated partial thromboplastin time. Despite the high prevalence of malaria in the study area, there has been little published research on the effects of Plasmodium infection on coagulation parameters. OBJECTIVE: The aim was to assess the effect of malaria on basic coagulation parameters among patients attending Dembia Primary Hospital and Makisegnit Health Center. METHODS: A cross-sectional study was carried out from January to March 2020. The study involved 120 participants. Blood specimens were collected, which were analyzed using a Huma Clot Due Plus analyzer. The collected data were entered into EpiData and exported to SPSS version 21 for analysis. Non-parametric statistical methods were employed to analyze the data. The results were considered statistically significant if the p-value was less than 0.05. RESULTS: Individuals infected with Plasmodium exhibit coagulation disorders with elevated levels of PT (Prothrombin Time), APTT (Activated Partial Thromboplastin Time), and INR (International Normalization Ratio) in comparison to healthy controls. The median PT, APTT, and INR values for infected cases were measured at 20.5 [8.6], 39.5 [17.9], and 1.8 [0.9], respectively, while healthy controls had measurements of 15.1 [2.5], 28.8 [8.3], and 1.3 [0.2] (p ≤ 0.001). The severity of coagulation disorders increased with an increase in parasitemia levels. The type of Plasmodium species present had a significant impact on PT and INR values (p ≤ 0.001), whereas APTT did not show any significant impact across the Plasmodium species (p > 0.05). CONCLUSION: The results of this study found that malaria has a substantial impact on various blood clotting parameters, including PT, APTT, and INR. Parasitemia severity is significantly associated with extended PT and INR, implying that the higher the parasitemia, the longer it takes for blood to clot. Furthermore, the study discovered that the PT and INR levels differed based on the type of Plasmodium species responsible for the infection.

The spectrum of neutralizing and non-neutralizing anti-FVIII antibodies in a nationwide cohort of 788 persons with hemophilia A.

Objectives: Anti-factor VIII (FVIII) antibodies have been reported to exhibit both neutralizing and non-neutralizing characteristics. This is the first study investigating the full spectrum of FVIII-specific antibodies, including non-neutralizing antibodies, very-low titer inhibitors, and inhibitors, in a large nationwide population of persons with hemophilia A of all severities. Methods: All persons with hemophilia A (mild (FVIII > 5-40 IU/dL)/moderate [FVIII 1-5 IU/dL)/severe (FVIII < 1 IU/dL)] with an available plasma sample who participated in the sixth Hemophilia in the Netherlands study between 2018 and 2019 were included. The presence of anti-FVIII antibodies of the immunoglobulin A, M, and G isotypes and IgG subclasses, along with antibody titer levels, were assessed using direct-binding ELISAs. FVIII specificity was assessed using a competition-based ELISA approach. The inhibitor status was determined using the Nijmegen ultra-sensitive Bethesda assay (NusBA) and the Nijmegen Bethesda assay (NBA). Results: In total, 788 persons with hemophilia A (336 (42.6%) mild, 123 (15.6%) moderate, 329 (41.8%) severe hemophilia) were included. The median age was 45 years (IQR 24-60), and the majority (50.9%) had over 150 exposure days to FVIII concentrates. Within our population, 144 (18.3%) individuals had non-neutralizing FVIII-specific antibodies, 10 (1.3%) had very low-titer inhibitors (NusBA positive; NBA negative), and 13 (1.6%) had inhibitors (both NusBA and NBA positive). IgG1 was the most abundant FVIII-specific antibody subclass, and the highest titer levels were found for IgG4. In individuals without a reported history of inhibitor development, no clear differences were observed in antibody patterns between those who were minimally or highly exposed to FVIII concentrates. IgG4 subclass antibodies were only observed in persons with a reported history of FVIII inhibitor or in those with a currently detected (very low-titer) inhibitor. Conclusion: In this cross-sectional study, we identified non-neutralizing antibodies in a relatively large proportion of persons with hemophilia A. In contrast, in our population, consisting of persons highly exposed to FVIII concentrates, (very low-titer) inhibitors were detected only in a small proportion of persons, reflecting a well-tolerized population. Hence, our findings suggest that only a small subpopulation of non-neutralizing FVIII-specific antibodies is associated with clinically relevant inhibitors.

Evaluating the effects of hypoxic storage on platelet function and health using a novel storage system.

BACKGROUND: Thousands of units of whole blood (WB) and blood components are transfused daily to treat trauma patients. Improved methods for blood storage are critical to support trauma-related care. The Hemanext ONE® system offers a unique method for hypoxic storage of WB, with successfully demonstrated storage of clinically viable RBCs. This work evaluated the system for the storage of WB, focusing on platelet health and function. STUDY DESIGN AND METHODS: WB was collected from healthy donors and processed through the Hemanext ONE® system. Hemoglobin oxygen saturation (HbSO2) levels of WB were depleted to 10%, 20%, or 30% of total HbSO2 and then stored in PVC bags sealed in oxygen-impermeable bags (except for normoxic control) with samples collected on days 1, 7, and 14 post-processing. Flow cytometry assessed the activation and apoptosis of platelets. Clot dynamics were assessed based on aggregometry and thromboelastography assays, as well as thrombin generation using a calibrated-automated thrombogram method. RESULTS: Hypoxic storage conditions were maintained throughout the storage period. Hypoxia triggered increased lactate production, but pH changes were negligible compared to normoxic control. Storage at 10% HbSO2 had a significant impact on platelet function, resulting in increased activation and reduced clot formation and aggregation. These effects were less significant at 20% and 30% HbSO2. DISCUSSION: This study indicates that platelets are sensitive to hypoxic storage and suffer significant metabolic and functional deterioration when stored at or below 10% HbSO2.

Effects of Extracorporeal Membrane Oxygenation on the Coagulation System.

This study aimed to investigate the effects of long-term awake extracorporeal membrane oxygenation (ECMO) on the coagulation system in a sheep model. A total of ten healthy sheep were included in the study, with 5 sheep in each group. In the veno-arterial ECMO (V-A ECMO) group, cannulation was performed in the right carotid artery and the right external jugular vein. In the veno-venous ECMO (V-V ECMO) group, a dual-lumen catheter was utilized to insert into the right external jugular vein. After initiating ECMO, the sheep were recovered from anesthesia and remained awake for 7 days. The target activated clotting time (ACT) goal was set at 220-250 s. In both groups, the actual ACT fluctuated around 250 s with the dose of heparin gradually increasing, reaching almost 60 IU/kg/min at the end of the experiments. Moreover, the activated partial thromboplastin time (APTT) and thrombin time (TT) values were significantly higher in the V-A ECMO group compared to the V-V ECMO group, despite receiving the same doses of heparin. Although laboratory test results fluctuated within a normal and reasonable range, infarct foci in the kidneys were observed in both groups at the end of the study.

Clot time ratio (CTR) and treatment outcomes in Apixaban-treated atrial fibrillation patients.

There are clinical situations where information about the anticoagulant effects of Apixaban could be useful. Specialised methods for measuring Apixaban concentrations are not available at all medical laboratories while methods for measuring the functional effects of Apixaban, using clot time ratio (CTR), can be performed in most medical laboratories around the clock using well-established measurement procedures. The aim of this study was to investigate CTR in trough and peak samples during Apixaban treatment of atrial fibrillation and to correlate the findings to bleeds and thrombotic events. Three trough- and three peak samples from 61 patients (31 on Apixaban 5 mg twice daily and 30 on Apixaban 2.5 mg twice daily) were analysed with MRX PT DOAC. Patients were followed for 30 + /-15 months, and bleeds and thrombotic events were documented. The effect of Apixaban could be measured with MRX PT DOAC and there was a statistically significant difference between CTR in trough samples compared to peak samples (p < 0.001). A total of 21 patients suffered bleeds during follow-up; two patients suffered major bleeds, and 19 suffered minor bleeds. Patients with major bleeds had both mean peak- and mean trough CTR above the respective first to third quartile (Q1-Q3) range. Four patients suffered thromboembolic events. Generally, the peak CTRs were below or in the lower end of the peak Q1-Q3 for these patients. The new test MRX PT DOAC can be used to measure the effect of Apixaban during the treatment of atrial fibrillation. High mean peak- and mean trough CTR were seen in 2 patients with major bleeds, and low peak CTR was seen in 4 patients with thromboembolic events.

Effect of Reduced INR in Early Pregnancy on the Occurrence of Preeclampsia: A Retrospective Cohort Study.

To investigate the effect of reduced early-pregnancy activated partial thrombin time (APTT), prothrombin time (PT), and international standardized ratio (INR) on the risk of preeclampsia. A total of 8549 pregnant women with singleton births were included. Early pregnancy APTT, PT, and INR levels, with age, birth, prepregnancy body mass index, fibrinogen (FBG), thrombin time (TT), D-dimer (DD2), antithrombin III (ATIII), fibrin degradation products (FDP) as confounders, generalized linear model of APTT, the relative risk of PT and INR when INR reduction. After adequate adjustment for confounders, the relative risk of preeclampsia was 0.703 for every 1 s increase in plasma PT results in early pregnancy, and for every 0.1 increase in plasma INR results, the relative risk of preeclampsia was 0.767. With a PT less than the P25 quantile (<11 s), the relative risk of preeclampsia was 1.328. The relative risk of preeclampsia at an INR less than the P25 quantile (<0.92) was 1.24. There was no statistical association between APTT on the risk of preeclampsia. The relative risk of preeclampsia is strongly associated with a decrease in PT and INR in early pregnancy. PT and INR in early pregnancy were a potential marker in the risk stratification of preeclampsia. Focusing on reduced PT and INR levels in early pregnancy can help to identify early pregnancies at risk for preeclampsia.

Determination of procoagulant activity in human normal immunoglobulin preparations for therapeutic use by FXIa chromogenic assay: Evaluation of test kit sensitivity, reference standard performance and product formulation effects on the FXIa assay.

In 2010, the reporting of thrombotic adverse events for one subcutaneous and certain intravenous immunoglobulins (IGs) raised some concerns. In Europe, regulatory bodies rapidly revised compendial specifications for therapeutic IGs to ensure they do not exhibit thrombogenic (procoagulant) activity (PCA). At the global level, a working group (GWG) was launched with the aim of assessing PCA measurement methods and limits, considering results obtained by human IG manufacturers during in-process controls. The GWG created three dedicated subgroups to investigate the FXIa chromogenic assay, the non-activated partial thromboplastin time (NAPTT) test and the thrombin generation assay (TGA). The European Directorate for the Quality of Medicines & HealthCare (EDQM) was responsible for co-ordinating the subgroup in charge of evaluating the FXIa chromogenic assay in a study that assessed the sensitivity and robustness of two commercial chromogenic FXIa test kits. The impact of IG product formulation on FXIa recovery and the suitability of PCA-containing IG products as potential reference standards/controls were also assessed. IG materials representative of marketed products were provided to four laboratories for a study that was carried out in two steps: 1) two chromogenic FXIa test kit manufacturers assessed the performance and determined optimal test conditions by their respective methods, 2) two OMCLs studied both kits using an optimised study design. Regarding sensitivity, the study results identified suitable dose-response intervals and limits with both chromogenic FXIa test kits. This allowed the establishment of dilution ranges for optimal detection of FXIa/PCA in 5 % and 10 % IG products in the range of 1-6 mIU/mL. However, careful optimisation of the sample dilutions was required (notably to avoid potential matrix effects) and the choice of the mode of data acquisition (kinetic or end-point method) contributed to sensitivity in routine use. Importantly, the composition of IG products was of minor concern for FXIa determination with both test kits. Potential reference materials evaluated in the study behaved as expected and could be useful should a separate reference standard to the FXIa WHO IS be deemed necessary in future.

INVESTIGATION OF A POINT-OF-CARE VISCOELASTIC COAGULATION MONITOR AND ITS COMPARISON TO THROMBOELASTOGRAPHY IN CLINICALLY HEALTHY AFRICAN ELEPHANTS (LOXODONTA AFRICANA).

Elephant endotheliotropic herpesvirus (EEHV) can induce fatal hemorrhagic disease (HD) in African elephants (Loxodonta africana). Once clinical signs develop, progression is rapid, even with aggressive treatment. There is a critical need to develop point-of-care diagnostic tests to aid in identification of EEHV-HD prior to the onset of overt clinical signs. Study objectives were to investigate a novel, point-of-care viscoelastic coagulation monitor (VCM Vet), compare the results to thromboelastography (TEG), and report traditional hemostatic analytes in adult African elephants. Whole blood was collected from seven clinically healthy elephants (four females and three males, 18-47 yr) and analyzed in duplicate via VCM Vet and kaolin-activated TEG 1-3 and 30 min following collection, respectively. Separated plasma was frozen for ancillary coagulation testing. Both analyses generated quantifiable clotting reactions with variables (median [range]) describing clot formation rate (VCM Vet, clot time = 682 s [530-987 s], clot formation time = 244 s [186-744 s], Alpha = 40° [14-47°]; TEG, reaction time = 6.2 min [3.7-11.8 min], kinetic time = 1.3 min [0.9-2.6 min], Alpha = 70° [57-77°]), clot strength (VCM Vet, maximum clot formation = 34 units [20-45 units]; TEG, maximum amplitude = 75 mm [69-80 mm], shear elastic modulus strength = 14.7 Kdynes/s [11.3-19.5 Kdynes/s]), and clot lysis (VCM Vet, lysis index at 30 min = 100% [100-99%], lysis index at 45 min = 98% [95-100%]; TEG, lysis index at 30 min = 0% [0-0.4%], lysis index at 60 min = 1.4% [0-2.6%]) recorded. Additional testing (median [range]) included D-dimer concentration (33 ng/ml [28-94 ng/ml]), prothrombin time (12.4 s [12.2-13.2 s]), activated partial thromboplastin time (17.2 s [14.2-18.8 s]), and fibrinogen concentration (297 [282-383] mg/dL). Tracings generated by VCM Vet and TEG were clinically similar, and there was visual agreement and minimal difference between quantitative variables for duplicate tests. VCM Vet is a promising, user-friendly tool for use in identification and management of coagulopathies in African elephants.

Assessing hypercoagulability and VTE risk using thromboelastography and Khorana score in women with cancers receiving chemotherapy.

Venous thromboembolism (VTE) is a common occurrence in cancer and chemotherapy increases thrombosis risk. Current risk assessment models such as the Khorana score (KS) and its modifications have limitations in female cancers. We assessed the coagulation profile of a group of women cancer patients under chemotherapy using thromboelastography (TEG) to determine if this can inform VTE risk assessment. Cancer patients who planned to receive chemotherapy were recruited. Baseline demographics, cancer data, BMI, Khorana Score (KS), and VTE risk factors were recorded and patients were followed for 6 months, for any thrombotic events. A total of 36 patients aged 35-85 (18 breast, 11 endometrial, 7 ovarian cancer) were evaluated. Hypercoagulability was detected in 63% of patients post-chemo cycle 1 and 75% post-cycle 2, with a significant increase in MA (maximum amplitude) and CI (clotting index), reduction in R (reaction time), K (clot kinetics), and LY30 (lysis time after 30 min of MA). KS showed only 7% of patients were high risk, 23% were low, and 70% were intermediate risk. MA and CI significantly increased in patients with intermediate and high-risk KS when compared with the low-risk patients and MA was positively correlated with KS. Five patients developed actual VTE; 100% of the tested ones were hypercoagulable either post-cycle 1 or 2 and 80% were KS intermediate risk. TEG is a hypercoagulability marker and TEG-MA and CI can potentially assess VTE risk. Larger studies are needed to assess the utility of TEG as an adjuvant to KS to better predict VTE in specific female cancers.

Effect of Centhaquine on the Coagulation Cascade in Normal State and Uncontrolled Hemorrhage: A Multiphase Study Combining Ex Vivo and In Vivo Experiments in Different Species.

Centhaquine is a novel vasopressor acting on α2A- and α2B-adrenoreceptors, increasing venous return and improving tissue perfusion. We investigated the effects of centhaquine on blood coagulation in normal state and uncontrolled hemorrhage using ex vivo and in vivo experiments in different species. Thromboelastography (TEG) parameters included clotting time (R), clot kinetics [K and angle (α)], clot strength (MA), and percent lysis 30 min post-MA (LY30). In normal rat blood, centhaquine did not alter R, K, α, MA, or LY30 values of the normal vehicle group or the antithrombotic effects of aspirin and heparin. Subsequently, New Zealand white rabbits with uncontrolled hemorrhage were assigned to three resuscitation groups: Sal-MAP 45 group (normal saline to maintain a mean arterial pressure, MAP, of 45 mmHg), Centh-MAP 45 group (0.05 mg kg-1 centhaquine plus normal saline to maintain a MAP of 45 mmHg), and Sal-MAP 60 group (normal saline to maintain a MAP of 60 mmHg). The Sal-MAP 45 group was characterized by no change in R, reduced K and MA, and increased α. In the Centh-MAP 45 group, TEG showed no change in R, K, and α compared to saline; however, MA increased significantly (p = 0.018). In the Sal-MAP 60 group, TEG showed no change in R, an increase in α (p < 0.001), a decrease in K (p < 0.01), and a decrease in MA (p = 0.029) compared to the Centh-MAP 45 group. In conclusion, centhaquine does not impair coagulation and facilitates hemostatic resuscitation.

Coagulation Testing in Real-World Setting: Insights From a Comprehensive Survey.

The objective of this survey was to gain a real-world perspective on coagulation testing by evaluating the availability of various coagulation laboratory tests, assessing specific analytic and postanalytic steps in clinical laboratories in Korea.Participants were surveyed using a 65-question questionnaire specifically focused on their coagulation testing practices related to prothrombin time (PT), activated partial thromboplastin time (aPTT), plasma-mixing studies, lupus anticoagulant (LA) tests, platelet function tests, coagulation factor assays, and the composition of hemostasis and thrombosis test panels. The survey was performed between July and September 2022.The survey achieved a 77.9% (81 of 104) response rate. PT or aPTT tests were performed directly at all participating institutions, followed by D-dimer and fibrinogen tests, platelet function test, and plasma-mixing studies in order of frequency. Variations existed in the performance of mixing test and LA assessment. Patterns of coagulating testing differed depending on the size of the hospital. The survey revealed that most laboratories conducted coagulation tests following the international guidelines such as Clinical Laboratory Standards Institute guidelines and the Korean Laboratory Certification system. However, some coagulation tests, including mixing test and LA tests, are yet to be standardized in Korea.Continuous education on coagulation test methods and internal and external quality control are required to encourage laboratories to enhance the performance of coagulation testing.

Eficacia y seguridad de la profilaxis con emicizumab en la hemofilia A: estudio de 13 pacientes / Efficacy and safety of prophylaxis with emicizumab in hemophilia A: A study of 13 patients

Introducción: Emicizumab es el primer tratamiento no sustitutivo para profilaxis en hemofilia A grave. Objetivos: Describir los resultados de nuestros pacientes en profilaxis con emicizumab, según la práctica clínica habitual. Material y métodos: Seguimiento de 13 pacientes desde el inicio de la profilaxis, registro de hemorragias, cirugías, reacciones adversas y necesidad o no de tratamiento factorial. Se midieron los niveles plasmáticos en las visitas de seguimiento; la técnica ha sido coagulativa en una etapa, modificada mediante dilución 1:20. Resultados: La mediana de niveles plasmáticos fue de 52,2mg [30,7-71,9]. La profilaxis resultó segura y eficaz; solamente se contabilizó una hemorragia espontánea a lo largo del tiempo y no precisó tratamiento. No hubo episodios tromboembólicos ni reacciones graves de hipersensibilidad, anafilaxia o anafilactoides. La incidencia de reacciones en el lugar de la inyección fue del 8%. El abordaje perioperatorio en las intervenciones menores se llevó a cabo sin tratamiento factorial coadyuvante, en 2 cirugías mayores se precisó una dosis de concentrado de FVIII plasmático en el paciente con hemofilia A sin inhibidor y FVII en el paciente con inhibidor, y fue suficiente para parar la hemorragia. Conclusión: Este estudio demostró que la farmacocinética de emicizumab y su vida media aseguran niveles óptimos con tratamiento profiláctico a las dosis establecidas en la ficha técnica.(AU)

Introduction: Emicizumab is the first non-replacement therapy for prophylaxis in severe hemophilia A. Aims: The principal aim of this study is to describe the results of our patients in prophylaxis with emicizumab, according to the usual clinical practice. Material and methods: Follow-up of 13 patients from the start of prophylaxis, recording of bleeding, surgeries, adverse reactions and the need or not for factor therapy. Plasma levels were measured at follow-up visits, the technique was coagulative in one stage, modified by 1:20 dilution. Results: Median plasma levels were 52.2mg [30.7–71.9]. Prophylaxis was safe and effective; only one spontaneous haemorrhage was recorded over time and no treatment was required. There were no thromboembolic events or serious hypersensitivity, anaphylaxis or anaphylactoid reactions. The incidence of injection site reactions was 8%. Perioperative management in minor interventions was carried out without adjuvant factorial therapy, in 2 major surgeries a dose of plasmatic FVIII concentrate was required in the patient with hemophilia A without inhibitor and FVII in the patient with inhibitor, and it was sufficient to stop the bleeding. Conclusion: This study demonstrated emicizumab pharmacokinetics and its half life ensure optimal levels with prophylaxis treatment at doses established in the technical data sheet.(AU)

Assessing coagulopathy and endothelial dysfunction in pediatric venous malformation: A thromboelastometry and syndecan-1 study.

OBJECTIVE: The occurrence of unpredictable pain crises are the principal determinant of the quality of life for patients with venous malformations (VM). A definite coagulation phenomenon, characterized by an increase in D-dimer levels and the presence of phleboliths within the malformation, has been previously reported. By applying Virchow's triad and evaluating intralesional samples, our objective is to delineate the coagulation profile and the extent of endothelial dysfunction within the malformation. METHODS: With the authorization of the Ethics Committee, a research project was undertaken on intralesional and extralesional blood samples from 30 pediatric patients afflicted with spongiform VM. Thromboelastometry analyses were performed using ROTEM Sigma, and the concentration of syndecan-1 was determined by ELISA. RESULTS: In the ROTEM analyses, the A5, A10, and maximum clot firmness (MCF) values were below the established reference ranges in the intralesional samples in both the EXTEM and INTEM assays, indicating that intralesional clots had significant instability. Furthermore, during the investigation of the delayed fibrinolysis phase using recombinant tissue plasminogen activator (rtPA) in EXTEM analysis, widespread hyperfibrinolysis was observed intralesional. Additionally, analysis of syndecan-1 showed significant differences between extralesional and intralesional levels (p < .026) and controls (p < .03), suggesting differences in the state of endothelium. CONCLUSIONS: For the first time, we developed a comprehensive understanding of the coagulopathic profile of VM and the role of endothelial dysfunction in its pathogenesis. These findings will enable the implementation of targeted therapies based on the individual coagulation profiles.

Establishment of Normal Reference Intervals for Coagulation Test Indicators in Children.

BACKGROUND: The objective of this study is to determine the standard reference intervals for coagulation function and coagulation factors in children across various age groups. METHODS: A statistical analysis was conducted on prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), thrombin time (TT), and coagulation factors (II, V, VII, X, VIII, IX, XI, and XII) in 389 healthy children who underwent health checkups and presurgical examinations at the Children's Hospital of Zhejiang University School of Medicine. The children were categorized into four age groups. RESULTS: The established normal reference ranges are as follows: PT (seconds): 10.00 - 12.26 for 1 month - 3 years, 10.24 - 12.66 for 3 - 18 years; APTT (seconds) : 24.82 - 35.65 for 1 month - 1 year, 25.20 - 32.30 for 1 - 18 years; Fib (g/L): 1.21 - 2.44 for 1 month - 1 year, 1.48 - 2.70 for 1 - 3 years, 1.69 - 3.60 for 3 - 18 years; TT (seconds): 18.48 - 23.06 for 1 month - 1 year, 17.80 - 21.26 for 1 - 18 years; coagulation factor II (%): 68.77 - 105.07 for 1 month - 1 year, 78.20 - 119.40 for 1 - 18 years; V (%): 74.24 - 140.96 for 1 month - 3 years, 70.64 - 132.01 for 3 - 18 years; VII (%): 56.34 - 113.00 for 1 month - 18 years; X (%): 49.17 - 105.57 for 1 month - 1 year, 64.34 - 115.24 for 1 - 18 years; VIII (%): 43.53 - 130.07 for 1 month - 1 year, 45.92 - 144.90 for 1 - 18 years; IX (%): 28.55 - 69.17 for 1 month - 1 year, 46.29 - 97.48 for 1 - 18 years; XI (%): 44.64 - 139.00 for 1 month - 1 year, 57.50 - 139.98 for 1 - 18 years; XII (%): 30.16 - 94.48 for 1 month - 1 year, 36.88 - 115.50 for 1 - 18 years. CONCLUSIONS: This study successfully established standard reference intervals for coagulation function and coagulation factors in children of various age groups in Hangzhou, China.

Pulmonary hypertension is associated with hypocoagulability in dogs: a retrospective analysis of 66 cases (2013-2021).

OBJECTIVE: To describe coagulation profiles in dogs with echocardiographic evidence of pulmonary hypertension (PH), to compare them to coagulation profiles in dogs without echocardiographic evidence of PH, and to determine the relationship between coagulation profiles and echocardiographic probability of PH. ANIMALS: 66 dogs with PH (cases) and 86 dogs without PH (controls). METHODS: Retrospective evaluation of records between 2013 and 2021 of dogs that had both an echocardiogram and a coagulation panel performed within 7 days. Dogs that received antithrombotics within 7 days of evaluation and dogs diagnosed with congenital or acquired coagulopathy or other severe systemic disease that could lead to coagulopathy were excluded. Dogs with a low echocardiographic probability of PH were also excluded. The dogs were divided into a PH group and non-PH group based on echocardiographic results. Demographic, clinicopathologic, and traditional coagulation parameters and VCM Vet (Entegrion) parameters were compared between the 2 groups. RESULTS: Dogs with PH were significantly older (median, 11 years vs 9.5 years, P = .02) and had a significantly lower body weight (median, 7.3 kg vs 19.3 kg, P < .001) than controls. Dogs with PH also had a significantly greater percent increase in prothrombin time (PT; P = .02), partial thromboplastin time (PTT; P < .0001), and fibrinogen (P = .045); however, their antithrombin concentration was lower (P = .005) compared to controls. Eight of 65 dogs (12.3%) in the PH group and 1/86 (1.2%) dogs in the non-PH group had an elevation of PT and/or PTT greater than 50% above the reference interval (P = .005). Dogs with PH had 11.9 times (95% CI, 1.5 to 97.9; P = .02) greater odds of being hypocoagulable than dogs without PH based on PT and PTT. CLINICAL RELEVANCE: This study demonstrated an association between a moderate to high echocardiographic probability of PH and a hypocoagulable state in dogs as determined by traditional coagulation assays. It underscores the importance of monitoring the coagulation status in canine patients with PH, particularly before initiating antithrombotic medications.