BACKGROUND: Nephrotic syndrome (NS) is associated with a high risk of thrombotic complications. In this group of patients, routine local tests for assessing hemostasis do not accurately reflect hypercoagulable state. Global functional tests for assessing hemostasis, including thrombodynamics (TD), are considered promising for assessing disorders in the blood coagulation system of these patients.
OBJECTIVE: To compare the rate of hypercoagulability according to routine hemostatic tests and TD and to evaluate the factors associated with increased risk of thrombotic complications in patients with chronic glomerulonephritis (CGN).
METHODS: The study included 94 patients with active CGN who were not receiving anticoagulant therapy; 63 (80.3%) patients had NS, and 31 (19.7%) had active CGN without NS. Hemostasis parameters were assessed using local coagulation tests and TD test. Using logistic regression analysis, factors associated with the risk of thrombosis were assessed.
RESULTS: Of the 94 patients with active CGN in 63 without preventive anticoagulant therapy, hypercoagulability according to routine tests was detected in 6 (9.5%) patients with NS and in 3 (9.7%) patients without NS (p<0.05). Hypercoagulability according to the TD test was detected in 24 (53.9%) patients with NS and in 5 (32.2%) without NS (p<0.05). The formation of spontaneous clots was observed in 29 (30.9%) of patients with CGN, most of them 24 (83%) with NS. 10.6% of patients in our cohort experienced thromboembolic events. The risk of thromboembolic events according to the univariate regression analysis was associated with older age, higher lipid levels, use of glucocorticosteroids and detection of spontaneous clots by the TD test. No association of thromboembolic events with abnormalities in routine hemostasis tests was obtained.
CONCLUSIONS: In patients with CGN with nephrotic syndrome, hypercoagulability is detected in 9.5% of cases with routine coagulation tests and in 53.9% of cases with TD test. Detection of spontaneous clots by TD test is associated with a risk of thromboembolic events.
Обоснование. Нефротический синдром (НС) связан с высоким риском тромботических осложнений. У этой группы пациентов рутинные локальные тесты для оценки гемостаза не отражают точно состояние гиперкоагуляции. Перспективными для оценки нарушений в свертывающей системе крови этих больных считаются глобальные функциональные тесты оценки гемостаза, в том числе тромбодинамика (ТД). Цель. Сравнить частоту гиперкоагуляции по данным рутинных тестов оценки гемостаза и ТД и установить факторы риска тромботических осложнений у больных хроническим гломерулонефритом (ХГН). Материалы и методы. В исследование включены 94 больных активным ХГН, не получающих антикоагулянтную терапию. У 63 (80,3%) пациентов диагностирован НС, а у 31 (19,7%) – активный ХГН без НС. Параметры гемостаза оценивали с использованием локальных рутинных методов оценки и теста ТД. С помощью моно- и многофакторного логистического регрессионного анализа определены факторы, связанные с риском тромбообразования. Результаты. Из 94 больных ХГН у 63 без профилактической антикоагулянтной терапии гиперкоагуляция по рутинным тестам оценки гемостаза выявлена у 6 (9,5%) с НС и у 3 (9,7%) – без НС (p<0,05). Гиперкоагуляция по тесту ТД выявлена у 24 (53,9%) больных с НС и у 5 (32,2%) – без НС (p<0,05). Образование спонтанных сгустков отмечено у 29 (30,9)% больных ХГН, у большинства из них – 24 (83%) – c НС. У 10,6% больных в нашей когорте отмечались тромбоэмболические события. Риск развития тромбоэмболических событий по результатам монофакторного регрессионного анализа ассоциирован со старшим возрастом, более высоким уровнем липидов, приемом глюкокортикостероидов и выявлением спонтанных сгустков по тесту ТД. Достоверной связи тромбоэболических событий с отклонениями в рутинных тестах гемостаза не получено. Заключение. У больных ХГН с НС гиперкоагуляция выявляется в 9,5% случаев при выполнении рутинных тестов оценки гемостаза и в 53,9% случаев при выполнении теста ТД. Выявление спонтанных сгустков по тесту ТД сопряжено с риском тромбоэмболических событий.

Patients with liver cirrhosis often exhibit complex alterations in their hemostatic system that can be associated with both bleeding and thrombotic complications. While prophylactic correction of abnormal coagulation parameters should be avoided, an individualized approach is recommended prior to invasive procedures, whereby specific preventive measures to stabilize hemostasis should be based on the periprocedural bleeding risk. While the haemostatic system of patients with compensated cirrhosis is often in a rebalanced haemostatic state due to a parallel decline in both pro- and anti-haemostatic factors, a decompensation of liver cirrhosis can lead to destabilization of this fragile equilibrium. Since conventional coagulation tests do not adequately capture the complex changes in the hemostatic system in cirrhosis, functional analysis methods such as viscoelastic tests or thrombin generation assays can be used for evaluating the coagulation status. This review describes the underlying pathophysiological changes in the hemostatic system in liver cirrhosis, provides an overview of diagnostic methods and discusses therapeutic measures in case of bleeding and thrombotic complications.
Patienten mit Leberzirrhose weisen komplexe Veränderungen des hämostatischen Systems auf, die sowohl mit Blutungs- als auch mit thrombotischen Komplikationen einhergehen können und im Rahmen des klinischen Managements berücksichtigt werden sollten.Während eine prophylaktische Korrektur abnormaler Gerinnungsparameter vermieden werden sollte, ist vor invasiven Prozeduren ein individualisiertes Vorgehen zu empfehlen, wobei sich spezifische Präventionsmaßnahmen zur Stabilisierung der Gerinnung am periprozeduralen Blutungsrisiko orientieren sollten.Weiterhin gilt zu beachten, dass sich die hämostatischen Veränderungen in Abhängigkeit des Stadiums der Erkrankung unterscheiden. Während sich das hämostatische System bei kompensierter Zirrhose oftmals in einem Gleichgewicht befindet, kann das Auftreten einer akuten Dekompensation zu einer Destabilisierung dieses Zustands führen.Da konventionelle Gerinnungstests die komplexen Veränderungen des hämostatischen Systems bei Zirrhose nicht adäquat erfassen, können funktionelle Analysemethoden, wie viskoelastische Testverfahren oder Thrombingenerierungstests bei der Evaluation des Gerinnungsstatus hilfreich sein.Die vorliegende Übersichtsarbeit beschreibt die zugrunde liegenden pathophysiologischen Veränderungen des hämostatischen Systems bei Leberzirrhose, liefert einen Überblick über geeignete Diagnostikmethoden und thematisiert Therapiemaßnahmen im Falle von Blutungs- und thrombotischen Komplikationen.

UNASSIGNED: Elevated ambient pollution exposure is potentially linked to thromboembolism. However, the mechanisms by which particulate matter (PM) interferes with the balance of hemostatic system remain unclear. This study investigates PM-mediated hemostatic changes in individuals across unique seasonal variations of ambient pollution.
UNASSIGNED: This prospective study was conducted between February and July 2020 during alterations in ambient pollution in Chiang Mai, Thailand. Blood tests from 30 healthy subjects were assessed at four-week intervals, four times in total. Various coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor (vWF), platelet count, and platelet functions, were evaluated. A mixed-effects model was used to analyze the impact of high PM2.5 and PM10 on hemostatic parameters.
UNASSIGNED: Thirty male subjects with mean age of 38.9 ± 8.2 years, were included. High levels of PM2.5 and PM10 were significantly associated with PT shortening, with no such effect observed in aPTT. PM2.5 and PM10 values also positively correlated with vWF function, while vWF antigen levels remained unchanged. Soluble P-selectin showed a strong positive association with PM2.5 and PM10 levels. Platelet function analysis revealed no correlation with PM values.
UNASSIGNED: Short-term exposure to elevated PM2.5 and PM10 concentrations was linked to shortened PT and enhanced vWF function in healthy individuals. Exploring the impact of these changes on clinically relevant thrombosis is crucial. Additional studies on the pathogenesis of pollution-related thrombosis are warranted for maintaining good health.

Direct oral anticoagulants (DOACs) have significant advantages over vitamin K antagonists including lack of need for routine laboratory monitoring. However, assessment of DOAC effect and concentration may be important to guide clinical management including need for DOAC reversal, particularly in acute or emergent situations. In this manuscript, the authors describe tests to screen for DOAC presence and tests that have demonstrated equivalence to gold standard testing for quantifying DOAC exposure. They also discuss the effect of DOACs on other coagulation assays and strategies for monitoring unfractionated heparin in patients with concomitant DOAC exposure.

The term \'routine coagulation\' typically applies to hemostasis tests routinely performed in hematology laboratories, often available 24/7, and potentially ordered urgently. These tests would comprise of the prothrombin time (PT), the PT converted to an international normalized ratio, the activated partial thromboplastin time (often called partial thromboplastin time in North American laboratories) and potentially the thrombin time, the D-dimer assay, and fibrinogen assays. Although other tests could feasibly be offered (testing feasible), there are good reasons for not including all of these other tests in all routine coagulation laboratories.

UNASSIGNED: Viscoelastic assays have widely been used for evaluating coagulopathies but lack the addition of shear stress important to in vivo clot formation. Stasys technology subjects whole blood to shear forces over factor-coated surfaces. Microclot formation is analyzed to determine clot area (CA) and platelet contractile forces (PCFs). We hypothesize the CA and PCF from this novel assay will provide information that correlates with trauma-induced coagulopathy and transfusion requirements.
UNASSIGNED: Blood samples were collected on adult trauma patients from a single-institution prospective cohort study of high-level activations. Patient and injury characteristics, transfusion data, and outcomes were collected. Thromboelastography, coagulation studies, and Stasys assays were run on paired samples collected at admission. Stasys CA and PCFs were quantified as area under the curve calculations and maximum values. Normal ranges for Stasys assays were determined using healthy donors. Data were compared using Kruskal-Wallis tests and simple linear regression.
UNASSIGNED: From March 2021 to January 2023, 108 samples were obtained. Median age was 37.5 (IQR 27.5-52) years; patients were 77% male. 71% suffered blunt trauma, 26% had an Injury Severity Score of ≥25. An elevated international normalized ratio significantly correlated with decreased cumulative PCF (p=0.05), maximum PCF (p=0.05) and CA (p=0.02). Lower cumulative PCF significantly correlated with transfusion of any products at 6 and 24 hours (p=0.04 and p=0.05) as well as packed red blood cells (pRBCs) at 6 and 24 hours (p=0.04 and p=0.03). A decreased maximum PCF showed significant correlation with receiving any transfusion at 6 (p=0.04) and 24 hours (p=0.02) as well as transfusion of pRBCs, fresh frozen plasma, and platelets in the first 6 hours (p=0.03, p=0.03, p=0.03, respectively).
UNASSIGNED: Assessing coagulopathy in real time remains challenging in trauma patients. In this pilot study, we demonstrated that microfluidic approaches incorporating shear stress could predict transfusion requirements at time of admission as well as requirements in the first 24 hours.
UNASSIGNED: Level II.

Coagulation disorders in critically ill patients presenting with bleeding can be multicausal. The drugs applied can interfere and impair the coagulation cascade. Point-of-care (POC) coagulation assays may resolve difficult therapeutic situations in critical illness. We report on a 73-year-old critically ill male patient with massive hematuria after bladder lithotripsy. The patient was on low molecular weight heparin therapy due to recent pulmonary embolism. He was subjected to repeated surgical hemostasis which was ineffective despite massive transfusion protocol and normal standard coagulation profile. Additional POC coagulation assays were obtained and were indicative of platelet dysfunction. We revised his medical therapy and suspected the possible drug influence on platelet aggregation. After discontinuation of target drug, platelet aggregation increased whereas hematuria stopped. Coagulation disorders in intensive care unit patients are often multifactorial. Standard laboratory tests are unreliable in complex refractory bleeding and may result in inappropriate therapeutic decisions. Stepwise approach with assessment of clinical parameters, present therapy, and a combination of POC coagulation tests is the key to optimal therapeutic management.

UNASSIGNED: Intravenous lipid emulsion is used in the rescue treatment of certain poisonings. A complication is interference with laboratory analyses. The aim of this study was to determine the impact of intravenous lipid emulsion on routine laboratory analysis of coagulation parameters ex vivo and determine if any of the analytical techniques remain reliable.
UNASSIGNED: Samples were obtained from 19 healthy volunteers and divided in triplicate. One sample served as a control, and the other two were diluted to simulate the treatment of an average adult with Intralipid® 20 per cent Fresenius Kabi 100 mL (dilution-1) or 500 mL (dilution-2). Coagulation tests performed were prothrombin time, activated prothrombin time, D-dimer concentration and fibrinogen. Coagulation testing was performed by three techniques. Test-1 was performed on a Sysmex CN6000 analyzer. Test-2 was performed with a manual mechanical endpoint method using the semi-automated Stago KC4 Delta. Test-3 involved high-speed centrifugation before repeat testing on the Sysmex CN6000 analyzer.
UNASSIGNED: For test-1, only nine (47 per cent) samples in dilution-1 could be analyzed for coagulation tests, and no coagulation tests could be analyzed for dilution-2 because of lipaemia. For test-2 and test-3, all samples could be analyzed, and all results of both testing methods fell within the limits of the laboratory reference range.
UNASSIGNED: Difficulties in laboratory analysis of patients having received intravenous lipid emulsion are due to multiple factors. Most automated coagulation analyzers use optical measurements, which can be unreliable in the presence of a high intravenous lipid concentration. By altering the lipaemia in the testing solution using high-speed centrifugation or by using manual mechanical endpoint detection, we were able to obtain reliable results. These findings are limited by the use of an ex vivo method and healthy volunteers.
UNASSIGNED: This ex vivo model confirms that Intralipid® interferes with routine coagulation studies. It is important that clinicians are aware and inform their laboratories of its administration.

UNASSIGNED: There are important pharmacological differences between direct oral anticoagulants (DOAC) and a deeper knowledge of how they influence different aspects of hemostasis in patients on treatment is desirable.
UNASSIGNED: Blood samples from patients on dabigatran (n = 23), rivaroxaban (n = 26), or apixaban (n = 20) were analyzed with a fibrin network permeability assay, a turbidimetric clotting and lysis assay, the calibrated automated thrombogram (CAT), plasma levels of thrombin-antithrombin complex (TAT) and D-dimer, as well as DOAC concentrations, PT-INR and aPTT. As a comparison, we also analyzed samples from 27 patients on treatment with warfarin.
UNASSIGNED: Patients on dabigatran had a more permeable fibrin network, longer lag time (CAT and turbidimetric assay), and lower levels of D-dimer in plasma, compared with patients on rivaroxaban- and apixaban treatment, and a more permeable fibrin network than patients on warfarin. Clot lysis time was slightly longer in patients on dabigatran than in patients on rivaroxaban. Warfarin patients formed a more permeable fibrin network than patients on apixaban, had longer lag time than patients on rivaroxaban (CAT assay), and lower peak thrombin and ETP compared to patients on treatment with both FXa-inhibitors.
UNASSIGNED: Results from this study indicate dabigatran treatment is a more potent anticoagulant than apixaban and rivaroxaban. However, as these results are not supported by clinical data, they are probably more related to the assays used and highlight the difficulty of measuring and comparing the effect of anticoagulants.

BACKGROUND: There are significant differences in the activated partial thromboplastin time (APTT) critical values reported in different studies, most of which does not make recommendations for any specific clear detection systems. The International Council for Standardization in Hematology (ICSH) recommends that APTT critical values be established based on the reagent type, coagulation factor sensitivity and heparin response. The objective of this study was to establish APTT critical values by using different reagents and based on single coagulation factor deficiencies.
METHODS: The APTT values were determined in commercial endogenous coagulation factor-deficient plasma at concentrations of 1 IU/dL, 2 IU/dL, 5 IU/dL, 10 IU/dL, 20 IU/dL, and 30 IU/dL by using four assay systems. The retrospective collection of data from patients who lacked factor VIII (FVIII), FIX, or FXI alone was performed. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of APTT for identifying patients with an endogenous coagulation factor activity < 5 IU/dL.
RESULTS: The APTT values in the plasma samples with the same concentrations of endogenous coagulation factors were significantly different among the four assay systems (P < 0.001). The suggested critical values of APTT were 40.0 s for Sysmex CS5100 (Actin FSL), 58.0 s for Sysmex CS5100 (Actin), 51.8 s for STA-R Evolution (STA-PTTA), and 64.8 s for ACL TOP 700 (HemosIL SynthasIL). On the basis of the ROC curve, the optimal threshold values for APTT (STA-PTTA) were 55.8 s in patients with a simple deficiency of FVIII (sensitivity = 100%, specificity = 85.7%, area under the ROC curve (AUC) = 0.982), 54.3 s in patients with a simple deficiency of FIX (sensitivity = 100%, specificity = 92.9%, AUC = 0.986), and 71.7 s in patients with a simple deficiency of FXI (sensitivity = 100%, specificity = 94.1%, AUC = 0.992), which were closer (difference of 0.6-2.5 s) to the cutoff points for commercial plasma at equal factor levels.
CONCLUSIONS: APTT critical values need to be established for different reagents based on the presence of a single coagulation factor deficiency.