This case report describes interference from heterophilic antibodies in D-dimer assay. The interference was suspected due to discrepancies between D-dimer concentrations in the original sample and diluted samples, as well as inconsistent clinical findings. The patient\'s medical history, laboratory results, and imaging studies were considered in the investigation. Heterophilic antibodies, likely developed during the SARS-CoV-2 infection, were identified as the probable cause of interference. The interference was confirmed through various methods, including dilution studies, blocking heterophilic antibodies, and comparing results with an alternative D-dimer method. This case highlights the importance of recognizing and addressing interference in D-dimer testing, emphasizing the need for collaboration between clinicians and laboratory specialists.

BACKGROUND: Vitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent factors (VKDFs), resulting in higher factor (F)II levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents.
OBJECTIVE: To evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK.
METHODS: We retrospectively assessed consecutive cases from 2002 to 2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as international normalized ratio correction/improvement of ≥0.5 after VK.
RESULTS: Two hundred ninety-two patients (males, 58.2%; adults, 85.6%; median age, 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care, 71.6% with active liver disease, and 28% deceased at discharge) and 25% to 38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios of ≤0.84 to 0.91 and FIIE-FII differences of >0.04 U/mL had similar modest sensitivity (47.7%-69.3%) and modest to good specificity (67.1%-91.5%) for VKD. FII/FIIE ratios of <0.86, suggestive of VKD (sensitivity, 47.7%; specificity, 90.2%), were more common in patients deficient in only VKDF (P = .0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (P = .0002). Patients with and without probable VKD (based on FII/FIIE ratios of <0.86) had similar mortality, bleeding, and rates of prothrombin complex concentrate and red cell transfusions (P ≥ .78), but fewer with probable VKD received plasma and fibrinogen replacement (P ≤ .024).
CONCLUSIONS: FII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies.

DIE HäMOPHILIE A WIRD DURCH EINEN MANGEL ODER DEFEKT DES GERINNUNGSFAKTORS VIII VERURSACHT. DER KLINISCHE VERLAUF IST DURCH SPONTAN AUFTRETENDE MUSKEL- UND GELENKBLUTUNGEN GEKENNZEICHNET, DEREN WAHRSCHEINLICHKEIT MIT DER INDIVIDUELLEN FAKTOR VIII-AKTIVITäT (FVIII:C) KORRELIERT. EINE AKTUELLE STUDIE AUS CHINA ZEIGTE JETZT, DASS MITTELS DER CLOT-WAVEFORM-ANALYSE DIE FVIII:C VORAUSGESAGT UND DIE THERAPIE ENTSPRECHEND SKALIERT WERDEN KANN.

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.

BACKGROUND: Historically, von Willebrand factor (VWF) activity assays utilized ristocetin despite limitations including poor limits of detection and high imprecision. Newer VWF activity assays such as the INNOVANCE® VWF Ac assay, however, do not rely on ristocetin to measure platelet-dependent VWF function. The purpose of this study was to evaluate the analytical and clinical performance of the Siemens Healthineers INNOVANCE VWF Ac Assay on the Siemens BCS® XP and the Sysmex® CS-2500 systems in a large reference laboratory setting.
METHODS: Performance indicators for the INNOVANCE VWF Ac assay were the limit of quantitation (LoQ), precision, and method comparison. Method comparison studies were performed using remnant plasma patient samples from routine coagulation tests and analyzed using both the INNOVANCE VWF Ac assay and the Siemens Healthineers ristocetin-dependent BC von Willebrand Reagent.
RESULTS: Evaluation of the INNOVANCE VWF Ac assay on the BCS® XP and CS-2500 systems demonstrated good precision and a lower LoQ compared to the BC von Willebrand Reagent. Method comparisons support the use of the INNOVANCE VWF Ac assay on the BCS® XP and CS-2500 systems to measure platelet-dependent VWF function. The INNOVANCE VWF Ac assay was able to further assist in von Willebrand disease classification in 6/7 (86%) samples when the result was below the LoQ for the BC von Willebrand Reagent (ristocetin cofactor activity).
CONCLUSIONS: These data are consistent with the 2021 American Society of Hematology/International Society on Thrombosis and Haemostasis/National Hemophilia Foundation/World Federation of Hemophilia von Willebrand disease guidelines that suggest using newer assays such as the INNOVANCE VWF Ac assay in place of ristocetin cofactor activity assays.

BACKGROUND: In the literature, there are no studies about the transfusion threshold for neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). In order to facilitate accurate interpretation of coagulation results in these neonates, we aimed to generate specific reference intervals in this specific population.
METHODS: This retrospective study included all HIE neonates admitted from 2014 to 2022 to undergo TH. All infants during TH underwent blood exams, including the coagulation profile. Our primary outcome was to assess the estimates of the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles for each parameter on admission (before transfusion). By the receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) and the best cut-off point were used to evaluate the ability of the prothrombin time expressed as international normalized ratio (PT-INR) to predict the risk of any bleeding.
RESULTS: A total of 143 infants were included in this study. On admission, the median fibrinogen value was 205 mg/dL, prothrombin time 18.6 seconds, PT-INR 1.50, activated partial thromboplastin time 38.3 seconds, thrombin time 18.6 seconds, antithrombin 57.0%. The optimal cut-off of PT-INR in predicting the risk of any bleeding was greater than 1.84 (AUC .623, p = .024).
CONCLUSIONS: For the first time, we proposed the percentiles of coagulation parameters in our cohort of neonates with HIE. Furthermore, we found that a PT-INR greater than 1.84 can significantly predict the risk of any bleeding. Further studies are needed to determine if a restrictive versus a liberal transfusion approach can be equally safer for these high-risk infants.