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Journal of Thrombosis and Haemostasis :... Nov 2020This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test...
Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: Update of the guidelines for lupus anticoagulant detection and interpretation.
This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed recommendations on how to handle testing in anticoagulated patients, and the timing of testing. Also, routine coagulation tests are advised to obtain more information on the coagulation background of the patient, and when necessary, anti-Xa activity measurement for heparins or specific assays for direct oral anticoagulants should be performed. The three-step procedure with two test systems (diluted Russell's viper venom time and activated partial thromboplastin time [aPTT]) is essentially not changed. Silica remains the preferable activator in the aPTT assays, but ellagic acid is not excluded. We advise simultaneous performance of the mixing and confirmatory step, in each sample with a prolonged screening test. The confirmatory step can also be performed on a mixture of patient plasma and normal pooled plasma. Cutoff values should be established in-house on at least 120 normals, with transference of the manufacturer's cutoffs as an alternative. Reporting of results has not been changed, although more attention is focused on what clinicians should know. Patient selection for LA testing has been expanded.
Topics: Antiphospholipid Syndrome; Blood Coagulation Tests; Humans; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Prothrombin Time; Reference Standards; Thrombosis
PubMed: 33462974
DOI: 10.1111/jth.15047 -
Seminars in Thrombosis and Hemostasis Sep 2022Lupus anticoagulant (LA) is one of the three criteria antiphospholipid antibodies (aPLs) employed in classification, and by default diagnosis, of antiphospholipid... (Review)
Review
Lupus anticoagulant (LA) is one of the three criteria antiphospholipid antibodies (aPLs) employed in classification, and by default diagnosis, of antiphospholipid syndrome (APS). Detection of LA is not via calibrated assays but is based on functional behavior of the antibodies in a medley of coagulation assays. A prolonged clotting time in a screening test is followed by demonstration of phospholipid dependence and inhibitory properties in confirmatory and mixing tests, respectively, which are modifications of the parent screening test. Complications arise because no single screening test is sensitive to every LA, and no test is specific for LA, because they are prone to interference by other causes of elevated clotting times. Several screening tests are available but the pairing of dilute Russell's viper venom time (dRVVT) with LA-sensitive activated partial thromboplastin time (aPTT) is widely used and recommended because it is proven to have good detection rates. Nonetheless, judicious use of other assays can improve diagnostic performance, such as dilute prothrombin time to find LA unreactive with dRVVT and aPTT, and the recently validated Taipan snake venom time with ecarin time confirmatory test that are unaffected by vitamin K antagonist and direct factor Xa inhibitor anticoagulation. Expert body guidelines and their updates have improved harmonization of laboratory practices, although some issues continue to attract debate, such as the place of mixing tests in the medley hierarchy, and areas of data manipulation such as assay cut-offs and ratio generation. This article reviews current practices and challenges in the laboratory detection of LA.
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Blood Coagulation Tests; Factor Xa Inhibitors; Humans; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Phospholipids; Prothrombin Time; Vitamin K
PubMed: 35649428
DOI: 10.1055/s-0042-1744363 -
International Journal of Laboratory... Feb 2021The prothrombin time (PT) represents the most commonly used coagulation test in clinical laboratories. The PT is mathematically converted to the international normalized... (Review)
Review
The prothrombin time (PT) represents the most commonly used coagulation test in clinical laboratories. The PT is mathematically converted to the international normalized ratio (INR) for use in monitoring anticoagulant therapy with vitamin K antagonists such as warfarin in order to provide test results that are adjusted for thromboplastin and instrument used. The INR is created using two major PT 'correction factors', namely the mean normal PT (MNPT) and the international sensitivity index (ISI). Manufacturers of reagents and coagulometers have made some efforts to harmonizing INRs, for example, by tailoring reagents to specific coagulometers and provide associated ISI values. Thus, two types of ISIs may be generated, with one being a 'general' or 'generic' ISI and others being reagent/coagulometer-specific ISI values. Although these play a crucial role in improving INR results between laboratories, these laboratories reported INR values are known to still differ, even when laboratories use the same thromboplastin reagent and coagulometer. Moreover, ISI values for a specific thromboplastin can vary among different models of coagulometers from a manufacturer using the same method for clot identification. All these factors can be sources of error for INR reporting, which in turn can significantly affect patient management. In this narrative review, we provide some guidance to appropriate ISI verification/validation, which may help decrease the variability in cross laboratory reporting of INRs.
Topics: Humans; International Normalized Ratio; Prothrombin Time; Reference Standards
PubMed: 32979036
DOI: 10.1111/ijlh.13349 -
Journal of Thrombosis and Haemostasis :... Sep 2020The COVID-19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated... (Review)
Review
The COVID-19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID-19. The clinical presentation of COVID-19-associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D-dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial-sepsis-associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID-19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID-19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.
Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; COVID-19; Cytokines; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Inflammation; Lung; Lymphocytes; Partial Thromboplastin Time; Protease Inhibitors; Prothrombin Time; Sepsis; Thrombosis
PubMed: 32558075
DOI: 10.1111/jth.14975 -
Clinical Chemistry and Laboratory... Jan 2022The coagulation system is not fully developed at birth and matures during the first months of infancy, complicating clinical decision making within hemostasis. This...
OBJECTIVES
The coagulation system is not fully developed at birth and matures during the first months of infancy, complicating clinical decision making within hemostasis. This study evaluates coagulation parameters at birth and two months after birth, and tests whether cord blood can be used as a proxy for neonatal venous blood measurements.
METHODS
The Copenhagen Baby Heart Study (CBHS) and the COMPARE study comprise 13,237 cord blood samples and 444 parallel neonatal venous blood samples, with a two month follow-up in 362 children.
RESULTS
Because coagulation parameters differed according to gestational age (GA), all analyses were stratified by GA. For neonatal venous blood, reference intervals for activated partial thromboplastin time (APTT) and prothrombin time (PT) were 28-43 s and 33-61% for GA 37-39 and 24-38 s and 30-65% for GA 40-42. Reference intervals for international normalized ratio (INR) and thrombocyte count were 1.1-1.7 and 194-409 × 10/L for GA 37-39 and 1.2-1.8 and 188-433 × 10/L for GA 40-42. Correlation coefficients between umbilical cord and neonatal venous blood for APTT, PT, INR, and thrombocyte count were 0.68, 0.72, 0.69, and 0.77 respectively, and the distributions of the parameters did not differ between the two types of blood (all p-values>0.05).
CONCLUSIONS
This study describes new GA dependent reference intervals for common coagulation parameters in newborns and suggests that cord blood may serve as a proxy for neonatal venous blood for these traits. Such data will likely improve clinical decision making within hemostasis among newborn and infant children.
Topics: Blood Coagulation; Blood Coagulation Tests; Child; Female; Hemostasis; Humans; Infant; Infant, Newborn; Partial Thromboplastin Time; Prothrombin Time
PubMed: 34752018
DOI: 10.1515/cclm-2021-0967 -
Journal of Thrombosis and Haemostasis :... Apr 2020In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases...
BACKGROUND
In the recent outbreak of novel coronavirus infection in Wuhan, China, significantly abnormal coagulation parameters in severe novel coronavirus pneumonia (NCP) cases were a concern.
OBJECTIVES
To describe the coagulation feature of patients with NCP.
METHODS
Conventional coagulation results and outcomes of 183 consecutive patients with confirmed NCP in Tongji hospital were retrospectively analyzed.
RESULTS
The overall mortality was 11.5%, the non-survivors revealed significantly higher D-dimer and fibrin degradation product (FDP) levels, longer prothrombin time and activated partial thromboplastin time compared to survivors on admission (P < .05); 71.4% of non-survivors and 0.6% survivors met the criteria of disseminated intravascular coagulation during their hospital stay.
CONCLUSIONS
The present study shows that abnormal coagulation results, especially markedly elevated D-dimer and FDP are common in deaths with NCP.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Betacoronavirus; Blood Coagulation; COVID-19; China; Coronavirus Infections; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Pandemics; Partial Thromboplastin Time; Pneumonia, Viral; Prothrombin Time; Retrospective Studies; SARS-CoV-2; Young Adult
PubMed: 32073213
DOI: 10.1111/jth.14768 -
International Journal of Laboratory... Jul 2021The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous... (Review)
Review
The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID-19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID-19 patients. Elevated D-dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID-19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID-19 patients but have currently no place in diagnosis or management in COVID-19 patients. For monitoring the heparin anticoagulant therapy, the anti-Xa assay is suggested, because the severe acute-phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.
Topics: Antibodies, Antiphospholipid; Biomarkers; Blood Coagulation Factors; Blood Coagulation Tests; COVID-19; Disseminated Intravascular Coagulation; Factor Xa; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Heparin, Low-Molecular-Weight; Humans; Partial Thromboplastin Time; Platelet Count; Prothrombin Time; SARS-CoV-2; Thrombelastography; Thrombin; Thrombophilia
PubMed: 34288440
DOI: 10.1111/ijlh.13547 -
Annals of Laboratory Medicine Nov 2023Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT),... (Review)
Review
Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Evidence indicates that not only an abnormal waveform but also peak times and heights in derivative curves of CWA are useful for the evaluation of hemostatic abnormalities. Modified CWA, including the PT with APTT reagent, dilute PT (small amount of tissue factor [TF]-induced clotting factor IX [FIX] activation; sTF/FIXa), and dilute TT, has been proposed to evaluate physiological or pathological hemostasis. We review routine and modified CWA and their clinical applications. In CWA-sTF/FIXa, elevated peak heights indicate hypercoagulability in patients with cancer or thrombosis, whereas prolonged peak times indicate hypocoagulability in several conditions, including clotting factor deficiency and thrombocytopenia. CWA-dilute TT reflects the thrombin burst, whereas clot-fibrinolysis waveform analysis reflects both hemostasis and fibrinolysis. The relevance and usefulness of CWA-APTT and modified CWA should be further investigated in various diseases.
Topics: Humans; Hemostatics; Thrombosis; Thrombin; Prothrombin Time; Hemostasis
PubMed: 37387486
DOI: 10.3343/alm.2023.43.6.531 -
Frontiers in Public Health 2023Cardiac arrest (CA) can activate blood coagulation. This study aimed to explore the potential prognostic value of prothrombin time-international normalized ratio (INR)...
BACKGROUND
Cardiac arrest (CA) can activate blood coagulation. This study aimed to explore the potential prognostic value of prothrombin time-international normalized ratio (INR) in post-CA patients.
METHODS
The clinical data of eligible subjects diagnosed with CA was extracted from the MIMIC-IV database as the training cohort. Restricted cubic spline (RCS), Kaplan-Meier (K-M) survival curve, and Cox regression analyses were conducted to elucidate the association between the INR and all-cause mortality of post-CA patients. Subgroup analysis, propensity score matching (PSM), and inverse probability of treatment (IPTW) were also conducted to improve stability and reliability. Data of the validation cohort were collected from the eICU database, and logistic-regression analyses were performed to verify the findings of the training cohort.
RESULTS
A total of 1,324 subjects were included in the training cohort. A linear correlation existed between INR and the risk of all-cause death of post-CA patients, as shown in RCS analysis, with a hazard ratio (HR) >1 when INR exceeded 1.2. K-M survival curve preliminarily indicated that subjects with INR ≥ 1.2 presented lower survival rate and shorter survival time, and the high level of INR was independently associated with 30-day, 90-day, 1-year, and in-hospital mortalities, with multivariate-adjusted HR of 1.44 (1.20, 1.73), 1.46 (1.23, 1.74), 1.44 (1.23, 1.69), and 1.37 (1.14, 1.64), respectively. These findings were consistent and robust across the subgroup analysis, PSM and IPTW analyses, and validation cohort.
CONCLUSIONS
We systematically and comprehensively demonstrated that elevated INR was associated with increased short- and long-term all-cause mortality of post-CA patients. Therefore, elevated INR may be a promising biomarker with prognosis significance.
Topics: Humans; International Normalized Ratio; Prothrombin Time; Retrospective Studies; Reproducibility of Results; Prognosis
PubMed: 36741950
DOI: 10.3389/fpubh.2023.1112623 -
[Rinsho Ketsueki] the Japanese Journal... 2020Acquired coagulation inhibitors have become a popular area of research because they cause severe bleeding tendency in many patients. The use of acquired coagulation...
Acquired coagulation inhibitors have become a popular area of research because they cause severe bleeding tendency in many patients. The use of acquired coagulation inhibitors requires rapid and precise diagnosis. Some acquired coagulation inhibitors show prolongation in the activated partial thromboplastin time (APTT) and/or prothrombin time (PT). To diagnose these disorders, mixing test is very useful. However, lupus anticoagulant related disorders, such as lupus anticoagulant hypoprothrombinemia syndrome (LAHPS), are difficult to diagnose because they are sometimes associated with a reduction in factor VIII and are thus difficult to distinguish from acquired hemophilia. Acquired factor XIII deficiency and acquired von Willebrand syndrome (AvWS) are easily overlooked because they show normal value in several patients with APTT and PT. Here I describe the diagnostic method for these disorders. In particular, five acquired coagulation inhibitors that appear to be clinically significant are studied.
Topics: Antiphospholipid Syndrome; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Humans; Lupus Coagulation Inhibitor; Partial Thromboplastin Time; Prothrombin Time
PubMed: 32759565
DOI: 10.11406/rinketsu.61.779