-
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 -
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 -
Methods in Molecular Biology (Clifton,... 2017Diluted Russell Viper Venom Time (dRVVT) has become the most popular test to detect Lupus Anticoagulant (LA). dRVVT is more sensitive than other global tests employed to...
Diluted Russell Viper Venom Time (dRVVT) has become the most popular test to detect Lupus Anticoagulant (LA). dRVVT is more sensitive than other global tests employed to detect LA and is not affected by inhibitors of factor VIII or IX. The test is most successfully implemented if you observe three steps in its execution: screening, mixing, and confirmatory studies. Interference due to the presence of heparin in tested plasma must be excluded by means of thrombin time (TT). The prior use of Vitamin K Antagonists (VKAs) or Non-vitamin K Oral Anticoagulants (NOACs) must also be evaluated by means of International Normalized Ratio, or specific tests, respectively.
Topics: Administration, Oral; Anticoagulants; Humans; International Normalized Ratio; Lupus Coagulation Inhibitor; Prothrombin Time; Quality Control; Reference Values; Thrombin Time; Vitamin K
PubMed: 28804828
DOI: 10.1007/978-1-4939-7196-1_14 -
Transfusion Feb 2019Dried plasma is logistically superior for hemostasis management because it can be transported and stored under nonfrozen conditions and quickly reconstituted at the... (Comparative Study)
Comparative Study
BACKGROUND
Dried plasma is logistically superior for hemostasis management because it can be transported and stored under nonfrozen conditions and quickly reconstituted at the point of care, enabling prehospital administration. Velico Medical has developed a spray-drying system to be integrated into routine blood center work streams for spray drying single donor plasma units. This study compared the quality of the spray-dried plasma (on-demand plasma [ODP]) with fresh frozen plasma (FFP).
STUDY DESIGN AND METHODS
ODP units (n = 60) were manufactured from never frozen fresh plasma, which was pretreated with glycine-hydrochloric acid and stored at 1to 6°C. Paired aliquots were frozen and stored at -18°C or less. After 31 to 33 days, ODP samples were reconstituted with water for injection and comprehensively characterized in parallel with paired FFP. The quantities of plasma dried and rehydration fluid were predetermined, ensuring comparable total protein concentration in ODP and paired FFP.
RESULTS
ODP is comparable to FFP in global coagulation function as assessed by activated partial thromboplastin time and prothrombin time and in clot formation evaluated by thrombelastography. Compared to FFP, ODP had greater than 80% levels of functional coagulation factors and related proteins and chemistry analytes except for Factor XIII (74%). Pretreatment mitigated cleavage of high-molecular-weight von Willebrand factor multimers by spray drying and resulted in 60% vWF:ristocetin cofactor activity in ODP compared to FFP.
CONCLUSIONS
ODP demonstrates coagulation function comparable to that of FFP. The spray drying system can be implemented in blood centers and is capable of producing units of ODP.
Topics: Blood Donors; Desiccation; Factor VIII; Female; Humans; Male; Partial Thromboplastin Time; Plasma; Prothrombin Time; von Willebrand Factor
PubMed: 30443975
DOI: 10.1111/trf.15035 -
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 -
Marine Drugs Nov 2023Alginate-based materials have gained significant attention in the medical industry due to their biochemical properties. In this article, we aimed to synthesize...
Alginate-based materials have gained significant attention in the medical industry due to their biochemical properties. In this article, we aimed to synthesize Cotton-Alginate-Copper Composite Materials (COT-AlgCu). The main purpose of this study was to assess the biochemical properties of new composites in the area of blood plasma coagulation processes, including activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT). This study also involved in vitro antimicrobial activity evaluation of materials against representative colonies of Gram-positive and Gram-negative bacteria and antifungal susceptibility tests. The materials were prepared by immersing cotton fibers in an aqueous solution of sodium alginate, followed by ionic cross-linking of alginate chains within the fibers with Cu(II) ions to yield antimicrobial activity. The results showed that the obtained cotton-alginate-copper composites were promising materials to be used in biomedical applications, e.g., wound dressing.
Topics: Copper; Alginates; Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Blood Coagulation; Prothrombin Time; Partial Thromboplastin Time; Ions
PubMed: 38132946
DOI: 10.3390/md21120625 -
Activated Partial Thromboplastin Time and Prothrombin Time Mixing Studies: Current State of the Art.Seminars in Thrombosis and Hemostasis Sep 2023Mixing studies have long been in the clinical laboratory armamentarium for investigating unexpected, prolonged activated partial thromboplastin time (aPTT) or... (Review)
Review
Mixing studies have long been in the clinical laboratory armamentarium for investigating unexpected, prolonged activated partial thromboplastin time (aPTT) or prothrombin time (PT). The purpose of the mixing study is to identify whether the aPTT/PT prolongation is secondary to a factor deficiency versus an inhibitor, which would present as a "corrected" and "noncorrected" mixing study, respectively. The differentiation between a factor deficiency and inhibitor may likely further direct clinical decisions, including additional diagnostic testing or factor replacement therapy. While aPTT/PT mixing studies are simple tests to perform, there is a lack of standardization for both the testing protocol and the interpretation of what is considered to be a corrected or noncorrected mixing study result. This review will describe the common indications for the mixing test, preanalytic variables that may affect mixing study performance, and describe several methods for interpreting the results of aPTT and PT mixing tests.
Topics: Humans; Prothrombin Time; Partial Thromboplastin Time; Blood Coagulation Tests; Blood Coagulation Disorders; Reference Standards
PubMed: 36055261
DOI: 10.1055/s-0042-1756196