Relationship between short activated partial thromboplastin times, thrombin generation, procoagulant factors and procoagulant phospholipid activity

Franchini

2014

Semin Thromb Hemost

110

The incidence of venous thromboembolism (VTE) is well recognized to increase with aging. Concurrently, the plasma concentrations of many coagulation factors (e.g., fibrinogen, factor [F] V, FVII, FVIII, and FIX) increase with aging, as does von Willebrand factor (VWF), thrombin generation, and platelet activation. Data are conflicting regarding age-related changes in the natural anticoagulants, including protein C, protein S, and antithrombin. Changes are also observed with components of the fibrinolytic pathway. All in all, aging is associated with a variety of hemostasis changes that on balance reflects a heightened procoagulant status compared with earlier age. It has to be recognized that as this occurs in the otherwise normal general population, this can also be considered a normal phenomenon of progressive life. An element of this heightened procoagulant status may reflect ongoing inflammatory processes, given some markers, notably FVIII and fibrinogen, are acute phase reactants. A variety of acquired prothrombotic risk factors (e.g., cancer, autoimmune disorders, and diabetes) also gradually develop with aging, some of which may induce profound abnormalities of hemostasis, and confound the age-related changes in hemostasis, as well as their influence on thrombotic risk. In this article, we review the changes in hemostasis markers measurable within many hemostasis laboratories, and consider many of the important implications for clinical and laboratory practice. Apart from representing an increased thrombotic risk, additional considerations entail the potential need (1) to utilize age-adjusted normal ranges (e.g., for D-dimer), (2) to consider the consequence on previous diagnoses (e.g., "mild type 1" von Willebrand disease [VWD], where VWF test results may "normalize" with aging), and (3) to consider the effect of these changes of risk factors on the (perceived) therapeutic efficacy of antithrombotic medications such as aspirin.

Section: Fibrinolytic System Proteins and Agingmentioning

confidence: 99%

Aging Hemostasis: Changes to Laboratory Markers of Hemostasis As We Age—A Narrative Review

Franchini

2014

Semin Thromb Hemost

110

“…64 Short aPTTs are also associated to presence of elevated levels of FV, FIX, FXI, and FXII, as well as increased thrombin generation. 62,65 In general, pathological aPTT prolongations can be observed in the presence of a variety of clinical conditions, which include deficiencies of clotting factors of the intrinsic (i.e., FXII, FXI, FIX, and FVIII) and common (i.e., FII, FV, and FX) pathways, von Willebrand disease (VWD), DIC, 66 therapy with heparin (especially UFH) or dabigatran, lupus anticoagulant (LAC), 67 as well as in patients with supratherapeutic dose of low-molecular-weight heparin, VKAs, and DOACs inhibiting FXa (i.e., rivaroxaban, apixaban, and edoxaban). 53…”

Section: Leading Causes Of Pathological Shortening and Prolongationmentioning

confidence: 99%

“…41 Shortened aPTTs are often associated with elevated levels of procoagulant phospholipids, potentially released from damaged cells due to preanalytical and collection issues. 62,65 Spurious causes of prolongation of the aPTT include contamination with exogenous heparin or EDTA salts, drawing primary blood tubes at less than 89% of their nominal volume, 36 the presence of hyperbilirubinemia and hypertriglyceridemia in the specimen when the aPTT is measured using conventional instrumentation without dedicated wavelengths, 39 delayed separation (i.e., from 6 to 24 hours) of specimens stored at both room temperature and 4°C. 69 As for the PT, analytical errors are obvious causes of both spurious decrease or increase in aPTT.…”

Section: Leading Cause Of Spurious Shortening and Prolongationmentioning

confidence: 99%

Dangers in the Practice of Defensive Medicine in Hemostasis Testing for Investigation of Bleeding or Thrombosis: Part I—Routine Coagulation Testing

Franchini

2014

Semin Thromb Hemost

Defensive medicine is a term conventionally used for defining the medical (mal)practice of ordering medically questionable diagnostic testing, procedures, or visits, or to avoid high-risk patients or procedures. The practice of defensive medicine may primarily be aimed to reduce exposure to malpractice liability, to avoid patient criticism regarding "medical inaction," or to avoid "missing" some otherwise potential identifiable defect(s). Although the precise impact of defensive medicine in the field of laboratory testing is difficult to estimate from the current literature, the overuse or inappropriate use of laboratory resources ranges from 23 to 67%, and a large part of this can be attributed to medical liability concerns, with apparently little clinical awareness of the adverse consequences that may be associated with this practice. Essentially, performing inappropriate testing remarkably increases the risk of obtaining false-positive results due to statistical, preanalytical, and analytical reasons, thus triggering further and potentially even more invasive follow-up testing, inappropriate patient management, along with incremental increases of expenditure due to misuse of health care resources. As routine coagulation testing is commonly performed for the screening of patients with bleeding or thrombotic disorders, either a false-negative or a false-positive result may significantly impact on clinical outcomes and health care resources. The aim of this article is to describe the leading causes of physiological, pathological, therapeutic, and spurious variations of the prothrombin time, activated partial thromboplastin time, and D-dimer, as well as the potential clinical consequences emerging from the generation of false-negative and false-positive results with these tests.

“…First line analyses, which are also conventionally called " screening " tests, include the activated partial thromboplastin time (APTT) [12 -14] , prothrombin time (PT)/International Normalized Ratio (INR) [15 -17] , fibrinogen [18,19] , D-dimer [20,21] , and platelet count [22] . Thrombin generation assays [23,24] along with thromboelastography [25,26] are additional useful " global " tests of hemostasis, which have not found, however, widespread application in clinical and laboratory practice. Second line assays are typically those designed to provide further insights into abnormalities of screening tests, or used to monitor more accurately some antithrombotic therapies, and thereby include clotting factors assays [27] , ristocetin-induced platelet agglutination and VWF antigen tests [28] , anticardiolipin (aCL) IgG and IgM, anti-β (2) glycoprotein I (anti-β (2) GPI) antibodies IgG and IgM and phospholipid-dependent coagulation assays [29,30] , platelet function tests such as Platelet Function Analyzer-100 (PFA-100) and aggregometry [31,32] , assays for heparin-induced thrombocytopenia [33,34] , additional tests for thrombophilia screening including resistance to activated protein C, antithrombin, proteins C and S, and genetic polymorphisms/mutations (e.g., prothrombin G20210A and factor V Leiden) [35,36] along with ecarin clotting time, chromogenic anti-factor Xa and dilute Russell viper venom time (dRVVT) for monitoring novel anticoagulants [37,38] .…”

Section: Laboratory Hemostasismentioning

confidence: 99%

Laboratory hemostasis: milestones in Clinical Chemistry and Laboratory Medicine

Clinical Chemistry and Laboratory Medicine (CCLM)

2012

Self Cite

Hemostasis is a delicate, dynamic and intricate system, in which pro-and anti-coagulant forces cooperate for either maintaining blood fluidity under normal conditions, or else will prompt blood clot generation to limit the bleeding when the integrity of blood vessels is jeopardized. Excessive prevalence of anticoagulant forces leads to hemorrhage, whereas excessive activation of procoagulant forces triggers excessive coagulation and thrombosis. The hemostasis laboratory performs a variety of first, second and third line tests, and plays a pivotal role in diagnostic and monitoring of most hemostasis disturbances. Since the leading targets of Clinical Chemistry and Laboratory Medicine include promotion of progress in fundamental and applied research, along with publication of guidelines and recommendations in laboratory diagnostics, this journal is an ideal source of information on current developments in the laboratory technology of hemostasis, and this article is aimed to celebrate some of the most important and popular articles ever published by the journal in the filed of laboratory hemostasis.