Lupus Anticoagulant Testing: Activated Partial Thromboplastin Time (APTT) and Silica Clotting Time (SCT)

Author(s):  
Armando Tripodi ◽  
Veena Chantarangkul
Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4122-4122
Author(s):  
Celso A. Roprigues ◽  
Aline A. Martinez ◽  
Vania M. Morelli ◽  
Raniely C. Silveira ◽  
Maria Aparecida E. Noguti ◽  
...  

Abstract INTRODUCTION: To rule out the presence of LA antibodies, two or more assays that are sensitive to these antibodies must be negative. The dilute Russell’s Viper Venom Time (dRVVT) and the activated partial thromboplastin time (aPTT) using sensitive reagents have been employed to detect LA. The aim of this study was to assess the concordance level of aPTT using Platelin LS and dRVVT as screening tests to identify LA in patients with venous thromboembolism (VTE). METHODS: 94 patients (58 women, 62%) with VTE were evaluated. The detection of circulating inhibitor with Platelin LS and dRVVT was based on a prolonged clotting time and a prolonged 1:1 mixture of sample plasma and normal pooled plasma. The confirmation of the phospholipid dependency was performed only with dRVVT. RESULTS: Among the 94 patients, an abnormal test was found in 24 patients (26%) with aPTT and in 61 patients (65%) using dRVVT. After mixing tests, aPTT ratio remained long in 25% of patients with abnormal aPTT, and in 9.8% with long dRVVT. Five patients had a prolonged mixing study identified by both tests, which resulted in a substantial agreement between the two tests (Kappa= 0.78). Confirmatory tests for LA were positive in 5 out of the 6 patients with long dRVVT mixture, resulting in a prevalence of LA detected by dRVVT of 5.3%. The 5 patients with LA detected by dRVVT also had prolonged mixture with aPTT. CONCLUSION: Our results indicate that aPTT with Platelin LS is highly associated with the presence of LA detected by dRVVT and may be suitable as a screening test for LA in patients with VTE.


2008 ◽  
Vol 14 (3) ◽  
pp. 332-337 ◽  
Author(s):  
Gary W. Moore ◽  
Savita Rangarajan ◽  
Geoffrey F. Savidge

Lupus anticoagulants are a heterogeneous group of autoantibodies detected by their effects on phospholipid-dependent coagulation assays. Persistent lupus anticoagulants are associated with thrombotic disease, but not all are clinically significant. Antibody heterogeneity and reagent and test variability dictate that at least 2 tests, of different types, should be used to screen lupus anticoagulants. The objective of this study was to investigate whether the activated seven lupus anticoagulant assay detects clinically significant antibodies. Eighty-two patients with antiphospholipid syndrome (APS) and 32 with systemic lupus erythematosus + positive for activated seven lupus anticoagulant and who were without thrombosis, who were positive by activated seven lupus anticoagulant assay, were investigated for lupus anticoagulants by dilute Russell's viper venom time, dilute activated partial thromboplastin time, and Taipan snake venom time, and for anticardiolipin antibodies. Fifty-seven of the APS patients were positive for lupus anticoagulants in multiple assays, 25 in activated seven lupus anticoagulant alone. Fourteen of the latter group were previously positive in other antiphospholipid antibodies assays, and 11 had only been positive for lupus anticoagulants by activated seven lupus anticoagulant. Twenty-eight had elevated anticardiolipin antibodies, 6 of whom were from the group that was positive in activated seven lupus anticoagulant only. Eight of the systemic lupus erythematosus + lupus anticoagulants (without thrombosis) patients were positive for lupus anticoagulant by activated seven lupus anticoagulant alone and had only been positive in activated seven lupus anticoagulant previously, and none had elevated anticardiolipin antibodies. The remaining 24 patients were lupus-anticoagulant positive in multiple assays, and 9 had elevated anticardiolipin antibodies. Dilute Russell's viper venom time and Dilute activated partial thromboplastin time are widely used to detect lupus anticoagulants and are considered to detect clinically significant antibodies. Activated seven lupus anticoagulant detected antibodies in APS patients who were positive by these assays and also lupus anticoagulants undetectable by the dilute Russell's viper venom time/dilute activated partial thromboplastin time reagents used, demonstrating its utility as a first-line or second-line assay.


1993 ◽  
Vol 2 (1) ◽  
pp. 81-87 ◽  
Author(s):  
T Thomason ◽  
B Riegel ◽  
D Jessen ◽  
Smith SCJr ◽  
I Gocka ◽  
...  

OBJECTIVE: To evaluate the clinical safety of heparin titration and the procedural cost of anticoagulation measurement using bedside low-range activated clotting time. DESIGN: Quasi-experimental study using data gathered through retrospective record review. SETTING: Coronary care, medical intensive care and telemetry units of a community hospital. SUBJECTS: Sample of 102 patients undergoing elective percutaneous transluminal coronary angioplasty. INTERVENTION: Intravenous heparin therapy was titrated using low-range activated clotting time in 51 percutaneous transluminal coronary angioplasty patients. Data from this group were compared to a matched sample of 51 angioplasty patients whose intravenous heparin therapy was titrated using activated partial thromboplastin time. RESULTS: No differences in procedural, early or late complications were found between the groups. The cost of managing heparin therapy with low-range activated clotting time was less than with activated partial thromboplastin time. CONCLUSION: These results suggest that titrating heparin therapy based on bedside low-range activated clotting time for the angioplasty patients in this sample was as safe as with activated partial thromboplastin time. Use of bedside low-range activated clotting time saved money for the hospital.


2019 ◽  
Vol 45 (01) ◽  
pp. 022-035 ◽  
Author(s):  
Geoffrey Kershaw ◽  
Soma Mohammed ◽  
Giuseppe Lippi ◽  
Emmanuel Favaloro

AbstractThe activated partial thromboplastin time (APTT) assay is a very common coagulation test, used for several reasons. The test is conventionally used for assessing the contact factor (intrinsic) pathway of blood coagulation, and thus for screening deficiencies in this pathway, most typically factors VIII, IX, and XI. The APTT is also sensitive to contact factor deficiencies, including factor XII, prekallikrein, and high-molecular-weight kininogen. The APTT may also be elevated in a variety of conditions, including liver disease, vitamin K deficiency, and disseminated intravascular coagulation. The APTT can also be used for monitoring unfractionated heparin (UFH) therapy, as well as for screening lupus anticoagulant (LA) or for assessing thrombosis risk. Which of these separate uses is important to a given laboratory or clinician depends on the laboratory and the clinical context. For example, UFH sensitivity is important in hospital-based laboratories, where UFH therapy is used, but not in hospital-based laboratories where low-molecular-weight heparin (LMWH) is largely employed or where UFH may be assessed by anti-factor Xa testing, or in private/community laboratories not associated with a hospital system. High sensitivity to (low levels of) factors VIII, IX, and XI is generally preferred, as their deficiencies are clinically significant. Also preferred, but not usually achieved, is low sensitivity to factor XII and other contact factors, as these deficiencies are usually asymptomatic. Nevertheless, a good knowledge of factor sensitivity is usually needed, if only to help explain the reasons for a prolonged APTT in a given patient, or whether factor testing or other investigation is required. A good working knowledge of reagents sensitivity to LA is also advisable, especially when the reagent is used as part of a LA test panel, or else as a “general-purpose screening reagent.” The current report is aimed at providing some guidance around these questions, and is intended as a kind of “how to” guide, that will enable laboratories to assess APTT reagents in regard to their sensitivity to heparin, LA, and clotting factors. The report also provides some advice on generation of normal reference ranges, as well as solutions for troubleshooting prolonged APTTs, when performing factor testing or searching for inhibitors.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4149-4149
Author(s):  
Harry L. Messmore ◽  
Nancy J. Fabbrini ◽  
Ketty Badrinath ◽  
Richard Harriman ◽  
Omar Iqbal ◽  
...  

Abstract The direct thrombin inhibitors lepirudin and argatroban are widely used to treat heparin induced thrombocytopenia (HIT). It has been suggested that the Ecarin™ (Echis carinatus venom) clotting time may be superior to the activated partial thromboplastin time (APTT) for monioring purposes. We have prepared standard curves for lepirudin (Refludan™) and Argatroban covering therapeutic drug levels and corresponding APTT ratios (clotting time/control clotting time). Ecarin™ clotting time ratios were performed to demonstrate the practical application of these curves in the clinical care of patients. We report the case of an 80 year old man with HIT/HITT syndrome that occurred during therapy for deep vein thrombosis (DVT) with a low molecular weight heparin (LMWH). His initial coagulation studies were abnormal due to warfarin and LMWH therapy. The patient had a moderate impairment of renal function. Lepirudin therapy in a bolus dose of 14 mg (patient weight: 103.0 kg) resulted in supratherapeutic blood levels of drug and hematuria (Platelet count: 〉200 x 103). Dosage adjustment to maintain an APTT ratio of 1.5 for five days caused no hematuria, but thromboembolic complications occurred at that ratio. The in-vitro dose response curve for Lepirudin was compared with the Ecarin™ clotting time (ECT) ratio at those same concentration ranges in the same plasma. For comparison, Argatroban dose response curves in-vitro were made as well. ECT ratios were very similar to the APTT ratios in the patient’s samples. Representative ratios after the initial bolus, during the infusion period of five days and at the termination of that period are shown in the following table: Comparison of APTT and ECT Ratios APTT Ratio ECT Ratio 1.43 1.07 3.98 3.08 2.91 1.95 2.74 1.95 2.79 1.90 2.58 1.78 2.44 2.42 3.83 4.78 Conclusion: The ECT ratios reflect a steeper dose response curve than that observed with the APTT ratios. This may permit more accurate measurement of blood levels using ECT ratios.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2275-2275
Author(s):  
Jonathan Douxfils ◽  
François Mullier ◽  
Christian Chatelain ◽  
Bernard Chatelain ◽  
Dogné Jean-Michel

Abstract Abstract 2275 Introduction: Apixaban is direct factor-Xa inhibitor that reached the market for the prevention of venous thromboembolism in patients undergoing major orthopaedic surgery. It is also being evaluated in the reduction of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome and in the prevention of stroke in patients with non-valvular atrial fibrillation. Thanks to its predictable pharmacokinetic profile, biological monitoring is not required. Nevertheless, evaluation of plasma drug concentration may be valuable in specific situations such as recurrent thrombosis, bleedings, before urgent surgery, in case of bridging and in case of at least two risk factors among the following ones: drug interactions with caution, moderate renal impairment and moderate hepatic impairment; Monitoring may also be useful in infants, pregnant women or in extreme body weights, although no relevant data on drug levels associated with approximate therapeutic and harmful ranges are currently available. Material and Methods: Apixaban was spiked at increasing concentrations (0, 5, 10, 20, 50, 100, 200 and 500 ng/mL) in pooled citrated normal human platelet poor plasma (PPP) to measure Prothrombin Time (PT) and dilute PT with different thromboplastin, Thrombin Generation Assay (TGA) with different inducers and activity on different anti-Xa chromogenic assays. Activated Partial Thromboplastin Time with different reagents, Thrombin Time (TT), Ecarin Clotting Time (ECT) and Reptilase Time (RT), measurement of fibrinogen (Clauss method and PT-derived method) and antithrombin (anti-IIa and anti-Xa based chromogenic assays) were also tested. We also evaluated the impact of apixaban on assays used for the determination of lupus anticoagulant such as the DRVV-T.. (Screen and Confirm) as well as the PTT-LA.. and the Staclot-LA.. . Results and Discussion: As mentioned in previous studies, PT showed a weak sensitivity towards apixaban in comparison with the plasma range obtained in short pharmacokinetic studies. Indeed, the concentration needed to double the clotting time was 154 ng/mL with the most sensitive reagent while the mean Cmax obtained in a short PK study after one oral intake of 5 mg apixaban (dose given in atrial fibrillation) was 96 ng/mL. Therefore, the sensitivity of PT is not strong enough to allow accurate quantitative measurement of the plasma drug concentration (Table 1). Activated Partial Thromboplastin Time presented a better sensitivity but showed a plateau after 100 ng/mL reflecting the uselessness of this test for the quantification of apixaban. Thrombin Time, ECT and RT were logically not affected while DRVV-T.. showed a sensitivity of 205 ng/mL (Screen), which is once again not enough sensitive. On the opposite, chromogenic anti-Xa assays seemed to be very sensitive (Figure 2 and Table 1). Nevertheless, the relation was not always linear and some methodologies needed to be adapted to ensure a broader range of application. TGA (Figure 1) may be useful to assess the pharmacodynamics effects of apixaban on the coagulation process. Nevertheless, the turn around time and the lack of standardisation are currently limitations that restrict the use of this method. In the case of the exploration of an haemorrhagic event, specific tests such as RT, fibrinogen (Clauss and PT-derived method (dFib)), TT and clotting factor activity may be used. Apixaban did not interfere with these tests. Antithrombin determination if also of importance and chromogenic anti-IIa based assays should be used in face of patients treated with apixaban to avoid misdiagnosis since an overvaluation of 12% by 100 ng/mL was shown using one chromogenic anti-Xa based assay. Conclusion: PT may not be used as screening test to assess the risk of bleedings. A more specific and sensitive assay such as chromogenic anti-Xa assays using calibrators should be used to correctly assess the concentration of apixaban. Determination of lupus anticoagulant using DRVV-T.. and PTT-LA.. or Staclot LA.. as well as the determination of antithrombin using factor-Xa based chromogenic assays, were influenced by apixaban. Finally, standardization of the time between the last intake of apixaban and the sampling is mandatory. Figures: Disclosures: No relevant conflicts of interest to declare.


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