Biomedica Diagnostic/Antiphospholipid Syndrome/10/824 IVD

DVVtest® is a dilute Russell’s Viper Venom Time (dRVVT) test intended for the determination of Lupus Anticoagulants (LA) in human plasma. The assay is for in vitro diagnostic use.The identification of Lupus Anticoagulants (LA) in plasma is a diagnostic hallmark of the Antiphospholipid Syndrome (APS), an autoimmune disorder clinically characterized by arterial and venous thrombosis, recurrent spontaneous fetal loss, thrombocytopenia and neurological disorders. Lupus Anticoagulants are immunoglobulins of the IgG, IgM and IgA isotypes that prolong one or more of the in vitro phospholipiddependent coagulation tests: Activated partial thromboplastin time (aPTT), Dilute prothrombin time (dPT), Textarin time or dRVVT. LA autoantibodies are specifically directed against a variety of phospholipid binding proteins including β2-glycoprotein I (β2GPI), prothrombin, and annexin V which are complexed to various anionic phospholipids (e.g. cardiolipin, phosphatidylinositol and phosphatidylserine). The International Society for Thrombosis and Haemostasis, Scientific Subcommittee Criteria on Lupus Anticoagulants and Phospholipid-dependent Antibodies has recommended that LA be diagnosed using coagulation-based screening tests and a confirmatory test containing a high phospholipid concentration. DVVtest is the primary screening diagnostic test for LA with DVVconfirm serving as its companion high phospholipid-containing test to confirm the diagnosis of LA.

The DVVtest reagent contains Factor X activator isolated from Russell’s Viper Venom that directly activates Factor X to Factor Xa in the presence of phospholipids and calcium. Factor Xa activates prothrombin to thrombin, which converts fibrinogen to fibrin leading to detectable clot formation in plasma. This direct activation of Factor X bypasses the contact and intrinsic pathways in the coagulation cascade, thereby excluding interference from deficiencies of Factors VIII, IX, XI and XII, or their respective inhibitors. A positive DVVtest is indicated by a significant prolongation of the phospholipiddependent clotting time. If a patient is suspected to have LA, the DVVtest may also be performed on samples with a normal APTT as the formulation of the reagent increases the test’s sensitivity and specificity to LA.

DVVconfirm® is the high phospholipid containing coagulation reagent to be used in conjunction with DVVtest to confirm the presence of Lupus Anticoagulants (LA) in human plasma. The identification of Lupus Anticoagulants (LA) in plasma is a diagnostic hallmark of the Antiphospholipid Syndrome (APS), an autoimmune disorder clinically characterized by arterial and venous thrombosis, recurrent spontaneous fetal loss, thrombocytopenia and neurological disorders. Lupus Anticoagulants are immunoglobulins of the IgG, IgM and IgA isotypes that prolong one or more of the in vitro phospholipid-dependent coagulation tests: Activated partial thromboplastin time (aPTT), dilute prothrombin time (dPT), Textarin time or dRVVT. LA autoantibodies are specifically directed against a variety of phospholipid binding proteins including β2-glycoprotein I (β2GPI), prothrombin, and annexin V which are complexed to various anionic phospholipids (e.g. cardiolipin, phosphatidylinositol and phosphatidylserine). The International Society for Thrombosis and Haemostasis, Scientific Subcommittee Criteria on Lupus Anticoagulants and Phospholipid-dependent Antibodies has recommended that LA be diagnosed using coagulation-based screening tests and a confirmatory test containing a high phospholipid concentration. DVVtest is the primary screening diagnostic test for LA with DVVconfirm serving as its companion high phospholipid-containing test to confirm the diagnosis of LA. Like DVVtest, DVVconfirm reagent is formulated with Factor X activator isolated from Russell’s Viper Venom that directly activates Factor X to Factor Xa in the presence of phospholipids and calcium, and a high concentration of phospholipids. The clotting time of a plasma containing LA should be significantly shorter with DVVconfirm as compared to DVVtest. The presence of LA in plasma samples is confirmed when the ratio of the DVVtest clotting time to the DVVconfirm clotting time is greater than the range of the laboratory’s normal reference DVVtest/ DVVconfirm Ratio.

The LAtrol™ Abnormal Control (REF 816A) and LAtrol™ Normal Control (REF 816N) plasmas have been developed for use as part of daily quality control procedures for Lupus Anticoagulant (LA) testing. These control plasmas are designed to be used with ACTICLOT® dPT™ (REF 824), DVVtest® (REF 810/825), and DVVconfirm® (REF 815/815L). LAtrol Abnormal Control is a lyophilized preparation of a Lupus Anticoagulant plasma which has been determined to be positive for LA in accordance with the revised criteria of the International Society for Thrombosis and Haemostasis, Scientific and Standardization Committee’s (SSC) on Lupus Anticoagulant detection. LAtrol Normal Control is a lyophilized preparation of a multi-donor normal plasma pool. This normal plasma may also be used in mixing studies to determine the presence of inhibitors or factor deficiencies in patient plasmas that test positive using DVVtest and ACTICLOT dPT. Source plasmas for these products are processed in a manner consistent with established procedures to ensure that the plasma is platelet-poor.

Clinical studies show that a dilute prothrombin time test is an effective LA coagulation assay and can identify LA that are not detected by other tests such as a lupus-sensitive APTT and a dilute Russell’s Viper Venom test.

ACTICLOT dPT is a fully integrated dilute prothrombin time test for screening and confirming the presence of phospholipid-dependent LA autoantibodies. The screening protocol utilizes an activator reagent that contains a unique formulation of relipidated recombinant human tissue factor and calcium. The use of recombinant tissue factor in the formulation of the dPT test improves the test’s performance. In the confirmatory protocol, a uniquely formulated phospholipid reagent is used to demonstrate the phospholipid-dependent nature of the LA detected in samples that tested positive in the screening protocol.

Clotting is initiated by activating the extrinsic coagulation pathway with tissue factor in the presence of calcium ions. Tissue Factor binds to Factor VIIa resulting in the activation of Factor IX and Factor X. The subsequent conversion of prothrombin to thrombin by Factor Xa initiates clot formation by cleaving fibrinogen to fibrin. Activation of the tissue factor pathway bypasses the intrinsic (contact) pathway and excludes any interference from deficiencies of Factor XII.