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HelpTest ID DRVI2 Dilute Russell's Viper Venom Time (DRVVT) Mix Ratio, Plasma
Specimen Required
Only orderable as part of a reflex. For more information see DRVI1 / Dilute Russell's Viper Venom Time (DRVVT), with Reflex, Plasma.
Specimen Type: Platelet-poor plasma
Collection Container/Tube: Light-blue top (3.2% sodium citrate)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
Collection Instructions:
1. For complete instructions, see Coagulation Guidelines for Specimen Handling and Processing.
2. Centrifuge, remove plasma, and centrifuge plasma again.
3. Aliquot into a separate plastic vial, leaving 0.25 mL in the bottom of the centrifuged vial.
4. Freeze plasma immediately (no longer than 4 hours after collection) at -20° C or, ideally, -40° C or below.
Useful For
Detecting the presence or helping to exclude the presence of lupus anticoagulants (LA)
Identifying LA that do not prolong the activated partial thromboplastin time (APTT)
Evaluating unexplained prolongation of the APTT or prothrombin time clotting tests
Distinguishing LA from a specific coagulation factor inhibitor or coagulation factor deficiencies
Method Name
Only orderable as part of a reflex. For more information see DRVI1 / Dilute Russell's Viper Venom Time (DRVVT), with Reflex, Plasma.
Optical Clot-Based
Reporting Name
DRVVT Mix RatioSpecimen Type
Plasma Na CitSpecimen Minimum Volume
0.5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Plasma Na Cit | Frozen | 14 days |
Clinical Information
Lupus anticoagulants (LA) are immunoglobulins (IgG, IgM, IgA, or a combination of these) of autoimmune type that are specifically directed against antigenic complexes of negatively charged phospholipids (such as phosphatidylserine or phosphatidylethanolamine) and coagulation-related proteins (such as beta-2-glycoprotein I) or clotting factors (including prothrombin [factor II] or factor X), and which cause prolongation of phospholipid-dependent clotting time tests due to inhibition.
LA are functionally and clinically distinct members of a broader group of antiphospholipid autoantibodies that includes immunologically detectable anticardiolipin antibodies or antibodies against other phospholipid-protein complexes. LA interfere with specific coagulation factor-phospholipid interactions, typically causing prolongation of 1 or more phospholipid-dependent clotting time tests (eg, activated partial thromboplastin time [APTT], dilute Russell's viper venom time [DRVVT]) due to inhibition. This characteristic in vitro inhibition can be overcome by addition of excess phospholipid.
Because of the heterogeneous nature of LA antibodies, no single coagulation test can identify or exclude all LA. Currently, the International Society on Thrombosis and Haemostasis and the Clinical and Laboratory Standards Institute recommend testing for LA with at least 2 phospholipid-dependent clotting time assays based on different coagulation pathways and principles (eg, lupus-sensitive APTT and DRVVT).
In addition, given the potential for false-positive results in patients on anticoagulants, a profile or panel of coagulation tests is performed, including prothrombin time (PT), APTT, thrombin time (TT), and DRVVT. If the PT, APTT, and/or DRVVT are prolonged, additional testing may include mixing tests with normal plasma (to evaluate for inhibition) and the use of excess phospholipid in appropriate assay systems to evaluate for phospholipid-dependent inhibition. Additional reflexive testing helps determine presence or absence of anticoagulants and/or inhibitors to other factors.
The diagnosis of LA requires performance and interpretation of complex coagulation testing, as well as correlation with available clinical information, including evidence of persistence of LA over time (≥12 weeks).
The venom obtained from Russell's viper (Vipera russelli) contains enzymes that directly activate coagulation factors V and X, bypassing the activation of factors VII, VIII, IX, XI, and XII, and therefore, the effect of deficiencies or inhibitors of these factors. Diluting the phospholipid necessary for the clotting factor interactions increases the sensitivity to LA and the likelihood of identifying a phospholipid-dependent inhibitor that may not be detected by other coagulation tests with higher phospholipid content (eg, LA-insensitive APTT reagents).
The DRVVT screen ratio test is one of several available in vitro tests that may be used to screen and confirm for presence of LA or to help exclude LA. DRVVT testing is used in conjunction with other appropriate coagulation tests (reflexive testing panels) to assist in detection and confirmation of LA or help exclude their presence.
The DRVVT may be abnormally prolonged (DRVVT screen ratio ≥1.20) by LA as well as coagulation factor deficiencies, anticoagulant effects, or other types of coagulation factor inhibitors.
Specimens with abnormal results (DRVVT screen ratio ≥1.20) are subjected to reflexive testing. With the reflexive testing, the sensitivity of DRVVT testing for LA diagnosis is approximately 65% to 70%, and the specificity is 95% or higher.
It is advisable to use the DRVVT screen, mix and confirm ratio results in conjunction with other appropriate coagulation tests (reflexive testing panels) to diagnose or exclude LA.
Although LA cause prolonged clotting times in vitro, there is a strong association with thrombosis risk. However, not all patients with persisting LA develop thrombosis.
Reference Values
Only orderable as part of a reflex. For more information see DRVI1 / Dilute Russell's Viper Venom Time (DRVVT), with Reflex, Plasma.
<1.20
Normal ranges for children: not clearly established, but similar to normal ranges for adults, except for newborn infants whose results may not reach adult values until 3 to 6 months of age.
Interpretation
Dilute Russell's viper venom time screen ratio (<1.20):
A normal dilute Russell's viper venom time (DRVVT) screen ratio (<1.20) indicates that lupus anticoagulant (LA) is not present or not detectable by this method (but might be detected with other methods).
An abnormal DRVVT screen ratio (DRVVT screen ratio ≥1.20) may suggest presence of LA, however, other possibilities include:
-Deficiencies or dysfunction of factors I (fibrinogen), II, V, or X, congenital or acquired
-Inhibitors of factor V, or occasionally by inhibitors of factor VIII, or other specific or nonspecific inhibitors
-Anticoagulation therapy effects (see Cautions)
Further evaluation consists of performing mixing studies with an equal volume of normal pooled plasma (DRVVT 1:1 mix) to investigate the possibility of coagulation factor deficiency (suggested by DRVVT mix ratio <1.20) and to evaluate inhibition (suggested by DRVVT mix ratio ≥1.20) and mixing patient plasma with DRVVT reagent enriched in phospholipid (DRVVT confirmatory reagent) (DRVVT mix and DRVVT confirmation ratios).
Possible combinations of results include the following:
-DRVVT screen ratio ≥1.20, DRVVT mix ratio <1.20, and DRVVT confirmation ratio <1.20:
No evidence of LA. These data may reflect anticoagulation therapy effects or other (congenital or acquired) coagulopathy.
-DRVVT screen ratio ≥1.20, DRVVT mix ratio ≥1.20, and DRVVT confirmation ratio <1.20:
The prolonged and inhibited DRVVT (DRVVT screen and mix ratios) may reflect presence of a specific factor inhibitor (eg, factor V inhibitor), anticoagulation therapy effects or other nonspecific inhibitors as can be seen with monoclonal protein disorders, lymphoproliferative disease etc. Although LA cannot be conclusively excluded, the DRVVT confirmation ratio of ≤1.20 makes this less likely.
-DRVVT screen ratio ≥1.20, DRVVT mix ratio <1.20, and DRVVT confirmation ratio ≥1.20:
Although mixing study of the prolonged DRVVT screen and mix ratios provides no evidence of inhibition, additional phospholipid shortens the clotting time (DRVVT confirmation ratio), suggesting presence of LA.
-DRVVT screen ratio ≥1.20, DRVVT mix ratio ≥1.20, and DRVVT confirmation ratio ≥1.20:
The data are consistent with presence of LA, provided anticoagulant effect can be excluded (see Cautions)
Because no single coagulation test can identify or exclude all LAs, and because of the complexity of testing LA, one of the following Coagulation Consultation reflexive panel procedures are recommended if clinically indicated:
ALUPP / Lupus Anticoagulant Profile, Plasma
AATHR / Thrombophilia Profile, Plasma and Whole Blood
APROL / Prolonged Clot Time Profile, Plasma
DRVVT assays ordered as a single, stand-alone test should be interpreted within patient clinical context and close attention to medication use by patient (see Cautions).
Cautions
Residual platelets in frozen-thawed plasma can decrease sensitivity and specificity of lupus anticoagulants (LA) testing (false-negative results). Specimens that are to be frozen before testing must be centrifuged twice to remove as many of the platelets as possible before freezing.
Anticoagulation therapy effects such as warfarin (especially when the effect is supratherapeutic), excess heparin, direct thrombin inhibitors (eg, dabigatran [Pradaxa]), argatroban [Ancova], bivalirudin [Angiomax]), direct factor Xa inhibitors (eg, rivaroxaban [Xarelto], apixaban [Eliquis], edoxaban [Savaysa]) may result in a false-positive assay performance for LA. Clinical correlation and repeat testing remote (>1 week) from anticoagulation therapy is suggested.
Although the dilute Russell's viper venom time (DRVVT) reagents contain a heparin inhibitor (Polybrene) that is sufficient for neutralization of heparin (up to 1-2 U/mL), the results may not necessarily represent what would occur if no heparin were present in the specimen. Therefore, DRVVT results from heparinized plasma should be interpreted with caution.
DRVVT assays, when performed in isolation, will not distinguish LA from heparin or inhibitors of factors V or VIII, which may cause false-positive results of LA testing.
Excess heparin or inhibitors of factors V or VIII may cause false-positive results of LA testing, depending on the types of coagulation testing performed.
LA diagnosis does not have definite predictive value for associated clinical complications such as thromboembolic problems or fetal loss.
Serum anticardiolipin antibody testing (CLPMG / Phospholipid [Cardiolipin] Antibodies, IgG and IgM, Serum) and anti-beta-2 glycoprotein I (B2GMG / Beta-2 Glycoprotein 1 Antibodies, IgG and IgM, Serum) antibody testing should also be performed in conjunction with coagulation-based testing for LA to enhance detection of different types of antiphospholipid antibodies.
The DRVVT test will not detect all LA. Some LA may only be detectable by other tests such as the Staclot LA, activated partial thromboplastin time, and platelet neutralization procedure, or other methods.
Persistence of LA over time (12 weeks or more between positive testing results) is a clinically important criterion for the antiphospholipid antibody syndrome diagnosis.
Clinical Reference
1. Proven A, Bartlett RP, Moder KG, et al. Clinical importance of positive test results for lupus anticoagulant and anticardiolipin antibodies. Mayo Clin Proc. 2004;79(4):467-475
2. Gastineau DA, Kazmier FJ, Nichols WL, Bowie EJ. Lupus anticoagulant: an analysis of the clinical and laboratory features of 219 cases. Am J Hematol. 1985;19(3):265-275
3. Brandt JT, Triplett DA, Alving B, Sharrer I: Criteria for the diagnosis of lupus anticoagulant: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost. 1995;74(4);1185-1190
4. Arnout J, Vermylen J. Current status and implications of autoimmune antiphospholipid antibodies in relation to thrombotic disease. J Thromb Haemost. 2003;1(5):931-942
5. Pengo V, Tripodi A, Reber G, Rand JH, et al. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009;7:1737-1740. doi:10.1111/j.1538-7836.2009.03555.x
6. CLSI document H60-A
Method Description
The dilute Russell's viper venom time (DRVVT) mix assay is performed on the Instrumentation Laboratory ACL TOP. Patient plasma is mixed in a 1:1 ratio with normal pooled plasma and incubated for a specified time, then combined with a DRVVT screening reagent containing Russell's viper venom, phospholipids, heparin neutralizing agents, calcium, buffers, stabilizers, and sodium azide to trigger the coagulation process. Subsequently, the time to clot formation is measured optically using a wavelength of 671 nm.
The patient DRVVT mix clotting time is normalized by dividing the patient result by the mean DRVVT screening clotting time of normal pooled plasma to yield a ratio.(Package insert: CRYOcheck LA Check. Precision BioLogic, Inc; 01/2023)
Report Available
2 daysTest Classification
This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.CPT Code Information
85613