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Test Code DRVTI Dilute Russell Viper Venom Time (DRVVT), with Reflex, Plasma

Useful For

Detecting and confirming 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

Additional Tests

Test ID Reporting Name Available Separately Always Performed
DRVTK DRVVT Interpretation No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
DRVTJ DRVVT Mix and Confirm Reflexes, P No No
MDRVT DRVVT Mix Ratio No No
CDRVT DRVVT Confirmation Ratio No No

Testing Algorithm

If dilute Russell viper venom time (DRVVT) ratio is ≥1.2, then DRVVT mix and confirmation will be performed at an additional charge. 

If DRVVT ratio is <1.2, the DRVVT mix and confirmation will not be performed. 

A DRVVT interpretation will always be performed.

Method Name

Clot-Based Assay

Reporting Name

DRVVT Screen Ratio, w/Reflex, P

Specimen Type

Plasma Na Cit


Specimen Required


See Coagulation Studies in Special Instructions. 

 

Specimen Type: Platelet-poor plasma

Collection Container/Tube: Light-blue top (citrate)

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions:

1. Spin down, remove plasma, and spin plasma again.

2. Freeze specimen immediately at ≤-40° C, if possible.

Additional Information:

1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.

2. Each coagulation assay requested should have its own vial.


Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time
Plasma Na Cit Frozen 14 days

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross reject

Icterus

Mild OK; Gross reject

Other

NA

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 (beta-2-GPI) or clotting factors including prothrombin (factor II) or factor X, and 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 (APA) 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 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 (CLSI) 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 testing is recommended, including the prothrombin time (PT), APTT, thrombin time (TT), and the DRVVT. If the PT, APTT, 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 the presence or absence of anticoagulants 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 the Russell 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 that have a 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 the presence of LA or to help exclude LA.

 

The DRVVT may be abnormally prolonged (DRVVT screen ratio ≥1.2) by LA as well as coagulation factor deficiencies, anticoagulant effects, or other types of coagulation factor inhibitors.

 

Specimens with abnormal results (DRVVT screen ratio ≥1.2) are subjected to reflexive testing (DRVVT mix and confirmation ratios) as described in the Testing Algorithm (also see Interpretation).

 

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

Dilute Russell viper venom time screen ratio <1.2

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 viper venom time (DRVVT) screen ratio (<1.2):

A normal DRVVT screen ratio (<1.2) indicates that lupus anticoagulants (LA) is not present, or not detectable, by this method (but might be detected with other methods).

 

Abnormal DRVVT screen ratio (DRVVT screen ratio ≥1.2) may suggest the 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 <1.2) and to evaluate inhibition (suggested by DRVVT mix ratio ≥1.2) and mixing patient plasma with DRVVT reagent enriched in phospholipid (DRVVT confirmatory reagent) (DRVVT mix and DRVVT confirm ratios).

 

Possible combinations of results include the following:

-DRVVT screen ratio ≥1.2 and DRVVT mix ratio <1.2 DRVVT confirm ratio <1.2:

No evidence of LA. This data may reflect anticoagulation therapy effects or other (congenital or acquired) coagulopathy.

 

-DRVVT screen ratio ≥1.2 and DRVVT mix ratio ≥1.2 DRVVT confirm ratio <1.2:

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 confirm ratio of <1.2 makes this less likely.

 

-DRVVT screen ratio ≥1.2 and DRVVT mix ratio <1.2 DRVVT confirm ratio ≥1.2:

Although mixing study of the prolonged DRVVT (DRVVT screen and mix ratios) provides no evidence of inhibition, additional phospholipid shortens the clotting time (DRVVT confirm ratio), suggesting presence of LA.

 

-DRVVT screen ratio ≥1.2 and DRVVT mix ratio ≥1.2 DRVVT confirm ratio ≥1.2:

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, a combination or panel of coagulation tests is recommended:

LUPPR / Lupus Anticoagulant Profile

THRMP / Thrombophilia Profile

PROCT / Prolonged Clot Time Profile

 

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).

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 April;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 Jul;19(3):265-275

3. Brandt JT, Triplett DA, Alving B, Sharrer I: Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost 1995 Oct;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 May;1(5):931-942

5. Pengo V, Tripodi A, Reber G, 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

6. CLSI Laboratory Testing for Lupus Anticoagulant; Approved Guideline. CLSI document H60-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2014

Day(s) and Time(s) Performed

Monday through Friday

Analytic Time

1 day

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

This test has been cleared or approved by the U.S. 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-DRVVT

85613-DRVVT mix (if appropriate)

85613-DRVVT confirmation (if appropriate)

 

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DRVTI DRVVT Screen Ratio, w/Reflex, P In Process

 

Result ID Test Result Name Result LOINC Value
SRAT DRVVT Screen Ratio In Process