Dilute Russell's viper venom time

Russell's viper, Daboia russelii

Dilute Russell's viper venom time (dRVVT) is a laboratory test often used for detection of lupus anticoagulant (LA).^[1][2]

Mechanism

This in vitro diagnostic test is based on the ability of the venom of the Russell's viper to induce thrombosis. The coagulant in the venom directly activates factor X, which turns prothrombin into thrombin in the presence of factor V and phospholipid. In the dRVVT assay, low, rate-limiting concentrations of both Russell's viper venom and phospholipid are used to give a standard clotting time of 23 to 27 seconds. This makes the test sensitive to the presence of lupus anticoagulants, because these antibodies interfere with the clot-promoting role of phospholipid in vitro, and their presence results in a prolonged clotting time. A mixing study is then performed, which consists of adding an equal volume of the patient's plasma to normal plasma; in this study, one would expect the clotting time to return to the normal range if there was only a deficiency of coagulation factors alone. A prolonged clotting time of 30 seconds or greater that does not correct despite the mixing study suggests the presence of a lupus anticoagulant.^[3] An abnormal result for the initial dRVVT assay should be followed by a dRVVT confirmatory test.^[4] In this test, the inhibitory effect of lupus anticoagulants on phospholipids in the dRVVT can be overcome by adding an excess of phospholipid to the assay. The clotting times of both the initial dRVVT assay and confirmatory test are normalized and then used to determine a ratio of time without phospholipid excess to time with phospholipid excess. In general, a ratio of greater than 1.2 is considered a positive result and implies that the patient may have antiphospholipid antibodies. The dRVVT test has a higher specificity than the aPTT test for the detection of lupus anticoagulant, because it is not influenced by deficiencies or inhibitors of clotting factors VIII, IX or XI.

Variations in the test can affect the results.^[5]

Use in diagnosis

The dRVVT is one component of a workup of a suspected antiphospholipid antibody, the other component being the serological testing for anticardiolipin antibodies and anti-β2 glycoprotein-I antibodies using ELISA technology. The Sapporo criteria require at least one of the above laboratory tests to be positive and the patient to have at least one clinical manifestation of antiphospholipid syndrome, such as vascular thrombosis or fetal mortality/morbidity, in order to diagnose the antiphospholipid syndrome.^[6] Positive laboratory test results should be seen on two separate occasions at least six weeks apart in order for diagnosis. Antiphospholipid antibody syndrome is an important marker for recurrent thrombosis, and often warrants indefinite anticoagulant (blood thinner) therapy.

The criteria were defined in 1999, and revised in 2006.^[7]

References

1. Moore GW, Tugnait S, Savidge GF (2005). "A new-generation dilute Russell's viper venom time assay system for lupus anticoagulants: evaluation of detection utilising frozen reagents and controls". Br. J. Biomed. Sci. 62 (3): 127–32. PMID 16196459.
2. Triplett DA (September 2000). "Use of the dilute Russell viper venom time (dRVVT): its importance and pitfalls". J. Autoimmun. 15 (2): 173–8. doi:10.1006/jaut.2000.0414. PMID 10968905.
3. Thiagarajan P, Pengo V, Shapiro SS (1986). "The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants". Blood 68 (4): 869–74. PMID 3092888.
4. Hoppensteadt, DA; Fabbrini, N; -1#Bick, RL.; Messmore, HL; Adiguzel, C; Fareed, J; et al. (2008). "Laboratory Evaluation of the Antiphospholipid Syndrome". Hematol Oncol Clin North Am. 22 (1): 19–32. doi:10.1016/j.hoc.2007.10.009. PMID 18207063.
5. Moore GW, Savidge GF (April 2004). "Heterogeneity of Russell's viper venom affects the sensitivity of the dilute Russell's viper venom time to lupus anticoagulants". Blood Coagul. Fibrinolysis 15 (3): 279–82. doi:10.1097/00001721-200404000-00015. PMID 15060428.
6. Miyakis, S; Lockshin, MD; -1#Atsumi, T.; Branch, DW; Brey, RL; Cervera, R; Derksen, RH; De Groot, PG; et al. (2006). "International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)". Journal of Thrombosis and Haemostasis 4 (2): 295–306. doi:10.1111/j.1538-7836.2006.01753.x. PMID 16420554.
7. Kaul M, Erkan D, Sammaritano L, Lockshin MD (July 2007). "Assessment of the 2006 revised antiphospholipid syndrome classification criteria". Ann. Rheum. Dis. 66 (7): 927–30. doi:10.1136/ard.2006.067314. PMC 2497429. PMID 17337473.