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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]^{[non-primary source needed]}^[2]^{[non-primary source needed]}

Mechanism

This in vitro diagnostic test is based on the ability of the venom of the Russell's viper to induce thrombosis. The venom contains some substances (RVV-V and RVV-X) which directly activate factor V and factor X,^[3] which turns prothrombin into thrombin in the presence of phospholipid and calcium.^[4] 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.^{[citation needed]} 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.^[5] 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.^[5] An abnormal result for the initial dRVVT assay should be followed by a dRVVT confirmatory test.^[6] 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 1.3 is considered a positive result and implies that the patient may have antiphospholipid antibodies.^[7] 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 as the venom only activates factors V and X.^[3]^[4]

Variations in the test can affect the results.^[8]^{[non-primary source needed]}

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.^[9] 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.^[10]

References

^ 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.
^ 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.
^ ^a ^b "Snake venoms and the hemostatic system". Toxicon. 36 (12): 1749–1800. December 1998. doi:10.1016/S0041-0101(98)00126-3.
^ ^a ^b Kini, R. Manjunatha (2006-08-01). "Anticoagulant proteins from snake venoms: structure, function and mechanism". Biochemical Journal. 397 (Pt 3): 377–387. doi:10.1042/BJ20060302. ISSN 0264-6021. PMC 1533313 . PMID 16831131.
^ ^a ^b 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.
^ 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.
^ Swadzba, J; Iwaniec, T; Pulka, M; De Laat, B; De Groot, PG; Musial, J (September 2011). "Lupus anticoagulant: performance of the tests as recommended by the latest ISTH guidelines". Journal of thrombosis and haemostasis : JTH. 9 (9): 1776–83. doi:10.1111/j.1538-7836.2011.04420.x. PMID 21707912.
^ 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. ^{[non-primary source needed]}
^ 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.
^ 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.

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UpToDate Contents

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1. 凝固検査の臨床使用 clinical use of coagulation tests
2. 抗リン脂質抗体症候群の診断 diagnosis of antiphospholipid syndrome
3. 抗リン脂質抗体症候群の発症機序 pathogenesis of antiphospholipid syndrome
4. 小児における虚血性脳卒中：評価、初期マネージメント、および予後 ischemic stroke in children evaluation initial management and prognosis
5. 不育症の男女の評価 evaluation of couples with recurrent pregnancy loss

English Journal

Japanese Journal

Lupus anticoagulant測定の意義とその標準化 (第51回北海道支部例会) -- (シンポジウム臨床検査の進歩)

内藤澄悦,家子正裕
臨床病理 = The official journal of Japanese Society of Laboratory Medicine : 日本臨床検査医学会誌 66(1), 103-112, 2018-01
NAID 40021461882

APTT 検査およびループスアンチコアグラント検査の標準化

山﨑哲,内藤澄悦,静怜子,家子正裕
日本血栓止血学会誌 27(6), 636-643, 2016
… 査法である希釈ラッセル蛇毒時間（dRVVT）測定では，従来1 試薬のみが広く使用されてきたが，現在は複数の試薬選択が可能となっている．こうした背景から，APTT およびdRVVT に関する標準化策を模索すべく検討が行われてきた．APTT については，直接的な標準化が難しいと判断されたため，試薬特性を評価/表現する方法の確立を目指し，dRVVT については，試薬差や機種差を是正 …
NAID 130005250256

P2-27-2 dRVVT法によるループスアンチコアグラント検査結果が1.0未満の場合,検査の信頼性はない(Group83 不育症2,一般演題,第64回日本産科婦人科学会学術講演会)

杉俊隆
日本産科婦人科學會雜誌 64(2), 676, 2012
NAID 110009583375

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