Dilute Russell's viper venom time (dRVVT) is a laboratory test often used for detection of lupus anticoagulant

Lupus anticoagulant

Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. It is important to note that this disease name is actually a misnomer...

 (LA).

Variations in the test can affect the results.

Mechanism

This in vitro diagnostic test is based on the ability of the venom of the Russell's viper

Daboia

Daboia is a monotypic genus of venomous Old World viper. The single species, D. russelii, is found in Asia throughout the Indian subcontinent, much of Southeast Asia, southern China and Taiwan...

 to induce thrombosis

Thrombosis

Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...

. The coagulant in the venom directly activates factor X

Factor X

Factor X, also known by the eponym Stuart-Prower factor or as prothrombinase, is an enzyme of the coagulation cascade. It is a serine endopeptidase .-Physiology:...

, which turns prothrombin into thrombin

Thrombin

Thrombin is a "trypsin-like" serine protease protein that in humans is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the first step of the coagulation cascade, which ultimately results in the stemming of blood loss...

 in the presence of factor V

Factor V

Factor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor...

 and phospholipid

Phospholipid

Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

. 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 anticoagulant

Lupus anticoagulant

Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. It is important to note that this disease name is actually a misnomer...

s, 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. An abnormal result for the initial dRVVT assay should be followed by a dRVVT confirmatory test. 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 is more sensitive than the aPTT test for the detection of lupus anticoagulant

Lupus anticoagulant

Lupus anticoagulant is an immunoglobulin that binds to phospholipids and proteins associated with the cell membrane. It is important to note that this disease name is actually a misnomer...

, because it is not influenced by deficiencies or inhibitors of clotting factors VIII

Factor VIII

Factor VIII is an essential blood clotting factor also known as anti-hemophilic factor . In humans, Factor VIII is encoded by the F8 gene...

, IX

Factor IX

Factor IX is one of the serine proteases of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes hemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to...

 or XI

Factor XI

Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the F11 gene....

.

Use in diagnosis

The dRVVT is one component of a workup of a suspected antiphospholipid antibody

Antiphospholipid syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...

, the other component being the serological testing for anticardiolipin antibodies and anti-β2 glycoprotein-I antibodies using ELISA

ELISA

Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

 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 (also known as Hughes syndrome). Positive laboratory test results should be seen on two separate occasions at least twelve weeks apart in order for diagnosis. Antiphospholipid antibody syndrome is an important marker for recurrent thrombosis, and often warrants indefinite anticoagulant

Anticoagulant

An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...

(blood thinner) therapy.

The criteria were defined in 1999, and revised in 2006.