Dilute Russell Viper Venom Time (dRVVT)

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

This diagnostic test is based on the ability of the venom of the Russelli viper to accelerate blood clotting. 

Venom contains the enzymes RVV-V and RVV-X which activate factor V and factor X, which converts prothrombin into thrombin in the presence of phospholipid and calcium.

The  dRVVT assay, uses a low, rate-limiting concentrations of both Russell’s viper venom and phospholipid to give a standard clotting time of 30 to 40 seconds.

The low rate limiting concentrations of Russell’s viper venom and phospholipid are used to give a clotting time of 23-27 seconds.

In the presence of lupus anticoagulant antibodies an interference with the clot promoting role of phospholipid occurs, resulting in a prolonged clotting time of 30 seconds or greater, and this does not correct with the addition of an equal volume of normal plasma suggesting the presence of a lupus anticoagulant.

The  dRVVT assay  is sensitive to the presence of lupus anticoagulants, because these antibodies interfere with the clot-promoting role of phospholipids in vitro.

The presence of a lupus anticoagulant results in a prolonged clotting time. 

May be the best test to identify lupus anticoagulant positive patients at risk for thrombosis.

An initial dRVVT positive assay should be followed by a dRVVT confirmatory test: in this test the inhibitory effect of lupus anticoagulants on phospholipids can be overcome by adding excess phospholipid to the assay.

If the clotting times of the initial dRVVT and the confirmatory test are normalized with the excess phospholipid a determination ratio can be made comparing the times with or without excess phospholipid.

Mixing study: consists of adding an equal volume of the patient’s plasma to normal plasma; expecting  the clotting time to be significantly shortened if there was only a deficiency of coagulation factors alone. 

A prolonged clotting time beyond a 3SD cutoff that does not correct despite the mixing study suggests the presence of a lupus anticoagulant.

A ratio of time without phospholipid excess to time with phospholipid excess of greater than 1.2 is considered a positive result, and implies the presence of antiphospholipid antibodies.

This test is more sensitive than the aPTT in detecting a Lupus anticoagulant, because it is not influenced by deficiencies or inhibitors of clotting factors VIII, IX, or XI.

The inhibitory effect of lupus anticoagulants on phospholipids in the dRVVT can be overcome by adding an excess of phospholipid to the assay.

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. 

A ratio of greater than 1.3 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.

The dRVVT  it is not influenced by deficiencies or inhibitors of clotting factors VIII, IX or XI as the venom mainly activates only factors V and X.

dRVVT tests are strongly affected by the direct oral anticoagulants (DOACs) and false positive LA results are obtained particularly with rivaroxaban.

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

Other component being the serological testing for anticardiolipin antibodies and anti-β2 glycoprotein-I antibodies using ELISA technology.

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.

The Antiphospholipid antibody syndrome is an important marker for recurrent thrombosis.