Mixing study

Mixing study

Mixing studies are tests performed on blood plasma used to distinguish factor deficiencies from factor inhibitors, such as lupus anticoagulant, or specific factor inhibitors, such as antibodies directed against factor VIII. Mixing studies take advantage of the fact that factor levels that are 50 percent of normal should give a normal Prothrombin time (PT) or Partial thromboplastin time (PTT) result.[1]


Test method

If the problem is a simple factor deficiency, mixing the patient plasma 1:1 with plasma that contains 100% of the normal factor level results in a level ≥50% in the mixture (say the patient has an activity of 0%; the average of 100% + 0% = 50%). The PT or PTT will be normal (the mixing study shows correction). However, if there is an inhibitor that inactivates the added clotting factor, the resulting factor level will be low and the clotting test will be prolonged (fails to correct). Therefore, correction with mixing indicates factor deficiency; failure to correct indicates an inhibitor.

Time-dependent inhibitors

Unfortunately, it is not as simple as that. Some inhibitors are time dependent. In other words, it takes time for the antibody to react with and inactivate the added clotting factor. The clotting test performed immediately after the specimens are mixed may show correction because the antibody has not had time to inactivate the added factor. A test performed after the mixture is incubated for 2 hours at 37°C will show prolongation. Nonspecific inhibitors like the lupus anticoagulant usually are not time dependent; the immediate mixture will show prolongation. Many specific factor inhibitors are time dependent, and the inhibitor will not be detected unless the test is repeated after incubation (factor VIII inhibitors are notorious for this).

Abnormal coagulation test results

A common problem is an unexplained increase in the PT and/or PTT. The first thing to do is get a fresh sample and repeat the test. Another consideration is heparin. It is possible that the blood sample was mistakenly drawn though a running line. Interference by heparin can be detected by absorbing the heparin with a resin (“Heparsorb”) or by using an enzyme to digest the heparin (“Hepzyme”). Also, the patient's history should be checked: Is the patient on any anticoagulants? Does the patient have liver disease? Provided that the abnormal result is reproduced on a good specimen and there is no obvious explanation from the history, the next thing to do is a mixing study. If the mixing study shows correction and no prolongation with incubation, factor assays will need to be done to look for factor deficiency, starting with VIII and IX since they are the most common deficiencies. It is useful to do a few vitamin K–dependent and a few nonvitamin K–dependent factors to be sure that the problem is not accidental or surreptitious warfarin ingestion.

Factor deficiencies

If the mixing study fails to correct, then you need to think about an inhibitor. The most common inhibitor is a nonspecific inhibitor such as a lupus anticoagulant. Perform a test to demonstrate a phospholipid-dependent antibody, such as a platelet neutralization procedure. Spontaneous specific inhibitors against clotting factors occur (i.e. not in hemophiliacs), most often against factor VIII. This can occur in patients with systemic lupus, [monoclonal gammopathies, other malignancies, during pregnancy and for no apparent reason (idiopathic). These patients can have devastating bleeding. The thing to do is identify the specific factor involved and find out how high the titer is. If the patient has a low titer inhibitor, try to overwhelm it with high doses of the factor. If the patient has a high titer antibody against factor VIII, try porcine factor VIII or prothrombin complex concentrates to stop the bleeding. Prednisone will often lower the titer over time. Intravenous immunoglobulin has been reported to also help but it does not seem to work for hemophiliacs with an inhibitor.


Wikimedia Foundation. 2010.

Игры ⚽ Поможем написать курсовую

Look at other dictionaries:

  • Mixing test — Mixing studies are used to distinguish factor deficiencies from factor inhibitors (lupus anticoagulants or specific factor inhibitors such as antibodies directed against factor VIII). Mixing studies take advantage of the fact that factor levels… …   Wikipedia

  • Mixing patterns — refer to systematic tendencies of one type of nodes in a network to connect to another type. For instance, nodes might tend to link to others that are very similar or very different. This feature is common in many social networks, although it… …   Wikipedia

  • Mixing (mathematics) — In mathematics, mixing is an abstract concept originating from physics: the attempt to describe the irreversible thermodynamic process of mixing in the everyday world: mixing paint, mixing drinks, etc. The concept appears in ergodic theory the… …   Wikipedia

  • Code-mixing — Sociolinguistics Areas of study Accent · Dialect Discourse analysis Language varieties …   Wikipedia

  • Assortative mixing — In the study of complex networks, the term assortative mixing refers to a bias in favor of connections between network nodes with similar characteristics. [cite journal author = M. E. J. Newman year = 2003 title = Mixing patterns in networks… …   Wikipedia

  • Chaotic mixing — An example of chaotic mixing In chaos theory and fluid dynamics, chaotic mixing is a process by which flow tracers develop into complex fractals under the action of a time varying fluid flow. The flow is characterized by an exponential growth of… …   Wikipedia

  • 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] …   Wikipedia

  • SNARE (protein) — Molecular machinery driving vesicle fusion in neuromediator release. The core SNARE complex is formed by four α helices contributed by synaptobrevin, syntaxin and SNAP 25, synaptotagmin serves as a calcium sensor and regulates intimately the… …   Wikipedia

  • Dealer inc — (Lozz Switchblade) is a rap duo. Formed back in 1998, the then unnamed rap duo of MC Lozz and MC Switchblade collaborated together for the first time on the Slim Shady cover, Hi My Name Is...Will Lynch . An instant success, the tune exploded on… …   Wikipedia

  • Seiche lémanique — Pour les articles homonymes, voir Seiche. L expression seiche lémanique recouvre deux types d ondes stationnaires dans les lacs. Les unes concernent la surface libre, interface entre l air et l eau, les autres impliquent la thermocline, interface …   Wikipédia en Français

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”