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Tissue Thromboplastin Inhibition Test

Here is a question that appeared on the Clinical Laboratory Science (CLS) Educators’ list: “We are trying to figure out the principle, procedure for the tissue thromboplastin inhibition (TTI) test. We are aware that it seemingly is no longer performed, but feel there is a good chance that the ASCP could potentially ask questions about it on their certification exam. Can anyone clarify this test for us? Somehow we are having trouble understanding what we are finding in the literature.

I provided this answer for the list:

The TTI test is synonymous with the dilute prothrombin time (DPT) test. Here is the description from my old textbook, Corriveau DM, Fritsma GA. Hemostasis and Thrombosis in the Clinical Laboratory. Lippincott, 1988:

“In the tissue thromboplastin inhibition test, PT reagent is diluted 1:50 or 1:500 with saline. The dilution is prewarmed, then 0.1 mL of dilute reagent is mixed with 0.1 mL of the test plasma and the mixture is incubated for 3 minutes. CaCl2 (0.025 molar) is forcibly added and a timer started. PNP is tested at the same time, and the results are compared. If the ratio of patient plasma interval to PNP interval is 1.3 or greater, lupus anticoagulant is presumed to be present. A ratio of 1.1 or less is considered to be normal, and lupus anticoagulant is absent.”

The test was developed in Dr. Doug Triplett’s Midwest Hemostasis laboratory, and is now usually called the DPT. Some still use it, although in 2009 the ISTH discouraged its use as being poorly reproducible in Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, De Groot PG; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009;7:1737-40. However, those who continue to use it swear by it for its sensitivity.

Comments (1)
Lupus Anticoagulant
Herb Crown
Sep 13, 2012 11:16am

Hi George and CLS Educators. Yes George is correct, it is a
Hi George and CLS Educators. Yes George is correct, it is a lab developed test used in the detection of a lupus anticoagulant (LA). We routinely perform this test even though the ISTH does not recommend it any longer. I have previously written about it.

Lupus anticoagulants rarely affect the extrinsic pathway and most facilities are unable to recognize it because our commercially available kits do not test for it. The DPT has an important role to play in conjunction with a complete LA work up as long as one understands its major weakness, that being its sensitivity to heparin and the false positives that come from specimens submitted for testing which are contaminated with heparin. Without understanding this, and not evaluating the specimen for heparin, I can understand this would be one of the reasons the assay is reported as “being poorly reproducible”.

A complete LA workup should evaluate the common, intrinsic, and extrinsic pathways.

Regards,
Herb Crown
St. Louis University Hospital Coagulation Reference Lab

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