Category: Screening Assays

Promacta and Brown Plasma

From John Mitsios, MD at Cornell. Hi George! I had a question regarding the effects of eltrombopag (Promacta®, a TPO stimulating agent), which is typically given to patients with immune thrombocytopenic purpura (ITP), on routine coagulation assays. The reason for this question is that it has been observed in some patients that at high doses the plasma turns a reddish-brown color. This observation was recently published in West KA, Leitman SF, Flegel WA. Muddy waters in therapeutic plasma exchange. Transfusion 2014;54:2157. The color change also causes interference with spectrophotometric assays. In particular is was observed that total bilirubin measured by the the diazo method resulted in lower concentrations being reported. Some of these
patients are given Coumadin since they are at risk of thrombosis when on Promacta. My question is, do you think that the presence of this drug would interfere with turbidometric (optical) clot based assays? Thank you and I look forward to hearing from you.

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Pre-surgical Screening Reprise

I’d like to draw your attention to some recent responses to the November 8, 2013 post by Jeanne Isabel entry about pre-surgical screening.

Factor VII Padua Mutation

As a followup to the July 30 Discordant PT Results, George presented this problem to a colleague in the booth of one of the major hemostasis materials distributors in the Clinical Laboratory Expo, thereby “spoiling his day.” Nevertheless, he had the answer by days’ end, confirming the response posted by Dr. Vadim Kostousov. This was further confirmed by Dr. Emmanuel Favaloro on July 3. Thanks to all who contributed to this interesting case.

Discordant PT Results

George is attending the annual AACC meeting at McCormick Place in Chicago. A colleague described a puzzling case in which a patient has a prolonged prothrombin time (PT) using a 1.3 ISI thromboplastin reagent (Stago) and a normal PT when using Dade (Siemens) Innovin. The findings are consistent on repeat split specimens, the PTT is normal, and the patient is not bleeding. Any ideas?

Prolonged-Circulation Factor IX

Biogen Idec released Alprolix®, their prolonged circulation recombinant factor IX concentrate soon after it was cleared by the FDA, March 28, 2014. Alprolix may be administered as little as once a week when used for factor IX deficiency (Hemophilia B) prophylaxis. The concentrate’s pharmacokinetics and efficacy were established using the partial thromboplastin time (PTT), identified as the “one-stage clotting assay (OSC)” by the distributor.

Buyue Y and Sommer JM, Biogen Idec, presented the poster referenced in the attached abstract at the International Society on Thrombosis and Hemostasis Standardization Subcommittee meeting in Milwaukee, June 23–25, 2014 describing the relative sensitivities of three PTT reagents, one each using ellagic acid, kaolin, or silica and concluded the ellagic acid-based is more sensitive than the others, indicating that the type of PTT reagent you use profoundly affects your factor assay results. Read more »

Hyperglycemia and Prolonged PTT

From “BJ:” I recently cared for a 60 yr old type 2 diabetic in hyperglycemic hyperosmolar state. Initial serum glucose 960. The partial thromboplastin time (PTT) was initially 78 seconds without clear reason. The international normalized ratio (INR) was 1.4. The prothrombin time (PT) was not initially checked. I felt that the value was likely spurious and I repeated the test a few hours later, with normal result. At that time blood glucose had improved to within the 300s with fluids and insulin. Are you aware of a mechanism whereby severe hyperglycemia can cause the PT/PTT to result artifactually high?
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More on Shortened PTT

From Anita Elledge, MT (ASCP), blood bank/coagulation supervisor, Sierra Vista Regional Health Center, AZ: Our coagulation testing is done on a Stago Compact instrument. The linear range is 20–200 s for the activated partial thromboplastin time (APTT, PTT). We have a policy that any PTT result <22 s must be redrawn, not just rerun the same sample, because it is said that a low PTT result should not occur and is almost always due to a bad collection. I can’t seem to find any documentation that confirms the < 22 s result being a point for this “recollect.” Can you give me a resource for information or any further help with this?

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Pre-Surgical Screening

Prof. Jeanne Isabel, Medical Laboratory Science Program Director, Northern Illinois University, forwarded the following question, posted to the American Society for Clinical Laboratory Science Consumer Forum:

“We run prothrombin time assays with international normalized ratios (PT/INRs) on most all patients pre-procedure regardless of whether they take Coumadin or heparin. I have done some research and this is the general practice but I am wondering if there is a better test. Most of our patients are on Aspirin and/or Plavix or Lovenox rather than Coumadin or heparin. Does the PT/INR reflect the use of these medications or is there a study that would better indicate a risk for bleeding? We do activated clotting times (ACTs) in procedures with the use of heparin. Does that also reflect the anticoagulation affect of Aspirin and Plavix?”

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