Register Login

Establishing the PTT-based UFH Therapeutic Range

A  March 22 entry from Robyn Coleman, Senior Scientist, Coagulation, Haematology, Sullivan Nicolaides Pathology, Queensland, Australia:

Dear George, I am seeking some direction on APTT therapeutic ranges for UFH. We are facing a change to our APTT reagent. The cohort of patients we would have traditionally used to validate UFH therapeutic range (TR) for APTT, essentially well patients on UFH post knee and hip replacement, no longer exist in the world dominated by DOAC use. The uptake of using chromogenic anti-Xa to monitor UFH is not universal. We also have the added complication of servicing rural and remote areas where using anti-Xa is not viable. However, we can provide APTT as part of our routine coagulation panel. I would welcome comments or suggestions to overcome this gap in our validation process.

Hello, and thank you for your question. I’ve turned to colleague and friend, Mayukh Sarkar, Ph.D., MLS (ASCP) CM for his experience with the PTT therapeutic range. Here is Mayukh’s response: for UFH therapeutic range determination, I have used any in-house hospital patients who were on UFH without warfarin (INR<1.3) but not patients who were getting UFH prophylactic therapy (which I understand was being used in this instance). I also tried to minimize (10–20%) using ECMO/post-cardiac surgery patients who were on UFH, but sometimes this was difficult.  My first aim was always to verify the existing therapeutic range with change of APTT lot and I analyzed between 60-100 samples (in this case there is no limitation for using patients on ECMO or post-cardiac surgery patients). You can also validate a new UFH TR with a minimum of 20 patients. I hope this helps, and if needed I can answer any follow-up questions.

From Robyn, March 24, 2024: Thanks for posting my question. I see from the reply from Mayukh I may not have been specific enough. We are facing a change of reagent brand, not just a change of lot. I take Mayukh’s point that we just may have to accept any patient on UFH in a direct comparison and “ transfer “ our current TR of 65 -90 sec to the new reagent type.

For a lot change, we generally get the main lab instrument (Sysmex CS 5100) to reflex test all APTT with the TEST  function (a new lot of current reagent) . With this approach, we generally get about 600 patients within a week across our reportable range. It becomes very “set and forget” as the tests are done contemporaneously to minimise pre-analytical variables. Data extraction and compilation are very easy.

My more targeted question should be about assessing the specificity of response to UFH  for a new reagent type per the various published guidelines. To give context, we generally do about 11,000  APTTs a month with only 200 of them being for UFH  monitoring. This is spread across 22 labs and 30 instruments ( CS, CN, and CA types from Sysmex). We currently use Triniclot HS, ( sold in Australia by STAGO ). They are discontinuing the manufacture of this product and have given us 12 months’ notice to find an alternative. Thank you for posting and I look forward to more responses. I have always enjoyed your forum as it provides excellent depth of guidance.

Thank you for your kind words, Robyn. Here is a further response from Mayukh: I completely understand the procedure that was explained for changing to a new lot of PTT in the CS5100. I have done that myself and agree that it is a very easy way to extract data. If Robyn is asking for guidance regarding what reagent the lab should select for changing from their current reagent I would strongly advocate for using Actin FS or Actin FSL (lupus sensitive) from Siemens, which should be validated to be used on the CS5100.
Regarding the specificity of response by a new reagent concerning UFH–there are no set guidelines. We follow the PTT values vs chromogenic anti-Xa UFH (0.3–0.7 IU/mL) to set the range (with INR < 1.3 always, and not repeating one patient collection more than 2X). With Siemens Actin FS/ FSL–what I have seen is that with lot variations the HTR was pretty constant between 45–75 secs.

From Geo: Robyn, here’s a useful reference for validating a new reagent: Marlar RA, Gausman J. The optimum number and types of plasma samples necessary for an accurate activated partial thromboplastin time-based heparin therapeutic range. Arch Pathol Lab Med. 2013; 137: 77-82. doi: 10.5858/arpa.2011-0516-OA. PMID: 23276178.

Additionally, please access pages 18–19, Multisite Validation in DeVries H, Fritsma GA: Chapter 2, Quality Assurance in Hematology and Hemostasis Testing in Keohane EM, Otto CN, Walenga JN; Rodak’s Hematology: Clinical Principles and Applications, Sixth Edition, Elsevier.  BTW, the seventh edition of Rodak is due for a 2024 release. In the seventh, Mayukh and I are co-authors of Chapter 2.

From Dr. Emmaneul Favaloro sent 4-2-24: Robyn, maybe I am missing something; you said you are doing 200 APTTs a month for monitoring heparin therapy? Why aren’t you saving these samples for anti-Xa testing and then creating a dose-response curve from the data? While people are plugging their papers: these may be helpful.

  • Favaloro EJ, Kershaw G, Mohammed S, Lippi G. How to optimize activated partial thromboplastin time (APTT) testing: Solutions to establishing and verifying normal reference intervals and assessing APTT reagents for sensitivity to heparin, lupus anticoagulant, and clotting factors. Semin Thromb Hemost. 2019;45:22–35. doi: 10.1055/s-0038-1677018. PMID: 30630206
  • Favaloro EJ, Mohammed S, Vong R, McVicker W, Chapman K, Swanepoel P, Kershaw G, Cai N, Just S, Connelly L, Prasad R, Brighton T, Pasalic L. Verification of the ACL Top 50 family (350, 550 and 750) for harmonization of routine coagulation assays in a large network of 60 laboratories. Am J Clin Pathol. 2021;156:661–78. doi: 10.1093/ajcp/aqab004. PMID: 33891005




Comments (0)
Anticoagulant Therapy

No comments here.

Leave a Reply