From Pamela Owens at Tricore in Albuquerque:
1. What therapeutic ranges are folks using for the pentasaccharide fondaparinux (Arixtra)? How were the ranges determined? The ranges in the Arixtra package insert are extremely narrow.
2. Concerning the monitoring of low molecular weight heparin (LMWH): Are labs publishing separate therapeutic ranges for once-a-day dosing versus twice-a-day dosing? How were those ranges determined? What ranges are labs using for once a day dosing? There seems to be more info in the literature concerning twice a day dosing.
Thanks!
Hi, Pam
Here is the package insert information from Glaxo Smith Kline, which includes the therapeutic ranges you reference as being narrow:
In patients undergoing prophylactic treatment with once daily fondaparinux SC injections of 2.5 mg, the mean peak plasma concentration is 0.39 to 0.50 mg/L at 3 hours post-dose. The minimum concentration is 0.14 to 0.19 mg/L.
In patients with symptomatic deep vein thrombosis or pulmonary embolism with fondaparinux injections of 5 mg (body weight <50 kg), 7.5 mg (body weight 50 to 100 kg), and 10 mg (body weight >100 kg) once daily, the mean peak concentration is 1.20 to 1.26 mg/L and the mean minimum concentration is 0.46 to 0.62 mg/L.
These numbers are derived from pharmacokinetic studies completed during fondaparinux’ (Arixtra’s) phase III clinical trials, and they certainly need clinical follow-up studies to create more realistic ranges.
Based on these, we publish the following ranges at UAB:
For a 2.5 mg daily SC dose, levels of 0.2-0.4 mg/L are anticipated
For a 7.5 mg daily SC dose, levels of 0.5-1.5 mg/L are anticipated
For LMWH, we collect four hours after SC injection and use the following ranges:
Prophylactic, 40 mg SC/24 hours: 1.0-2.0 anti-Xa units/mL
Therapeutic, 1 mg/kg/12 hours: 0.5-1.0 anti-Xa unit/mL
For both LMWH and fondaparinux, monitoring is only necessary in patients < 50 kg or with body mass index of 30 and above, renal disease, pregnancy, and cancer. We also monitor LMWH if the dose exceeds 150 mg/day. Our reference for LMWH monitoring isHirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants. American College of Chest Physicians Evidence-based clinical practice guidelines (8th edition). Chest 2008;133:141-59S. The ranges are derived from clinical observation.
My wife says I should provide you with “ammo” to get the doc
My wife says I should provide you with “ammo” to get the doctor to change their mind. Here it is. We are told by my wife’s hem-onc that the PTT will be the same whether the patient is therapeutic or not when on Lovenox or Arixtra. In addition, the dosage levels provided by the manufacturers are just a starting point and only by monitoring via the anti-Xa test can the doctor be sure the patient is therapeutic the entire time. For example, Lovenox is recommended for 1ml/Kg for a 24 hr dosage, however, after monitoring with the Xa test, my wife required 2mL/Kg to remain therapeutic. Therapeutic ranges are 0.6-1.8 four hours after dosage with a trough of 0.6 an hour prior to the next dosage.
Hello “KarinVirgil” and thank you for your comments. You are correct, the PTT is insensitive to low molecular weight heparin (Lovenox, enoxaparin) and to the synthetic pentasaccharide, fondaparinux (Arixtra). The standard assay is the chromogenic or the clot-based anti-Xa heparin assay. Following your initial comment, I would have gone on to say that in general, Lovenox and Arixtra need no laboratory monitoring, however, as their dose-response is predictable. Pathologists are likely to tell you the anti-Xa assay is being ordered too often. However, monitoring is necessary if the patient has kidney disease, is pregnant, has cancer, or is significantly overweight or underweight. You don’t say whether your wife falls into one of these categories, however it is apparent from your second message that she does need monitoring. Fortunately, more and more medical center laboratories are providing the assay on a speedy turn-around basis as Lovenox and now especially Arixtra gain in popularity. For more information on this, go to the American College of Chest Physicians’ September 2008 publication on Antithrombotics and Thrombolytics, free from www.ACCP.com. Their publication is regarded as the worldwide standard for the management of all anticoagulants. Geo
re: juliahil
My wife is Factor V Leiden (hetero) with a h
re: juliahil
My wife is Factor V Leiden (hetero) with a history of DVT, PE and now two strokes. In our ten years fighting her clotting disorder there are few things more frustrating that physicians with out-of-date information. A PTT or INR level is USELESS when on Lovenox or Arixtra. The ONLY mechanism to accurately measure therapeutic levels for these two drugs is the anti-Xa factor test. The therapeutic levels differ for each drug so check the manufacturing site for more info. Most testing facilities take up to a week to get the results, but if you are lucky, you’ll find one that does it in a day. Hope this helps!
We have a physician that continues to order PTT for his Love
We have a physician that continues to order PTT for his Lovenox patients. He says he needs to know the bleeding status of his patients. We have advised him to monitor with anti-X assay, not the PTT. What is appropriate?