Why does not heparin in prophylactic doses affect the PTT? and if it does not affect the coagulation profile, how does it protect against thrombosis? Why does not enoxaparin or LMWH in general affect the PTT?
Hello, Dr. Mohamed, and thank you for another thought-provoking pair of questions. Low dose unfractionated heparin, administered subcutaneously at 5000 units every 8 to 12 hours to prevent venous thromboembolic disease, prolongs the partial thromboplastin time (PTT) only slightly, to just beyond the upper limit of the reference interval. Though largely replaced by low molecular weight heparin, low-dose unfractionated heparin is effective at preventing thrombosis associated with orthopedic surgery, obstetric conditions, trauma surgery, and inflammatory medical conditions. Because low dose unfractionated heparin is not associated with bleeding risk, there is no requirement for monitoring. If monitoring is desired, the anti-Xa heparin assay provides a more sensitive means than the PTT, and the target range is about 0.2 anti-Xa units/mL. Bolan CD, Kelin HG. Chapter 27: Blood component and pharmacologic therapy of hemostatic disorders. In Kitchens CS, Alving BM, Kessler CM. Consultative Hemostasis and Thrombosis. Saunders, 2007.
Unfractionated heparin activates antithrombin and, because the unfractionated heparin molecule is long enough to promote molecular approximation, supports antithrombin’s serine protease inhibition effect against coagulation factors XIa, IXa, Xa, and IIa (thrombin). These reactions have a synergistic effect, profoundly prolonging the PTT. Low molecular weight heparin, whose shorter molecules predominantly support the anti-Xa effect, prolongs the PTT only slightly. The degree of prolongation is too small for the PTT to be an effective means for monitoring, but the anti-Xa is linear and effective. Hoffman M. Heparins: clinical use and laboratory monitoring. Lab Med 2010:41: 621-626.
We’ve had two interesting sentinel events recently where pat
We’ve had two interesting sentinel events recently where patients on q8hr low dose UFH had major bleeding, one retroperitoneal and one epidural with paraplegia. In both cases, dosing was confirmed and anti-Xa levels were supertherapeutic (PTT > or = 120 seconds in both cases). This led us to look at LD UFH responses. We have found 5-20 cases/month of PTTs greater than 100 seconds in patients on LD UFH. Denominator still unclear but majority of patients are treated with LMWH. Most affected patients have been small, Asian and often with renal dysfunction. In talking to other centers, this seems to be a commonly seen but little discussed issue.