Advantages of PTT levels: Theoretically, PTT levels could provide a more holistic view of coagulation, which in some situations could be a more accurate measurement of the true biological clotting tendency e. Overall, most hospitals seem to be moving towards monitoring heparin infusions based on Xa levels, rather than PTT values.
There is no patient-centered evidence that one monitoring system is superior to the other. Various protocols differ slightly. The below protocol isn't recommended for daily use. Rather, it's merely intended as a rough guide to the significance of various PTT and Xa levels.
Other causes include pregnancy, malignancy, liver disease, and renal disease Kennedy et al. The PTT makes it appear that the patient isn't therapeutically anticoagulated, but in fact the patient is experiencing clinical anticoagulation!
This is potentially dangerous, because persistent up-titration of heparin in attempts to increase the PTT could actually lead to iatrogenic hemorrhage due to excessively high heparin concentration. Factor VIII and fibrinogen levels may also be measured directly, to provide some indirect support to the diagnosis although these tests often take a while to return. Management: Pseudo-heparin resistance is fundamentally a monitoring failure. Management involves avoiding the use of PTT to titrate the heparin infusion, for example: 1 If anti-Xa monitoring is available, this should be used to titrate the heparin infusion.
As many hospitals are shifting towards the routine use of anti-Xa levels for all monitoring of heparin infusions, the entity of pseudo-heparin resistance may disappear. Unfortunately, a similar phenomenon can occur with direct thrombin inhibitors — which may be even harder to diagnose more on this below. This usually results from systemic inflammation. Increased heparin clearance e. Titrating heparin infusion to target an Xa level is generally superior to targeting PTT in the context of heparin resistance Levine If Xa levels aren't available, an alternative strategy might be to titrate heparin based on thromboelastography.
This avoids the entire issue of heparin resistance. There is no high-quality evidence regarding optimal management here. Transition to a direct thrombin inhibitor might be superior, for the following reasons: 1 Evidentiary support for the use of direct thrombin inhibitors in the ICU is greater than for the use of antithrombin-III concentrates. For example, many studies describe the use of argatroban infusions among ICU patients, including specifically patients with heparin resistance Bachler et al.
Alternatively, the use of antithrombin-III concentrate supplementation seems to be limited to case studies. As such, the safety of antithrombin-III is difficult to evaluate. The two drugs interact in a synergistic fashion, so they must be combined with considerable caution and sophistication. In contrast, transitioning to argatroban monotherapy is straightforward and easily achieved with standard ICU protocols. Administration of antithrombin-III won't fully resolve this situation.
Thus, continuing heparin may theoretically perpetuate an iatrogenic cycle of heparin use, antithrombin-III reduction, and antithrombin-III repletion. Thus, enoxaparin is a preferred agent — especially in patients with unusual weight or pharmacokinetics. However, enoxaparin doses may be roughly correlated into dalteparin doses as follows below. Dosing with tinzaparin and nadroparin is less clear, as different formulations may have variable amounts of anti-Xa activity. Dalteparin is typically measured in terms of anti-Xa units, rather than in milligrams.
For example, units of dalteparin is roughly equivalent to 50 mg of enoxaparin. However, the ratio of anti-Xa vs. Recently, some authors have suggested dosing enoxaparin in a more finely graded fashion as shown below for patients with borderline renal function Shaikh This dosing scheme has yet to gain widespread acceptance, but it might be a consideration in very select situations with close monitoring of anti-Xa levels.
Numerous recent studies seem to be converging on a dose of 0. This dose has the following advantages: i Twice-daily dosing avoids sub-therapeutic trough levels it's possible that the trough levels are the primary determinant of efficacy. Correcting the dose for weight increases the likelihood of obtaining target drug levels. Using a single formula is simpler to apply and more closely mirrors the pharmacokinetics of enoxaparin which is linear.
For patients with very unusual weight or borderline renal function, consider obtaining an anti-Xa level to monitor the heparin effect.
This is typically done after the third dose, but could probably be done sooner unless renal function is really awful, the trough heparin levels will be low and won't contribute substantially to the following peak level.
For twice-daily prophylactic enoxaparin, the target anti-Xa level is 0. It is provided in relatively fixed doses, usually q24hrs. It works via enhancing anti-thrombin's inhibition of factor Xa.
Use of fondaparinux can help avoid unnecessary workup and empiric therapy for possible HIT. Use of 2. Disadvantages of fondaparinux compared to LMWH Fondaparinux has a very long half-life at hours.
This can be problematic if the patient needs an urgent procedure or develops bleeding. Thus, full therapeutic anticoagulation with fondaparinux is not generally very useful in the ICU. Fondaparinux may be more expensive. Possible procedure in near-term. Weight kg: 7. Medscape monograph on fondaparinux.
Monitoring generally isn't necessary, but may be indicated in specific situations e. An anti-Xa level may be obtained three hours after a dose of fondaparinux. However, a specific calibration curve should be used for fondaparinux — if doubt exists about which test and cutoff values to use, discuss with the laboratory.
Many hospitals will lack a fondaparinux-calibrated anti-Xa level assay. This has numerous physiologic effects as shown above e. They are active against both fluid-phase and clot-bound thrombin unlike heparin, which acts only on fluid-phase thrombin. PTT prolongation is generally used to titrate the dose of a direct thrombin inhibitor. INR prolongation is problematic, as this can make it difficult to transition to warfarin. Assays for clotting factors and fibrinogen may be falsely prolonged causing the lab to register falsely low values.
They are not dependent on anti-thrombin III levels Pharmacokinetics are generally more predictable than those of heparin especially bivalirudin, which doesn't bind to plasma proteins.
Bivalirudin's short half-life 25 minutes may make it easier to stop, compared to a heparin infusion with half-life close to 45 minutes. Lack of any reversal agent. This could be problematic for patients with hepatic dysfunction on argatroban — wherein the half-life may be considerable. Bivalirudin has traditionally been used more in the cardiac catheterization laboratory. J Invas Cardiol. Circulation , 88 :I Circulation , — Aggregate results from 6 randomized, controlled trials.
Evidence for a complex interaction in a multicenter trial. Problems inherent in existing heparin protocols. J Thorac Cardiovasc Surg. Ann Thorac Surg. Low molecular weight heparin during instability in coronary artery disease. Eur Heart J. Download references. You can also search for this author in PubMed Google Scholar. Reprints and Permissions. Arjomand, H. Unfractionated versus fractionated heparin for percutaneous coronary intervention.
Curr Cardiol Rep 4, — Download citation. Issue Date : July Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search SpringerLink Search. Abstract Since the advent of percutaneous coronary intervention PCI , intravenous unfractionated heparin has been the primary antithrombotic therapy to prevent periprocedural ischemic complications.
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