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Clot Through the Heart...And You're to Blame?

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Christa Kirk
Seattle Children's Hospital
Seattle, WA, USA

Using heparin for ventricular assist devices (VAD) is like a great song from the 1980's. You're really happy it's on but you know it's going to get a little hairy. Preventing device thrombosis can definitely cause a lot of head banging as well. The risks of bleeding and clotting are both present; however, the need to maintain device patency and prevent embolic sequelae must be tempered by the risks associated with bleeding.

Device thrombosis was previously thought to be of minor concern; however, recent data has shown the rate is increasing. Starling and colleagues reported a significant increase in thromboses from 2.2% - 8.4% in three large U.S. centers [1]. Additionally, data analyzed from INTERMACS highlighted that time to thrombosis, from device implantation, has decreased from 18.6 to 2.7 months [2].

Heparin is considered the treatment of choice in the acute phases of prevention and treatment of device thromboses. However, you know how heparin is...you play your part and it plays its games [10]. One of the biggest challenges we have in utilizing heparin is our inability to fully understand whether or not it is working. Alternative monitoring strategies are available; however, moving away from activated partial thromboplastin time (aPTT) is often a matter of debate.

Heparin is an incredibly complex molecule and management of heparin therapy can be misunderstood. The manufacturers for most devices recommend monitoring aPTTs with a goal of 60-80 seconds. However, that information is misguided. Based on only one study, the goals for aPTT were established as 1.5-2.5 times baseline. In that institution, this translated to an aPTT goal of 60-85s. Since that time, this has become the "gold standard" for monitoring heparin's anticoagulant effects in all populations everywhere [3]. PTT can be affected by multiple endogenous factors including antithrombin III, fluctuation in factor levels, and hemolysis - all of which are present during times of stress and inflammation. Lactase dehydrogenase (LDH), which is elevated in the presence of hemolysis, has been shown to prolong aPTT independently of anticoagulation [4,5,6]. Therefore, aPTT may be an unreliable measure of heparin's activity but remains essential as an overall measure of physiological anticoagulation status.

Approximately ten years ago, some institutions began monitoring heparin with unfractionated heparin activity (UFH) levels. The Antithrombotic Therapy and Prevention of Thrombosis guidelines (CHEST) from 2008 included recommendations to titrate heparin based on UFH levels or to correlate an institution-specific aPTT to an UFH goal range. Many institutions have complied with these recommendations; however, not many institutions have created guidelines based on UFH levels for device anticoagulation. Due to the inflammatory nature created by VAD placement or in post-thrombotic states, the time has come to find a strategy for monitoring patients without solely relying on aPTT.

In all fairness to aPTT, it is important to note that UFH activity levels can be affected by physiological factors present during hemolysis as well. UFH levels are measured spectrophotometrically which means interpretation is determined by color and can be artificially lowered by anything that can change the color of blood (e.g. lipemia or elevated bilirubin). Additionally, UFH activity levels can be artificially lowered in the presence of low antithrombin III levels which are commonly associated with hemolysis [8].

Many of us have been confounded when PTT disagrees with UFH levels and multiple studies have recognized this frustrating discrepancy [5,6,9]. A recent study by Adatya and colleagues, showed that during mechanical circulatory support, aPTT levels and UFH activity levels are most discordant when LDH is >2.5 times baseline or when INR is ≥1.5 both of which can be elevated during times of stress and inflammation [4]. When this occurs, we either ignore the level we don't like or stubbornly rely on aPTT, biting our fingernails, recognizing that aPTTs between 60-80 seconds are probably doing nothing to anticoagulate our patients. In this scenario, would following UFH activity goals while assessing aPTTs independently be better? In most cases, if the overall goal is anticoagulation, I'm just going to say it, yes.

As we know, the first level after instituting this practice will be an UFH level of 0.11units/mL with a PTT>150s. Of course, the patient will be "oozing" but not bleeding and there "might be some concern for a clot". What is the best method for interpretation and clinical application? Other factors must be analyzed to assess overall anticoagulation status.

Why is the aPTT elevated?
  • Elevated LDH or INR
  • Variance in coagulation factors (fibrinogen or antithrombin III)
  • Acute phase reactants (factor VIII)
Can we believe the UFH activity level?
  • Elevated bilirubin
  • Lipemia
  • Elevated plasma free hemoglobin
Clinical Status?
  • Clinically significant bleeding or oozing?
  • Presence of clot in the devise or other known risk factors?
Other thoughts?
  • Is the aPTT telling us that the patient is more likely to bleed for a reason unrelated to haparin?
  • Would a TEG (thromboelastograph0 or thrombin time be useful?
  • Are we adequately anticoagulating the patient and, more importantly,are we okay with this lower level of anticoagulation?

By having this (internal or external) discussion, the aPTT becomes a barometer for the patient's risk of clotting versus bleeding which supports more or less aggressive treatment. The UFH activity level, if valid, remains as a guide for heparin adjustment. With available lab monitoring, there really isn't one "rock star" value for understanding the true anticoagulation status of our patients. By relying on more stable UFH activity goals to direct anticoagulation and using other clinical data, including a classic like aPTT, to guide decision making, we can finally stop giving device anticoagulation such bad name. ■

Disclosure Statement: The author has no conflicts of interest to disclose; however, she would like to gratefully acknowledge Jon Bon Jovi for his contribution to all matters of the heart.


  1. Starling RC, Blackstone EH, Smedira NG. Increase in left ventricular assist device thrombosis. N Engl J Med. 2014;370(15):1465-1466. Accessed 20140410. doi: http://dx.doi.org/10.1056/NEJMc1401768.
  2. Kirklin JK, Naftel DC, Kormos RL, et al. Interagency registry for mechanically assisted circulatory support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device. J Heart Lung Transplant. 2014;33(1):12-22. Accessed 20140114. doi: http://dx.doi.org/10.1016/j.healun.2013.11.001.
  3. Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med. 1972;287(7):324-327.
  4. Adatya S, Uriel N, Yarmohammadi H, et al. Anti-factor xa and activated partial thromboplastin time measurements for heparin monitoring in mechanical circulatory support. JACC: Heart Failure. 2015;3(4):314-322.
  5. Guervil DJ, Rosenberg AF, Winterstein AG, Harris NS, Johns TE, Zumberg MS. Activated partial thromboplastin time versus antifactor xa heparin assay in monitoring unfractionated heparin by continuous intravenous infusion. Ann Pharmacother. 2011;45(7-8):861-868. Accessed 20110722. doi: http://dx.doi.org/10.1345/aph.1Q161.
  6. Stehlik J, Johnson SA, and Selzman C. Gold standard in anticoagulation assessment of left bentricular assist device patients? how about bronze. JACC: Heart Failure. 2015;3(4):323-324-326
  7. Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P, American College of Chest Physicians. Antithrombotic and thrombolytic therapy for ischemic stroke: American college of chest physicians evidence-based clinical practice guidelines (8th edition) Chest. 2008;133(6 Suppl):630S-669S.
  8. Kostousov V, Nguyen K, Hundalani SG, Teruya J. The influence of free hemoglobin and bilirubin on heparin monitoring by activated partial thromboplastin time and anti-xa assay. Arch Pathol Lab Med. 2014;138(11):1503-1506. Accessed 20141031. doi: http://dx.doi.org/10.5858/arpa.2013-0572-OA.
  9. Trucco M, Lehmann CU, Mollenkopf N, Streiff MB, Takemoto CM. Retrospective cohort study comparing activated partial thromboplastin time versus anti-factor xa activity nomograms for therapeutic unfractionated heparin monitoring in pediatrics. Journal of Thrombosis and Haemostasis. 2015;13(5):788-794.
  10. Bon Jovi, Jon. "You Give Love a Bad Name" Slippery When Wet. CD. Island/Mercury. 1986. Google play, Accessed 8/19/15 (https://play.google.com/music).

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