Should I use aPTT or anti-Xa levels to monitor my patient on IV heparin infusion?

Despite more than half a century of use unfractionated heparin (UFH), the optimal method to monitor its anticoagulation effect remains unclear, with arguments for and against continued use of activated partial thromboplastin time, aPTT) vs switching to antifactor Xa heparin assay (anti-Xa HA). 1-4

The advantage of aPTT include decades of use and familiarity by providers, and its relative accessibility, ease of automation and cost.1 Its disadvantages include variation among the sensitivities of different aPTT reagents as well as susceptibility to factors that do not reflect intrinsic heparin activity (eg, liver dysfunction, hypercoagulable states). 1,2 Thus patients may receive unnecessarily high or low heparin doses because of physiologic and non-physiologic influences on aPTT.

In contrast, since anti-XA HA measures the inhibition of a single enzyme (factor Xa)1, it is a more direct measurement of heparin activity, with less variability and minimal interference by certain biological factors (eg, lupus anticoagulants). Anti-Xa monitoring may also improve the time to therapeutic anticoagulation and lead to fewer dose adjustments compared to aPTT monitoring.2

The disadvantages of anti-Xa HA include inaccuracy in the setting of hypertriglyceridemia (>360 mg/dL), hyperbilirubinemia (total bilirubin >6.6 mg/dL), recent use of low molecular weight heparin, fondaparinux and direct oral factor Xa inhibitors. Its relative expense and generally less laboratory availability among healthcare facilities may also limit its use in monitoring patients on therapeutic UFH. 1-3

Somewhat unsettling is the frequent discordance between aPTT and anti-Xa values having been reported in 46% to 60% of instances that may result in either thromboembolic or bleeding complications. 1,4 One study reported that aPTT may be therapeutic only 35% of the time that anti-Xa is also therapeutic! 2

What’s clearly missing are definitive studies that can shed light on the clinical impact of these intriguing findings on patient outcomes. So stay tuned!

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  1. Guervil DJ, Rosenberg AF, Winterstein AG, et al. Activated partial thromboplastin time versus antifactory Xa heparin assay in monitoring unfractionated heparin by continuous intravenous infusion. Ann Pharmacother 2011;45:861-68.
  2. Whitman-Purves E, Coons, JC, Miller T, et al. Performance of Anti-factor Xa versus activated partial thromboplastin time for heparin monitoring using multiple nomograms. Clinical and Applied Thromosis/Hemostasis 2018;24:310-16.
  3. Fruge KS, Lee YR. Comparison of unfractionated heparin protocols using antifactory XA monitoring or activated partial thrombin time monitoring. Am J Health-System Pharmacy. 2015; 72: S90-S97,
  4. Samuel S, Allison TA, Sharaf S, et al. Antifactor XA levels vs activated partial thromboplastin time for monitoring unfractionated heparin. A pilot study. J Clin Pharm Ther 2016;41:499-502.
  5. doi:10.1111/jcpt.12415.
Should I use aPTT or anti-Xa levels to monitor my patient on IV heparin infusion?

My patient with headache following a fall has a pink cerebrospinal fluid but the lab reports it xanthochromic. Isn’t xanthochromia supposed to describe yellow discoloration only?

Although xanthochromia literally means yellow color, when it comes to describing the color of the cerebrospinal fluid (CSF), a more liberal—but perhaps misleading— definition of xanthochromia extending to other colors, such as pink and orange, is commonly found in the literature. 1-5

In the presence of red blood cells (RBCs) in the subarachnoid space, as seen in subarachnoid hemorrhage (SAH), 3 pigments are formed by the breakdown of hemoglobin in the CSF: oxyhemoglobin, methemoglobin, and bilirubin. Oxyhemoglobin is typically red but has also been reported to appear orange or orange-yellow with dilution.6  Methemoglobin is brown and bilirubin is yellow. Of these pigments, only bilirubin can be formed solely from in vivo conversion, while oxyhemoglobin and methemoglobin may also form after CSF has been obtained (eg, in tubes).  Due to the suboptimal reliability of visual inspection, some have argued for the routine use of spectrophotometry of the CSF instead in patients with suspected SAH.7

In our patient, the “pink xanthochromia” may be related to RBC breakdown either due to a SAH or as a result of hemolysis in the sample tubes themselves, especially if there was a delay in processing the specimen. Even if he had “true xanthochromia” with yellow discoloration of CSF, make sure to exclude other causes besides SAH, such as high CSF protein, hyperbilirubinemia, rifampin therapy, and high carotenoid intake (eg, carrots).



  1. Seehusen DA, Reeves MM, Fomin DA. Cerebrospinal fluid analysis. Am Fam Phys 2003;68:1103-8.
  2. Edlow JA, Bruner KS, Horowitz GL. Xanthochromia. A survey of laboratory methodology and its clinical implications. Arch Pthol Lab Med 2002;126:413-15.
  3. Lo BM, Quinn SM. Gross xanthochromia on lumbar puncture may not represent an acute subarachnoid hemorrhage. Am J Emerg Med 2009;27:621-23.
  4. Koenig M. Approach to the patient with bloody or pigmented cerebrospinal fluid. In Irani DN, ed, Cerebrospinal fluid in clinical practice. 2009.
  5. Welch H, Hasbun R. Bacterial infections of the central nervous system. In Handbook of Clinical Neurology, 2010.
  6. Barrows LJ, Hunter FT, Banker BQ. The nature and clinical significance of pigments in the cerebrospinal fluid. Brain 1955; 58: 59-80.
  7. Cruickshank A, Auld P, Beetham R, et al. Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. Ann Clin Biochem 2008;45:238-44.

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My patient with headache following a fall has a pink cerebrospinal fluid but the lab reports it xanthochromic. Isn’t xanthochromia supposed to describe yellow discoloration only?