eISSN: 1731-2531
ISSN: 1642-5758
Anaesthesiology Intensive Therapy
Current issue Archive Manuscripts accepted About the journal Supplements Editorial board Reviewers Abstracting and indexing Subscription Contact Instructions for authors Publication charge Ethical standards and procedures
Editorial System
Submit your Manuscript
SCImago Journal & Country Rank
vol. 56
Letter to the Editor

Prophylactic range anti-factor Xa activity 24 hours after subcutaneous injection of 40 mg of enoxaparin in a patient with an epidural catheter in situ

Piotr F. Czempik

  1. Department of Anesthesiology and Intensive Care, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland Transfusion Committee, University Clinical Center of Medical University of Silesia in Katowice, Katowice, Poland
Anaesthesiol Intensive Ther 2024; 56, 1: 86–88
Online publish date: 2024/03/29
Article file
- Prophylactic range.pdf  [0.08 MB]
Get citation
PlumX metrics:

Dear Editor,

We present a case report of a 37-year- old female patient who was admitted electively to the local intensive care unit (ICU) following extensive ovarian cancer surgery – hysterectomy with bilateral adnexa, omentectomy, removal of neoplastic infiltrations (sigmoid colon, sigmoid mesentery, small intestine), appendectomy, aspiration of free fluid (2000 mL), insertion of a pelvic drain. The patient received general anesthesia with continuous epidural anesthesia. Directly before surgery approximately 4200 mL of fluid was drained from the right pleural cavity. There was no comorbidity other than obesity (BMI 38.3 kg m–2). History revealed past cigarette smoking (no smoking in the last month) and no drug history. At admission to the ICU the patient was hemodynamically unstable, supported with norepinephrine (0.22 µg kg–1 min–1), with no signs of peripheral perfusion deficit (capillary refill time < 2 s). On day 2 of the ICU stay (D2) hemoglobin concentration dropped from 85 to 57 g L–1 (Table 1); therefore urgent ultrasound examination of the abdominal and pelvic cavity was performed (no abnormalities) and gynecological consultation was requested. The operator allowed for the administration of pharmacological thromboprophylaxis and 40 mg of enoxaparin (Clexane, Sanofi-Aventis, Germany) was administered subcutaneously (approximately 18 hours after conclusion of surgery). One unit of packed red blood cells (PRBC) was transfused according to the local hospital guidelines on PRBC use in non-bleeding hospital patients [1]. Our patient had multiple risk factors for thrombosis, with high risk of venous thromboembolism (VTE) according to the Padua Prediction Score for Risk of VTE (9/11 points) [2] and the Caprini Score for VTE (8 points, 4% risk of VTE) [3]. The extra risk factor for VTE in our patient was PRBC transfusion. On the other hand, our patient had an epidural catheter in situ, with increased risk of an epidural hematoma when administered even with a standard prophylactic dose of enoxaparin. Therefore, to optimize the dose of low-molecular-weight heparin (LMWH), we performed a coagulation screen directly before and 4 hours after administration of enoxaparin (Table 1). To our surprise the anti-factor Xa activity (chromogenic assay; HemosIL, Werfen, Poland) 24 hours after a standard prophylactic dose of enoxaparin was 0.14 and increased to 0.30 IU mL–1 4 hours following subcutaneous injection, both results being within the prophylactic activity reference range. The patient was discharged from the ICU on the same day with a recommendation that an epidural catheter should be removed 36 hours following the last enoxaparin sodium dose. Written informed consent was obtained from the subject.


Selected laboratory parameters during hospitalization

Laboratory parameterAdmD1 pmD2 amD2 pmD3 amD3 pmReference range
Creatinine (mg dL–1)0.880.920.680.630.51–0.95
eGFR (mL min–1)> 60> 60> 60> 60> 60
CrCl (mL min–1)7364869388–128
Blood urea nitrogen (mg dL–1)–20.0
Urea (mg dL–1)32.432.144.816.6–48.5
Bilirubin (mg dL–1)0.390.240.250.3–1.2
Haemoglobin (g L–1)11385576367115–150
Platelets (× 103 µL–1)652745485470528130–400
Fibrinogen (Clauss) (mg dL–1)924550430471460430200–393
Prothrombin time (s)–12.5
Prothrombin activity (%)–120.0
Thrombin time (s)15.815.515.515.816.310.3–16.6
D-dimers (ng mL–1)760466733599418454565272< 500
aPTT (s)32.232.737.437.932.536.625.4–36.9
Anti-factor Xa (IU mL–1)0.140.300.1–0.3
Antithrombin (%)7375–120

[i] Adm – admission to hospital, aPTT – activated partial thromboplastin time, CrCl – creatinine clearance according to Cockcroft-Gault, D – day of the intensive care unit stay, eGFR – estimated glomerular filtration rate according to Modification of Diet in Renal Disease, INR – international normalized ratio

Low-molecular-weight heparins are produced by depolymerization of unfractionated heparin. Anticoagulant potency of LMWHs depends on their anti-factor Xa and negligible anti-factor IIa activities [4]. The chromogenic assay for anti-factor Xa constitutes the gold standard for monitoring therapy with both LMWH and fondaparinux [5]. However, it is worth mentioning that anti-factor Xa activity is a pharmacokinetic marker changing with absorption constant, volume of distribution, and clearence. Deterioration of clinical condition may change pharmacokine-tic properties of LMWHs [6]. The peak effect of LMWHs is present 3-5 hours after subcutaneous injection; their half-life is on average 4-5 hours [7]. The half-life of enoxaparin is approximately 7 hours [8]. International guidelines on antithrombotic medication and regional anesthesia recommend, to minimize the risk of an epidural hematoma, a 12-hour time interval between the last prophylactic dose of LMWH and epidural catheter removal [9]. In the study by Douketis et al., 12 out of 25 patients receiving a higher prophylactic dose of enoxaparin (30 mg s.c. twice daily) had anti-factor Xa activity > 0.1 IU mL–1 at the time of epidural catheter removal (on aver-age 10.4 hours after the last dose of LMWH) [10]. In our case the anti-factor Xa activity after a single dose of 40 mg of enoxaparin was still within the prophylactic reference range 24 hours after the injection. This is concerning since the most recent regional anesthesia guidelines suggest measuring anti-factor Xa activity in patients receiving high doses of LMWH and keeping it ≤ 0.1 IU mL-1 before high-risk regional anesthesia interventions, such as removal of an epidural catheter [9]. We were not able to explain this fact. Renal failure and advanced age are known factors delaying elimination of LMWH; however, in our patient neither of these was relevant. Anyway, the interpretation of a single anti-Xa activity measurement is challenging and should be cautious [9]. Given that prothrombin activity in our patient was at the lower reference limit (81%; reference range 80–120%), the activity of factor X could be slightly lowered. However, we are not able to resolve this issue as factor X activity was not determined. Nevertheless anti-factor Xa activity should not be affected by coagulation factor concentrations. On the other hand, there were factors that could potentially make the standard prophylactic dose of LMWH insufficient in our patient: excess weight (106 kg) [7], high platelet number (528 × 103 µL–1), high fibrinogen concentration (460 mg dL–1), low antithrombin activity (73%). Only because we measured anti-factor Xa activity we have potentially prevented a serious reginal anesthesia complication in the form of an epidural hematoma.

In conclusion, our case report shows that anti-factor Xa activity may be within the prophylactic reference range in a patient with normal renal function receiving a standard prophylactic dose of enoxaparin. Whether removal of an epidural catheter in this situation is safe in the context of epidural hematoma formation remains an unresolved issue. There is urgent need for prospective studies of chemical thromboprophylaxis with LMWHs in patients in whom continuous epidural anesthesia is used to assess the clinical utility of anti-factor Xa activity monitoring and its safe levels before regional anesthesia interventions.


Assistance with the article


Financial support and sponsorship


Conflicts of interest






Herzyk J, Wilczek D, Kopczyńska R, Czempik PF. A simple program to improve the appropriateness of red blood cell transfusions in non-bleeding hospital patients: a before-and-after study. Arch Med Sci 2024; 20: 317-320. doi: 10.5114/aoms/177281.


Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010; 8: 2450-2457. doi: 10.1111/j.1538-7836.2010.04044.x.


Caprini JA, Arcelus JI, Hasty JH, Tamhane AC, Fabrega F. Clinical assessment of venous thromboembolic risk in surgical patients. Semin Thromb Hemost 1991; 17 (Suppl 3): 304-312.


Pavoni V, Gianesello L, Conti D, Ballo P, Dattolo P, Prisco D, Görlinger K. “In less than no time”: feasibility of rotational thromboelastometry to detect anticoagulant drugs activity and to guide reversal therapy. J Clin Med 2022; 11: 1407. doi: 10.3390/jcm11051407.


Babin JL, Traylor KL, Witt DM. Laboratory moni-toring of low-molecular-weight heparin and fondaparinux. Semin Thromb Hemost 2017; 43: 261-269. doi: 10.1055/s-0036-1581129.


Piwowarczyk P, Szczukocka M, Cios W, et al. Population pharmacokinetics and probability of target attainment analysis of nadroparin in different stages of COVID-19. Clin Pharmacokinet 2023; 62: 835-847. doi: 10.1007/s40262-023-01244-4.


Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 (2 Suppl): e24S-e43S. doi: 10.1378/chest.11-2291.


Pannucci CJ, Prazak AM, Scheefer M. Utility of anti-factor Xa monitoring in surgical patients receiving prophylactic doses of enoxaparin for venous thromboembolism prophylaxis. Am J Surg 2017; 213: 1143-1152. doi: 10.1016/j.amjsurg.2016.08.010.


Kietaibl S, Ferrandis R, Godier A, et al. Regional anaesthesia in patients on antithrombotic drugs: Joint ESAIC/ESRA guidelines. Eur J Anaesthesiol 2022; 39: 100-132. doi: 10.1097/EJA.00-00-000000001600.


Douketis JD, Kinnon K, Crowther MA. Anticoagulant effect at the time of epidural catheter removal in patients receiving twice-daily or once-daily low-molecular-weight heparin and continuous epidural analgesia after orthopedic surgery. Thromb Haemost 2002; 88: 37-40.

This is an Open Access journal, all articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2024 Termedia Sp. z o.o.
Developed by Bentus.