Lumbar Puncture and the Anticoagulated Patient

Authors: Anne Flower, DO (EM Resident Physician, University of Kentucky, @Flow_Pow) and Jonathan Bronner, MD (Associate Program Director, University of Kentucky, @Bronski_EM) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

A 78-year-old male is brought to the emergency department by EMS.  The patient is ill-appearing, lying on a stretcher with his eyes closed. The patient’s wife explains that her husband had been generally not feeling well this morning, complaining of headache, fever, chills, and pain in his back and neck.  He has a medical history of hypertension, DM2, Afib, and CAD.  He does take a “blood thinner.”  Physical exam reveals a patient with altered mental status, GCS = 11, wincing with pain as you move his head, but no obvious signs of trauma.   Vital signs are BP 145/90, HR 110, RR 18, T 39C, O2 sat 98% on room air.

The differential diagnosis is broad, but the primary concern is CNS infection in a patient taking anticoagulants.

What are the special considerations for lumbar puncture in the anticoagulated patient?  Does the type of anticoagulant impact clinical decision-making?

Bacterial Meningitis is a rapidly progressive, potentially fatal infection that is a “can’t miss” diagnosis for emergency physicians.  Prevention of neurological injury and disability depends on timely diagnosis and treatment. Lumbar puncture is the gold standard for diagnosis and antibiotics are the treatment.^1,2  Obtaining CSF studies is an urgent concern, but may not be emergent as therapy can be initiated before results are obtained when clinical suspicion is high.³  Recent investigation of CT before LP has shown that not all patients need imaging and that CT can delay time to antibiotics.⁴  Delayed time to antibiotics has been shown to hurt patients, with a mortality increase of up to 30%.⁵

The Infectious Disease Society of America has established the following guidelines for indications to perform CT before lumbar puncture:³

• Immunocompromised state
• History of central nervous system (CNS) disease (mass lesion, stroke, or focal infection)
• New onset seizure (within one week of presentation)
• Papilledema
• Abnormal level of consciousness
• Focal neurologic deficit

This patient will need a meningitis workup starting with labs (CBC, CMP, PT/ PTT, INR, blood cultures, urine), imaging (CXR, noncontrast head CT), and lumbar puncture.

Initial labs show a white blood cell count of 20 x 10⁹/L, INR of 3.0.  He is taking Warfarin.

Lumbar Puncture is relatively contraindicated in patients with INR > 1.4 due to concern for iatrogenic spinal hematoma leading to possibly irreversible neurologic injury.^6-9 Therefore, all patients who are therapeutically anticoagulated with Warfarin (INR >2.0) are at increased risk.  Actual incidents of spinal hematoma after LP are quite rare, with as few as 35 reports in literature from 1974-2014.¹⁰  A recent study demonstrated that prothrombin complex conjugate (PCC) could be given to anticoagulated patients and INR corrected to <1.5 within 2 hours, allowing lumbar puncture to be performed.¹¹  However, there was a 6% risk of thromboembolic event in this small retrospective study, and the accepted rate of thromboembolic event in PCC is roughly 2%. PCC has a high degree of utility in reversing anticoagulation in patients who may be hemorrhaging, but its use in a non-emergent bleeding scenario is less clear.

This patient takes a single anticoagulant, but many patients are prescribed dual therapy, with aspirin being the most common medication overall. The AABB recommeds a platelet count of at least 50,000/μL for safely completing a lumbar puncture, though it also states that the evidence for this recommendation is weak.¹² In one study of cancer patients, 199 LPs were performed on patients with platelet counts of 20,000/μL or less, and 742 LPs were performed with platelet counts between 21,000/μL and 50,00/μL, without any cases of major bleeding.¹³  Platelet counts do not predict bleeding risks in patients taking Asprin or Plavix since these medications effect platelet funtion, rather than number.  Additionally, these platelets will be inactivated for their lifetime of 7-10 days.

Anesthesia literature supports holding anticoagulation for a period of time before elective spinal procedures to avoid bleeding complications, suggesting that 5 days is appropriate for Warfarin.¹⁴ Additional research has demonstrated decreased rates of traumatic spinal taps when performed under fluoroscopy guidance.¹⁵

This patient should be given antibiotics (Vancomycin 25mg/kg loading dose, Ceftriaxone 2g BID, Ampicillin 2g q4h, +/- acyclovir 10mg/kg TID), a non-contrast head CT should be performed, and the patient should be admitted to the hospital for treatment of presumptive bacterial meningitis.  The standard of care is to administer Dexamethasone (0.15mg/kg) before antibiotics, with evidence supporting a protective benefit against hearing loss.¹⁶  After the patient is admitted there may be further plans for lumbar puncture after consultation with hematology (to discuss PCC) or interventional radiology (to discuss fluoroscopic guidance).

Case Summary

1. Antibiotics are critical in treatment of bacterial meningitis and administration should not be delayed by lumbar puncture.
2. Spinal hematoma is a documented risk for anticoagulated patients, especially those undergoing surgery or invasive procedures.
3. Lumbar puncture should be delayed in patients with INR > 1.4.
4. Factor replacement and anticoagulant reversal have certain indications in major bleeding, but their use in preparation for procedures is less well-defined.

The next patient is a 45-year-old female presenting to the emergency department with “the worst headache of her life.”  She has never had a migraine headache, and this headache came on suddenly about 10 hours ago, was maximal in onset, and has not decreased despite her attempts to rest.  She has a history of a proximal femoral DVT and is currently taking Rivaroxaban (Xarelto).

Vital signs are BP 130/95, HR 80, RR 16, T 37C, O2 sat 99% on room air.

The differential is again broad, but the main concern is for subarachnoid hemorrhage (SAH) in a patient taking an anticoagulant.

Rivaroxaban has a black box warning for spinal hematoma due to case reports of traumatic and nontraumatic hematomas in anticoagulated patients, but this is exceedingly rare for a patient on single agent anticoagulation.^17,18  There is currently no prospective research into performing LP on patients who are therapeutically anticoagulated on the newer generations of non-vitamin K antagonists, termed direct oral anticoagulants (DOACs).

This patient’s initial noncontrast head CT is negative for signs of acute bleed or mass effect, but hemorrhage cannot be ruled out.  CT performed more than 6 hours after headache onset has been shown to be 90% sensitivity for SAH, indicating that up to 1 in 10 bleeds could be missed when presentation is delayed.¹⁹ This patient will need an urgent lumbar puncture.

The patient did not take her medication yet today, meaning her last dose was around 30 hours ago.  The half-life of Rivaroxaban is 5-9 hours, much shorter than that of the older vitamin-K antagonists.  Anticoagulation is considered resolved after 5 half-lives, when only around 3% of the drug remains in the body, and spinal procedures are often performed within 24 hours of last dose.¹⁸

• Dabigatran (Pradaxa) – 12 to 17 hours; five half-lives will have elapsed by day 2.5 to 3.5 after the last dose.
• Rivaroxaban (Xarelto) – 5 to 9 hours; five half-lives will have elapsed by day 1 to 2 after the last dose.
• Apixaban (Eliquis) – 8 to 15 hours; five half-lives will have elapsed by day 1.5 to 3 after the last dose.
• Edoxaban (Savaysa) – 6 to 11 hours; five half-lives will have elapsed by day 1.3 to 2 after the last dose.

Unlike INR for Warfarin, there is not one specific laboratory value that reliably indicates coagulation status in patients taking DOACs. Obtaining coagulation studies like PT, aPTT, thrombin time is reasonable, but may not relate directly to bleeding risk.²⁰ Anti-factor Xa tests may be available at some institutions, but these results may not be timely for decision-making in urgent LP.²¹  Additionally, some institutions use thromboelastography (TEG) or other novel point of care tests to determine coagulation status, but these practices are not yet the standard of care.²²

Reversal of the newer classes of anticoagulants is possible, and more options are becoming available.  Currently in cases of hemorrhage the following can be considered:²³

• Activated charcoal (if anticoagulation taken in previous few hours, Rivaroxaban may not bind)
• Idarucizumab (Praxbind) for Dabigatran (Pradaxa)²⁴
• Kcentra (prothrombin complex concentrate [human]) and FEIBA (factor eight inhibitor bypassing activity)

This patient’s presentation is concerning for subarachnoid hemorrhage, and initial CT scan was not diagnostic.  She is taking Rivaroxaban, but at 30 hours since last dose she is not therapeutically anticoagulated.  In the case of intracranial bleed, hemorrhage control should dictate treatment, and risk of subsequent thrombosis is of secondary concern. Lumbar puncture should be performed and treatment initiated based on CSF findings.  Anticoagulation may be held until diagnosis or for at least 6 hours after the procedure for the greatest safety margin.

Case Summary

1. Lumbar puncture after non-diagnostic CT is the standard of care for SAH for headache over 6 hours (if imaging occurred > 6 hours from symptom onset).
2. Patients taking anticoagulants, especially DOACs, present a unique concern for spinal hematoma after LP
3. There is no single test to evaluate bleeding risk.
4. Timing since last dose is critical since DOACs have short half lives.

Pearls

• Lumbar puncture is a diagnostic gold standard for several serious pathologies, but is not always emergent.
• Consider thrombosis vs hemorrhage risk.

Pitfalls

• Obtain accurate medication list and last dose history in all patients before LP.
• Coagulation studies alone may not identify all patients at risk for bleeding complications.
• Do not delay abx, for CT or LP, in patients with high suspicion for meningitis.
• Do not restart anticoagulants immediately after LP.
• Do not let diagnostic testing obscure clinical judgement.

References / Further Reading:

1. Gorelick PB, Biller J. Lumbar puncture. Technique, indications, and complications. Postgrad Med 1986; 79:257.
2. The diagnostic spinal tap. Health and Public Policy Committee, American College of Physicians. Ann Intern Med 1986; 104:880.
3. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267.
4. Hasbun R, Abrahams J, Jekel J, and Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med, 2001; 345: 1727-33.
5. Koster-Rasmussen R, Korshin A, and Meyer CN. Antibiotic treatment delay and outcome in acute bacterial meningitis. J Infect, 2008; 57: 449-54.
6. Choi S, Brull R. Neuraxial techniques in obstetric and non-obstetric patients with common bleeding diatheses. Anesth Analg 2009; 109:648.
7. Ruff RL, Dougherty JH Jr. Complications of lumbar puncture followed by anticoagulation. Stroke 1981; 12:879.
8. Pitkänen MT, Aromaa U, Cozanitis DA, Förster JG. Serious complications associated with spinal and epidural anaesthesia in Finland from 2000 to 2009. Acta Anaesthesiol Scand 2013; 57:553.
9. Sinclair AJ, Carroll C, Davies B. Cauda equina syndrome following a lumbar puncture. J Clin Neurosci 2009; 16:714.
10. Brown MW, Yilmaz TS, Kasper EM. Iatrogenic spinal hematoma as a complication of lumbar puncture: What is the risk and best management plan? Surg Neurol Int. 2016; 7:581-9.
11. Laible, Mona et al. Treatment With Prothrombin Complex Concentrate to Enable Emergency Lumbar Puncture in Patients Receiving Vitamin K Antagonists. Annals of Emergency Medicine 2016; 68:340.
12. Kaufman RM, Djulbegovic B, Gernsheimer T, Kleinman S, Tinmouth AT, Capocelli KE, et al. Platelet Transfusion: A Clinical Practice Guideline from the AABB. Ann Intern Med. 2015; 162:205.
13. Howard SC, Gajjar A, Ribeiro RC, Rivera GK, Rubnitz JE, Sandlund JT, et al. Safety of lumbar puncture for children with acute lymphoblastic leukemia and thrombocytopenia. JAMA 2000; 284:2222.
14. Domingues, Renan, Bruniera, Gustavo, Brunale, Fernando, Mangueira, Cristóvão, & Senne, Carlos. Lumbar puncture in patients using anticoagulants and antiplatelet agents. Arquivos de Neuro-Psiquiatria 2016; 74(8):679.
15. Eskey CJ, Ogilvy CS. Fluoroscopy-guided lumbar puncture: decreased frequency of traumatic tap and implications for the assessment of CT-negative acute subarachnoid hemorrhage. AJNR Am J Neuroradiol 2001; 22:571.
16. Brouwer MC, Heckenberg SG, de Gans J, et al. Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis. Neurology 2010; 75:1533.
17. Black box warning https://www.xarelto-us.com. Accessed August 27, 2017.
18. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med 2010; 35:64.
19. Backes D, Rinkel GJ, Kemperman H, et al. Time-dependent test characteristics of head computed tomography in patients suspected of nontraumatic subarachnoid hemorrhage. Stroke 2012; 43:2115.
20. Cuker A, Siegal DM2 Crowther MA, Garcia DA. J Am Coll Cardiol.  Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants. 2014; 64:1128.
21. Becker RC, Yang H, Barrett Y, et al. Chromogenic laboratory assays to measure the factor Xa–inhibiting properties of apixaban—an oral, direct and selective factor Xa inhibitor. J Thromb Thrombolysis. 2011; 32:
22. Ebner M, Birschmann I, Peter A, Spencer C, Härtig F, Kuhn J, et al. Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants. Crit Care. 2017; 21:32.
23. Pollack CV, Jr. New oral anticoagulants in the ED setting: a review. American Journal of Emergency Medicine 2012; 30: 2046.
24. Vosko MR, Bocksrucker C, Drwiła R, Dulíček P, Hauer T, Mutzenbach J, Schlimp CJ, Špinler D, Wolf T, & Zugwitz Real-life experience with the specific reversal agent idarucizumab for the management of emergency situations in dabigatran-treated patients: a series of 11 cases. J Thromb Thrombolysis 2017; 43: 306.

Photos

1. Pixabay CC0 Creative Commons. Accessed 09/02/17. https://pixabay.com/en/brain-question-mark-alzheimer-s-2546101/
2. Pixabay CC0 Creative Commons. Accessed 09/02/17. https://pixabay.com/en/blood-cells-red-medical-medicine-1813410/