59 year old male patient known case of Rheumatic heart disease underwent Aortic valve replacement and Mitral valve replacement 35 years ago and was on Warfarin, Digoxin and Metoprolol. Patient underwent decompression craniotomy for subarachnoid haemorrhage in December 2021 and was on warfarin and inj. enoxaparin therapy. Patient was followed up for PT-INR. Patient was admitted in Medicine ICU for Warfarin Associated Coagulopathy (WAC) on 15^th January 2022. On examination, patient was found to be normal. PT-INR- 1.85, aPTT-31.5, rest other investigations was normal. ECG was suggestive of Atrial Fibrillation, CXR showing aortic and mitral prosthetic valves. NCCT head-Subdural haemorrhage. Serial NCCT head was done which revealed no increase in amount of bleed, Neurological opinion was taken who suggested conservative management. Warfarin and Enoxaparin was withhold and raised PT-INR was treated with inj. Vitamin K 10mg iv stat and 4 Fresh Frozen Plasma; and digoxin and levipil was continued. Patient was symptomatically better. Patient was planned for cranioplasty but surgery was postponed as he came out to be COVID positive and home quarantined; however he was monitored continuously with PT-INR every 2 days to decide on Warfarin therapy.

Patient posted for cranioplasty after 2 months. On examination, patient was conscious, HR-48/min irregularly irregular, NIBP-120/70 mmHg, spo2-96% on room air. On systemic Examination: CNS-Conscious, Plantar reflex-bilateral extensors. CVS-S1, S2 heard with valve clicking sound. R/S-clear, P/A-soft, non-tender. Airway assessment-mouth opening 3 finger and Mallampatti grading II. On laboratory investigations: Random blood glucose-157, Hb-12.2gm%, WBC-4,170/mm3, platelet-1.42lac/ mm3, PT-INR- 1.28, aPTT-37, serum sodium-138, serum potassium-4.34, urea-17, creatinine-1.13. Liver panel was found to be normal. ECG shows atrial fibrillation with bradyarrythmia and reverse hockey stick appearance which is suggestive of digoxin toxicity, CXR showing aortic and mitral prosthetic valves. NCCT head reveals hypodense area in right paramedian cerebellar hemisphere, chronic lacunar infarct in right caudate nucleus, craniotomy defect noted in right fronto-temporo-parietal bones. 2D echocardiography shows post double valve replacement, no paravalvular mitral regurgitation, aortic regurgitation, mild tricuspid regurgitation, no pulmonary arterial hypertension, normal left ventricle and right ventricle function, normal inferior vena cava, no clot effusion, no vegetation, LVEF 60%. Cardiologist asked to stop digoxin 2 days prior to OT with continuous ECG monitoring; stop warfarin and shift to bridging therapy and patient can be taken for surgery with high risk consent.

Pre-operative management-warfarin was stopped 5 days prior to surgery, inj. Enoxaparin 0.6ml subcutaneously OD started and stopped 12 hours prior to surgery and patient can be taken for surgery if PT-INR<1.2, patient was asked to continue metoprolol, levipil. Fresh electrolytes, PT-INR and repeat ECG was asked on the day of surgery, arrangement of blood and FFP, 7 French double lumen, arterial cannula were arranged, post-operative ventilator was kept stand-by. Patient was given Tab. Pantoprazole 40mg and Tab. Alprazolam 0.25mg 12 hours before surgery. Patient was kept NBM for 6 hours for solids and clear fluids were permitted until 2 hours prior to surgery. Written and informed risk consent was taken. Patient was taken inside the OT, multi-para monitors attached including ECG, NIBP and pulseoxymeter. Two wide-bore 18G intravenous access taken, arterial cannula was secured in right radial artery for hemodynamic monitoring and 7 French double lumen central line secured in right IJV for CVP measurement. On OT day PT-INR was 1.20, serum potassium was 4 mg/dl and ECG shows atrial fibrillation with bradyarrythmia. Our plan of anaesthesia was general anaesthesia with endotracheal tube placement. Premedications given including inj. Ondansetron 4 mg iv, inj. Glycopyrrolate 0.2 mg iv, inj. Midazolam 1 mg iv and antibiotic given intravenously 30 min prior to surgery. Pre-oxygenation was done using 100% oxygen for 5 minutes and induction started using inj. Fentanyl 100 mcg and inj. Etomidate 12 mg, Inj. Vecuronium 6 mg was given and airway was secured using cuffed endotracheal tube no. 8. Intubation was smooth and uneventful. Inj. Paracetamol 1 gm given before incision for pre-emptive analgesia. Intraoperatively vecuronium and fentanyl infusion was started for analgesia. Intraoperatively, hemodynamics was managed under normal range. Total input was 1800 ml crystalloids and total output was 420 ml (220 ml urine and 200 ml blood). At the end of procedure, patient was reversed with inj. Glycopyrrolate 0.5 mg and inj. Neostigmine 2.5 mg and extubation was smooth and uneventful. Before shifting patient was vitally stable and was not on any inotropic support. Arterial cannula was removed and pressure was applied for 15 min to avoid hematoma formation. Postoperatively, patient was asked to start anticoagulants with cardiologist opinion.

Patients with mechanical prosthetic heart valves have a serious risk of thromboembolism, bleeding and valve dysfunction if appropriate anticoagulation is not achieved. Patients with new generation prosthetic mechanical mitral valves should receive warfarin to a target INR of 2.5-3.5 and for older types of valves the target INR should be 3.5-4.5 [1]. 

Warfarin-Associated Coagulopathy (WAC) is a well-documented side effect of its therapy, despite its undeniable value in the management of thromboembolic illness. A cornerstone of WAC management is Vit K replacement. Mild WAC without bleeding can often be managed with warfarin withdrawal alone. Low-dose oral vitamin K (1-2.5 mg) is sufficient and provides the same degree of international normalised ratio correction by 24 h as intravenous therapy for excessive international normalised ratio increase in the absence of bleeding. With the underlying problem corrected, the stable patient with WAC and minimal haemorrhage can also receive oral vitamin K. Major bleeding should first be treated with factor replacement for prompt coagulopathy correction, using either fresh-frozen plasma or a prothrombin complex concentrate. To provide long-lasting correction, high-dose vitamin K (10 mg) should be administered concurrently by intravenous infusion [2]. In this patient WAC was managed with inj. Vitamin K 10 mg iv stat and 4 FFP transfusion.

Digoxin, a cardiac glycoside, which acts by inhibiting the Na-K-ATPase pump, slows heart rate by lengthening the duration of the cardiac action potential and increasing inotropy. Digoxin does have several important adverse effects. When considering the perioperative administration of digoxin, one should remember that myocardial oxygen consumption may be increased, even in the presence of the non-failing, non-dilated heart, after the administration of the drug. This patient did not show any signs of acute decompensation. Owing to its narrow therapeutic index it is important to implement therapeutic drug monitoring, especially in the elective perioperative setting. Cardiac toxicity tends to present before other signs of toxicity, due to the predilection of digoxin for cardiac muscle. Toxicity is manifestated with bradyarrythmia, hyperkalemia and ECG showing reverse hockey stick appearance. This patient showed bradyarrythmia with reverse hockey stick appearance for which cardiologist stopped digoxin 2 days prior to OT with continuous ECG monitoring [3]. 

These patients if posted for elective or emergency non-cardiac surgeries, it becomes tricky for anaesthesiologist as discontinuation of anticoagulation in the perioperative period can lead to a potentially fatal thromboembolism while continuing it could result in considerable bleeding during surgery. According to several studies, patients with mechanical valve prostheses with atrial fibrillation are at an increased risk of thromboembolism when warfarin is withholded with risk ranging from 1% to 20% [2,4-6]. The prosthetic valve itself may get occluded by thrombus in 1-13% of cases. The INR should be within the normal range prior to the surgery due to the significant risk of bleeding. Perioperative heparinization has been suggested for patients with heart valves by both the European Society of Cardiology and the Fourth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy [7] to reduce the risk of thrombosis resulting from the return to a normal INR.

The strategy for perioperative anticoagulation in patients undergoing major surgery is based more on the assessment of the risk of thromboembolism than the risk of haemorrhage. Two risk groups can be formed from the patients. Warfarin is withheld for five days before surgery in the low-risk group but no alternative anticoagulation is administered. Unfractionated or low molecular weight heparin should be used as an aggressive alternative anticoagulant in high-risk patients. Stop LMWH a minimum of 12 hours and UFH 6 hours before surgery. LMWH or UFH should be started once haemostasis has been achieved and in most of the cases, at least 6 hours following surgery. Stop UFH/LMWH when INR >2.0 on at least two consecutive days. Use LMWH as an outpatient if patient is discharged before INR >2.0 [8]. 

FFP is required in emergency surgery to counteract the effects of warfarin; the dosage is individualised and titrated till INR 1.5. Furthermore, because large doses of vitamin K may cause resistance to warfarin when it is restarted after surgery, it may also be given intravenously in small doses.

59 year old patient known case of Rheumatic heart disease, hypertension with dual valve replacement with history of Warfarin associated Coagulopathy post craniotomy posted for cranioplasty had features of digoxin toxicity with ECG showing Atrial fibrillation, bradyarrythmia and reverse hockey stick appearance as digoxin has a very narrow therapeutic range. Warfarin was stopped 5 days prior to OT and shifted to bridging therapy. Patient was kept hemodynamically stable intraoperatively, ECG was monitored carefully for bradyarrythmia and atrial fibrillation. Postoperatively, anticoagulants and digoxin therapy was started under cardiologist opinion. No thrombo-embolic phenomenon and bleeding was noted intraoperatively and postoperatively. Therefore, it is best to normalize the coagulation profile right before the procedure and continue anticoagulation as soon as possible.

1. Bayliss, A. et al. “What Is the Optimal Level of Anticoagulation in Adult Patients Receiving Warfarin Following Implantation of a Mechanical Prosthetic Mitral Valve?” Interactive Cardiovascular and Thoracic Surgery, vol. 6, no. 3, 2007, pp. 390-396.

2. Patriquin, C. and M. Crowther. “Treatment of Warfarin-Associated Coagulopathy with Vitamin K.” Expert Review of Hematology, vol. 4, no. 6, 2011, pp. 657-667.

3. Virgadamo, S. “Digoxin: A Systematic Review in Atrial Fibrillation, Congestive Heart Failure and Post Myocardial Infarction.” World Journal of Cardiology, vol. 7, no. 11, 2015, p. 808.

4. Live, C. et al. “Management of Anticoagulation Before and After Elective Surgery: Risks Associated with Temporarily Stopping Warfarin Therapy.” 1506.

5. Gohlke-Barwolf, C. “Valve Disease: Anticoagulation in Valvar Heart Disease: New Aspects and Management during Non-Cardiac Surgery.” Heart, vol. 84, no. 5, 2000, pp. 567-572.

6. Cannegieter, S.C. et al. “Thromboembolic and Bleeding Complications in Patients with Mechanical Heart Valve Prostheses.” Circulation, vol. 89, no. 2, 1994, pp. 635-641.

7. Zhang, H. et al. “Optimal Oral Anticoagulant Therapy in Chinese Patients with Mechanical Heart Valves.” European Journal of Pharmaceutical Sciences, vol. 144, 2020, pp. 11-17.

8. Love, C.J. “Perioperative Management of Anticoagulation in Patients Undergoing Cardiac Rhythm Device Procedures: A Bridge to Nowhere?” Pacing and Clinical Electrophysiology, vol. 33, no. 4, 2010, pp. 383-384.