Emergency rapid reversal of coumarin associated over-anticoagulation in a case of ruptured ovarian hemorrhagic cyst for surgery: A case report

INTRODUCTION

Over-anticoagulation is not uncommon in patients who fail to follow up with their coagulation profile. The annual incidence of major bleeding in patients taking oral Vitamin K antagonists is approximately 2%/year.^[1] Commonly used oral Vitamin K antagonists are warfarin and nicoumalone. They competitively inhibit the enzyme epoxide reductase. Patients taking these medications require regular monitoring of the international normalized ratio (INR) for dosage adjustments; otherwise can result in various events ranging from easy bruising to life-threatening intracranial bleeding. Treatment options available for emergency reversal of over-anticoagulation are injection of Vitamin K, fresh frozen plasma (FFP), recombinant factor VIIa, factor VIII inhibitory bypassing activity (FEIBA), and prothrombin complex concentrate (PCC). Depending on the severity of bleeding, these agents are used either alone or in tandem. Other factors to consider are the cost and availability of these agents, which can cause delays in management, resulting in significant adverse events.

CASE REPORT

A 36-year-old female presented to the casualty with complaints of severe generalized abdominal pain with hematuria. History revealed that she had undergone aortic valve replacement in 2019 and was on tablets nicoumalone 3 mg and tablets aspirin 75 mg with irregular monitoring of anticoagulation. On examination, the patient was fully conscious and oriented. Vitals showed tachycardia of 130 beats/min, blood pressure (BP) of 130/70 mmHg, examination of heart and lungs were unremarkable, and abdominal examination revealed gray-turner sign and suprapubic tenderness. A complete blood count revealed hemoglobin of 5 mg/dL, INR value was >27.5, and partial thromboplastin time ratio was 7.02. Ultrasonography of the abdomen and pelvis revealed a left ruptured hemorrhagic ovarian cyst with resultant hemoperitoneum. 2D echocardiography showed no paravalvular leak. The patient was shifted to the intensive care unit (ICU) and planned for laparoscopic left salpingooophorectomy with drainage of the hemoperitoneum. The central line and arterial line were placed, and arterial blood gas showed respiratory alkalosis. Oozing was noted from the lines, and hematuria continued. Meanwhile, 3 units of packed red blood cells (RBCs) and 8 units of FFP were transfused. Vitamin K 5mg IV was given. As per the hematologist, an injection of recombinant factor VIIa (novoseven) 2 mgs with PCC of 1500 units was given. The repeat INR value became 0.97. Three hours later, from the time of ICU admission, the patient was taken for surgery.

The patient was shifted to the operating room, all standard monitors were attached, and invasive BP monitoring was done. The patient was induced with IV fentanyl 100 mcg, IV propofol 50 mgs, muscle relaxant cisatracurium. Intubation was done by a senior anesthesiology consultant. Two liters of hemoperitoneum drainage and left salpingo-oophorectomy with cauterization of an active bleeding point from the epiploic vein were done laparoscopically. Intraoperatively, 1 unit of packed RBC was transfused, and urine output was adequately achieved. The patient was not extubated on the table in view of significant chances of transfusion-related acute lung injury (TRALI) and was later extubated in the ICU. Post-procedure hemoglobin was 9.2 mg/dL, and INR was 1.55. Injection of enoxaparin 60 mg subcutaneously was started 12 h post-surgery for protection of mechanical aortic valve. Post-surgical recovery was unremarkable, INR was stabilized, and 2 days later, the patient was shifted to the ward and later discharged with appropriate instructions.

DISCUSSION

Oral Vitamin K antagonists are used to prevent arterial and venous thromboembolism. A commonly used class of drugs is coumarins, which include warfarin and nicoumalone. They are structurally similar to Vitamin K and competitively inhibit Vitamin K epoxide reductase, thereby preventing the regeneration of reduced Vitamin K. In our case report, the patient was using nicoumalone.

The advantages of nicoumalone over warfarin are nicoumalone, which has a rapid onset of action, which induces therapeutic prothrombin levels 36 h after the initial dose and prompt reversal. Assessment of the level of anticoagulation is done by prothrombin time/INR, which measures factors II, VII, and X.^[2] The therapeutic range of INR for metallic heart valves is 2.5–3.5. Adverse effects of coumarins can range from minor bruises to major life-threatening bleeding due to their narrow therapeutic index, significant drug, dietary and disease interactions, and CYP2C9 mutations. According to a multicenter study, the three variables for increased risk of bleeding were as follows: Age >70 years, first 90 days of anticoagulation, and INR >4.5.^[3]

There are various treatment options available to reverse the over-anticoagulation. The reversal agents and the factors reversed by them are given in Table 1.

CONCLUSION

Over-anticoagulation is not uncommon, but these patients presenting with hemorrhage requiring urgent major surgery are rare. Hence, swift diagnosis and reversal are of utmost priority. In this case, various treatment options were used in tandem to reverse the over-anticoagulation. As an anesthetist and critical care physician, it is important to stabilize, optimize, diagnose, and treat the condition with the aid of various other specialties in a limited amount of time to prevent adverse events that can be fatal.