Thrombotic Risk after a Major Bleeding During Anticoagulation: A Clinical Case.

We report on a 81-year-old female admitted to the emergency department for the occurrence of abdominal pain after a minor trauma. She was on treatment with warfarin for atrial fibrillation. The abdominal computed tomography (CT) angiography revealed a retroperitoneal hematoma (RH) of the left iliopsoas muscle with no evidence of active bleeding. The international normalized ratio exceeded the upper recommended anticoagulation limit. Prothrombin complex concentrates (PCCs) were used for anticoagulation reversal. Two days later, the patient presented acute dyspnea and a pulmonary CT angiography showed an embolus in the right pulmonary artery. Enoxaparin was started. Thoracic symptoms improved and a second abdominal CT angiography revealed a reduction in RH. Apixaban was started from day 11. No further bleedings occurred and clinical conditions improved. Anticoagulation reversal with PCCs rapidly restores hemostasis, but, on the other side, the thrombotic risk due to their procoagulant effect should be considered.

Introduction

According to the International Society on Thrombosis and Haemostasis definition,[1] 2.4%–4% of patients treated with oral anticoagulant therapy with Vitamin K antagonists (VKAs) experience a major bleeding. Management of a bleeding event in patients treated with VKAs is based on therapy withdrawal, administration of Vitamin K, hemodynamic support (volume resuscitation with fluids or red blood cell transfusion), and in life-threatening cases, on the use of reversal agents.[2] Surgery or radiologic intervention should be considered in case of continuous active bleeding. Although fresh frozen plasma can be given in this situation, the use of prothrombin complex concentrates (PCCs) in a small infusion volume gives a rapid full recovery of coagulation parameters.[3] When PCCs are used as reversal, the thrombotic risk related to both the intrinsic effect of the agent and to the prothrombotic predisposition of the patient should be considered.

Case Report

We report on a 81-year-old female admitted to the emergency department for the occurrence of abdominal pain after a minor trauma. She was on treatment with warfarin for atrial fibrillation and a previous cardioembolic stroke event. The computed tomography (CT) angiography of the abdomen revealed a retroperitoneal hematoma (RH) of the left iliopsoas muscle sized 12 cm × 10 cm with no evidence of active bleeding. The iliac venous system was compressed by the RH with no evidence of thrombosis [Figure 1]. The international normalized ratio (INR) at admission was 6.6, and hemoglobin value was normal (13.7 g/dl). Reversal with 3-factor PCC at the dosage of 25 U/Kg was administered, and a normal value of INR was achieved soon after. Hemoglobin level was 12 g/dl at 24 h. However, 2 days later, the patient developed dyspnea and tachypnea (respiratory rate over 30 breaths for minute); arterial oxyhemoglobin saturation was 78% in room air with severe hypoxia (40 mmHg) and normocapnia (45 mmHg). Systolic blood pressure and heart rate were normal. A pulmonary CT angiography revealed a thrombus in the right pulmonary artery with the involvement of the superior, medium, and inferior lobar branches and a mild pleural effusion [Figure 2]. At echocardiography, no signs of right ventricular failure due to pressure overload were found [Figure 3]. There was a mild increase in troponin I level (0.26 ng/ml, normal value. <0.04 ng/ml) with normal levels of N-terminal pro-B-type natriuretic peptide. The hemoglobin value was stable (12 g/dl) without renal impairment (creatinine clearance according to Cockcroft-Gault = 77 ml/min); therefore, treatment with enoxaparin at the dosage of 0.75 mg/Kg every 12 h was started and continued for 4 days. Enoxaparin dose was increased at 1 mg/Kg every 12 h at day 5 and continued until day 10. Thoracic symptoms improved and a second CT angiography of the abdomen revealed a mild reduction in RH volume. At this point, the oral anticoagulation with a direct inhibitor of factor Xa apixaban (5 mg every 12 h) was introduced. No further bleedings occurred, and clinical conditions subsequently improved.

Figure 1

Computed tomography angiography of abdomen (coronal view): Retroperitoneal hematoma (marked by white arrow) of left iliopsoas muscle sized 12 cm × 10 cm with no evidence of active bleeding. The retroperitoneal hematoma compressed iliac venous system without evidence of venous thrombosis.

Figure 2

Pulmonary computed tomography angiography (sagittal view): Thrombus of right pulmonary artery with the involvement of superior, medium, and inferior lobar branches.

Figure 3

Two-dimensional echocardiography in apical view: Early diastolic pulmonary regurgitation velocity <2.4 m/s.

Discussion

In patients receiving VKAs experiencing a major bleeding the use of a reversal agent is recommended. Treatment options include the use of Vitamin K and PCCs. The intrinsic hypercoagulable state of patients candidate to receive VKAs may be exacerbated by the infusion of PCCs. The use of PCCs is associated with an increased risk of both venous and arterial thrombosis during the recovery period.[4] In this patient, the use of PCCs together with the compression of the venous iliac vessels acted as triggers for the occurrence of intermediate-low risk pulmonary embolism.[5] Since the stability of hemoglobin values and of RH size, parental anticoagulation with enoxaparin was started. Phase 3 trials on the use of non-VKAs oral anticoagulants (NOACs) in patients with venous thromboembolism showed similar efficacy compared to heparin/VKA.[6] However, because of their better safety profile compared to standard anticoagulation (as showed in trials on atrial fibrillation and in subgroup analyses on pulmonary embolism), the use of a NOAC was preferred.[78]

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Conflicts of interest

There are no conflicts of interest.