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Apixaban/enoxaparin sodium/heparin Bleeding events and thrombocytopenia: 9 case reports

In a prospective study involving 100 patients, who underwent pleurectomy and decortication for malignant pleural mesothelioma between May 2016 and August 2018, 9 patients (6 men and 3 women) aged 62–78 years were described, who developed bleeding events, including haemothorax, disseminated intravascular coagulation (DIC), haemoptysis, haematuria, unspecified bleeding or thrombocytopenia (heparin-induced) following anticoagulation therapy with apixaban, enoxaparin sodium or heparin [not all routes and dosages stated]. The patients, who were scheduled to undergo pleurectomy and decortication for malignant pleural mesothelioma, started receiving chemical antithrombotic prophylaxis with a single dose of SC heparin [unfractionated heparin] 5000 units within 2 hours of initiating surgery. They received mechanical prophylaxis with external pneumatic compression sleeves (during and after the surgery) in addition to chemical thromboprophylaxis with 5000 units of heparin [unfractionated heparin] every 8 hours after surgery. However, 3 patients, who had symptomatic venous thromboembolism (VTE), developed haemothorax: one patient developed haemothorax after 1 day, prior to experiencing multiple symptomatic upper-extremity deep vein thromboses (DVTs); one patient, who had right popliteal and left soleal DVT, experienced increased bloody output from the chest tube 7 days following initiation of therapeutic enoxaparin sodium [enoxaparin; and 18 days following initiation of heparin], and one patient, who had left internal jugular vein DVT, was discharged on enoxaparin sodium 80mg twice per day and was re-hospitalised 6 days following discharge (13 days following initiation of enoxaparin sodium and 18 days following initiation of heparin) with a haemothorax requiring return to the operating room. Of the remaining, one patient developed DIC with massive blood loss from small-vessel sources intraoperatively; two patients developed haemothorax after 1–16 days, and one patient developed haematuria and haemoptysis after 3 days, and required an interventional bronchoscopy to address oozing from the right upper lobe. The two remaining patients, and the two patients, who developed haemothorax, and haematuria and haemoptysis, developed heparininduced thrombocytopenia (HIT) during follow-up [not all times to reactions onsets clearly stated]. Anticoagulation was discontinued for the patient, who experienced increased bloody output from the chest tube, and the patient required placement of an inferior vena cava (IVC) filter. The patient was discharged on apixaban 5mg twice per day. However, after 2.5 months of apixaban therapy, the patient experienced another episode of bleeding (unspecified). Hence, anticoagulation with apixaban was discontinued. Heparin was immediately discontinued for the 4 patients, who developed HIT and they were transitioned to bivalirudin. The patient, who developed DIC with massive blood loss from small-vessel sources, died in