Enoxaparin sodium/heparin/tenecteplase

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a case series, six patients (5 men, 1 woman) aged 34−82 years were described, who developed haematoma during treatment with heparin, enoxaparin sodium or tenecteplase for atrial fibrillation, pulmonary embolism or prophylaxis [not all routes, dosages and durations of treatment to reactions onset stated].

Case 1: The 72-year-old man, who had multiple comorbid conditions, was admitted to ICU for acute respiratory distress syndrome (ARDS) secondary to COVID-19 infection. He required mechanical ventilation and intubation. Prior to ICU admission, he had completed a course of off-label use of azithromycin followed by two doses of convalescent anti SARS CoV 2 plasma [convalescent plasma] therapy. During the hospitalisation, he developed new-onset of atrial fibrillation and received anticoagulation with heparin. His INR was closely monitored and ranged between 2 and 2.5. Eight days following the heparin initiation, a significant decrease in haemoglobin level was noted. Follow-up imaging showed a large right gluteal and hamstring haematoma. Heparin was discontinued and conservative therapy was initiated which led to a progressive size reduction of the haematoma. He was later transferred to a chronic respiratory care unit for concurrent chronic respiratory failure.

Case 2: The 34-year-old man was diagnosed abroad with COVID-19 pneumonia and required non-invasive ventilation. He was transferred from another country and received off-label use of hydroxychloroquine and azithromycin for five days. Prior to the transfer, he was diagnosed with segmental pulmonary embolism. He received tenecteplase (single dose) followed by unspecified systemic therapeutic anticoagulation. On admission, brain imaging revealed multiple foci of micro haemorrhage in the subcortical white matter with massive subarachnoid bleed and a left cerebellar and right frontal stroke. After admission, his condition continued to deteriorate with worsening of COVID-19 related ARDS, multiple fungal and bacterial infections. He eventually passed away.

Case 3: The 66-year-old man, who had history of hypertension, was transferred to COVID-19 ICU with diagnosis of COVID-19 infection. He was initiated on off-label use of IV dexamethasone 6mg daily for increased oxygen requirements followed by a dose of off-label tocilizumab. Ten days after admission, remdesivir was started as it became available. Unfortunately, he had severe ARDS and required intubation and mechanical ventilation. His hospital stay was complicated by new-onset of atrial fibrillation for which enoxaparin sodium [enoxaparin] was started. More than twenty days after the anticoagulation initiation, a significant decrease in his haemoglobin level was noted with haemodynamic instability and required blood transfusion. An abdominal computed tomography angiography showed haematoma in his right gluteus medius muscle. In addition, smaller right quadratus femoris muscle and obturator internus muscle haematomas with ongoing active bleeding were noted, which required multiple embolisations. After embolisation and transfusion, he became stable and was transferred to the respiratory care unit for weaning off mechanical ventilation.

Case 4: The 50-year-old man, who had history of hypertension and chronic kidney disease (CKD), was admitted for COVID-19 infection with respiratory failure and required mechanical ventilation. He was initiated on off-label use of two doses of tocilizumab and off-label use of IV dexamethasone 6mg daily for 10 days. On the day of admission, he received SC heparin 5000 units three times daily for DVT prophylaxis. Nine days later, he developed massive and persistent haematuria secondary to haematoma which required multiple blood transfusions and urinary bladder irrigation frequently. His condition continued to deteriorate. He died due to the progression of the acute respiratory distress syndrome severe sepsis and multiple organ failure.

Case 5: The 82-year-old man, who had a history of dementia, coronary artery disease (CAD) status post percutaneous transluminal coronary angioplasty (PTCA) on unspecified dual antiplatelet therapy, hypertension, chronic kidney disease, heart failure with low ejection fraction was admitted for COVID-19 pneumonia. On admission, he was started on off-label use of IV dexamethasone 6mg daily and prophylactic dose of SC heparin 5000 units twice daily. One week after the admission, he progressed into respiratory failure and required intubation and mechanical ventilation. He was found to be hypotensive with significant drop in haemoglobin (haemorrhagic shock) secondary to haematoma. Massive transfusion protocol was activated. Heparin and unspecified dual platelet therapy were immediately ceased. His family requested for comfort care and no further futile interventions. He eventually passed away due to haemorrhagic shock.

Case 6: The 57-year-old woman, who had history of asthma, diabetes and hypertension, was admitted with COVID-19 pneumonia. She was initiated on a prophylactic dose enoxaparin sodium [enoxaparin] due to high clinical suspicion of pulmonary embolism and off-label use of IV dexamethasone 6mg daily for 10 days. During her stay, she developed increasing oxygen requirements. She was placed on a non-rebreather facemask with 15 L/min flow of oxygen. Six days after the initiation of anticoagulation, she developed hypotension with significant drop in haemoglobin. CTA revealed left rectus abdominus haematoma and multiple retroperitoneal haematomas which were associated actively bleeding arteries. Artery embolisation was due to recurrent bleeding and persistent haemorrhagic shock. In addition, she had significant haematuria. The active bleeding was controlled and she was stabilised and transferred to the chronic respiratory care unit.