Mr. SS was a 48-year-old man who presented to the emergency department with complaints of right calf and ankle swelling for 1 day associated with mild shortness of breath. Lower extremity ultrasound quickly confirmed an acute right femoral and popliteal deep vein thrombosis. CT angiogram of the chest was negative for pulmonary embolus (PE). Two weeks earlier, Mr. SS had suffered a traumatic right intertrochanteric hip fracture when he fell off a ladder at home. At that time, he underwent open reduction and internal fixation of the right hip without complication. He was discharged home on warfarin for venous thromboembolism (VTE) prophylaxis. At the time of his return to the hospital, his INR was 1.4 and his current level of activity was touch toe weight-bearing of the right leg.
The ED physician paged the hospitalist on call, who was already at home for the evening. Following a telephone discussion, Mr. SS was given 7.5 mg of subcutaneous fondaparinux (Arixtra) in the ED. Mr. SS was then transferred up to the regular nursing floor and admitted by a house doctor employed by the hospital. The house doctor continued the fondaparinux at a dose of 7.5mg daily.
At approximately 10 a.m. the following day, Mr. SS was up in the bathroom. He became acutely short of breath and called out for help. Before he could return to bed, he was noted to be ashen in appearance, and he lost consciousness along with his pulse and respirations. A code blue was called, but despite more than an hour of resuscitation, Mr. SS expired. An autopsy was performed and confirmed a large saddle pulmonary embolism as the cause of death. The hospitalist on call never saw Mr. SS before he died.
Complaint
Mr. SS was an English professor at the local university. He left behind a wife and four children. A relation in the medical field reviewed the records and discovered that Mr. SS only received 7.5 mg of fondaparinux despite the fact that Mr. SS weighed more than 100 kg (265 pounds). The Food and Drug Administration–approved dose of Arixtra for the treatment of acute venous thromboembolism is based on tertile of weight (5 mg if less than 50 kg; 7.5 mg if between 50-100 kg; and 10 mg if more than 100 kg). The complaint alleged that Mr. SS was underdosed and therefore needlessly developed a pulmonary embolism. Had Mr. SS received the FDA-approved dose of fondaparinux based on his weight, he would be alive and well today.
The complaint was filed against the ED physician, the hospitalist on call, and the house doctor.
Scientific principles
Outcome studies confirm that the vast majority of patients (more than 95%) who receive adequate anticoagulation in the setting of acute venous thromboembolism (DVT/PE) will be alive at discharge, 30 days, and at 1 year. In fact, of all the variables possibly associated with VTE recurrence, the only one demonstrated by logistic regression to be statistically significant with respect to VTE recurrence is the failure to achieve and maintain adequate anticoagulation. Properly conducted phase II dose ranging studies with Arixtra (REMBRANDT) ultimately led to the tertile weight-based dosing regimen that was studied in the phase III trial (MATISSE) that led to Arixtra’s FDA approval and the recommendations for dosing in the Arixtra package insert.
Complaint rebuttal and discussion
The defense argued that the dosing recommendations in the Arixtra package insert were guidelines and not in and of themselves the standard of care. Mr. SS did not have a normal INR on presentation and the defense argued it was reasonable clinical judgment on behalf of the providers involved to use that dose that best balanced efficacy and safety. The defense further argued that based on the timing of the PE (approximately 12 hours after the 7.5 mg fondaparinux dose), Mr. SS should have been in a therapeutic range in regard to drug concentration.
In other words, Mr. SS still would have had more drug in his body 12 hours after a 7.5-mg dose than he would at 24 hours following a 10-mg dose. As such, Mr. SS would have had a fatal PE regardless. The plaintiff attacked the clinical judgment defense as unreasonable. There simply was no reason not to use the proven and recommended dose for SS. To do anything less was unnecessary experimentation on Mr. SS by the physicians involved.
Ironically, during deposition testimony, the hospitalist on call confirmed that he never discussed the Arixtra dose with the ED physician. He further testified that had he known that the ED physician was only going to give 7.5 mg, he would have increased the dose to 10 mg himself.