GI Bleed in a Hemodialysis Patient with Calciphylaxis and Paroxysmal Atrial Fibrillation: Should Warfarin therapy be continued?

Calciphylaxis is a late complication of end-stage renal disease (ESRD) affecting ~1–4% patients on hemodialysis, with a mortality rate of \u3e50%. Cutaneous manifestations include necrotic, non-healing ulcers most commonly in the lower extremities. Visceral organ vasculopathy often occurs as well. Warfarin is a possible risk factor due to its effect on the inhibition of Matrix GLa protein. Under the influence of hyperphosphatemia, vascular smooth muscle cells can undergo ectopic calcification in absence of the MGLa protein. The issue of anticoagulation in dialysis patients has therefore been debated, as Warfarin may potentially induce vasculopathy and increase risk of bleeding, such as hemorrhagic strokes and GI bleeds. A 64-year-old male with ESRD, non-compliant with dialysis, presented with lower extremity pain. Patient was noted to have large, malodorous, bilateral lower extremity ulcers with necrosis and eschars. Punch biopsy of the ulcers demonstrated acute inflammation with calcium deposits and thrombi within the blood vessels, suggestive of Calciphylaxis. Patient was started on Sodium Thiosulfate and Sevelamer for hyperphosphatemia. Atrial fibrillation was incidentally found on EKG, and due to high risk of stroke based on the CHA2DS-VASc score, patient was started on Heparin and bridged to Warfarin on discharge. Patient was readmitted 3 months later to the ICU with septic shock. Lower extremity ulcers appeared to be healing, but he reported several episodes of hematochezia (INR=2.0, hemoglobin=5.2). Warfarin was therefore held and patient was transfused. EGD showed no evidence of upper GI bleed, however patient refused colonoscopy. Patients on dialysis are at increased risk of bleeding due to defective primary hemostasis. The most serious source of bleeding is gastrointestinal, which accounts for 3–7% of all deaths in the dialysis population. Current guidelines for management of atrial fibrillation by the American Heart Association recommend warfarin for oral anticoagulation in patients with ESRD who have a CHA2DS2-VASc score of 2 or greater to prevent thromboembolic events. Our patient with ESRD and Calciphylaxis presented with new-onset atrial fibrillation and therefore started on Warfarin due to high CHA2DS2-VASc score. However patient developed a GI bleed with worsening anemia requiring transfusion, prompting discontinuation of Warfarin. It is therefore questionable whether the risk-benefit assessment based on CHA2DS2-VASc is appropriate for dialysis patients. Unfortunately, all the data available on the subject of Warfarin in ESRD patients are observational without any randomized-clinical trials. Therefore no objective criteria exist to modify the anticoagulation guidelines in dialysis patients

Therapeutic misadventure with a beta blocker during a thyroid storm in an undiagnosed hyperthyroid Patient.

Thyroid storm (TS) is a rare life threatening endocrine emergency. Estimates for mortality rate for untreated TS ranges from 50%-90%[1,2].; however if managed appropriately, mortality drops to less than 20%[2]. Management can include glucocorticoids, propranolol, propylthiouracil(PTU) or methimazole and iodine solution. Each have established roles in controlling the hyperdynamic state in the storm. What is not well established is subclinical cardiomyopathy that may exist with chronic uncontrolled hyperthyroidism. We present a case in which propranolol, used appropriately, led to cardiovascular collapse during the management of a thyroid storm. 48 year old female with a medical history significant for hypertension presented with a 1 day history of severe dyspnea. On arrival vitals were: BP 177/103, pulse 127, RR 28 and pulse ox 92% on room air. She had anasarca and a GCS of 6. She was intubated for airway protection. Head CT was normal. Labs were sodium 128, bicarbonate 18, glucose 38, anion gap 14, lactic acid 5, leukocytes of 12000, Hb 7.3. ABG was pH 7.04, PCO2 45, PaO2 138 on 100% O2 at PEEP of 10, immediately after intubation. TSH was undetectable, FT4 was \u3e 8ng/dL with FT3 of 11pg/mL. Echocardiogram showed EF of 45%, RV dilation and biatrial enlargement. She received glucocorticoids, PTU and oral propranolol. Shortly afterwards she became bradycardic, hypotensive then developed pulseless electrical activity (PEA) despite glucagon and aggressive IV fluids. ROSC was achieved after 8 minutes of ACLS protocol. Within minutes she became bradycardic and hypotensive again then became pulseless again despite glucagon and attempts at transcutaneous pacing. After ROSC with ACLS protocol, she was eventually stabilized with aggressive IV fluid, 5 vasopressors and a bicarbonate drip. That night, she had a third cardiac arrest. After ROSC, an emergency bedside laparotomy was performed for decompression of compartment syndrome. Her hospital course was complicated by hematologic abnormalities requiring multiple blood products, gastrointestinal blood loss, NSTEMI and dialysis dependent renal failure. The concept of thyrocardiac disease must be kept in mind when managing a thyroid storm. In long standing hyperthyroidism, the resulting cardiomyopathy is compensated by tachycardia and increased sensitivity to catecholamines [3]. This compensatory mechanism depends on tachycardia to maintains adequate cardiac output. Failure to consider this led to our therapeutic misadventure. Current management of TS includes the use of propranolol to lessen the adrenergic effect on the heart and to inhibit peripheral conversion of T4 to T3. This patient’s experience suggested that abrupt disruption of this compensatory state with beta blockade puts the body at risk for cardiovascular collapse. Until management guidelines are updated, it is imperative to for clinicians to avoid beta blockers or use short acting beta blockers with extreme caution when managing TS