Case Presentation: A 72-year-old female with chronic kidney disease and recently diagnosed IgG lambda monoclonal gammopathy presented to clinic with six months of progressive weakness and failure to thrive. She reported breathlessness after several steps, a 10-kilogram weight loss, frequent falls, lightheadedness, easy bruising, and dysphagia. There was concern for light chain (AL) amyloidosis, before confirmatory workup could be undertaken, the patient presented to the emergency department (ED) following a pre-syncopal episode. Examination revealed anasarca, periorbital purpura, macroglossia, enlarged submandibular glands, and diffuse upper extremity ecchymoses. Laboratory workup was notable for: hemoglobin 9.7 mg/dL, creatinine 1.98 mg/dL (baseline 1.5 – 1.7), urinalysis with 502 mg/dL protein, baseline high-sensitivity troponin 186 ng/L and 178 ng/L at two hours, BNP >60,000 pg/ml, lactate 2.4 mmol/L, and D-dimer 11,315 ng/mL. Computed tomography with angiography of the chest demonstrated acute bilateral segmental pulmonary emboli with evidence of right heart strain. The patient was initiated on a heparin infusion and transferred to the cardiac intensive care unit (ICU). In the ICU, the patient was in atrial fibrillation with rapid ventricular response. Digoxin and a continuous diuretic infusion were initiated. Pathology from fat aspirate stained positive for Congo red, and mass spectrometry confirmed a peptide profile consistent with AL (lambda)-type amyloid deposition. Transthoracic echocardiogram demonstrated an abnormal global longitudinal strain pattern with apical sparing. Unfortunately, the patient developed progressive renal failure causing respiratory failure from volume overload. The patient’s hemoglobin dropped to 5.9 mg/dL and her heparin infusion was stopped. No source of bleeding was ultimately identified. The patient was transitioned to comfort cares and she died on hospital day five.
Discussion: Amyloidosis is a group of disorders associated with extracellular deposition of amyloid fibrils that may involve numerous organs including the kidneys, nerves, heart, gastrointestinal tract, liver, bone, or joints. Cardiac involvement is particularly common with rates in the 60-70% range, and transthyretin amyloidosis is implicated in approximately 13% of HFpEF cases. In patients with cardiac involvement, thrombotic events are observed at rates of 5-10% with the most pro-thrombotic factors including the presence of heart failure, atrial fibrillation, and atrial myopathy. However, bleeding risk also increases due to increased capillary fragility, gastrointestinal involvement, factor X deficiency, and renal failure. This case highlights an evolving conversation surrounding the indications for, and safety of anticoagulation in cardiac amyloidosis.
Conclusions: Current guidelines suggest that active thromboembolic disease in the setting of cardiac amyloidosis warrants anticoagulation therapy. However, while our patient certainly had indications for anticoagulation, namely pulmonary embolism and atrial fibrillation, the acute drop in hemoglobin suggests that acute blood loss anemia may have contributed to her poor outcome. Thus, anticoagulation must be balanced with the increased bleeding risk. Moreover, this case raises the question as to whether patients without active thromboembolism or pro-thrombotic risk factors warrant preventive antithrombotic therapy, and with which agent. To address this, additional prospective studies are needed.