Case Presentation: A 73-year-old male with a past medical history of hypertension, benign prostatic hypertrophy, gastroesophageal reflux disorder, latent tuberculosis, and no smoking history presented with 4 days of chills, dyspnea, diarrhea, and dysuria. Initial vital signs were notable for SpO2 88% on room air and HR 110s. Labs were notable for VBG with slight respiratory alkalosis (pH 7.42, pCO2 37), Hgb 20.2 g/dL, Hct 58%, and WBC 22.9 K/uL. Urinalysis demonstrated pyuria and hematuria, and he was treated empirically with ceftriaxone for a urinary tract infection. His oxygen requirements rapidly increased in the hours following admission to high-flow nasal cannula at 50 L/min and 100% FiO2. ABG confirmed hypoxemia with paO2 65 mm Hg on 80% FiO2. Curiously, he had minimal respiratory symptoms and was in no respiratory distress with lungs clear to auscultation. Chest x-ray demonstrated bibasilar atelectasis, and chest CTA was negative for PE or parenchymal disease. TTE with bubble was negative for shunt, V/Q scan was normal, and methemoglobin was not elevated. Pulmonary infectious workup was negative. Erythropoietin (EPO) was low (2mU/mL), suggesting primary polycythemia. With elevated A-a gradient and otherwise negative workup, the most likely cause of hypoxemia was felt to be hyperviscosity due to erythrocytosis causing V/Q mismatch. He underwent therapeutic phlebotomy of 500 mL with decrease in Hct to 49% and improvement in hypoxemia. He was weaned to room air at the time of discharge.
Discussion: Bloodletting (therapeutic phlebotomy) is an ancient treatment spanning at least 3000 years and is rarely used today. Erythrocytosis is defined as Hgb concentration >16.5g/dL or Hct ≥ 49% in males (2016 WHO classification)1. Absolute erythrocytosis, an increase in RBC mass, may be caused by autonomous production of RBCs (primary polycythemia such as polycythemia vera [PV]) or in response to elevated EPO (secondary polycythemia). Complications of erythrocytosis are mainly related to increased viscosity from elevated RBCs and normal blood volumes causing slowing of capillary blood flow and reduction of oxygen transport2. Viscosity of the blood increases significantly when Hct is >60%. In a multivariable logistic regression analysis study, erythrocytosis was associated with MI, stroke, and composite cardiovascular events1. For patients with PV, lowering Hct below 45% is recommended to decrease risk of thrombotic events3. Therapeutic phlebotomy decreases blood viscosity and improves cerebral perfusion4. This treatment is less commonly used for patients with secondary polycythemia but has been shown to improve symptoms5.
Conclusions: This patient with severe, rapidly progressive hypoxemia represented a diagnostic challenge with an extensive negative workup, including no parenchymal abnormalities or shunts identified. Elevated hematocrit and low EPO led to the diagnosis of primary polycythemia, and he was empirically treated with therapeutic phlebotomy for suspected hyperviscosity, with complete resolution of his hypoxemia.