An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease

Am J Respir Crit Care Med. 2014 Mar 15;189(6):727-40. doi: 10.1164/rccm.201401-0065ST.


Background: In adults with sickle cell disease (SCD), an increased tricuspid regurgitant velocity (TRV) measured by Doppler echocardiography, an increased serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level, and pulmonary hypertension (PH) diagnosed by right heart catheterization (RHC) are independent risk factors for mortality.

Methods: A multidisciplinary committee was formed by clinician-investigators experienced in the management of patients with PH and/or SCD. Clinically important questions were posed, related evidence was appraised, and questions were answered with evidence-based recommendations. Target audiences include all clinicians who take care of patients with SCD.

Results: Mortality risk stratification guides decision making. An increased risk for mortality is defined as a TRV equal to or greater than 2.5 m/second, an NT-pro-BNP level equal to or greater than 160 pg/ml, or RHC-confirmed PH. For patients identified as having increased mortality risk, we make a strong recommendation for hydroxyurea as first-line therapy and a weak recommendation for chronic transfusions as an alternative therapy. For all patients with SCD with elevated TRV alone or elevated NT-pro-BNP alone, and for patients with SCD with RHC-confirmed PH with elevated pulmonary artery wedge pressure and low pulmonary vascular resistance, we make a strong recommendation against PAH-specific therapy. However, for select patients with SCD with RHC-confirmed PH who have elevated pulmonary vascular resistance and normal pulmonary capillary wedge pressure, we make a weak recommendation for either prostacyclin agonist or endothelin receptor antagonist therapy and a strong recommendation against phosphodiesterase-5 inhibitor therapy.

Conclusions: Evidence-based recommendations for the management of patients with SCD with increased mortality risk are provided, but will require frequent reassessment and updating.

Publication types

  • Practice Guideline

MeSH terms

  • Adult
  • Anemia, Sickle Cell / complications*
  • Anemia, Sickle Cell / drug therapy
  • Anemia, Sickle Cell / mortality
  • Anticoagulants / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Antisickling Agents / therapeutic use
  • Cardiac Catheterization
  • Decision Support Techniques
  • Echocardiography, Doppler
  • Erythrocyte Transfusion
  • Humans
  • Hydroxyurea / therapeutic use
  • Hypertension, Pulmonary / diagnosis*
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / mortality
  • Hypertension, Pulmonary / therapy*
  • Phosphodiesterase 5 Inhibitors / therapeutic use
  • Risk Assessment
  • Severity of Illness Index


  • Anticoagulants
  • Antihypertensive Agents
  • Antisickling Agents
  • Phosphodiesterase 5 Inhibitors
  • Hydroxyurea