The first treatment guidelines developed for pulmonary hypertension in sickle cell disease are now available from the American Thoracic Society.
Because more effective treatments have extended the lives of patients with the disease, their risk of mortality from pulmonary hypertension and elevated tricuspid regurgitant jet velocity has increased. Until now, however, there has been no standardized approach for identifying and managing these conditions.
The guidelines are published in the March 15 issue of the American Journal of Respiratory Critical Care Medicine (doi: 10.1164/rccm.201401-0065ST).
The multidisciplinary committee that wrote the guidelines defined mortality risk as a tricuspid regurgitant velocity (TRV) of at least 2.5 m/second; an N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level of at least 160 pg/mL; or pulmonary hypertension (PH) confirmed by a right heart catheterization (RHC).
Patients with elevated mortality risk should be treated with hydroxyurea as first-line therapy. Chronic transfusion therapy for patients who are not candidates for or responsive to hydroxyurea is noted as a "weak recommendation."
For those with RHC-confirmed pulmonary hypertension, venous thromboembolism, and no additional risk factors for hemorrhage, indefinite – not limited – anticoagulant therapy is recommended.
For patients with either an elevated TRV or an elevated NT-pro-BNP level, the guidelines strongly recommend against pulmonary hypertensive–specific therapies such as prostanoid, endothelin-receptor antagonist, and phosphodiesterase-5 inhibitor therapy.
The same guidance was given for patients who have RHC-confirmed PH.
While the guidelines recommend against targeted therapies for RHC-confirmed pulmonary hypertension, a trial of either a prostanoid or an endothelin-receptor antagonist is recommended for patients with confirmed PH and elevated pulmonary vascular resistance, normal pulmonary capillary wedge pressure, and related symptoms. These patients should not be given phosphodiesterase-5 inhibitor therapy as first-line treatment.
The lack of both large-scale clinical trials in this population and integrated standards of care limit the guidelines’ effect, Dr. Elizabeth S. Klings, who chaired the guidelines committee, noted in a written statement.
"Management of [these patients] will ultimately be a collaborative effort including adult and pediatric pulmonologists, cardiologists, and hematologists," added Dr. Klings of the department of medicine at Boston University.
Dr. Klings receives support from NIH grant R21HL107993.
Dr. Susan Millard, FCCP, comments: The guidelines are a breath of fresh air. I feel they are very well thought out. More research needs to be done on the therapies for pulmonary hypertension, but the authors of these guidelines admit that there is a paucity of data in this area.
Dr. Susan Millard
In addition, more collaboration is needed between our pulmonary, hematology, oncology, and cardiology specialties. Pulmonologists do not perform right heart catheterizations, but when we ask cardiologists about pulmonary hypertension concerns, we regularly get shot down by the ones who feel that echocardiograms are sufficient to look for this problem. Yet when we want help managing these patients, they don’t want to do that either because it is pulmonary hypertension. You need a dedicated group of people locally to workup these patients.
There are not many experienced pulmonary hypertension centers easily accessible for both adult and pediatric patient referrals. It is difficult, for example, to refer patients out of state and get it approved by insurance companies.
Dr. Susan Millard is a pediatric pulmonologist, Helen DeVos Children’s Hospital, Grand Rapids, Mich.; and CHEST board member.