Suggested approach to screening, diagnosis and management of pulmonary hypertension in SCD
| 1. Screening for pulmonary hypertension by echocardiography |
| • Perform echocardiography every 1 to 3 y, OR |
| • Perform echocardiography based on one or more findings consistent with increased risk: |
| – Dyspnea on exertion |
| – Limited exercise capability as determined by the 6-minute walk test (<350 m) |
| – History of thromboembolism |
| – Pulse oximetry <96% at rest |
| – Previous echocardiogram with TRV of ≥2.5 m/sec |
| – Physical findings of right-sided heart failure: lower extremity edema, hepatomegaly, or jugular venous distension |
| – Elevated serum N-terminal proBNP concentration |
| – Elevated serum creatinine concentration (>1.0 mg/dL for severe sickling phenotype and >1.4 mg/dL for mild sickling phenotype) |
| – LDH >475 U/L or reticulocyte count >300 000 |
| – Serum ferritin >1000 ng/ml |
| 2. Actions to be taken based on the results of echocardiography |
| • TRV <2.5 m/sec: Ensure that patient is being managed according to NHLBI guidelines83 |
| • TRV 2.5-2.9 m/sec, right ventricle normal by echocardiography, no findings suggestive of pulmonary hypertension: Ensure patient being managed according to NHLBI guidelines83 and repeat echocardiogram yearly |
| • TRV 2.5-2.9 m/sec, right ventricular hypertrophy by echocardiography, and/or other findings consistent with increased pulmonary hypertension risk: Ensure patient being managed according to NHLBI guidelines83 ; refer to pulmonary hypertension expert for right heart catheterization |
| • TRV of ≥3.0 m/sec: Ensure patient is being managed according to NHLBI guidelines83 and refer to expert in pulmonary hypertension for right heart catheterization |
| 3. Actions to be taken based on the results of right heart catheterization |
| • mPAP <25 mm Hg: pulmonary hypertension not present: Ensure patient is being managed according to NHLBI guidelines83 and repeat echocardiogram yearly |
| • mPAP ≥25 mm Hg and PCWP ≤15 mm Hg: precapillary pulmonary hypertension |
| – Perform ventilation/perfusion scan of lung and consider long-term anticoagulation if segmental defect found |
| – Refer for overnight polysomnography to evaluate for sleep-disordered breathing including obstructive sleep apnea; provide appropriate intervention if present |
| – Chronic low-flow oxygen by nasal cannula if pulse ox <90% |
| – Refer to expert in pulmonary hypertension for follow-up and consideration whether therapy with endothelin receptor blocker or prostacyclin agent should be attempted* |
| – Consider initiating therapy with hydroxyurea if patient is not receiving this medication or with exchange blood transfusion program if patient does not tolerate or respond to hydroxyurea |
| – Consider allogeneic hematopoietic stem cell transplantation with low-intensity conditioning regimen if patient has HLA-matched sibling.† |
| • mPAP ≥25 mm Hg and PCWP >15 mm Hg: postcapillary pulmonary hypertension |
| – Refer to cardiologist to evaluate for left ventricular systolic or diastolic dysfunction; manage according to established guidelines for left ventricular failure74 |
| – Consider initiating therapy with hydroxyurea if patient not receiving this medication or with exchange blood transfusion program if patient does not tolerate or respond to hydroxyurea |
| – Consider allogeneic hematopoietic stem cell transplantation with low-intensity conditioning regimen if patient has HLA-matched sibling |
| 1. Screening for pulmonary hypertension by echocardiography |
| • Perform echocardiography every 1 to 3 y, OR |
| • Perform echocardiography based on one or more findings consistent with increased risk: |
| – Dyspnea on exertion |
| – Limited exercise capability as determined by the 6-minute walk test (<350 m) |
| – History of thromboembolism |
| – Pulse oximetry <96% at rest |
| – Previous echocardiogram with TRV of ≥2.5 m/sec |
| – Physical findings of right-sided heart failure: lower extremity edema, hepatomegaly, or jugular venous distension |
| – Elevated serum N-terminal proBNP concentration |
| – Elevated serum creatinine concentration (>1.0 mg/dL for severe sickling phenotype and >1.4 mg/dL for mild sickling phenotype) |
| – LDH >475 U/L or reticulocyte count >300 000 |
| – Serum ferritin >1000 ng/ml |
| 2. Actions to be taken based on the results of echocardiography |
| • TRV <2.5 m/sec: Ensure that patient is being managed according to NHLBI guidelines83 |
| • TRV 2.5-2.9 m/sec, right ventricle normal by echocardiography, no findings suggestive of pulmonary hypertension: Ensure patient being managed according to NHLBI guidelines83 and repeat echocardiogram yearly |
| • TRV 2.5-2.9 m/sec, right ventricular hypertrophy by echocardiography, and/or other findings consistent with increased pulmonary hypertension risk: Ensure patient being managed according to NHLBI guidelines83 ; refer to pulmonary hypertension expert for right heart catheterization |
| • TRV of ≥3.0 m/sec: Ensure patient is being managed according to NHLBI guidelines83 and refer to expert in pulmonary hypertension for right heart catheterization |
| 3. Actions to be taken based on the results of right heart catheterization |
| • mPAP <25 mm Hg: pulmonary hypertension not present: Ensure patient is being managed according to NHLBI guidelines83 and repeat echocardiogram yearly |
| • mPAP ≥25 mm Hg and PCWP ≤15 mm Hg: precapillary pulmonary hypertension |
| – Perform ventilation/perfusion scan of lung and consider long-term anticoagulation if segmental defect found |
| – Refer for overnight polysomnography to evaluate for sleep-disordered breathing including obstructive sleep apnea; provide appropriate intervention if present |
| – Chronic low-flow oxygen by nasal cannula if pulse ox <90% |
| – Refer to expert in pulmonary hypertension for follow-up and consideration whether therapy with endothelin receptor blocker or prostacyclin agent should be attempted* |
| – Consider initiating therapy with hydroxyurea if patient is not receiving this medication or with exchange blood transfusion program if patient does not tolerate or respond to hydroxyurea |
| – Consider allogeneic hematopoietic stem cell transplantation with low-intensity conditioning regimen if patient has HLA-matched sibling.† |
| • mPAP ≥25 mm Hg and PCWP >15 mm Hg: postcapillary pulmonary hypertension |
| – Refer to cardiologist to evaluate for left ventricular systolic or diastolic dysfunction; manage according to established guidelines for left ventricular failure74 |
| – Consider initiating therapy with hydroxyurea if patient not receiving this medication or with exchange blood transfusion program if patient does not tolerate or respond to hydroxyurea |
| – Consider allogeneic hematopoietic stem cell transplantation with low-intensity conditioning regimen if patient has HLA-matched sibling |
NHLBI, National Heart, Lung, and Blood Institute.
There have been reports that some treatments effective for pulmonary arterial hypertension in patients without SCD also improve SCD-related pulmonary hypertension with hemodynamic parameters consistent with pulmonary arterial hypertension.85-87
Successful lung transplantation, with intensive pre- and postoperative transfusion support, has been reported in a Hb SS patient with refractory pulmonary hypertension. The patient was maintained with a hemoglobin S percent <10% after transplant through exchange blood transfusion.22