Pulmonary hypertension ( PH ) is defined as an elevation of the resting mean pulmonary arterial pressure ( greater than or equal to 25 mmHg ) as determined by right heart catheterization ( RHC ).
There are several potential etiologies for elevation in mean pulmonary artery pressure in people with sickle cell disease ( SCD ).
Chronic hemolytic anemias, including sickle cell disease, may result in pulmonary vascular changes leading to pulmonary arterial hypertension ( PAH ), and are placed in Group 1 of the current classification.
This type of pulmonary hypertension may occur in up to 10% of those with sickle cell disease and accounts for 40 to 50% of cases of pulmonary hypertension.
The second most common type of pulmonary hypertension in sickle cell disease is pulmonary venous hypertension ( PVH ), assigned to Group 2 in the current classification, which is associated with an elevated pulmonary capillary wedge pressure of greater than or equal to 15 mmHg. This is often associated with left ventricular diastolic dysfunction.
Pulmonary hypertension also occurs in the setting of chronic lung disease, chronic thromboembolic disease, or can be due to unclear or multiple mechanisms ( Groups 3, 4, and 5 of the classification, respectively ). Because these circumstances may also be present in individuals with sickle cell disease, a thorough evaluation of mechanisms and comorbidities should be undertaken if PH is found.
Initial testing for pulmonary hypertension has been done with an echocardiography assessment to estimate pulmonary artery pressure using tricuspid regurgitant jet velocity ( TRV ), but diagnosis requires right heart catheterization and direct measurement of the pulmonary arterial pressure and vaso-reactivity of the vessels.
Transient elevation in TRV has been observed during acute vaso-occlusive episodes in individuals with sickle cell disease, which may not reflect baseline values or present chronic pulmonary hypertension.
The main symptoms of pulmonary hypertension include shortness of breath during routine activity, such as climbing two flights of stairs; fatigue; lethargy; chest pain; palpitations; syncope; peripheral edema; and decreased appetite. Careful history taking is needed to distinguish symptoms related to the anemia of sickle cell disease itself from the new onset of symptoms related to the development of pulmonary hypertension.
Observational studies show an increase in all-cause mortality for adults with sickle-cell anaemia ( SCA ) with an elevated tricuspid regurgitant jet velocity by echocardiography,although this association has not been found in children.
In children and young adults with relatively normal renal function, only 25–30% of those with an elevated tricuspid regurgitant jet velocity may have an elevated pulmonary artery pressure measured by right heart catheterization.
Older adults with sickle-cell anaemia and a high tricuspid regurgitant jet velocity are more likely to have an elevated pulmonary pressure, although 40% of those with a high tricuspid regurgitant jet velocity will have an elevated wedge pressure suggesting left heart disease.
A commonly associated finding is renal insufficiency.
The Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy ( walk-PHaSST ) study was published outside of the range of the evidence review for these guidelines and thus was not included. This study enrolled 33 subjects with sickle cell disease and pulmonary hypertension defined by an elevated tricuspid regurgitant jet velocity of greater than or equal to 2.7 m/sec and a 6-minute walk distance ( 6MWD ) of 150–500 meters.
Right heart catheterization was required in the tricuspid regurgitant jet velocity greater than or equal to 3.0 m/sec group; all subjects were randomized to Sildenafil or placebo regardless of findings at right heart catheterization.
This study was closed early due to an increase in serious adverse events associated with Sildenafil use; estimation of results by futility analysis suggested no improvement in 6MWD would be demonstrated if the study continued.
These data confirm earlier data that right heart catheterization is necessary to confirm the presence of pulmonary hypertension and distinguish the mechanism of disease before considering therapy for pulmonary hypertension.
It is unknown if intervention for sickle cell disease ( e.g., transfusion or Hydroxyurea ) would change the all-cause mortality associated with an elevated tricuspid regurgitant jet velocity. ( Xagena )
NIH - Evidence-Based Management of Sickle Cell Disease - Expert Panel Report, 2014