Previous episodes of acute chest syndrome (risk increases with number of previous episodes)
Patients with hemoglobin SC disease (Sickle C disease): may present with cor pulmonale without frequent antecedent acute chest syndrome episodes (due to higher Hct with increased blood viscosity -> increased sickling in precapillary pulmonary circulation)
Pulmonary hypertension has been described most frequently in patients with SCD with histologic lesions similar to those found in IPAH, including plexiform lesions in 1 case series
However, the prevalence of PAH in SCD is not clearly established.
The largest study of patients with SCD, which defined PH echocardiographically by the presence of tricuspid regurgitation jet velocity (TRV) greater than or equal to 2.5 m/s, found that 32% of patients had PH
However, using a TRV >2.5 m/s on echocardiography to define PH can lead to a substantial number of false positive cases of PH not confirmed by right heart catheterization
When a TRV >3.0 m/s was used, corresponding to an estimated systolic PAP of >41 mm Hg, only 9% of the cohort met the criteria for PH.
Right heart catheterization was carried out in only 18 of 63 patients with TRV >2.5 m/s. In this subpopulation, PH defined by a mean PAP >25 mm Hg was confirmed in 17 patients; however, pulmonary wedge pressure was elevated in some patients.
A substantial proportion of patients with SCD have pulmonary venous hypertension: 46% in 1 study of 26 patients with SCD and PH
In addition, some patients present with a hyperkinetic state with moderate elevation in mean PAP and normal PVR.
Thus, although it appears that some patients with SCD do develop PAH, the prevalence of PAH in SCD is undoubtedly much lower than 32%
Prospective epidemiologic studies using echocardiographic screening and direct hemodynamic confirmation with right heart catheterization in all patients with suspected PH are ongoing and will evaluate the precise prevalence of PAH in SCD.
The mechanism of PAH in SCD remains uncertain.
A probable hypothesis is that chronic hemolysis results in high rates of nitric oxide consumption and produces a state of resistance to nitric oxide bioactivity
Consequently, smooth muscle guanosine monophosphate, a potent vasodilator/antiproliferative mediator, is not activated
Microangiopathic hemolytic anemia and thrombocytopenia in primary pulmonary hypertension. N Engl J Med 1972;287:869–70
Pulmonary hypertension and right heart failure in patients with