Under-recognized complications in patients with paroxysmal nocturnal haemoglobinuria: raised pulmonary pressure and reduced right ventricular function.
Pulmonary hypertension is becoming a recognized complication of the hereditary and acquired haemolytic anaemias, associated with a poor prognosis. Recently we reported that patients with paroxysmal nocturnal haemoglobinuria (PNH) have high levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker associated with both right and left ventricular dysfunction and cardiac dysfunction. In the current study we evaluated a cohort of patients (N = 29) with haemolytic PNH for elevated pulmonary artery systolic pressure and cardiac function by Doppler-echocardiography. Of the 29 patients, eight were further studied using cardiac magnetic resonance imaging (MRI), as well as two additional patients (number of patients studied using cardiac MRI = 10). Plasma from the first cohort (N = 29) demonstrated intravascular haemolysis associated with a 12-fold increase in median nitric oxide (NO) consumption when compared with healthy volunteers (P < 0·001). Doppler echocardiography demonstrated normal left ventricular function and elevated pulmonary artery systolic pressure in 41% of patients. Cardiac MRI from the second cohort (N = 10) demonstrated depressed right ventricular function in 80% of PNH patients tested, and 60% had findings suggestive of subclinical small pulmonary emboli. Together, these data suggest a high prevalence of haemolysis-associated NO scavenging, Doppler-estimated systolic pulmonary hypertension, and depressed right ventricular function in patients with PNH.
Department of Haematology, St. James's Institute of Oncology, Leeds, UK. anitahill@nhs.net
Anita
A
Hill
Robert J
RJ
Sapsford
Andrew
A
Scally
Richard
R
Kelly
Stephen J
SJ
Richards
Gus
G
Khurisgara
Mohan U
MU
Sivananthan
Peter
P
Hillmen
D000293:Adolescent; D000328:Adult; D000368:Aged; D015150:Echocardiography, Doppler; D006321:Heart / Q000503:physiopathology*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D016278:Ventricular Function, Right / Q000502:physiology; D055815:Young Adult
D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain