Clinical and Laboratory Predictors Of Elevated TRV In Sickle Cell Anaemia

Pulmonary hypertension (PH) has become an increasingly recognized complication in sickle cell anaemia (SCA) and is a major cause of morbidity and mortality. Though the burden of SCA in sub-Saharan Africa is high, there is paucity of data on SCA-associated PH with little or no attention given to it in routine patient care. The current study therefore sought to determine the prevalence of PH and its associated risk factors among adult patients with SCA. This was a cross-sectional study involving 76 clinically stable, hydroxyurea-naive participants. We obtained socio-demographic and clinical history. Measurement of Tricuspid Regurgitant jet Velocity (TRV) was obtained via transthoracic echocardiography and lung function was assessed using spirometry and pulse oximetry. Other investigations were complete blood counts, free plasma haemoglobin, serum urea and creatinine. Twenty-five (32.9%) of study participants had elevated TRV (≥ 2.5m/s) on Doppler echocardiography, which was suggestive of raised pulmonary artery systolic pressure. There were significant associations between elevated TRV and steady-state haemoglobin (p < 0.001), blood urea level (p = 0.030), presence of chronic leg ulcers (p = 0.043) and oxygen saturation (p < 0.001) and these may be identifiable and modifiable risk factors for selective screening with echocardiography in a resource poor setting. DOI : 10.14302/issn.2372-6601.jhor-18-2139 Corresponding Author: Jane S. Afriyie-Mensah, Department of Medicine and therapeutics, School of Medicine and Dentistry,College of Health Sciences university of Ghana, Accra, Ghana, Email: jafriyiemensah@yahoo.com .


Introduction
Pulmonary involvement in sickle cell disease (SCD) has been shown to be a major factor affecting morbidity and mortality, being recognized also as an important determinant of survival 1,2 .This has become apparent in recent times as increased numbers of SCD patients reach adulthood due to improved survival strategies in childhood 3 . The lungs are common sites of hypoxic and ischaemic injury, emboli from marrow infarcts/fat necrosis with increased propensity to developing pneumonias 4 . Chronic lung complications in sickle cell disease describes a state of permanent damage to the lung parenchyma and vasculature.
Manifestations include interstitial abnormalities/fibrosis, restrictive lung disease and pulmonary hypertension in its severe form 5 . Emerging evidence have consistently shown that pulmonary hypertension (PH) complicated by right heart failure is a major cause of mortality among adult patients with disease, particularly those with homozygous disease, sickle cell anaemia (SCA) [6][7][8] .
Pulmonary hypertension is usually asymptomatic in the early stages but may be characterized by dyspnoea on exertion, hypoxaemia, progressive worsening of pulmonary function tests (PFTs) and right heart failure when severe 9 . Even in advanced stages, the elevation in pulmonary artery systolic pressures (PASP) has been shown to be mild to moderate in sickle cell patients compared to those with idiopathic or scleroderma associated PH, yet the former presents with equivalent symptoms of severe dyspnoea, exercise limitation, hypoxaemia and progressive right heart failure 10 . This spells out the need for screening and early identification of elevations in PASP using non-invasive means such as trans-thoracic echocardiography (ECHO) instead of invasive right heart catheterization (RHC), which is the diagnostic procedure. This is a validated tool for detecting early rise in pumonary artery pressure, with PH being more likely if the tricuspid regurgitant jet velocity (TRV) is ≥ 2.5m/s. The prevalence of elevated TRV using echocardiography is estimated to be 25-30% among SCA patients and 10-25% in those with genotype SC 6,8,11 . However, studies have reported that only about 6-11% of patients with TRV ≥ 2.5m/s on ECHO have confirmed pulmonary hypertension on right heart catheterization 12,13 . Notwithstanding, elevated TRV ≥ 2.5m/s in sickle cell patients has been significantly associated with decreased exercise tolerance and increased mortality estimated to be about 40% at 40 months of follow-up and is therefore considered an independent risk factor for death among these patients 6,14,15 . According to the official American Thoracic Society (ATS) practice guideline 16     Assessing the association with other vascular complications in SCA, the current study found a significant relationship between TRV and chronic/ recurrent leg ulcers (p = 0.043) but not with priapism (p=0.253). Although we also found a significant association between serum urea and TRV, which compares with findings in previous studies, the former is not a measure of kidney function and measurement of urine microalbumin would have been a better marker of early renal involvement 6,11,38,39 .
Frequency of sickling crisis, which is considered a marker of disease severity among SCA patients was not statistically different between the groups with elevated TRV and those without 39  In conclusion, steady-state Hb is a significant risk factor for elevated TRV in SCA, with increased risk when steady-state Hb is 6.9g/dl or less. In view of this finding, we recommend that steady-state Hb could be used to selectively identify SCA patients who need screening for PH, particularly in low resource settings.
Also, measures to reduce or prevent hyperhaemolysis in SCA patients such as hydroxyurea and chronic scheduled transfusions should be considered in our setting, although the latter may not be immediately feasible in low income countries.

Acknowledgement
We are grateful to all sickle cell patients who