# Sickle Cell Disease and Cardiovascular Risk- Red Cell Exchange SCD-CARRE

> **NIH NIH UH3** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $2,667,908

## Abstract

As patients with sickle cell disease (SCD) live to adulthood, the chronic impact of sustained hemolytic anemia 
and episodic vaso-occlusive events take their toll, with the progressive development of cardiopulmonary organ 
dysfunction. This culminates in the development of pulmonary hypertension, left ventricular diastolic heart 
disease, dysrhythmia, chronic kidney disease and sudden death, all major cardiovascular complications of SCD 
for which there are no approved or consensus therapies. The risk of having pulmonary hypertension and diastolic 
heart disease can be non-invasively assessed by laboratory tests (NT-proBNP) and Doppler-echocardiography 
(estimated pulmonary artery systolic pressure). A recent meta-analysis of approximately 6000 patients with SCD
demonstrated that patients with elevated tricuspid regurgitant jet velocity (TRV), which is an Dopplerechocardiographic measurement that estimates the pulmonary artery systolic pressure, walked an estimated 
30.4 meters less in a 6 minute walk test than those without elevated TRV, and elevated TRV was associated 
with high mortality (hazard ratio of 4.9). In two large registry cohorts of adult patients with SCD, we found that 
approximately 20% of the adult SCD population have high values for both biomarkers, defined as a TRV ≥ 2.5 
meters per second AND a NT-proBNP ≥ 160 pg/mL, and that the 12-month mortality rate is 7.9% in this group 
as compared to 0.5% in patients with normal TRV or NT-proBNP values, with a risk ratio for hospitalization of 
1.6. This suggests that a simple screening profile of TRV and NT-proBNP can identify about 20% of patients 
with SCD at the highest risk of death and hospitalization. Given the increased mortality and early loss of 
functional capacity associated with cardiovascular disease in SCD adults, it is important to test effective 
therapeutic interventions in such patients. Red blood cell transfusions are administered by either simple or 
exchange transfusion, the latter removes the patients blood and replaces it with transfused red blood cells. 
Exchange transfusions have proven effective for acute treatment of almost all SCD complications, including 
severe acute chest syndrome, stroke, splenic or hepatic sequestration, and multi-organ failure, and are also 
used chronically for stroke prevention and recurrent acute chest syndrome. In this study we hypothesize that 
monthly exchange transfusion will limit disease progression, improve exercise capacity, and prevent interval 
episodes of vaso-occlusive painful crisis and the acute chest syndrome that acutely increases pulmonary 
pressures and cause right heart failure. We propose to perform a clinical trial to evaluate the effects of automated 
exchange blood transfusion on patient morbidity and mortality, compared to standard of care among 150 adult 
high risk SCD patients. The trial will leverage existing coordinating center infrastructure at the University of 
Pittsburgh and will involve 22 experienc...

## Key facts

- **NIH application ID:** 10694551
- **Project number:** 7UH3HL143192-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Mark T Gladwin
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,667,908
- **Award type:** 7
- **Project period:** 2022-09-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10694551

## Citation

> US National Institutes of Health, RePORTER application 10694551, Sickle Cell Disease and Cardiovascular Risk- Red Cell Exchange SCD-CARRE (7UH3HL143192-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10694551. Licensed CC0.

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