Sickle cell disease (SCD) remains the most common monogenic disorder worldwide, yet more than a century after its formal discovery, our treatment options and approach to care remain underdeveloped. Despite scientific progress, care for SCD continues to lag behind other chronic conditions, in part due to a lack of consensus on straightforward medical decision-making—driven by a persistent paucity of data and compounded by historical neglect, systemic inequities, and clinical heterogeneity. To truly serve this vulnerable population, we must move toward a more comprehensive, personalized approach to adult care—one that mirrors the individualized pain management plans routinely used in acute care settings. While much of the foundational work in SCD has been in pediatrics, this manuscript focuses on the adult population, where the burden of disease increases and access to specialized care declines. We emphasize the importance of considering genotype, hematologic profile, comorbid conditions, psychosocial context, and health literacy when developing treatment plans in shared decision-making with our patients. Ultimately, we hope this manuscript provides practical insights to help clinicians answer the daily complex questions surrounding sickle cell care: whom to treat and which interventions offer the most meaningful benefit for that particular patient.

1.
Osunkwo
I
,
Andemariam
B
,
Minniti
CP
, et al
.
Impact of sickle cell disease on patients' daily lives, symptoms reported, and disease management strategies: results from the international Sickle Cell World Assessment Survey (SWAY)
.
Am J Hematol
.
2021
;
96
(
4
):
404
-
417
.
2.
Bathla
T
,
Lotfollahzadeh
S
,
Quisel
M
,
Mehta
M
,
Malikova
M
,
Chitalia
VC
.
End organ affection in sickle cell disease
.
Cells
.
29
May
2024
;
13
(
11
).
3.
Lee
MT
,
Piomelli
S
,
Granger
S
, et al
; STOP Study Investigators.
Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results
.
Blood
.
2006
;
108
(
3
):
847
-
852
.
4.
Sarnaik
S
,
Soorya
D
,
Kim
J
,
Ravindranath
Y
,
Lusher
J.
Periodic transfusions for sickle cell anemia and CNS infarction
.
Am J Dis Child
.
1979
;
133
(
12
):
1254
-
1257
.
5.
Ware
RE
,
Helms RW; SWiTCH
Investigators
.
Stroke with transfusions changing to hydroxyurea (SWiTCH)
.
Blood
.
2012
;
119
(
17
):
3925
-
3932
.
6.
DeBaun
MR
,
Jordan
LC
,
King
AA
, et al
.
American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults
.
Blood Adv
.
2020
;
4
(
8
):
1554
-
1588
.
7.
Biller
E
,
Zhao
Y
,
Music-Aplenc
L
, et al
.
Red cell exchange: a concise review of indications and management
.
Blood
.
2017
;
130
(
suppl 1
):
4800
.
8.
Sickle Cell Disease and Cardiovascular Risk—Red Cell Exchange Trial (SCD-CARRE)
. ClinicalTrials.gov identifier: NCT04084080. Updated
24
April
2025
.
9.
Alan
S
,
Sharma
D
,
Pecker
LH
.
Prophylactic red cell transfusions for sickle cell disease pregnancy: increased use of therapy could transform outcomes
.
Curr Opin Hematol
.
2024
;
31
(
6
):
285
-
293
.
10.
Oteng-Ntim
E
,
Oakley
LL
,
Robinson
V
, et al
.
Prophylactic exchange transfusion in sickle cell disease pregnancy: a TAPS2 feasibility randomized controlled trial
.
Blood Adv
.
2024
;
8
(
16
):
4359
-
4369
.
11.
Prophylactic Transfusion in Pregnant Women With Sickle Cell Disease
. ClinicalTrials.gov. Identifier: NCT06979492. Posted
13
May
2025
.
12.
Zakieh
A
,
Mercure-Corriveau
N
,
Lanzkron
S
, et al
.
Chronic automated red cell exchange therapy for sickle cell disease
.
Transfusion
.
2024
;
64
(
8
):
1509
-
1519
.
13.
Kelly
S.
Logistics, risks, and benefits of automated red blood cell exchange for patients with sickle cell disease
.
Hematology Am Soc Hematol Educ Program
.
8
Dec
2023
;
2023
(
1
):
646
-
652
.
14.
Choi
J
,
Markantonis
JE
,
De Simone
N
,
Nero
A
,
Kim
J
,
Sarode
R.
Hemoglobin S target of <50% as compared to 30% in chronic red cell exchange for secondary stroke prevention in sickle cell disease
.
J Clin Apher
.
2023
;
38
(
6
):
677
-
684
.
15.
McGann
PT
,
Ware
RE
.
Hydroxyurea therapy for sickle cell anemia
.
Expert Opin Drug Saf
.
2015
;
14
(
11
):
1749
-
1758
.
16.
Charache
S
,
Terrin
ML
,
Moore
RD
, et al
; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia.
Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia
.
N Engl J Med
.
1995
;
332
(
20
):
1317
-
1322
.
17.
Steinberg
MH
,
Barton
F
,
Castro
O
, et al
.
Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment
.
JAMA
.
2003
;
289
(
13
):
1645
-
1651
.
18.
Steinberg
MH
,
McCarthy
WF
,
Castro
O
, et al
; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia and MSH Patients' Follow-Up.
The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: a 17.5 year follow-up
.
Am J Hematol
.
2010
;
85
(
6
):
403
-
408
.
19.
American Society of Hematology
.
Hydroxyurea and Transfusion Therapy for the Treatment of Sickle Cell Disease: A Pocket Guide for the Clinician
.
2014
.
20.
Ogu
UO
,
Okoye
HC
,
Nnodu
OE
,
Lanzkron
S.
Hydroxyurea at escalated dose versus fixed low-dose for sickle cell disease: a systematic review and meta-analysis
.
Am J Hematol
.
2023
;
98
(
12
):
1767
-
1777
.
21.
American Society of Hematology
.
ASH Clinical Practice Guidelines on Dosing and Monitoring of Hydroxyurea for Sickle Cell Disease
.
2024
.
Hematology.org
.
22.
Smart
LR
,
Segbefia
CI
,
Latham
TS
, et al
.
Prospective identification of variables as outcomes for treatment (PIVOT): study protocol for a randomised, placebo-controlled trial of hydroxyurea for Ghanaian children and adults with haemoglobin SC disease
.
Trials
.
2023
;
24
(
1
):
603
.
23.
Morrison
SJ
,
Dandapani
S
,
Kohn
TP
, et al
.
Impact of hydroxyurea on follicle density in patients with sickle cell disease: a cross-sectional study of ovarian tissue
.
Blood Adv
.
2024
;
8
(
19
):
5227
-
5234
.
24.
Sewaralthahab
S
,
Alsubki
LA
,
Alhrabi
MS
,
Alsultan
A
.
Effects of hydroxyurea on fertility in male and female sickle cell disease patients. A systemic review and meta-analysis
.
PLoS One
.
2024
;
19
(
6
):
e0304241
.
25.
Pecker
LH
,
Cameron
K.
Sickle cell disease and infertility risks: implications for counseling and care of affected girls and women
.
Expert Rev Hematol
.
2024
;
17
(
8
):
493
-
504
.
26.
Nahata
L
,
Creary
SE
,
Quinn
GP
,
Shillingford
J
,
Pecker
LH
.
Fertility counseling and sickle cell disease: clinical and ethical challenges for adolescent boys
.
Blood Adv
.
2023
;
7
(
18
):
5533
-
5537
.
27.
Kroner
BL
,
Hankins
JS
,
Pugh
N
, et al
;
Sickle Cell Disease Implementation Consortium
.
Pregnancy outcomes with hydroxyurea use in women with sickle cell disease
.
Am J Hematol
.
2022
;
97
(
5
):
603
-
612
.
28.
Hydroxyurea Exposure Limiting Pregnancy and Follow-Up Lactation (HELPFUL)
. ClinicalTrials.gov. Identifier: NCT04093986. Posted
18
September
2019
.
29.
James
AH
,
Strouse
JJ
.
How I treat sickle cell disease in pregnancy
.
Blood
.
29
February
2024
;
143
(
9
):
769
-
776
.
30.
Alan
S
,
Mendez-Marti
SR
,
Zik
C
,
Ershler
WB
.
Advancing through challenges: current strategies in sickle cell disease management
.
Ann Blood
.
2024
;
9
:
14
.
31.
Polek
A
,
Sobiczewski
W
,
Matowicka-Karna
J.
[P-selectin and its role in some diseases]
.
Postepy Hig Med Dosw
.
2009
;
63
:
465
-
470
.
32.
Ataga
KI
,
Kutlar
A
,
Kanter
J
, et al
.
Crizanlizumab for the prevention of pain crises in sickle cell disease
.
N Engl J Med
.
2017
;
376
(
5
):
429
-
439
.
33.
Abboud
MR
,
Cançado
RD
,
De Montalembert
M
, et al
.
Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial
.
Lancet Haematol
.
2025
;
12
(
4
):
e248
-
e257
.
34.
Anderson
A
,
El Rassi
F
,
Khemani
K
, et al
.
Primary analysis of Spartan: a phase 2 trial to assess the efficacy and safety of crizanlizumab in patients with sickle cell disease related priapism
.
Blood
.
2023
;
142
(
suppl 1
):
146
.
35.
A Study to Assess the Safety and Efficacy of Inclacumab in Participants With Sickle Cell Disease Experiencing Vaso-Occlusive Crises
. ClinicalTrials.gov. Identifier: NCT04935879. Posted
24
June
2021
.
36.
Niihara
Y
,
Miller
ST
,
Kanter
J
, et al
; Investigators of the Phase 3 Trial of L- glutamine in Sickle Cell Disease.
A phase 3 trial of l-glutamine in sickle cell disease
.
N Engl J Med
.
2018
;
379
(
3
):
226
-
235
.
37.
Alan
S
,
Kanter
J.
Advances in pharmacotherapy for sickle cell disease: what is the current state of play?
Expert Opin Pharmacother
.
2024
;
25
(
10
):
1325
-
1334
.
38.
Kassim
AA
,
DeBaun
MR
.
The range of haploidentical transplant protocols in sickle cell disease: all haplos are not created equally
.
Hematology Am Soc Hematol Educ Program
.
2023
;
2023
(
1
):
532
-
541
.
39.
Sharma
A.
How I treat sickle cell disease with gene therapy
.
Blood
.
2024
;
144
(
26
):
2693
-
2705
.
40.
Prince
E
,
Loeser
P
,
Early
M
,
Carroll
CP
,
Lanzkron
S
,
Pecker
LH
. “
Buprenorphine, it works so differently”: adults with sickle cell disease describe transitioning to buprenorphine for treatment of chronic pain
.
J Pain
.
2024
;
25
(
3
):
632
-
641
.
41.
Alan
S
,
Fusisi
R
,
Holley
D
, et al
.
Empowering minds, easing pain: the role of talk therapy in sickle cell disease
.
J Sickle Cell Disease
.
2024
;
1
(
suppl 1
):yoae002.024.
42.
Palermo
TM
,
Lalloo
C
,
Zhou
C
, et al
.
A cognitive-behavioral digital health intervention for sickle cell disease pain in adolescents: a randomized, controlled, multicenter trial
.
Pain
.
2024
;
165
(
1
):
164
-
176
.
43.
Jonassaint
CR
,
Lalama
CM
,
Carroll
CP
, et al
.
Digital cognitive behavioral therapy vs education for pain in adults with sickle cell disease
.
Blood Adv
.
2024
;
8
(
24
):
6257
-
6266
.
44.
Pecker
LH
,
Maher
JY
,
Law
JY
,
Beach
MC
,
Lanzkron
S
,
Christianson
MS
.
Risks associated with fertility preservation for women with sickle cell anemia
.
Fertil Steril
.
2018
;
110
(
4
):
720
-
731
.
45.
Schroeder
P
,
Fulzele
K
,
Forsyth
S
, et al
.
Etavopivat, a pyruvate kinase activator in red blood cells, for the treatment of sickle cell disease
.
J Pharmacol Exp Ther
.
2022
;
380
(
3
):
210
-
219
.
46.
Xu
JZ
,
Conrey
A
,
Frey
I
, et al
.
A phase 1 dose escalation study of the pyruvate kinase activator mitapivat (AG-348) in sickle cell disease
.
Blood
.
2022
;
140
(
19
):
2053
-
2062
.
47.
Saraf
SL
,
Hagar
R
,
Idowu
M
, et al
.
Multicenter, phase 1 study of etavopivat (FT-4202) treatment for up to 12 weeks in patients with sickle cell disease
.
Blood Adv
.
2024
;
8
(
16
):
4459
-
4475
.
48.
Grismore
C
,
Roberts
LR
,
Lister
ZD
, et al
.
Barriers to care for adults with sickle cell disease: a qualitative descriptive study
.
Health Expect
.
2025
;
28
(
3
):
e70310
.
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