1/ Sickle cell anaemia results from inheritance of 2 mutated beta globin genes leading to an HbSS phenotype.
Red cells containing this haemoglobin molecule are prone to becoming deformed/elongated under low oxygen tension, forming the characteristic sickle shape
Red cells containing this haemoglobin molecule are prone to becoming deformed/elongated under low oxygen tension, forming the characteristic sickle shape
2/ These red cells can obstruct capillaries leading to tissue infarction, and carry oxygen poorly once deformed, leading to a worsening cycle of hypoxaemia and sickling - this is at it's most dangerous in the acute chest syndrome (see #bukumedicine for more about this)
3/ Sickle cell anaemia can be treated with hydroxycarbamide- this has traditionally been used as an oral chemotherapy drug and so seems like an odd choice in sickle cell anaemia but has huge benefits including... (data from studies in children)
4/
- Improved overall survival
- Reduced hospital admissions
- Reduced painful crises + acute chest crises
- Reduced stroke incidence
- Reduced transfusions
- Rather than increasing infection rates as you would expect with an oral chemotherapy drug it appears to reduce them 😮
- Improved overall survival
- Reduced hospital admissions
- Reduced painful crises + acute chest crises
- Reduced stroke incidence
- Reduced transfusions
- Rather than increasing infection rates as you would expect with an oral chemotherapy drug it appears to reduce them 😮
5/ The way that it achieves these benefits is two-fold
a) It puts the marrow under 'stress' leading to the production of foetal haemoglobin (HbF) instead of HbS. This is better at oxygen carriage and does not sickle
b) Reduces intravascular white/red cell/endothelial adhesion
a) It puts the marrow under 'stress' leading to the production of foetal haemoglobin (HbF) instead of HbS. This is better at oxygen carriage and does not sickle
b) Reduces intravascular white/red cell/endothelial adhesion
6/ The higher the HbF, the greater the benefit so we aim for a maximum tolerated dose of HC➡️⬆️HbF (not letting neutrophil count<1)
In the UK it is advised to be used from 9 months of age to reduce complications of SCA and improve survival
In the UK it is advised to be used from 9 months of age to reduce complications of SCA and improve survival
7/ Some FAQ's about hydroxycarbamide in SCA;
- As a type of chemo does it cause bone marrow damage and therefore risk leukaemia or myelodysplasia?
NO evidence of this with 17 years follow up in MDS patients. No evidence of acquired mutations after 8 years of treatment in SCA pts
- As a type of chemo does it cause bone marrow damage and therefore risk leukaemia or myelodysplasia?
NO evidence of this with 17 years follow up in MDS patients. No evidence of acquired mutations after 8 years of treatment in SCA pts
8/
-Does hydroxycarbamide delay growth or cognitive development?
NO evidence of this with 15 years of follow up from treatment starting at 6 months old
-Does hydroxycarbamide delay growth or cognitive development?
NO evidence of this with 15 years of follow up from treatment starting at 6 months old
9/
-Is fertility affected?
NO evidence in women. Harder to know in men as SCA disease process impairs spermatogenesis. For this reason post-pubertal males should be offered sperm analysis and cryopreservation
Consider cessation if trying to conceive
-Is fertility affected?
NO evidence in women. Harder to know in men as SCA disease process impairs spermatogenesis. For this reason post-pubertal males should be offered sperm analysis and cryopreservation
Consider cessation if trying to conceive
10/
-Is it teratogenic?
Probably (possible association with pregnancy losses) therefore women of childbearing age should use contraception when not actively trying to conceive.
They should discuss with their SCA team if considering starting a family to discuss options
-Is it teratogenic?
Probably (possible association with pregnancy losses) therefore women of childbearing age should use contraception when not actively trying to conceive.
They should discuss with their SCA team if considering starting a family to discuss options
11/
In summary hydroxycarbamide is a fantastic drug for patients with SCA for whom it is indicated (the majority of patients).
There are some historical concerns about it but most have increasing evidence to disprove them
#MedTwitter #FOAMed #MedEd #MedStudentTwitter
In summary hydroxycarbamide is a fantastic drug for patients with SCA for whom it is indicated (the majority of patients).
There are some historical concerns about it but most have increasing evidence to disprove them
#MedTwitter #FOAMed #MedEd #MedStudentTwitter
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