Blood screen may spot potential complications in sickle cell children
Testing for proteins could be useful tool for doctors in resource-poor areas
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Testing blood levels of certain clotting proteins may help clinicians identify serious complications of sickle cell disease (SCD) in children, a study showed, a finding that could be especially useful in resource-poor settings.
Data indicated that vaso-occlusive crises (VOCs) in children with SCD were associated with elevated levels of VWF and normal ADAMTS13 levels, while a higher VWF-to-ADAMTS13 ratio may be indicative of stroke.
Neutrophils, a type of immune cell, were significantly elevated in children with VOCs and those experiencing a stroke compared with children with steady-state SCD, while the number of immature red blood cells was significantly higher in the VOC group.
Blood cells and clotting markers “may serve as alternatives to imaging for screening and detecting high-risk SCD complications,” the researchers wrote, though they noted a need for further studies to confirm the utility of these blood biomarkers.
The study, “Elevated VWF with normal ADAMTS13 in pediatric sickle cell disease: links to crises and ischemic stroke,” was published in Blood Vessels, Thrombosis & Hemostasis.
Lack of access to diagnostic tools hampers diagnosis
SCD is a genetic disorder marked by an abnormal form of hemoglobin, the protein red blood cells use to carry oxygen through the body. The abnormal hemoglobin is prone to forming clumps in blood cells, deforming them into the sickle shape that gives the disease its name.
These deformed blood cells can get stuck in blood vessels, blocking normal blood flow and causing the painful episodes known as VOCs. Problems with blood flow can also increase the risk of stroke for people with SCD, especially children.
Doctors in wealthy countries often rely on imaging equipment such as CT and MRI scans to detect complications such as VOCs and stroke. But this equipment is expensive and inaccessible in many poorer regions.
SCD is common in sub-Saharan countries such as Kenya. But expensive medical equipment is hard to come by, and this combination means many children with SCD aren’t diagnosed correctly and, as a result, don’t get the life-saving care they need.
“This increases the likelihood of the children with SCD dying from [VOCs or stroke], further pointing to the need for alternative screening and diagnostic tools that are more accessible and easier to implement in under-resourced hospitals,” the researchers wrote.
In search of more accessible tools, four scientists in Kenya looked at two proteins, VWF and ADAMTS13. These proteins play key roles in regulating blood clotting, and they are often involved when blood flow is blocked or disturbed.
The scientists hypothesized that levels of VWF and/or ADAMTS13 might be elevated in SCD patients experiencing a VOC or stroke. This would support the use of these proteins as biomarkers for use in blood tests that are cheaper and more accessible than advanced imaging.
Protein levels linked to SCD
The researchers measured VWF and ADAMTS13 levels in 112 children aged 2 to 14. Thirty-two had steady-state SCD, 24 had SCD-related VOCs, 24 had SCD-related strokes, and 32 did not have SCD.
Results showed that VWF protein activity tended to be higher in SCD patients than in kids without the disease, and was particularly higher among children with SCD who were experiencing VOC or stroke. Differences reached statistical significance between SCD patients experiencing VOCs and healthy children.
At the same time, ADAMTS13 levels were significantly higher among SCD patients without complications than in kids without the disease, but tended to show values between these two groups in SCD patients with VOC or stroke.
“Elevated VWF [levels] with normal ADAMTS13 … levels is likely indicative of VOC in pediatric SCD,” the researchers wrote.
A ratio of VWF levels to VWF activity to ADAMTS13 levels was significantly elevated in the stroke group, compared with the steady-state SCD group and the VOC group. This suggests that this ratio could be a marker of stroke in children with SCD.
The scientists noted that more work is needed to further validate these clotting proteins as markers of complications in SCD.
When the team looked at other blood markers, they found that SCD patients experiencing a VOC or stroke had significantly higher counts of inflammatory immune cells called neutrophils relative to healthy children and those with steady-state SCD. This likely reflects the body’s immune system kicking into gear in response to SCD-related damage to blood vessels, the scientists said, noting that this type of immune response may worsen blood-flow problems in SCD.
All three groups of children with SCD also had low hemoglobin and red blood cell counts compared with healthy controls, indicative of the anemia that often develops in people with the disease. The researchers noted that the combination of inflammation and anemia may modulate the activity of clotting proteins, including VWF and ADAMTS13.
“This study showed that [SCD is] associated with a complex interplay of anemic and inflammatory states that may modulate the VWF-ADAMTS13 axis,” the researchers wrote.
