Major Topics: Sickle Cell Disease ,Bone Marrow and Stem Cell Transplant,Sickle Cell Trait and G6PD,Students and Teachers, Physicians, Nurses and Health Care Providers,Sickle Cell Newborn Screening
Sub-Topics - Click on a question below
Sickle Trait and Malaria protection
SCA is an autosomal recessive disease caused by a point mutation in the hemoglobin beta gene (HBB) found on chromosome 11p15.4.Carrier frequency of HBB varies significantly around the world, with high rates associated with zones of high malaria incidence, since carriers are somewhat protected against malaria. About 8% of the African American population are carriers.
It is believed that the unusually high frequency of sickle cell trait (Hb AS) in individuals with African and Mediterranean ancestry has been maintained due to the reduced mortality from malaria infections when compared with individuals who do not carry the hemoglobin variant (Hb AA). The (Hb S) variant appears to decrease the risk of infection by the malaria parasite, Plasmodium falciparum. Although malaria is fatal in individuals with Hb SS, the protection from infection appears to operate in a (Hb S) dose-dependant manner (Aluoch JR. Higher resistance to Plasmodium falciparum infection in patients with homozygous sickle cell disease in western Kenya. Trop Med Int Health 2(6): 568-571 (1997)). That is, individuals with Hb SS have an even lower risk of infection than individuals with Hb AS.
A person with sickle cell trait should still take malaria protection. It will not stop and infection. It may make the infection less invasive.
Oniyangi O, Omari AAA. Malaria chemoprophylaxis in sickle cell disease. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003489. DOI: 10.1002/14651858.CD003489.pub2 at http://www2.cochrane.org/reviews/en/ab003489.html full text PDF http://www.thecochranelibrary.com/SpringboardWebApp/userfiles/ccoch/file/CD003489.pdf
and CDC guidelines at http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/malaria.aspx#990
In Denver, Lane and Githens (1985) observed the splenic syndrome (severe left-upper-quadrant abdominal pain) in 6 nonblack men with sickle cell trait who developed symptoms within 48 hours of arrival in Colorado from lower altitudes. The authors discussed the possibility that nonblacks may be at greater risk of trouble because of lack of other genetic make-up that through evolution has come to ameliorate the effects of the sickle gene in Africans. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=3974118
Kark et al. (1987) studied the frequency of sudden unexplained death among enlisted recruits during basic training in the U.S. Armed Forces from 1977 to 1981. They found that death rates per 100,000 were 32.2 for sudden unexplained deaths, 2.7 for sudden explained deaths, and zero for nonsudden deaths among black recruits with hemoglobin AS, as compared with 1.2, 1.2, and 0.7 among black recruits without hemoglobin S and 0.7, 0.5 and 1.1 among nonblack recruits without hemoglobin S. Among black recruits the relative risk of sudden unexplained death (hemoglobin AS vs nonhemoglobin S) was 27.6, whereas among all recruits this risk was 39.8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=3627196
There is an excellent review at the Harvard Sickle Cell Web site at http://sickle.bwh.harvard.edu/sickle_trait.html
Morbidity Associated With Sickle Cell Trait by Bruce L. Mitchell, M.D. Senior Associate Consultant at the Community Internal Medicine Department of the Mayo Clinic Jacksonville and the Mayo Primary Care Center in Kingsland, GA. http://www.dcmsonline.org/jax-medicine/2000journals/june2000/morbidity.htm
Scuba diving and sickle cell trait http://scuba-doc.com/sickle.htm
For clinical guidelines for sickle cell trait complications see:
Specific Problems: Sickle Cell Trait
Diagnosis and Counseling: Sickle Cell Trait
Sports trainers warn about sickle cell trait
GARY MIHOCES, USA TODAY http://www.baxterbulletin.com/apps/pbcs.dll/article?AID=/20070814/NEWS01/708140312/1002/NEWS01
Devard Darling has the blood condition called sickle cell trait. So did his twin brother, Devaughn, who died during a 2001 offseason team workout while both were football freshmen at Florida State.
Now a fourth-year NFL wide receiver with the Baltimore Ravens, Devard welcomes a report issued Wednesday by the National Athletic Trainers' Association aimed at raising awareness of the condition and addressing how to manage it.
"We know what happened to my soul mate and twin brother. Anything I can do to prevent that and save lives, I'm all for it," he said in a phone interview.
The report was released in Anaheim, Calif., at NATA's annual convention. Darling participated in the news conference.
Echoing the NCAA position that the trait is "not a barrier to outstanding athletic performance," NATA says "no sickle trait athlete is ever disqualified, because simple precautions seem to suffice."
The sickle cell gene is inherited. NATA says it is most common in people (including one in 12 African-Americans) originating from malarial regions and that "over the millennia, carrying one sickle cell gene fended off death from malaria."
Sickle cell trait differs from the disease sickle cell anemia, in which two sickle cell genes are present. "It's typically a benign condition outside of an intense, sustained physical activity," said Scott Anderson, head athletic trainer at the University of Oklahoma and co-chairman of NATA's sickle cell task force. But the report says during exertion, sickle cells can change red blood cells from round to sickle-shaped, create a "logjam" in blood vessels and kill. NATA links "sickling" to the deaths of nine athletes in the past seven years, including five college football players.
One NATA guideline: Athletes with the trait should sit out Day 1 football conditioning tests such as mile runs and repeated sprints "because several deaths have occurred from participation" in such workouts. "There seems to be something peculiar about that," Anderson said.
While the report said all 50 states screen at birth for sickle cell, Anderson said athletes typically don't know if they have it when they arrive at the college level. The NATA report says a survey of NCAA Division I-A schools found 64 percent responding said they screened for sickle cell. Anderson said screening is vital.
Heat, dehydration, altitude and asthma can increase the risk or sickling, the report says. It recommends cessation of activity when symptoms such as cramping, pain, swelling and shortness of breath occur.
The medical examiner's report in Florida didn't specify a cause of death for Devaughn Darling. It noted sickle cell trait was present. "I believe it had some effect on him, definitely," Devard Darling said. "My teammates, who were there at the time, said he was saying he couldn't see, he was blacking out. Clearly, there were signs for him to stop. There was definitely room for coaches and athletic trainers to step in and say that's enough."
Devard said he's had no problems with the condition and has always done "all team activities." But, he added, "I know my body. It's important for young athletes as they grow to know their limitations. The No. 1 thing is staying hydrated. But there is a point at which you know something is not right. You need a little rest."
He added, "I'm sure it's not just me (participating in pro sports with sickle cell trait). They say one out of every 10 to 12 people of African descent carries the sickle cell trait. You know the high amount of African-Americans in pro sports."
Devaughn Darling collapsed during a rigorous team workout in February 2001. Afterward, Florida State withdrew clearance for Devard to play but offered to keep him on scholarship. He finished his college career at Washington State.
A Florida State University police investigation found the school's coaches and medical staff not responsible for the death. Last year, a judge approved a $2 million settlement between Florida State and the Darling family. The state paid $200,000, a limit set by state law. The family is petitioning the Florida Legislature for the rest. Devard has set up a foundation in his native Bahamas to support the brothers' "dream of bringing football home to the Bahamas and creating opportunities for young kids." The As One Foundation gets its name from the twins' hearts beating "as one" in the womb.
National Athletic Trainers Association Consensus Statement: Sickle Cell Trait and the Athlete http://www.nata.org/statements/consensus/sicklecell.pdf
Can all races have sickle cell trait?
Yes, sickle cell anemia and trait affects millions throughout the world. It is particularly common among people whose ancestors come from Sub-Saharan Africa, South America, Cuba, Central America, Saudi Arabia, India, and Mediterranean countries such as Turkey, Greece, and Italy. In the Unites States, it affects around 72,000 people, most of whose ancestors come from Africa. The disease occurs in about 1 in every 500 African-American births and 1 in every 1000 to 1400 Hispanic-American births. About 2 million Americans, or 1 in 12 African Americans, carry the sickle cell allele.
How did the HbS mutation evolve and why it persists today among certain populations?
Based on experimental evidence of a reduced incidence of malaria among people carrying sickle cells in their blood stream, it is now assumed that the presence of the sickle cell trait protects individuals against malaria. Malaria parasites that invade red blood cells of individuals carrying the trait die with the cells when the latter assume the sickle shape and adhere to the walls of the blood vessels.
The hemoglobin S (HbS) mutation that protects against malaria did not develop as a response to malaria itself. It occurred by chance. Those people without the mutation, living in areas where malaria epidemics were common, were at an increased risk to contract this infectious disease, getting symptoms of high fevers, headache, muscle pain, enlarged spleen, and anemia. People carrying only two HbA (non-sickle cell) genes often died in their first few year of life. Those who were lucky enough to carry the HbS gene when malaria struck, had a better chance of living. They would survive to produce children, and their HbS-carrying children in turn would have more HbS-carrying children.
Those with sickle cell disease (two HbS genes) would also die early in life due to complications from the disease itself. The result? After multiple generations of this natural selection, more and more people who had a single HbS gene and a single HbA gene survived to pass on their genes.
Although hemoglobin S is the most common adaptation that occurs in malaria-infested areas, others have also developed. Hemoglobin C and the Thalassemias have also evolved. Thalassemia affects the amount rather than the type of hemoglobin produced. Those people having one HbS and one HbC gene have a milder form of sickle cell disease than those with two HbS genes. And depending on the nature of the thalassemia mutation, those people born with one HbS gene and one beta-thalassemia gene can have conditions ranging from ordinary sickle cell disease to living almost symptom-free.
Adapted from Ragusa, et al
Sickle Cell Disease today is found in North America, Southern Italy, Northern Greece, Southern Turkey, the Middle East, Saudi Arabia, the Eastern Province of Central India, and primarily in equatorial Africa. It is believed that sickle cell started in four different regions, and from three different mutations. One of the mutations is believed to have occurred randomly in two different locations. Scientists have examined the haplotypes of individuals with Sickle Cell to trace where it is these different mutations came from. It is currently believed there are four haplotypes:
- Senegal haplotype from the Atlantic Coast of West Africa
- Benin haplotype from Central West Africa, Angola, and Kenya
- Bantu/Central African Republic haplotype from Zaire, the Central African Republic, Angola, and Kenya
- Asian haplotype from Eastern Province of Saudi Arabia, and Central India
Hemoglobin S in different races in the US - 1 out of every 625 white newborns in California have sickle cell trait: http://www.cdc.gov/genomics/hugenet/reviews/tables/sickle_Tables.htm#t1
What About Sickle Cell Trait and other traits
Question: What problems can I have if I have sickle cell trait and what is the differences in hemoglobin S concentrations
Answer: Sickle trait can cause you to have some blood in the urine and a slight increase in problems with kidney infections. Individuals with sickle trait can have pain if they go to very high altitudes, greater than 12,000 feet. Other than these uncommon problems, there should be not health problems from sickle trait. Individuals with sickle trait may have children with sickle cell disease if their partner also has sickle, thalassemia, or hemoglobin C trait.
The mutation that makes the sickle hemoglobin (HbS) confers at least two abnormal properties:
1) when de-oxygenated, HbS polymerizes to forms rods and fibers that cause
the sickle deformation, and
2) when oxygenated, the HbS molecule is more unstable than normal HbA and
may spontaneously decompose ( to met-hemoglobin, or to globin without heme)
These properties are known from decades of research with HbS, and can be
shown in test tubes. They are biophysical properties of the HbS molecule.
What does this mean for the blood and for sickle cell disease manifestations? The composition of hemoglobin in the red blood cells determines their ability to sickle and cause sickle cell disease problems.
I. People with sickle trait have one gene making HbS and one gene making HbA, so you would expect equal amounts of HbS and HbA in the RBC. The unstable property of HbS, however, means that not all of the amount of HbS made in the red blood cell (RBC) stays floating around in the RBC, because some of the HbS decomposes. Therefore, the RBC contents for a person with sickle trait has slightly less than 50% HbS, typically something like 55 to 60 percent HbA and 40 to 45 percent HbS. The predominance of HbA inhibits and dilutes the ability of HbS to show its polymerization property, and so sickle trait is not a form of sickle cell disease. People with sickle trait have no anemia, no painful episodes, no special susceptibility to infection, and no implications for life expectancy........ it is not sickle cell disease.
Question: My toddler son has Sickle Trait. I know that he can live a full, happy life with relatively no complications. However, will his having the Trait prevent him from any dreams, such as being accepted to a prestigious military academy? Can people with Sickle Trait enter the military? I understand about heights, what about submarines? Will strenuous athletics and endurance tests, i.e. underwater, be potential hazards for him? And throughout life, will he be able to participate in any sport which doesn't include highest altitudes?
Answer: Each individual is different & I cannot completely predict what will
happen with sports activities strenuous or endurance activities, but
people I have met with sickle trait include: an Olympic track competitor
from Ghana, a recreational scuba diver, 2 NFL pro football stars, a pro
soccer player in Europe, an Army major, and an Air Force Academy graduate.
(These are parents of children with sickle cell disease.) As far as I
know, the Air Force has some restrictions about people with sickle trait
being on the flight deck for combat aircraft, but they can fly support
aircraft - you would need to check for details & updates. Sickle cell
trait affects about 1 in 10 African Americans, so there must be many many
other people out there doing all kinds of things. The super-strenuous
activities that can cause problems for people with sickle cell are pushing
to the limits of human endurance (survival treks in the desert) or doing
things foolishly, such as trying to exercise at high altitude (climbing in
the Rocky Mountains) when dehydrated & out of shape & not adjusted to high
altitude. So I think that sickle trait should not limit your son's potential but, again, each person is different. There is an excellent review at the Harvard Sickle Cell Web site at http://sickle.bwh.harvard.edu/sickle_trait.html
Parents with Sickle Cell Trait
Question: My husband and I both have the sickle cell trait. We have one child together and she has only the trait. We were told that if we had more children then they would most likely have sickle cell disease. Is there any way to prevent my child from having the disease before it is conceived or before I carry it. If we have a child with sickle cell disease, what are the treatments available?
Answer: The risk of having a child with sickle cell disease if both parents have sickle cell trait is 25% with each pregnancy. See http://www.sicklecellsociety.org/education/inherit.htm
There is a newly-developed, very experimental, method for very early
testing for sickle cell disease. It was published two months ago in the Journal of the American Medical Assoc, and is highly controversial - doing in vitro fertilization and then testing the embryos for sickle genes before implanting in the mother's womb.
The Journal of the American Medical Association (JAMA)
"Couple Has Twins Born Unaffected With Sickle Cell Disease After Using Genetic Test Prior To In Vitro Fertilization" Technique holds promise for sickle cell carrier couples to have healthy babies CHICAGO — A couple who are both carriers of sickle cell disease, a common human blood disorder that is passed down in families, successfully gave birth to twins who were free of the disorder by using a genetic test on embryos to determine that they do not have the sickle cell mutation before being implanted into the woman's uterus. This is the first successful attempt to use this genetic procedure to enable a couple to have a child unaffected with sickle cell disease, according to an article in the May 12, 1999 issue of The Journal of the American Medical Association (JAMA).
In vitro fertilization (IVF) combined with a procedure called Preimplantation Genetic Diagnosis (PGD) can improve a woman's chances of having a healthy baby when there is a family history of inherited genetic diseases or conditions, or if a patient has experienced miscarriages caused by embryo chromosomal abnormality.
Embryo biopsy with PGD is a procedure utilized in conjunction with IVF to screen for genetic and/or chromosomal problems before an embryo is selected for uterine implantation. This is also called "pre-pregnancy diagnosis". A number of genetic disorders and/or chromosomal abnormalities can be identified through PGD including Muscular Dystrophy, Hemophilia, Sickle Cell Anemia, Cystic Fibrosis, Tay Sachs, Fragile X Syndrome, Turner Syndrome, Huntington disease and Down syndrome.
"PGD allows us to differentiate abnormal embryos from the normal embryos, so that only normal embryos are transferred to the uterus," said Dr. Andrew Levi," a board certified reproductive endocrinologist and founder of Park Avenue Fertility and Reproductive Medicine in Trumbull, Connecticut. "In select patients, IVF with PGD can significantly decrease miscarriage rates and help women at risk for miscarriage achieve a successful pregnancy."
Dr. Levi reports that the majority of couples who proceed with IVF in conjunction with PGD either have experienced recurrent miscarriages; prior unexplained IVF failures; have conceived with a fetus or child with a chromosome abnormality; or have an identifiable or inheritable genetic medical conditions.
IVF entails stimulation of a woman's ovaries to obtain multiple eggs, subsequent removal of the eggs from the woman's body, fertilization of the eggs with the patient's partner's sperm, and transfer of the fertilized eggs (embryos) back to the woman's uterus. Embryo biopsy with PGD is performed typically three days after fertilization and before embryo transfer.
For more information
With current practice, bone marrow transplantation for sickle cell disease requires that the bone marrow donor be a sibling who is an immunologic match (HLA type match) and does not have sickle cell disease (can have sickle trait, or no sickle gene). There is a 25% chance that any two siblings will be HLA matches for each other. There is a 75% chance that the offspring will have no sickle cell disease, from a couple who both have sickle trait. This means that there is a 25% x 75% (18.75%) chance of a suitable sibling donor for a child with sickle cell disease. Because of the low chances for a suitable donor, there have been few children with sickle cell disease eligible for bone marrow transplantation. The procedure itself is also risky, with approximately 5 - 10% chance of death, and another 8 - 12% chance of graft rejection (meaning that you go through the transplant process but end up still having sickle cell disease). These risks have restricted the bone marrow transplant furthe,r to children who have serious complications from their sickle cell disease, and feel that the risks are worth taking. We have 6 patients here in Atlanta with bone marrow transplantation for sickle cell disease (the
largest number of at any center in North America) out of approximately 600
children with sickle cell disease followed here in our center, so you can
see how few transplants there are.
New possibilities in transplantation are now being explored: other types of donors, such as an HLA- matched cord blood from an unrelated person, transplant without as much chemotherapy, transplant in mid-trimester of pregnancy (Children's Hospital of Philadelphia and Wayne State U in Detroit). ( If you are interested in the prenatal transplant and you appear to live in Philadelphia, may I suggest contacting Dr. Kwaku Ohene-Frempong at Children's Hospital of Philadelphia, through pediatric hematology-sickle cell at 215-590-3438) All of these approaches are very new (1 or 2 cases), controversial, and results have not yet been published. More information is expected in the next few years.
Other possibilities are treatment of sickle cell disease with medications.Hydroxyurea is now in wider use for making people with severe sickle cell
disease have fewer symptoms. Other medications are in active research and, again, more information is expected in the next few years.
So, overall, there are many possibilities for improvements in sickle cell disease treatment and cure on the horizon, and the future looks better
than it did just a few years ago. Furthermore, the course of sickle cell disease is unpredictable, and a child may have a quiet and mild case. I
hope that this information gives you a sense of the possibilities and the hope.
Donating Blood if you have Sickle Cell Trait
Question: I have Sickle Cell Trait, Can I donate blood?
Answer: For nearly all purposes, blood with sickle trait is OK. Our Red Cross in Atlanta, for example, assumes that many of the blood units collected are
from donors with sickle trait. The Blood Bank only tests for sickle trait
upon requested by the doctors ordering the blood for transfusion. There
are uncommon situations where the presence of any sickle hemoglobin might
cause problems (such as extensive transfusions for a patient with sickle
cell disease, making it hard to test how much of the blood is the
patient's own and how much is transfused blood).
Hematuria (Blood in the Urine) and Sickle Cell Trait
Question: I was wondering if I could get your opinion on a patient who I am a physician seeing a patient who has sickle trait and hematuria.
He is a 51 y.o. man healthy all his life who developed substantial hematuria, including passing of blood clots in the urine, in January. Workup at an outside hospital found that he was bleeding from the left kidney, but no source was apparent. He had a renal angiogram that was negative. There was no evidence of papillary necrosis. He had cystoscopy, including cystoscopy of the left ureter post-Stent, which showed blood and clot coming from the area of the left kidney itself. The procedure was limited, however, and no source of bleeding was seen. I saw him for a second opinion in April. The bleeding spontaneously stopped the next day.
Two weeks ago it started again. Cystoscopy here again showed bleeding from the left side. A renal angiogram was negative. All of his clotting parameters are normal.
Any thoughts on a person with massive hematuria and sickle trait. I have only seen minor hematuria with sickle trait, but have been told that this does occur. However, the absence of papillary necrosis seems odd. Thoughts?
Answer: I have seen a number of cases exactly as you describe. They always seem to be bleeding from the left side. Older literature suggests they will immediately start bleeding from the right if the left kidney is removed. The episodes are often precipitated by exercise.
Treatment has been very difficult in some of my patients. Strict bed rest appears to be very important for severe hematuria. I use vigorous IV hydration with D5W with 2 amps of bicarb to alkalinize the urine. I usually also give lasix to maintain diuresis and add potassium as needed. If this does not work, we add epsilon amino caprilic acid once the hematuria is microscopic. Outpatient treatment is the same with oral bicarbonate, water, lasix, and potassium as needed. This usually allows patients to treat most episodes very early and control many without our help. Some use EACA as an outpatient but I do that very rarely.
Prevention is very important. Dancing and basketball seem to be the worse precipitants so hydration before during and after are very important. I usually let the individual decide on limits. Some avoid precipitants and others just put up with the hematuria.
Some cases are very severe and resistant to therapy. I have had an occasional patients that requires transfusion and several that become iron deficient and require chronic oral iron.
Sickle Trait and G6PD
Question - My wife and have a question that local doctors can not seem to answer;
we were wonder if perhaps someone here could help. My wife has Sickle
Cell Trait while I have G6-PD blood deficeincy. We are worried that
there might be health problems for a baby being conceived with our blood
disorders. Your help is greatly appreciated. thank you
Answer - If the parents know that mother has sickle trait and father has no
abnormal hemoglobins, then the children might have either sickle trait or
normal hemoglobin. It would be important for father to have his hemoglobin
If the father has G-6PD deficiency and mother does not, there is a small
chance that children would have G-6PD deficiency also - probably less than
50% chance for girls, hardly any chance for boys. The genetics of G-6PD
are co-dominant for females.
If some child has both sickle trait and G-6PD deficiency, it is not a
bigger deal than G-6PD deficiency alone.
Overall, these hematologic conditions should not be regarded as major
worries that would bar a couple from having children
What is G6PD?
Answer: G6PD deficiency is a very common condition and is hereditary. It does not affect everyday life, but can cause high sensitivity to certain types of
chemicals and medications, with the chemical property of "oxidants."
These include mothballs, certain antibiotics for malaria, the sulfa
antibiotics including Bactrim, a dye called methylene blue, and a
vegetable called fava bean. The normal function of the enzyme G6PD
(glucose 6 phosphate dehydrogenase) in the red blood cell is to protect
the red blood cell contents from oxidation by such chemicals. A person
with G6PD deficiency has low levels or no G6PD, and the red blood cells
are not well-protected from these oxidant chemicals. When the person with
G6PD deficiency is exposed to large amounts of these substances, he can
suffer breakdown of red blood cells and become very anemic. His urine may
become very dark, like the color of Coca-Cola. His eyes may become
jaundiced (yellow-orange). The main implication of knowing that your son
has G6PD deficiency is to avoid these specific substances, and have it
listed in his medical record so that red blood cell breakdown problems can
be recognized rapidly. The red blood cells are usually OK, when they are
not exposed to oxidant stress.
Since this condition is hereditary, other family members may have G6PD
deficiency.G6PD deficiency tends to be more mild in people of African descent, and more severe in people of Mediterranean descent and Asian descent. The
lower the G6PD level in the red blood cells, the more severe the condition
is. For more information please see http://www.g6pd.org/g6pd/ and http://www.nlm.nih.gov/medlineplus/ency/article/000528.htm