FREQUENTLY ASKED QUESTIONS [FAQ's]
Many people will discover that questions they had often asked had already been asked by others and answered. This Section will feature such. References are provided for those who wish to read further on the subject. If your question is not here please use the discussion forums to ask it for yourself. This is the first of several batches of FAQ's.

Questions

Q 1: "Why is Sickle Cell Anaemia only found in Black people?" 

A 1: This is a very common mis-conception. Sickle cell anaemia (sca) is not "only found in Black people". White people in Greece, Sicily, Turkey, and their offspring around the world suffer from sickle cell anaemia (sca). In fact, the highest incidences of the sickle cell gene (S, for short) are not found in Africa; they are in India and Saudi Arabia [References 1 to 10].

Q 2: "Why do people with sickle cell anaemia not suffer from malaria?" 

A 2: A common mis-conception. People with sickle cell anaemia do suffer from malaria, and very badly too. Doctors who have been wrongly taught have been known to advise their sickle cell anaemia patients travelling from Europe to the Tropics not to bother taking anti-malarial tablets because the sickle cells make them immune to the parasite. Dangerous advice, as malaria is the commonest cause of sickle cell crisis in Africa [ See also Question 8. References 9, 11 to 14, 21 & 22].

Q 3: "Why then do Science teachers always talk about malaria and sickle cell anaemia?" 

A 3: Inadequate knowledge, or plain ignorance is the simple answer. I repeat: malaria affects sickle cell anaemia patients more seriously than it does others. A sickle cell anaemia child is one who has inherited sickle cell genes from both parents [S from father, and S from mother] producing the phenotype SS. A child inheriting a sickle cell gene [S] from just one parent, and a normal haemoglobin gene [A] from the other parent is called Sickle Cell Trait [AS phenotype]. This child does not have sickle cell anaemia, and reacts to malaria differently. Even those Science teachers who know this difference between sickle cell anaemia [2 haemoglobin S genes] and sickle cell trait [1 haemoglobin S gene] teach, wrongly, that the AS phenotype is immune to malaria. It certainly is not, but (and this is where the confusion arises) the sickle cell trait child before the age of 4 years, withstands better the lethal effects of malignant malaria (ie Plasmodium falciparum ) than either the sickle cell anaemia child [SS] or the child with normal haemoglobin genes from both parents [AA]. None of the 3 phenotypes is immune to malaria; they all are infected by the parasite, but whereas the AA and SS child can succumb to severe Falciparum malaria, the AS child is not prostrated by the disease. [References 9, 10 to 18, 20 & 21].

Q 4: "So what makes the difference between the sickle cell trait phenotype on the one hand, and the sickle cell anemia and normal haemoglobin phenotypes , on the other hand as far as malignant malaria is concerned?" 

A 4: The nature of the sickle haemoglobin S, together with the behaviour of the malaria parasite is what makes the difference. When the Anopheline mosquito bites a person and injects malarial parasites into the body, red cells are invaded and the parasites multiply in these erythrocytes (red cells) until they burst, releasing more parasites into the body, to produce severe febrile illness with serious consequences.
If the person infected has sickle cell anaemia [SS], then the mere onset of fever, diarrhoea, vomiting, and other complications precipitates serious sickle cell crisis. If the patient with malaria has entirely normal haemoglobin genes [AA] then the malarial parasites, unless quickly eliminated by vigorous treatment, can also prove catastrophic. In the sickle cell trait [AS], however, as soon as the parasite begins to multiply in the red cell, using up the cell's oxygen supply, the AS cell changes from round to sickle shape and does not reach bursting point before the spleen mops it up, preventing further progress of the disease. In childhood, this makes the difference between survival of the AS child, and death of AA and SS children.
But, it may be asked, if the AS child (with just 1 Haemoglobin S gene) appears to be thus protected from the lethal effects of Falciparum malaria, why is the SS person (with 2 Haemoglobin S genes) not doubly protected? The answer is that the fever, diarrhoea, vomiting have already provoked a sickle crisis before any beneficial effect of sickling-against-malarial-parasite can be seen. To be a sickle cell trait [AS] in a malarious environment appears to be better than not having sickle genes at all [AA], or having 2 sickle genes [(SS) - References , 10 to 18, 21 & 22].

Q 5: "So what really are these sickle cells?" 

A 5: Sickle cells are red blood cells with the potential to change from round to sickle shape under certain conditions. The term came into use when an American Physician, Dr James Herrick, in Chicago, observed in 1910 some peculiar shaped cells in the blood of a West Indian student. Lack of oxygen produced more sickle cells in the same sample of blood. This was the basis for the 'Sickling Test' in the early days. Blood sample was taken from a person, a drop placed on a glass slide, and examined under the microscope. The cells were seen to be round in shape. A thin cover slip placed on the sample is sealed round with vaseline so that no air got to the blood. If after several hours the cells remained round shape, then the person did not have sickle cells. Those whose blood cells turned sickle shape in a reasonably short time, were found to have sickle cell anaemia, while those whose blood cells took a long time to show sickle cells were termed sickle cell trait, especially when they were perfectly healthy and were not anaemic.
The majority of persons who tested Positive on Sickle Testing in the early days were Black, but later White people in the Mediterranean, Arabs in the Middle East, and Indians were also found to be Sickling Positve. Ability to test sickle positive was not acquired, but inherited. Those who inherit this ability from both parents were those who fell sick, and were found to have anaemia. Without testing the blood, it is not possible to identify a person who has inherited sickling from just one parent, because such a person is not sick, and looks exactly like those without sickle cells. Nobel Prize winner Linus Pauling proved in 1949 that sickle haemoglobin was a different protein from normal haemoglobin, known as Haemoglobin A. Sickle haemoglobin was first called haemoglobin B, but it made more sense to call it haemoglobin S whose property to gel up and crystallise, causing the cell membrane to alter shape in the absence of oxygen, differentiated it from normal Haemoglobin which remained fluid and non-rigid even in the absnece of oxygen. The 'haemoglobin electrophoresis' procedure which Pauling and his colleagues used in 1949 has formed the basis of quick laboratory identification of the differnet common haemoglobins [See the Clinical/Scientific FAQ's for the genes that code for the various haemoglobins and their electrophoretic properties].
Note that when we talk about Normal Haemoglobin being 'A', we are not talking about 'Blood Group A'. The two are quite different things. Haemoglobin A means 'Haemoglobin Type A'. If someone with Blood Group A, also has Haemoglobin AA Phenotype ['A' gene from father and 'A' from mother] it is sheer coincidnece, and the two things have nothing to do with each other. [References 19 & 20, 9 & 10].

Q 6: "Why are Scientists so excited about malaria and sickle cells?" 

A 6: Scientists have used the fact of this genetic mutation (which produced the sickle cell gene, equipping the trait carrier [AS] in a malarious environment to outlive in childhood both the double gene possessor [SS] and the no-sickle-gene possessor [AA]), to claim that here was one mechanism which allowed Darwinian Evolution to have taken place [See Scientific FAQ's and Konotey-Ahulu's response to this: Reference 9, pages 106-108 'Evolution and the sickle cell gene'].

Q 7: "Is this an example of the Natural Selection that they talk about?" 

A 7: Yes, Nature using the sickling mutation to select 'AS' for survival over and above the non-sickling 'AA' and the double sickling gene 'SS'. Natural selection (or adaptation) certainly does occur to equip people to live in different environments (eg deeper skin pigmentation is one case in point), but to extrapolate this phenomenon (of malaria 'selecting tougher people' through mutation to live in the tropics) for use as "proof" that Darwinian Evolution took place cannot be considered scientific in Konotey-Ahulu's understanding of Science [Reference 9].

Q 8: "What should one's attitude be regarding adult sickle cell traits and malaria?" 

A 8: Sickle traits (children and adults with AS phenotype) do suffer from malaria, though with less complications, and they need protection as others. Adults resident in highly malarious regions develop some kind of immunity against malaria whether they are AA or AS. The spleen which helps in producing immunity is usually shrunken in adult SS people, so they should always be doubly protected in malarious regions with prophylactic drugs and mosquito nets, as should other sickle cell disease phenotypes. Health workers in Europe and USA have been known to tell Africans with sickle cell anaemia [SS] travelling back to their malarious countries that they do not need anti-malarial cover because they are already protected by sickling. This is highly dangerous advice based on ignorance, because such patients have been known to return to the temperate zone, suffer devastating sickle crisis, and hardly anyone has thought of excluding malarial parasitaemia as the precipitating cause of the crisis. [See also Question 2. References 21 & 22].

Q 9: "What is the difference between Sickle Cell Anaemia and Sickle Cell Disease?" 

A 9: The Haemoglobin 'S' gene is not the only 'abnormal' haemoglobin gene which causes illness when inherited together with another haemoglobin S gene. Haemoglobin C, for instance, with its highest concentration in the world found in Upper Ghana and Burkina Faso, when inherited together with sickle haemoglobin S produces cold season rheumatism (sickle cell crisis) in the person with 'SC' phenotype [S from 1 parent, C from the other]. The haemoglobin S and C genes in West Africa are so common that 1 in 3 of the inhabitants has one trait or the other. Any West African visiting this web site has a 1 in 3 chance of being AS (one parent donating 'S' gene, and the other 'A') or AC (one parent passing on 'C' and the other 'A', making them AS or AC phenotypes and (if they have not had their blood tested) they do not know it. Take Dr Konotey-Ahulu, for instance; his mother was Sickle Cell Trait [AS] and she did not know it, and his father Haemoglobin C Trait [AC], and he did not know it. They had 11 children, 3 of whom had signs of 'cold-season rheumatism' known in the Krobo/Dangme/Ga tribes as hemkom/chwechweechwe. It was Dr Konotey-Ahulu who discovered in the late 1950's when he was reading Medicine that what he and all the Krobo/Dangme/Ga tribes-people had known over the centuries as hemkom/chwecwhweechwe was Sickle Cell Disease. His 3 siblings had Sickle Cell Haemoglobin C Disease [SC Phenotype]. The surviving 8 children of Dr Konotey-Ahulu's parents have the Phenotypes AS (2 of them), AC (2), and AA (4 of them) and they did not know it until they were tested.

'Sickle Cell Anaemia' is also sickle cell disease ('SS Phenotype'). The reason it is called sickle cell anaemia is because anaemia (low haemoglobin level) is the most obvious feature of the SS phenotype. Other haemoglobin genes can combine with sickle haemoglobin to cause sickle cell disease of varying degrees of severity, namely Haemoglbins D, E, G, K, O, Korle-Bu, Osu-Christiansborg, etc. Beta-Thalassaemia is not an abnormal haemoglobin gene (it is a gene for producing an insufficient amount of Normal haemoglobin), nor is Foetal Haemoglobin (which is Normal Haemoglobin for the baby in the womb, but which should disappear in adulthood). If Foetal Haemoglobin persists into adulthood it is known as Hereditary Persistence of Fetal Haemoglobin (HPFH) which can combine with sickle haemoglobin gene to cause disease. Similarly, a beta-thalassaemia gene can combine with Haemoglobin S to cause illness. So the sickle cell diseases can include the phenotypes SS (sickle cell anaemia), SC, SD, SE, SG, SK, SO, S Korle-Bu, SOsu-Christiansborg, SBeta-Thalassaemia, SFhereditary, etc. The various clinical presentations of the common phenotypes have been compared and contrasted in Konotey-Ahulu's book 'The Sickle Cell Disease Patient' [Reference 9].

Q 10: "How do I find out whether I have sickle cells or another haemoglobin gene?"

A 10: A simple test that can be done even in a little-equipped laboratory, involving placing a drop of blood on a glass slide, is all that is necessary to detect the presence of sickle cells. This simple Sickle Test is based on the fact that red blood cells which contain Haemoglobin S, can be made to alter their shape from round to sickle shape by adding a reducing agent to the blood [like a 2% solution of sodium meta-bisulphite], or by depriving the blood of oxygen through covering it on the slide using a cover-slip sealed round with vaseline. This primitive Test is still useful in rural areas in some countries. A quick method used to detect sicklers before a general anaesthetic is through a Solubility Test, using molarity phosphate buffer. The colour change that is used to detect Haemoglobin S, and which is useful in unmasking Sickle Cell Anaemia (SS) does not distinguish another Sickle Cell Disease like the SC phenotype (S abnormal, C abnormal) from the Sickle Cell Trait (AS - A normal, S abnormal) which is not a disease. Anaesthetists, please read that again and again until it sinks in, because there is a wealth of difference between anaesthetising an SC person, and an AS person. To think one is anaesthetising a Sickle Cell Trait (AS) when in fact an SC patient is lying on the operating table can make the difference between complications and a successful outcome. Remember, important though a 'Sickle Cell' Test is in revealing the presence or absence of Haemoglobin S, it is always necessary to do a Haemoglobin Electrophoresis to identify the true phenotype of a person who has not been transfused recently. Transfused blood in someone with abnormal haemoglobin is likely to confuse the person's true phenotype. For example, a sickle cell anaemia person (SS) who has recently received several units of normal blood will show A and S bands on electrophoresis, while an SC person will turn out to have 3 bands: A, S, and C. Haemoglobin electrophoresis will also reveal the presence of most other abnormal haemoglobins. [See below and Clinical/Scientific FAQ's].

Q 11: "What is sickle cell crisis?"

A 11: Sickle cell crisis occurs when a significant number of the red blood cells of a patient with Sickle Cell Disease (no normal-haemoglobin gene inherited, ie SS or SC, or SD, or S beta-Thalassaemia, or. .) alter their shape from the usual round-shape to sickle-shape. People often thought that all the red cells flowing in the blood vessels of someone with sickle cell disease were distorted and sickled. No, the red cells are usually round and malleable like those of a person without Haemoglobin S. It is when circumstances make the body's internal environment lack oxygen, or get too hot, or too 'acidic', or too sluggish, that red blood cells with Haemoglobin S change shape into sickle-shape (or mini-cigar shape), clogging up the tiny vessels and causing severe pains wherever the clogging up occurs - around joints, in the abdomen, in the head, in the male organ (priapism), in the ribs, in the bones of the back, and limbs, etc.

Q 12: "What are these circumstances that can give rise to sickle cell crisis?"

A 12: Fever, fatigue, high altitude (as when some SS person embarks a plane at Accra [sea-level] and disembarks the next day at Addis Ababa or Nairobi [7-8,000 ft]), diarrhoea and vomiting causing dehydration, prolonged squatting or curling up in a chair for hours thereby trapping blood cells in the legs without benefit of oxygenation in the lungs [the so-called tourniquet effect - see July Person History on this website], underwater swimming, pregnancy and prolonged labour, smoking, alcohol, opiates like morphine and heroin which suppress breathing, severe exercise, the rainy season especially when caught in the rain, cold weather, some personal idiosyncrasies like 'eating rice and beans', severe asthmatic attack, infections of organs like the the lung (pneumonia), urinary tract and gall bladder. Malaria is the commonest cause of sickle cell crisis in African countries. Sore throat, ear ache, tooth ache, leg ulcers are other infections that can spark off a sickle cell crisis. Poorly administered general anaesthetic, and depriving the patient of fluids for hours before surgery can be dangerous. A "nil by mouth" notice for one who is booked for surgery, without giving fluids intravenously could lead to the sad observation later: "The operation was successful, but the patient developed a stroke." Patients should always keep a diary, to tell them what caused their crisis. When patients feel well, and are not in crisis, they are said to be in the steady state. Experienced Nurses like Marion McTair of The National Sickle Cell Society (UK), and some Clinicians very wisely advise their patients to keep a diary meticulously, enabling them to identify the causes and circumstances of their sickle crises. In over 4 decades of practice, I personally know of no condition in Clinical Medicine, where the 'prevention is better than cure' adage has saved the lives of so many hundreds. Many of my patients with Sickle Cell Disease have passed 50 years of age through keeping a careful diary, which led them to the conclusion that going to bed before 10 pm every single night, and drinking plenty of water, sometimes more than 4 Litres of water a day, had kept them out of crisis for years.

Q 13: "Do Sickle Cell Traits (AS phenotype, with A greater than S, eg A=60%, S=37%) get into Sickle Cell Crisis like those with Sickle Cell Disease (SS, SC, Sb-Thal, etc)?"

A 13: No. If someone with 'Sickle Cell Trait' is found to develop sudden, severe musculo-skeletal pains like happens with Sickle Cell Anaemia, then the 'sickle trait diagnosis' as the cause of the problem is wrong. Look for another diagnosis. I have seen people referred to as 'Sickle Cell Trait' merely because the father is Sickle Test Positive, but the mother is not. "How can a person have Sickle Cell Disease when only one parent is a Sickler?", they ask. The answer is that, if the person has a sickle cell crisis, but the mother is 'Sickling Negative', then she will almost certainly be found to be 'POSITIVE' for Haemoglobin C or other mutant-haemoglobin gene which, together with the Haemoglobin S gene causes severe Ache/Ache disease like Sickle Cell Anaemia (SS). Read that again, and again: "If someone with 'Sickle Cell Trait' is found ..." Is that clear? "Sickle Negative" does not mean "Abnormal Haemoglobin Negative". Say that aloud. "Sickle Negative does not mean Abnormal Haemoglobin Negative". If the sickle cell test on someone is 'Negative', it does not mean the person is 'AA phenotype or Non-Ache/Non-Ache'. Sometimes even certain doctors insist that because Haemoglobin Electrophoresis shows 2 major bands - a Normal A band, together with the mutant S band, that makes it certain that they are dealing with a Sickle Cell Trait Phenotype. Not necessarily, for if the amount of S haemoglobin was quantified in someone in sickle cell crisis who showed Haemoglobins A and S on electrophoresis, then the amount of S will always be found to be greater than that of A haemoglobin, and that makes the person Sickle cell beta-Thalassaemia phenotype, (Two mutant genes for haemoglobin formation, namely an Ache/Ache Disease) and not Sickle Cell Trait (One mutant gene plus one normal gene). Read that again. "Sickle Negative does not mean 'Abnormal Haemoglobin Negative'..." Haemoglobin A which, when quantified, is less than Haemoglobin S, means a beta-thalassaemia gene. In the Sickle Cell Trait, the amount of sickle haemoglobin S is always less than that of normal Haemoglobin A. Is that clear? If you, the reader of this web site, have been having severe sickle cell crisis periodically, and you have been called 'sickle cell trait' merely because one of your parents was 'Sickle Cell Test Negative', then go back to your Doctor and ask for Haemoglobin Electrophoresis. You might find that you had a Sickle Cell Disease (Ache/Ache), like Sickle Cell beta-Thalassaemia (SA on electrophoresis, with S greater than A), or if you were athletic looking and you had a high haemoglobin level (like 15 g/dL or more), then you had Sickle Cell Haemoglobin C (SC phenotype, which is certainly not sickle Cell Trait). The common belief that when you have sickle cell disease you must also have anaemia, ie low haemoglobin level, is dangerously wrong. Sickle Cell Traits do not escape the consequences of incompetently-administered general anaesthesia, any more than those without sickle cells do. People with no abnormal haemoglobin whatever ie those with AA haemoglobin phenotype have been known to die under poorly administered general anaesthesia, such as when the doctor forgets to switch on the OXYGEN supply. These sad cases end up in a Coroner's Court. Should these circumstances of incompetently administered general anaesthesia be repeated with a Sickle Cell Trait person undergoing surgery, that patient would also die, but at post-mortem 'total sickling' would be reported. The patient would not be awake to report a 'sickle cell crisis', just as the unfortunate AA patients were unable to complain of lack of Oxygen before they died. Competently-administered general anaesthesia never threatened a Sickle Cell Trait as Consultant Anaesthetists Professor Kofi Oduro and Dr John Searle amply demonstrated. They administered general anaesthesia to 479 'sicklers' in Ghana over a period of 2 years, reporting their findings in the British Medical Journal 1972, Volume 4, pages 596-598 ['Anaesthesia in sickle cell states: A plea for simplicity.']. One of the reasons Anaesthetists are advised to give plenty of Oxygen preoperatively and post-operatively to any 'sickler' is that the correct diagnosis of 'Sickle Cell Trait' preoperatively is very poor. As mentioned above, the colour test used to unmask sickling does not distinguish between the SC phenotype (Ache/Ache), a disease-state which is notorious for fooling anaesthetists because of the patients' robust features and high haemoglobin status, and the Sickle Cell Trait (AS). SC-phenotype people suffer very badly when fluids are with-held before surgery, and their combined S & C haemoglobins solidify quicker than other haemoglobin combinations when things go wrong. I myself had once assumed that a healthy, robust man who died under anaesthesia for eye surgery in London was 'Sickle Cell Trait' until I met his AS widow with their SS and SC children. The mother had given her S gene to both daughters while the father's S and C genes were distributed between them. The man was not AS at all. He had Haemoglobin SC disease, and the colour sickle test had not distinguished between the Trait state (AS), and the Disease state (SC). For general anaesthesia therefore, my advice is to treat all sicklers as if they had the disease, and give plenty of Oxygen and fluids intravenously. [We shall come back to this again, and again. Watch for later instalments on sickle cells and flying. See also Chapter 30 in my 'The Sickle Cell Disease Patient', especially pages 362 to 371]

Q 14: "But did not 4 American Army Recruits with sickle cell trait die exercising at 4,000 feet?"

A 14: No, they did not die from Sickle Cell Trait. This rumour began in 1970 when SR Jones, RA Binder, and EM Donowho Jr published in the New England Journal of Medicine, Volume 282, pages 323-325, an article entitled: "Sudden death in sickle cell trait" where they stated that "violent exercise and residence at a moderately high altitude (4,000 ft; 1,220 m)" was capable of precipitating a fatal sickling crisis in sickle cell trait carriers. I researched that article, and wrote to the British Medical Journal January 15 1972 (Volume 1, pages 177 -178, 1972): "Actually, in their paper entitled 'sudden death in sickle-cell trait' the authors relied on the 'SA' electrophoretic pattern without quantification of A2, A, or S in three of their cases, and in the fourth who did not even have haemoglobin electrophoresis they were content to call it sickle-cell trait because 'a sickle cell preparation at autopsy was positive'". This flawed publication is typical of many articles which have maligned sickle cell traits, some of whom competed at the Mexico Olympic Games at more than 7,000 ft above sea level and beat the whole world. The fact is that, in a place like southern Ghana where 1 in 5 perfectly healthy people have the sickle cell trait, we should expect to find that 1 in 5 of all doctors, 1 in 5 of all thieves, 1 in 5 of all soldiers, 1 in 5 of all lawyers, 1 in 5 of hill climbers at 4,000 feet, 1 in 5 of all sudden deaths, 1 in 5 of people vomiting blood, 1 in 5 of all athletes, 1 in 5 of all prostitutes, 1 in 5 of the 'Black Star' Football Team, 1 in 5 of the many past Heads of State, 1 in 5 of all diabetics, 1 in 5 of all fools, 1 in 5 of all heart failure patients, 1 in 5 of those with cerebral palsy, 1 in 5 of all stammerers or stutterers, 1 in 5 of all rogues, 1 in 5 of all Left-handed people, and 1 in 5 of those southern Ghanaians reading this website will be expected to have the Sickle Cell Trait (AS). In fact, I have already told readers of this website that my own father had Haemoglobin C Trait (AC) and my mother Sickle Trait (AS, see Genealogy Tree). So very common are these Traits. If a Ghanaian dropped down dead in the USA, there was a 1 in 5 chance that he would be Sickle Cell Trait, and if at autopsy the Pathologist found a Positive Sickling Test, would he be entitled to publish the phenomenon as a case of "sudden death in a sickle cell trait"? Thus linking sudden death with sickle cell trait? Certainly not! But that is what has been known to happen in the past. Even deaths of Blacks due to violence at the hands of unscrupulous Prison Officers have been known before to have been attributed to the 'Sickle Cell Trait'. The spate of journal articles linking all kinds of symptoms with the 'Sickle Cell Trait' had become so alarming that Professor James Bowman and his colleague Dr S Bernstein in Chicago (University of Illinois) were forced to exclaim that "persons with sickle cell trait will no longer be able to become ill or even die lest they find themselves subject of case report" (Bowman JE, Bernstein S. 'Caution about preliminary reports'. Pediatrics 1977; Volume 59: pages 639 - 640). As I write this FAQ, a young lady from the north of England contacted me to ask for advice regarding her frequent painful spasms due, she said, to 'Sickle Cell Trait'. She then added (in passing) that she was born with cerebral palsy, and was wheel chair bound. The message obviously had not got through to her that cerebral palsy (not sickle cell trait) was the cause of her severe painful spasms. [We shall keep coming back to this, because of the numerous queries regarding 'The Sickle Cell Trait'. Meanwhile, a bright student reading this material is entitled to ask the question: "But is there not a disease in Ghana of which it is not true to say '1 in 5 of the sufferers will be found to have the Sickle Cell Trait (AS)'?" Answer: Yes, there is - Cerebral malaria. Professor JOO Commey and Colleagues in Accra ('Cerebral malaria in Accra, Ghana' Ghana Medical Journal, 1980, Volume 19, pages 68-72), confirming the known fact that sickle cell trait children (AS phenotype) were not represented in those dying from cerebral malaria, decided in 1985/86 to look at the phenotypes of 30 consecutive cases of cerebral malaria admitted to the Korle Bu Teaching Hospital. In a population where 1 in 5 of all consecutive hospital admissions would be expected to be Sickle Cell Trait (AS), "the results showed conclusively that there was not one sickle cell trait phenotype where at least four were expected" (Konotey-Ahulu in 'The Sickle Cell Disease Patient', page 95). That did not mean Sickle Cell Traits were not infected by the malarial parasite; what it meant was that they were not being admitted to hospital dying from cerebral malaria because not enough parasitized red cells matured to release huge numbers of malarial parasites to invade the brain. From this point of view the Sickle Cell Trait had protected the children from cerebral malaria. - See FAQ 2 -9]

Q 15: "What about urinating blood, which occurs frequently in sickle cell traits?"

A 15: Urinating blood does not occur frequently in sickle cell traits. First of all, we must remember that millions of people pass blood in the urine all over the world. If sickle cell traits did not ever pass blood in the urine from the same conditions that caused other people to pass blood in the urine (a symptom known as haematuria) they would be super human. Many articles purporting to describe haematuria in 'sickle cell traits' were, in fact, describing Sickle Cell haemoglobin C Disease patients (Ache/Ache SC phenotype) where "frequently" in my experience has been quantified as 2%, or 1 in 50. If a sickling POSITIVE person, with very high haemoglobin level of 16 or 17 g/dL, was found urinating blood I knew some doctors who would refer them to me as cases of 'Sickle Cell Trait'. The very high haemoglobin level was thought incompatible with Sickle Cell Disease. "Sickle Cell Trait it must be", they would say. When, however, haemoglobin electrophoresis was performed these "trait" people were most often found to have Sickle Cell Disease (SC), or if the haemoglobin level was less, they were SS or Sbeta-Thalassaemia. One eminent American Pathologist (an expert in post-mortem material) made the following statement: "Of the Hb SS, SC, Sbeta-Thalassaemia and AS states, gross haematuria is most frequently observed in Hb AS". To clinicians working in populations where 1 in 5 healthy persons, including international athletes, have the sickle cell trait (AS, with A greater than S) this statement is grossly incorrect, for that was not their experience. When that particular Pathologist (whom I knew personally) began his medical practice 'Haemoglobin C' had not been discovered. The SC phenotype would be known to him as 'Sickle Cell Trait', and he might unconsciously be carrying his previous terminology into the era of haemoglobin electrophoresis. It is desirable always to quantify the incidence of symptoms in sickle cell states. To tell even sickle cell disease patients (Ache/Ache) that they are certainly going to get haematuria is also not correct. They must always be told the proportion of patients of which sex, which phenotype, etc that get which symptom. For example, of 1,346 consecutive Sickle Cell Disease (Ache/Ache) patients seen by me, 13 of 642 females (2.0%) and 16 of 704 males (2.3%) had haematuria. There is no statistical difference in sex incidence. But there is significant statistical age group distribution with haematuria incidence. None due to sickling occurred below 5 years of age, "and the greatest number (37.9% of all haematuria cases) occurred in the 20-24 age group. No cases were found in the 44 patients aged 45 years and above. Of 1,319 consecutive patients at the Sickle Clinic 13 (2.2%) of 598 SS patients and 15 (2.5%) of 588 SC patients had haematuria. None of 148 other patients complained of passing blood in the urine. Thus, on the occasions when haematuria was found in Accra over 6 consecutive years in the Sickle Cell Clinic, young adults and child-bearing women would seem to be most affected, and then only the sickle cell disease patients (SS & SC phenotypes) were involved - The Sickle Cell Disease Patient, Chapter 17. On the other hand, haematuria in sickle cell traits as seen by Clinicians and not deduced from post-mortem material is very rare. For while 1 in 50 of sickle cell disease patients seen by the same Clinician (Dr Konotey-Ahulu) have been known to complain of passing blood in the urine "There is absolutely no doubt that the incidence of renal haematuria from in vivo sickling in sickle cell traits is very rare, being less than 1 in 1000 sickle traits per lifetime (definition of 'lifetime' is taken as the duration of life of the adult who is investigated). In other words", Dr Konotey-Ahulu goes on, "if one investigated 10,000 sickle trait adults for haematuria during their lifetime,...one would find less than 10 renal infarcts due to sickle cell trait". Continuing to come back to my own family, to say Dr Konotey-Ahulu's AS mother never passed blood in the urine during her entire life of 89 years adds little to the argument, but it is just mentioned for the record. The Sickle Cell Trait/haematuria over-emphasis, according to Dr Konotey-Ahulu, "is directly due to our ignorance of the existence of Haemoglobin C" until comparatively recently. Some reports, often quoted, like that of Goodwin and colleagues in Urology 1950, Volume 63, pages 79-96 entitled: 'Haematuria and sickle cell disease' were published before the discovery of haemoglobin C. The authors would have wrongly identified SC phenotype (Ache/Ache) as Sickle Cell Trait AS (Norm/Ache) because C haemoglobin (which does not sickle) was not discovered until 1951. Other conditions precipitating bleeding in the sickle cell trait kidney should always be looked for as, for example, in the patient of Weingler and Colleagues where bleeding from the kidney was associated with Von Willebrand's disease ('Gross haematuria associated with sickle cell trait and Von Willebrand's disease' - Journal of Urology 1979, Volume 122, pages 136-137.)"

Q 16: "So what would we do with a known Sickle Cell Trait (Hb A proportion greater than Hb S) passing blood in the urine?".

A 16: How did I manage such a patient in the past? First, I said to myself, look for what could cause bleeding in anybody else. In the tropics I made sure Bilharzia (Schistosomiasis haematobium) was not the problem. When it was, I treated it with Metrifonate or Praziquantel. Other causes of blood in the urine were quickly excluded, like bacterial infection (Eschericia coli, or Proteus, or Tuberculosis, etc), or stones in the kidney, or tumour in the urinary tract, or (in the male) prostate problems. Even in patients who did not have sickle cells, there would always be some for whom no cause for blood in the urine could be found. In these, as in the case of those who are Sickling 'Positive', I went on to find out whether someone kicked them in the back, or they had a car accident, or they were taking blood thinning drugs like Aspirin, or Anticoagulants, or platelet reducing agents, all of which could cause bleeding. If an examination of the inside of the bladder (cystoscopy) showed blood oozing from the Left ureter, (for the Left kidney almost always bled first in sickle cell states), and kidney scans, with an intravenous urogram (pyelography) revealed that part of the kidney was 'infarcted' then, and only then, should it be assumed that this was 'sickle cell haematuria'. Apart from infection, conditions like dehydration, haemo-concentration, enlarged spleens, and pregnancy were the circumstances that I have known to cause sickle cell infarction, which led to bleeding. I have known flying long distances (over 8 hours) to precipitate renal bleeding in a Sickle Cell Haemnogliopbin C Disease patient (SC phenotype) but I have never known flying to cause this in the AS phenotype. Look also for a combination of factors. When bleeding occurred, it was found (as demonstrated on page 213b, of 'The Sickle Cell Disease Patient') that the urine from the bleeding kidney had a heavy growth of bacteria. Although true renal infarction is rare (and remember it happens to those without sickle cells as well), when it occurs even in one sickle cell trait, the incidence is 100% in that one person in whom it occurs. It is no comfort to the sufferer for the Doctor to say "it is extremely rare". For example, Professor Yeboah and Colleagues at The Korle Bu Teaching Hospital found, between November 1972 and June 1975, that of 202 patients referred to them at the Urology Department with haematuria, only 9 (2%) were sickle-related, and these were all of the SC phenotype. (Yeboah and colleagues: 'The causes and management of haematuria in Accra, Ghana'. Ghana Medical Journal 1975, Volume 14, pages 299-306). For these 9 individuals, the condition was not rare. How were they managed? Treatment of established renal infarction is bed rest, and plenty of fluids (up to 12 Litres intravenously of Normal Saline has been given before, in 24 hours), with sterilisation of the urine with the appropriate antibiotic. This approach, with blood transfusion, in the very severe cases, has always been successful in stopping the bleeding in most patients. Surgery has little place in sickle cell kidney bleeding management. It requires to be pointed out that people have had one or both their kidneys removed rather unnecessarily. There needs to be great caution. Having said that, 1 in 5 of all malignant kidney tumour patients in southern Ghana should be found to have the Sickle Cell Trait. If the Surgeon decided to remove the kidney, it was because of the carcinoma, and not because of the sickle state. In the most severe cases of sickle cell haematuria in Ghanaian SC patients epsilon-amino-caproic acid (EACA) was tried by Bernard Ribeiro, Professor JMK Quartey, and myself with dramatic results [Ribeiro B, Quartey JMK, Konotey-Ahulu FID, 1979. 'Hydration and epsilon amino caproic acid as quick solution to haematuria in sickle cell disease.' Our procedure was: "5 g - EACA intravenously over 30 minutes followed by 1 g per hour until bleeding stopped. Correction of dehydration, with alkalination of urine, and treatment of infection should be tried before ACA is used." page 210 in 'The Sickle Cell Disease Patient', FAQ Reference 9] Remember that any symptomatic Sickle Cell Trait (AS) needs thorough investigation. Never should a symptom be attributed to the 'Sickle Cell Trait' without posing the question: "Could a non-sickler, ie AA (Norm/Norm) not have the same problem - a stroke, vomiting in an aeroplane, stomach pains, convulsions, osteo-arthritis, miscarriages, etc as this Sickle Trait has?" If, on the other hand, the symptoms are those of sickle cell disease (acute cold-season rheumatism, hip necrosis, multiple pigment gall stones, haemolytic jaundice, leg ulcers, acute visual problems, splenic pain, etc) then what appears to be a genuine 'AS' diagnosis needs looking at again as Dr Witkowska and Colleagues in Canada did and, lo and behold, discovered a new haemoglobin masquerading as normal Haemoglobin A. In other words their 'AS' was not-AS at all, but an entirely new haemoglobin plus haemoglobin S, the combination producing an Ache/Ache situation rather than the expected Norm/Ache phenotype 'AS'. [Witkowska HE, Lubin BH, Beuzard Y and colleagues: "Sickle cell disease in a patient with sickle cell trait and compound heterozygosity with haemoglobin Quebec-Chori". New England Journal of Medicine 1991; Volume 325, pages 1150-1154.]. Students researching these matters are advised also to look up my comments on this article: Konotey-Ahulu FID. "Beware of symptomatic sickle-cell traits" Lancet 1992, Volume 339, page 555 (in which I pointed out that the 'Sickle Cell Trait AS' may not be true sickle trait, and the 'Haemoglobin C Trait AC' may also be something else, as the "A" has been shown could stand for haemoglobin Quebec-Chori.]

Lessons to learn:

1. Never be content with being told that 'Sickle Cell Trait' is the cause of your serious symptoms like painful spasms, epilepsy, high blood pressure, headaches, renal failure, etc. 'Non-sicklers' also get these conditions, so get yourself investigated. One e-mail received from Mrs Helen Sachs in the USA asked whether 'Sickle Cell Trait' could change overnight into 'Sickle Cell Disease': "A 32-year old friend of mine died yesterday suddenly in hospital. Her mother asked the Doctor what happened, and he said my friend's Sickle Cell Trait suddenly changed into Sickle Cell Disease and she died". This genetic nonsense of a reply must not be fed to grieving relatives. Norm/Ache [Sickle Cell Trait - AS] does not suddenly change to Ache/Ache [Sickle Cell Disease - SS or SC], and it must also not be considered so normal for Sickle Cell Disease People to die suddenly in hospital that the sad event is made to look like a reasonable expected-event. Such sudden deaths must be taken as seriously as any other death.

2. Do not allow Insurance Companies to load your Premium because of Sickle Cell Trait, for it is not a disease. Even Sickle Cell Disease Patients are increasingly getting health insurance, now that each person is considered on an individual health performance basis. See Konotey-Ahulu FID. "Insurance and genetic testing". Lancet 1993, Volume 341: page 833 ]

3. If you are getting symptoms exactly like those with known sickle cell disease, yet you continue to be called "Sickle Cell Trait" then get a second opinion, because learning that you really have, say, Sickle Cell haemoglobin C Disease (SC) or Sickle Cell beta-Thalassaemia (Sbeta-Thal), and not Sickle Cell Trait (AS) could make you stop playing Rugby football where a tackle could rupture your enlarged spleen. To be called Sickle Cell Trait (Norm/Ache), when you have Sickle Cell Disease (Ache/Ache) and vice-versa (to be called Trait when you have the disease) is, in my opinion, very serious. Yet many, many, doctors and other health professionals do not know the difference between the two phenotypes. One woman, seeking advice from another website in the USA, said she had "the sickle cell anaemia trait" with some hip problems. Her error was not corrected in the reply given to her on that website, suggesting that the "expert" replying to queries also was in the dark as to the difference between "sickle cell anaemia" and "sickle cell trait". Now, take it from me, there is no such thing as "sickle cell anaemia trait", and if the reader of this website fails to spot that mistake then I need to repeat myself even more often than I have done already. How can a person be "Ache/Ache/Norm/Ache" all in one?

4. 'Addae's Criteria': Dr Reginald Addae, Ghanaian physician of the Military Hospital Accra, provided 10 simple criteria for scrutinisung all reported cases of symptomatology in 'sickle cell traits'. On page 364 of 'The Sickle Cell Disease Patient' I stressed: "Straightforward 'sickle cell trait' should not be diagnosed as the cause of clinical symptoms without first obtaining satisfactory answers" to 10 questions posed by Addae in the British Medical Journal, January 1, 1972, Volume 1, page 53: 'Sickle-cell Trait and Altitude'. These will be looked at later in the Academic FAQ's, but we must now add the exclusion of Haemoglobin Quebec-Chori as the 11th relevant criterion. Dr Addae's 10th criterion is worth mentioning here because we are dealing with blood in the urine: "Was there G-6PD Deficiency of the erythrocytes?" Now, this enzyme deficiency found commonly in Mediterranean Europeans and their descendants world-wide, is also found in about 1 in 6 West African males. This is often a harmless condition, until the person with the Glucose-6 Phosphate Dehydrogenase Deficiency takes medicines like Sulphonamides or certain antibiotics and pain killers, causing red blood cells to be dissolved and passed in the urine and turning it dark like coca-cola. If this common hereditary condition (passed on from mother to son, and from father to daughter) was not recognised in a Sickle Cell Trait person with a urinary tract infection, and the Doctor gave the person Sulphonamides, what could happen? The 'coca-cola urine' would wrongly, very wrongly, be attributed to the 'Sickle Cell Trait'. It is my established practice to include laboratory tests for these common red cell hereditary characteristics [Abnormal Haemoglobins and G-6PD Deficiency] in the investigation of any African, Mediterranean European, Middle East person, or Indian, referred to me for any reason.

5. Terms to Avoid: i. "I am a sickler". Some people use this term to mean they have sickle cell anaemia. Others use it to mean they have been tested and found to have sickle cell trait. Yet others use it to mean sickle cell disease of some sort. You can see the confusion this could cause. The term could then be seen to stand for the phenotypes: AS, SS, SC, SbetaThalassaemia, Sickle cell Hereditary Persistence of Fetal Haemoglobin (SFhereditary), or even SKorle Bu. Surely this is not right, so I advise people to add the phenotype always if they must use the term. "I am a sickler, SC", for example, is better than just "I am a sickler". If they do not know their phenotype, they should not say "I am a sickler" and leave it like that, because the doctor, or whoever they are talking to, may be tempted to assume that whatever they are suffering from is caused by sickle cell disease. This could be a serious mistake. Do you understand what I am saying? ii. "Heterozygous". I read in a reputable medical journal on 13th September 1997 the following statement made by a professor of haematology: "Avascular necrosis of femoral head in a patient with heterozygous (haemoglobin SC) sickle cell anaemia". Take it from me that there is no such thing as "heterozygous sickle cell anaemia". The term "sickle cell anaemia" always, without exception, denotes the HOMOZYGOUS STATE (SS). Moreover, the term "heterozygous" denotes dissimilar genes from one's parents, like SC, Sbeta Thalassaemia, SKorle Bu, etc. The reason I do not like the use of the term "heterozygous" is that the "AS" phenotype, which is not a disease (it is trait") is also "heterozygous" because dissimilar genes are present. To confuse the trait "AS" with the disease for example,"SC" disease, must never be allowed to happen. To make sure such confusion does not happen some wise doctors refer to the SC phenotype as a double heterozygous state. I prefer to avoid the term altogether when the actual phenotypes can be spelt out - "SC", "SS", "SFhereditary", "AS Trait". iii. "Sickle cell anaemia trait". There is no such thing. Please avoid this term. It is simply wrong. iv. "I have got sickle cell". Look at what is said under (i.) v. "Sickle cell anaemia disease". True, sickle cell anemia is also sickle cell disease, but always add the phenotype SS when you mention "sickle cell anaemia"so that it is not confused with the SC phenotype as the professor did. vi. "I have the SC Trait". The "SC Phenotype" is never a trait. It is a disease 0phenotype (two anormal genes for haemoglobin formation). This mistake continues to be made by many doctors, nurses, and insurance copmanies. DO NOT CALL THE SC PHENOTYPE SICKLE CELL TRAIT. The Trait is not a disease. The "S" & "C" in the phenotype "SC" do not stand for "Sickle" and "Cell", they stand for "Sickle-cell Haemoglobin-C". So "SC" phenotype means "Sickle Cell Haemoglobin C" phenotype. Is that clear?