Sickle Cell Anemia: When red blood cells look like sickles

As a young boy growing up in Nigeria, football (or soccer as it is called in the United States) was a religion unto itself. Yes, all of us in my small group of friends endured long church sermons every Sunday but that was just because our respective parents forced us to attend them. While the priest or pastor talked about the virtues of being a devout christian for hours on end we were secretly plotting the dribbling moves we planned to execute on the dirt road which we had converted into an imaginary football stadium by my childhood home. We played barefeet using a deflated makeshift game ball and with a passionate intensity that was out of all proportion to the actual importance of the games. Our games were fiercely competitive and we loved it that way. We played each game like life itself depended on it… as if armageddon would ensue if our team lost and we had to wait another turn to play again. Although we were all pretty much soccer mad, one of the members of my childhood posse wasn’t allowed to physically play the sport. His mother expressly forbade him from playing football for reasons unbeknownst to us. For the sake of respecting his privacy, we’ll refer to this friend of mine using “Ade” as a pseudonym. Ade’s mother would frequently let him hang out with the rest of us under the strict condition that he was never allowed to actually play football or any other sport. As all children do at one point or the other in life, we collectively decided to disobey Ade’s mum and convinced him to play on one fateful afternoon when our team was one player short. Ade was holding his own just fine in the game until he suddenly collapsed in intense pain. It was one of those odd moments that elicits enough emotion to burn a permanent image into your mind, and it did in mine. 23 odd years later I can still remember turning around and seeing Ade clutching his chest while rolling around in the dirt in what must have been some really intense pain. Thankfully, a local kiosk owner was willing and able to rush Ade to the hospital and saved his life for all practical purposes. While Ade’s mother was scolding the lot of us later on that evening for betraying her trust, she kept shouting out the following words: “Didn’t I tell you children that Ade wasn’t allowed to play under any circumstances? His sickle cell could have killed him!” I never quite fully understood what she meant by “his sickle cell could have killed him” until about 15 years later as a student of human genetics. It turns out that Ade’s mother was referring to a genetically inherited disease which directly affected the functionality of some vital cells in Ade’s blood.

Blood flow is the main means by which nutrients, minerals, and gases are transported throughout the human body. For example, the nutrients contained in the food we eat are absorbed into the bloodstream through tiny finger like projections called villi in the gut. These nutrients are then transported to the rest of the body via the bloodstream to facilitate growth and repair of various organs and tissues. The bloodstream is also the means by which the oxygen we breathe in through our nostrils and lungs is carried to various organs in the body to facilitate proper metabolic functions. A collection of 3 different cell types (white blood cells, red blood cells, platelets) and a liquid base called plasma make up human blood. In line with the inherent efficiency of mother nature, every one of the different cell types in blood serves a distinct advantageous purpose. The white blood cells act as your immune system’s “special forces” designed to seek out and destroy potential sources of illness in the body. Platelets act to quickly form a blood clot anytime the body is injured in order to prevent the injured individual from completely bleeding out and dying over time. Red blood cells are mainly responsible for transporting oxygen to the various tissues and organs in the body which in turn facilitates their proper function. Although white blood cells and platelets are extremely important for maintaining optimal function of the human body, red blood cells are perhaps even more critical as the human body simply cannot function for very long if at all without them and the associated oxygen that they transport to tissues and organs.

About 2% of the time in my home country of Nigeria, a child is born with a condition that causes him or her to have abnormal red blood cells. This condition is a genetically transmitted disease called Sickle Cell Anemia. It is the disease that caused my friend Ade to go crashing to the ground in a heap of pain during that fateful afternoon of soccer many years ago. In case you were wondering (like I initially did when I was learning about this condition) sickle cell anemia isn’t contagious… which in plain english means you cannot “catch it” from another person like you can the common cold for instance. Rather, it is genetically passed down from one generation to another. Thus a person afflicted with sickle cell anemia carries the disease right from the moment dad’s sperm fertilized mom’s egg to form him or her in mom’s womb. At this point you are probably wondering what the heck causes the red blood cells of sickle cell anemia patients to become abnormal and what an “abnormal” red blood cell looks like. These are fair and insightful questions considering what you have read so far… let’s delve deeper into the realm of science and find answers to them.

You may pause at this point if you need to read this introductory primer to DNA to help you better understand the material presented in the remainder of this article.

Humans generally have 22 pairs of somatic chromosomes and 2 sex chromosomes which contain all the DNA that codes for their physical and mental makeup. On a fundamental level, chromosomes are comprised of genes – an ordered sequence of nucleotides that contain the information required to build specific functional proteins in the body. Proteins are vital for maintaining life as they fulfill many important roles in the human body. Almost all functions in the body – from maintaining the physical structure and elasticity of your skin to conducting the crucial biochemical reactions that keep you and I alive – are facilitated by one or more proteins. Since proteins are so vital for the functionality of the human body, nature in its infinite wisdom gave each of us 2 copies of each gene… one from mom and the other from dad. The reason for this redundancy is simple… the chances that a protein of a specific type produced by mom’s genes and the version of that same protein from dad’s genes will both be faulty in the same individual are a lot less than if that individual had just one copy of the gene to rely on for the production of that particular protein. This is often the reason why an individual can live life in perfect health even if they have one faulty copy of an important gene. When an individual with one “busted” copy of a an important gene remains healthy, we technically refer to that gene as “autosomal recessive”. When an individual shows symptoms of illness due to just one “busted” copy of an important gene on the other hand, we technically refer to that gene as “autosomal dominant”.
 

 
Sickle cell anemia is an autosomal recessive disorder which results in the deformation of red blood cells into a shape that is very reminiscent of an actual sickle. This deformation is caused by a point mutation in the gene that codes for an important protein found inside red blood cells called hemoglobin. Hemoglobin serves the very important function of binding to oxygen molecules in the lungs, and releasing those same oxygen molecules when red blood cells travel to the capillaries (tiny blood vessels) connected to organs and tissues. A complete absence of hemoglobin containing red blood cells would result in the starvation of the tissues and organs in the body of the oxygen they need to thrive. A lack of oxygen delivery to the organs and tissues in the body will eventually cause them to shut down and result in almost instant death. This should put the importance of proper functioning red blood cells and the hemoglobin protein they contain squarely into focus in your mind.
 

The hemoglobin protein (just like any other protein) is formed by individual subunits called “amino acids” that are linked together in a specific order. There are a total of 20 naturally occurring amino acids that exist in our bodies. The sequence of nucleotides in a particular gene dictates the order of amino acids that join up to form the particular protein that said gene codes for. Specifically, little powerhouses (called ribosomes) in our cells latch onto a genetic message and generate an amino acid after reading off a “codon” which is the technical name for 3 consecutive base pairs within a gene. A point mutation in a genetic sequence simply means that a single nucleotide (A, C, G, or T) is in the wrong place in that genetic sequence. A fraction of the time, a point mutation causes the wrong amino acid to be inserted at that point in the chain of amino acids that form the primary structure of the protein. In the case of sickle cell anemia, the amino acid “Valine” is erroneously substituted for “Glutamic Acid” in the hemoglobin amino acid chain due to a single point mutation as illustrated in the figure below. This simple point mutation is all it takes to deform the hemoglobin protein, impairing its ability to effectively transport oxygen to the tissues and organs of the body.

 

The mutated form of hemoglobin that is symptomatic of sickle cell disease can have potentially devastating effects on human health. Normal red blood cells are flexible disc shaped structures… you can think of them as tiny little doughnuts without a hole in the middle. The natural shape of a normal red blood cell makes it flexible enough to meander and squeeze into little blood vessels and crevices of the circulatory system. This in turn pretty much means that no matter how small the blood vessel leading to the organ or tissue (provided they aren’t blocked by too much cholesterol and plaque), normal red blood cells can fit through those blood vessels and provide oxygen to the organ or tissue in question. Sickled red blood cells on the other hand are a lot less flexible and as a result of this, they can cause blockages in blood vessels because their inflexibility prevents them from meandering through some blood vessel branches in the circulatory system. The net result of this is that some tissues or organs can be deprived of oxygen for relatively long periods of time which leads to severe pain of the same sort that caused my friend Ade to collapse during that fateful football game many years ago. Perhaps even more serious than the occasional intense pain episode, eventual organ damage may occur in a sickle cell patient if his or her organs are deprived of oxygen too frequently because of this condition. The inflexibility of sickled red blood cells makes them prone to hemolysis or spontaneous bursting. As a result, sickled red blood cells last only about 10 to 20 days in the blood stream compared to 90 or 120 days for normal red blood cells. Although the human body is always making replacement red blood cells to compensate for natural cellular turnover, it is hard for the body to keep up in the sickle cell disease case because the sickled red blood cell turnover rate is so high. This is why the red blood cell count in sickle cell anemia patients is usually pretty low. Further, less red blood cells means less oxygen delivered to the muscles, tissues, and organs which often results in lower overall energy for the individual. This is why sickle cell patients often have low energy relative to their peers who don’t suffer from the disease.

Sickle cell disease is a lifelong illness but the good news is that medical technology has come so far as to considerably increase the lifespan of people with this condition. As a measure of our progress, consider the fact that the life expectancy of a person with sickle cell anemia is now about 40–60 years in the United states. In the 1970’s the average lifespan of a sickle cell anemia patient in the U.S. was 14 years. Also, developments in the field of stem cell engineering have actually developed hematopoietic stem cell transplant methods that show promise as a permanent cure for this condition. Hematopoietic stem cells are found in the bone marrow (i.e. the human analog to the spongy substance inside chicken bone if you’ve even bitten into a drumstick) and are the most potent blood cell type in the human body because they are amazingly capable of becoming any blood cell type through a maturation process called “differentiation”. I should also mention here that these hematopoietic stem cells are immortal for all practical purposes as they will mostly likely outlive the person that they exist in. Provided there is a genetic match between a sickle cell patient and a related donor, some hematopoietic stem cells may be transferred from the donor to the sickle cell patient without the immune system launching an angry campaign to reject the cells. Once these healthy hematopoietic stems cells settle in the recipient sickle cell patient, they will yield normal red blood cells which will compensate for the sickled variety produced by the patient’s own genes.

As you can no doubt tell by now, sickle cell anemia is nothing to “sneeze at”. It is a serious condition that has taken the lives of many people at far too young an age so as I type this in February 2016, I am exceedingly thankful that my friend Ade is still alive. It is still however important to note that for every Ade, there are probably 10 others that aren’t as lucky so we must pay attention to that and try to help as many of our fellow humans as possible survive or prevent this disease. In addition to the stem cell therapy discussed above, there are also preemptive measures you can take to find out if you and your partner stand a chance of passing on this disease to your potential future child. One of the best preemptive measures you can take is something called a carrier screen for the sickle cell trait. This will profile your genetics and that of your partner and tell you with 99% or greater certainty what your chances of having a child with sickle cell anemia are. With this knowledge in hand, you can then choose to go the route of in vitro fertilization or adoption if necessary. I gently encourage you to ask your obstetrician, gynecologist, or family doctor about this the next time you are in for a visit. Till next time friends, take care of yourselves and each other.
 
 
Without Wax
Oyolu B.C. Ph.D.
chubaoyolu.org
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