Sickles, blood disease and the Greek god Priapus

I saw the Carnal Carnival was coming up and this month’s theme is Blood. Blood disease, that shouldn’t be too hard I thought.

So I started thinking about blood diseases and remembered a disease I learnt about in undergraduate genetics classes called Sickle Cell Anaemia.

Sickle Cell Anaemia (SCA) is a very well characterised blood disease that changes the shape of red blood cells from the characteristic bi-concave disc (or doughnut shape as I usually explain to the undergrads I teach now) to an unusual crescent or ‘sickle’ shape.

I'm not saying SCA is associated with communism but it's a pretty big coincidence they both involve sickles if you ask me <pics:http://commons.wikimedia.org/wiki/File:Sicklecells4.jpg and http://commons.wikimedia.org/wiki/File:Hammer_and_sickle.svg>

The disease is caused by a recessive mutation in the haemoglobin gene that results in the unusual blood cell shape but also restricts the amount of oxygen that can be carried around. As a result, people who suffer from SCA find normal tasks exhausting and have a significantly reduced lifespan, down to about 42 in males and 48 in females respectively.

One of the major complications arising from your blood cells not being quite the right shape is that they get stuck moving through blood vessels. Patients also have very unusual blood chemistry because feedback systems that monitor the ‘quality’ of the blood identify low oxygen levels in the blood and compensate by increasing production of red blood cells to fix the problem. Of course the blood cells are impaired so it takes more mutated blood cells to carry around the required oxygen than it would normal cells. What you are left with is viscous blood with a higher than normal cell count that has a tendency to clot.

This can cause all sorts of problems, including blood vessel and organ damage. Generally painless, this disease is characterised by bouts of clots and tissue failure.

It was discussed in my undergraduate genetics classes because it has been suggested that SCA may be a selectable adaption to ENABLE survival. It turns out that the places that show the highest levels of SCA are tropical and sub-tropical locations and sub-Saharan Africa, pretty much anywhere you find malaria in high numbers.

As it turns out malaria requires normal shaped blood cells to reproduce. The mutation to the haemoglobin gene does limit the ability of the red blood cells to carry oxygen but this is preferential to dying from malaria. Interestingly the disease is worse when the haemoglobin gene you inherit from both parents is mutated but these people do not get malaria. If one parent has a wild-type or ‘normal’ copy of the haemoglobin gene then some children will receive both a mutated and a normal copy. These individuals produce both normal and mutated red blood cells and so are still susceptible to malaria but less so when compared to people with two ‘normal’ copies of the haemoglobin gene.

For those that are interested these are called Punnett squares and describe all the possible matings. SCA is the mutant haemoglobin, WT is the normal haemoglobin. Homozygous essentially means two of the same (i.e. homozygous SCA means two copies of the mutant gene). Heterozygous essentially means different two that are different (i.e. heterozygous SCA means one WT copy and one mutant copy)

SCA is a very interesting disease and deserves a serious discussion but when researching it I came across something I did not expect. ASPEN Syndrome. Association of Sickle cell disease, Priapism, Exchange transfusion, and Neurological events, is a mouthful of a syndrome.

In order to understand what is happening we have to remember some of the consequences of SCA, in particular increased blood viscosity and a tendency to clot.

Ever heard of the Greek god Priapus?

Nice ‘member’ he’s got there huh. In medical terms that’s a Priapism.

Its been estimated that up to 89% of men with SCA have suffered from ‘prolonged penile erection’ that can be intermittent or in some cases last many hours at a time. It seems that the increased viscosity and tendency to clot causes the flow of blood into the penis to pool. Females are not excluded and female priapism affects the clitoris, often it is referred to as clitorism.

There are a few ways that a Priapism can be alleviated. In most people pseudoephedrine or other amphetamines can induce erectile dysfunction. If that doesn’t work then we move to treatment option two, aspiration of blood from the corpus cavernosum under local anaesthetic, a.k.a. big needle to drain blood straight out of the penis.

Cool! A LEGO syringe! <http://www.flickr.com/photos/seanmichaelragan/5224385684/sizes/l/>

For SCA patients these approaches would simply exaggerate the priapism so most doctors perform a blood exchange transfusion. The new blood, from a non-SCA donor flushes the clots and results in detumescence (penis goes down). End of story, or is it.

It’s here that we reach the ‘N’ in ASPEN. This treatment option in SCA patients is increasingly being linked to neurological events from mild headaches to seizures and polarized weakness (generalised weakness affecting only one half of the body). These risks seem to be associated with all transfusions but due to the number of transfusions a SCA patient will receive in a lifetime they show a high prevalence of transfusion complications, including neurological events.

So there it is, a recessive mutation that alters protein structure, which in turn alters red blood cell morphology, which is sometimes advantageous but leads to global changes in blood physiology that can result in a never-ending erection. Treated with a blood transfusion that can result in significant neurological distress and it shares a name with a bunch of trees, a skiing resort in Colorado and an apple flavored soda sold in the 1980’s. Longish post but I think I covered some ground :).

References

Mantadakis E, Ewalt DH, Cavender JD, Rogers ZR, & Buchanan GR (2000). Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism. Blood, 95 (1), 78-82 PMID: 10607688
Swerdlow, P. (2006). Red Cell Exchange in Sickle Cell Disease Hematology, 2006 (1), 48-53 DOI: 10.1182/asheducation-2006.1.48
Claster, S. (2003). Managing sickle cell disease BMJ, 327 (7424), 1151-1155 DOI: 10.1136/bmj.327.7424.1151
Merritt AL, Haiman C, & Henderson SO (2006). Myth: blood transfusion is effective for sickle cell anemia-associated priapism. CJEM : Canadian journal of emergency medical care = JCMU : journal canadien de soins medicaux d'urgence, 8 (2), 119-22 PMID: 17175874