Sickle Cell Disease; The current approach to drug (Orthodox and Herbal) management and the rationale

Definition and Introduction

Just like the popular slogan

"All gold glitters but not everything that glitters is gold"

Every drug given in the treatment/management of any disease condition is managing a particular sign/symptom but at times, not all signs/symptoms are managed with drugs.

When sickle cell disease is been mentioned, almost everyone would have something to say about it especially those in the health profession because of their level of training.

What are there?

Applying the knowledge of our elementary biology, the body is made up of cells e.g red blood cells (RBCs), white blood cells (WBCs), platelet, et' cetera. Cells performing the same or similar function come together to form tissue and in this case, the blood. Blood is a liquid tissue that performs several functions including; transport of hormones, gases (function of RBCs), immunity, e.t.c.

Biochemically, RBC contains hemogloblin (Hb) which is made of two components; heme (iron containing part that gives the blood it red color) and globulin (chains of amino acid sequences). The adult hemoglobin (HbA) has two each of alpha and beta chains of amino acid sequences and any variation on any of the beta chains will result in abnormal hemoglobin. Sickle hemoglobin (HbS) arises from a mutation substituting thymanine for adenine on the 6th codon of the beta chain of the amino acids sequence leading to coding of valine instead of glutamate on position 6 of the Hb beta chain. This change gives HbS the physical property of polymer formation under deoxy condition and also changes in solubility and molecular stability.

Sickle cell disease (SCD) is a generic name for a group of inherited haemoglobin disorders characterized by the presence of sickle red cells in the blood which leads to clinical illness (disease). There are genetic disorders resulting from the presence of a pair of mutated form of hemoglobins. The commonest forms of SCD in our environment in order of prevalence are HbSS, HbSC and HbSβ-thal.

Drugs used in the management of sickle cell disease

The only curative approach to the management of sickle cell disease is allogenic bone marrow transplant which has some great limitations of finding a matching donor, age at which this cannot be done, e.t.c. With the knowledge of biotechnology, gene therapy is a promising curative approach to the management of sickle cell disease.

The drugs used in the management of SCD includes but not limited to the following;

• K+ containing fluids e.g. Darrow’s half strength.

• Analgesic

• Antimalarial

• Broad spectrum antibiotic.

• Routine drugs; Folic acid, Astymin, Zinc gluconate, Paludrine.

• Hydroxyurea

• Anti-sickling agents; Dioscovite, Nicosan.

• Anticoagulant

• Etilephrine or phenylephrine.

Note that iron was not included in the above mentioned drugs because the use of iron is contraindicated in sickle cell disease. This and some other factors will be discussed in my next post "Malaria and sickle cell disease." Please stay tuned!

Rationale for the use of the above mentioned drugs in Sickle cell disease.

1. K+ containing fluids e.g. Darrow’s half strenght. The activity of Na+-K+ ATPase is altered in sickle cell disease (SCD), which affects serum electrolyte levels. This alteration is associated with several complications in sickle cell patients. Below was a work done and published september, 2019 on "Serum Potassium, Sodium, and Chloride Levels in Sickle Cell Disease Patients and Healthy Controls: A Case-Control Study at Korle-Bu Teaching Hospital, Accra" by Charles et' al, 2019. Click to read. I quote

"There is higher efflux of K+ from the intracellular into the extracellular space in HbSS patients, which may lead to red cell membrane dysfunction and associated complications."

By implication, there's low level of potassium (Hypokalemia) in the intracelluar spaces especially during dehydration which is most often seen during crisis.

2. Analgesic; Painful crisis is a salient feature of sickle cell disease and is usually managed with narcotics and/or NSAIDs analgesic. Pain in SCD is majorly nociceptive in origin. However, it may also have a neuropathic component marked by tingling/burning sensation or numbness. In such cases, drugs such as pregabalin or carbamazepine will be useful.

3. Antimalarial; Infections generally are to be prevented and treated promptly not only in sickle cell disease. More insight will be given in my next post "Malaria and sickle cell disease", Please subscribe to our email to get the update.

4. Broad spectrum antibiotic; The underlying pathophysiology of acute chest symdrome includes vaso-occlusion of pulmonary vessels and microbial involvement. Implicated microbes include bacteria such as Pneumococcus, Haemophilus influenza, respiratory viruses, and atypical organisms such as Mycoplasma, Chlamydia, or Legionella. Osteomylitis which is the commonest skeletal complication of sickle cell disease often originates from bacteria (Salmonella spp, Staphylococcus species). In whichever case, it is advisable to use antibiotic with wide spectrum of activity.

5. Routine drugs (Folic acid, Astymin, Zinc tablet, proguanil);

• Folic acid is a nutritional supplement that plays a vital role in the synthetic pathway of red blood cells.

• Astymin is a multivitamin supplement. Any other multivitamin can be used except those containing iron.

• Zinc tablet; the role of zinc on the immunity system cannot be over emphasized, it is important to prevent any form infection in this category of patients and one of the ways to do that is to build the immune system.

• Proguanil (Paludrine); used in the prophylaxis of malaria.

6. Hydroxyurea; Hydroxyurea happens to be the mainstay drugs in management of SCD and have many applications in sickle cell disease such as prevention of stroke in high risk individuals, reduces the number of crisis e.t.c.

7. Anti-sickling agents (Dioscovite, Nicosan);

• Dioscovite is a nutritional supplement containing organic iodine and potassium thiocyanate that provides the thiocyanate (active ingredient) and it is sometimes called sulfocyanate or simply "yam vitamin" found in plants called nitrilosides among which are foods like African yam and cassava. International health product corporation have demonstrated that thiocyanate exert 100% inhibition on sickling of sickle cell. At the molecular level, thiocynate increases the solubility of homozgous sickle cell hemoglobin.

• Nicosan or Niprisan as it may be called is an anti-sickling supplement developed in Nigeria (though not readily available) from dried plant extracts. Eugenia caryophyllata, Piper guineense, Pterocarpus osun, and Sorghum bicolor are the herbal components of the Yoruba recipe upon which the antisickling drug Niprisan is based.

8. Anticoagulant is not usually given except when there is a suspected case of fat embolism of the bone marrow tissue to the lung. In some cases, bronchodilator e.g nebulized salbutamol may be given.

9. Etilephrine or phenylephrine; may be given in some forms of priapism, usually to irrigate the corpus cavernosum. Priapism is a genito-unrinary complication of sickle cell disease. Oral dose of pseudoephedrine or terbutaline can also be used together with other forms of non pharmacological approaches.

10. Iron chelators like deferoxamine and it likes are used in the developed nations to prevent failure of the cardiopulmonary system. It has been established the commonest cause of any tissue of the cardiopulmonary system is iron overload.

Recommendation

Some months back, I was discussing with a pediatrician in one of the top government hospitals in Abuja, Nigeria and she shared with me a story of her sickle cell patient that stopped visiting the sickle cell clinic of the hospital because of a new mixture taking at home by the patient. The mother of her patient shared with her that she mixes Malt drink with Tortoise blood for her child. This may sound weird and awkward but it actually worked for the patient as it reduces the frequency of crisis, hospital visitation and pains.

I felt something when i heard the story as it sounded familiar. When I was growing up, I saw the same thing happened.

Is it actually a good practice even when it works? Should the practice be encouraged? Whether YES or NO, we should bear in mind that this has not been scientifically proven and the toxicity profile has not been established to determine if there will be short and/or long effect arising from the practice.

I recommend that our Pharmaceutical and Medical research institutes and other health care researchers pick up this, research on, to see if the practice actually hold truth and if it is, what is responsible for the action and how it does it, the consequences of the practice either in short or long term or both.

Please feel free to share your thought, observation and comments in the comment box provided.

THANK YOU!