Sickle cell disease (SCD) is a lifelong inherited blood disorder that affects hemoglobin, the oxygen-carrying protein in red blood cells. Genetic mutations cause an unfavorable change in hemoglobin shape, leading to a "sickling" effect on red blood cells. SCD is associated with anemia, cardiovascular complications, and severe pain episodes.

SCD is the most common inherited blood disorder in the United States. It affects approximately 100,000 Americans and 20 million people globally. Given its prevalence and associated increased mortality risk, it is a blood disorder that cannot be ignored. Conventional therapies are available for potential cure and symptom management but are associated with high cost and unwanted side effects.

This article will discuss the process of diagnosing SCD and functional medicine options that can be used in conjunction with conventional therapies to reduce symptoms and prolong the lifespan of those living with SCD.

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What is Sickle Cell Anemia?

SCD, or sickle cell anemia, is a genetic disorder of abnormal hemoglobin synthesis. Mutations of the genes that code for the beta-hemoglobin chain result in the formation of a hemoglobin variant called Hemoglobin S (HbS) and a subsequent "sickling" of red blood cells (RBCs). RBCs in sickle cell disease lose their donut-like shape and instead look like crescents. Sickle cells do not travel through blood vessels smoothly and can block small vessels, leading to cardiovascular repercussions. People with SCD also suffer from anemia, which results from increased hemolysis, or destruction, of the abnormally shaped RBCs. This is why sickle cell anemia is classified as hemolytic anemia. Anemia may acutely worsen during a hemolytic crisis, a period characterized by significantly increased hemolysis over a short period of time.

What Causes Sickle Cell Anemia?

SCD is an inherited blood disorder, meaning that it is caused by the passing down of specific genes from parent to child. Humans have two beta-hemoglobin genes, one inherited from each parent. In sickle cell disease, both genes are mutated, leading to the predominance of the HbS subtype of the hemoglobin protein. (1)

Sickle cell trait (SCT) is the inheritance of one abnormal gene from one parent and one normal gene from the other. Most people with SCT have no signs or symptoms of disease, but in rare cases, such as dehydration or high altitude, they may experience a hemolytic crisis.

Sickle Cell Anemia Symptoms

Most symptoms associated with SCD arise from anemia and events called vaso-occlusive crises, characterized by blockages in blood flow. Symptoms generally begin to appear around six months of age. They vary in severity and may change over time. (2)

Healthy RBCs live for 120 days, but sickle cells live for 20 days at most. This causes anemia and poor oxygenation in the body. Fatigue is the most common symptom of anemia. Physiologic stressors can cause a hemolytic crisis, during which anemia symptoms will likely be more pronounced, and yellowing of the skin, called jaundice, can occur. (2, 3)

Episodes of severe pain, called pain crises, are one of the hallmark symptoms of SCD. Sickle-shaped RBCs are prone to causing blockages in small blood vessels; inadequate blood flow to the affected area causes tissue damage and pain. The pain can vary in intensity, duration, and frequency. (2)

Other symptoms related to poor circulation include (2):

• Delayed growth and development
• Swelling of the hands and feet
• Vision problems

Many complications can occur from SCD (1, 3):

• Acute chest crisis (ACS) is a life-threatening condition that occurs when sickle cells block vessels in the chest. It is characterized by sudden fever, chest pain, and abnormal lung findings on chest x-ray.
• Blood clots
• Damage to the kidneys and eyes
• Decreased immune function
• Frequent infections caused by damage induced by sickled RBCs to the spleen
• Gallstones caused by increased levels of bilirubin, a breakdown product of RBCs
• Leg ulcerations
• Pulmonary hypertension (high blood pressure in the lungs)
• Splenic sequestration can also be life-threatening if not treated quickly. It occurs when sickle cells pool in the spleen, causing a sudden drop in hemoglobin levels.
• Stroke

Due to these complications, people with SCD have up to a 30-year shorter life expectancy than those without (1).

Risk Factors for Sickle Cell Anemia

In the United States, most people with SCD are of African descent. Hispanic, Southern European, Middle Eastern, and Asian Indian ancestries also increase the risk of inheriting the disease.

How is Sickle Cell Anemia Diagnosed?

Most Americans are diagnosed with SCD through universal newborn screening, but those with SCT may be diagnosed in adulthood (1).

The diagnosis of SCD is made based on hemoglobin electrophoresis, which quantifies the presence of HbS in circulation.

A typical lab evaluation for symptomatic patients generally includes:

• Complete blood count (CBC): the table below outlines results characteristic of SCD
• Peripheral blood smear, a microscopic analysis of RBCs, identifies sickle cells
• Reticulocyte count, the percentage of immature RBCs in circulation
• Lactate dehydrogenase (LDH), a marker of tissue damage
• Comprehensive metabolic panel (CMP) to assess bilirubin levels, kidney function, and gallbladder function

Other Lab Tests to Check

Patients with SCD commonly have nutrient deficiencies, which are associated with increased disease severity. A micronutrient panel measures essential vitamins and minerals to assess nutritional status and guide appropriate dietary and supplemental treatment recommendations.

An advanced lipid panel measures predictive markers of cardiovascular disease. Stratifying cardiovascular risk can guide preventive treatment recommendations specific to the cardiovascular complications of SCD.

A multisystem health screening should be performed at least annually, including:

• Ordering a CMP to rule out kidney disease
• Blood pressure measurement to rule out high blood pressure
• A dilated eye exam performed by an ophthalmologist
• Physical exam assessing for symptoms of respiratory problems. Pulmonary function tests should be performed in patients with respiratory symptoms, like shortness of breath and wheezing.
• An echocardiogram may not be ordered annually but can be considered to screen for pulmonary hypertension and heart disease.

Sickle Cell Anemia Treatment

Conventional treatment options for SCD include (4, 5):

• Prescription medications to prevent RBC sickling, prevent pain crises, prevent disease complications, treat pain, and reduce infection risk
• Blood transfusions to manage anemia and prevent disease complications
• Blood and bone marrow transplant, the only potential cure for SCD

Functional Medicine Treatment for Sickle Cell Anemia

Nutrition

SCD is a chronic hypermetabolic condition, characterized by increased resting metabolic rate. Increased calorie, protein, and micronutrient intakes are required to compensate for this increased metabolism. To meet these nutritional requirements, patients with SCD should be encouraged to eat a healthy, diverse diet of nutrient-dense foods.

One large review article concluded that Americans with SCD were 20 times more likely to have clinical symptoms than Africans with SCD. At the time of this study, 80% of the African diet consisted of thiocyanate-containing foods, like sorghum, millet, cassava, and yams. Thiocyanate is a food compound that is converted to cyanate, a compound that can inhibit RBC sickling. Although no studies directly correlate the consumption of these foods to decreased disease severity, it may be beneficial to incorporate thiocyanate-containing foods into the diet.

Herbs & Supplements

Zinc levels are generally lower in patients with SCD compared to healthy controls. Because zinc deficiency can exacerbate complications of SCD, like short stature, decreased immune function, and increased susceptibility to infection, zinc status should be optimized in patients with SCD.

Elevated homocysteine is a risk factor for cardiovascular disease and may contribute to the risk of stroke in patients with SCD. B vitamins (i.e., riboflavin, B6, folate, and B12) can reduce elevated homocysteine levels.

Vitamin D deficiency can contribute to cardiovascular disease and is prevalent in patients with SCD. Deficiency should be treated with supplementation when identified.

Antioxidant therapy with omega-3 fatty acids, vitamin A, and zinc improves laboratory markers of hemolytic anemia. Take caution when supplementing high doses of vitamins C and E for prolonged durations of time, as some studies have concluded that these vitamins can induce hemolysis.

Studies indicate that up to 50% of patients with SCD have deficient nitric oxide, a natural molecule made by the body that causes a widening (vasodilation) of blood vessels and improves blood flow. Supplementing with nitric oxide's precursor, L-arginine, can increase the synthesis of nitric oxide and enhance immunity, antioxidant responses, wound healing, cardiovascular health, and prevent hemolytic crisis.

Lifestyle Modifications

Known triggers of pain crises that should be avoided when possible include (3):

• Cold weather
• Decongestant medications
• Dehydration
• Heavy physical labor
• High altitude
• Swimming in cold water

Avoid infections by washing hands frequently, eating a healthy diet, avoiding close contact with people who are sick, and getting regular dental exams (3).

Complementary and alternative medicine (CAM) modalities are especially effective at managing pain, anxiety, and depression. People using CAM experience less pain and fewer side effects than when using opioid medications. In this study, prayer, relaxation, massage, and exercise were most commonly implemented by SCD patients to manage pain.

Optimize cardiovascular health through modifiable lifestyle practices, which may include a Mediterranean diet, regular exercise, and quitting smoking.

Summary

Sickle cell disease is the most common inherited blood disorder in the United States, characterized by abnormal hemoglobin leading to anemia, chronic episodic pain, and severe cardiovascular complications. Sickle cell disease is usually lifelong, as no definitive curative therapies are currently available. Conventional treatment goals primarily focus on the prevention of symptoms and disease-related complications. For some, but not all, bone marrow transplant may be an option as a potential cure.

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Research suggests there are nutritional differences between people who have SCD and those who do not. Furthermore, it does appear that nutrient deficiencies and disease severity are related. Functional tests that assess nutritional status and stratify cardiovascular risk are important tools in detecting factors that may worsen SCD prognosis. A functional, integrative medical approach can improve the quality of life and prolong life for those living with SCD.