Sickle Cell Disease

Yohan Kim

First to described in 1904 by James B. Herrick. ◦ Found “elongated and sickle-shaped” red blood cells (RBCs) from

a patient suffering from anemia

A multisystem disease, associated with episodes of acute illness and progressive organ damage

Most common in African heredity population◦ Occurs in about 1 of every 500 births

Clinical management of sickle cell disease is still basic and no drugs have been developed that specifically tar-get the pathophysiology of this disease

Affects about 70,000 people in the US

Sickle Cell

Global distribution & Malaria

2 Types of Hemoglobin HbF(More O2), HbA(Less O2)◦ Newborn – 5:5~8:2, 6

months – 1:99

Sickled hemoglobin is caused by a mutation of the gene of HbA

In the amino acid sequence va-line takes the place of glutamic acid at the sixth position.

HbA become C-shaped or sick-led when the patient’s oxygen saturation is low.

Pathophysiology

Pathophysiology

Reduced flexibility impairs blood flow through vessels

Repeated de-oxygenation can damage the cells enough to make sickling permanent

short-lived (10 to 20 days instead of the normal 120 days)

Sickled RBC

No clear symptoms shown

Indications may be visible during growth

Newborns usually of normal length and weight at birth

Develop a gradually increasing deficit in height and weight as they age

After time of the normal adolescent growth spurt, they be-gin to catch up with their normal peers. ◦ (Girls 15 to 17, boys 18 to 19)

Delayed puberty also occurs.

Signs and symptoms

Treatment of sickle cell crisis is usually symptomatic

Referring the patient immediately

Referral

Based on analysis of hemoglobin

Protein electrophoresis or chromatography

Hemoglobin mass spectrometry and DNA analysis increasingly used ◦ Enable high-throughput testing.

Diagnostic test

HbSS - inherited two sickle cell genes (S); one from each par-ent. ◦ The most common type

HbSC - inherited a sickle cell gene (S) from one parent and a gene for abnormal hemoglobin (C) from the other ◦ 20% to 30% of cases, usually a milder form of sickle cell disease.◦

HbS beta thalassemia - one sickle cell gene from one parent and one gene for beta thalassemia from the other parent.

Other: HbSD, HbSE, and HbSO -inherited one sickle cell gene and one gene for an abnormal type of hemoglobin

HbAS - sickle cell trait

Differential diagnosis

Not a disease, generally regarded as an asymptomatic con-dition.

When compared to controls, is no difference

Some physiological differences during exercise or at high al-titudes

Following exercise -> increase in the number of sickled cells. ◦ exertional sickling

The presence of sickled cells after physical exertion is even greater at higher altitudes

Sickle cell trait

Explanations for sudden deaths due to sickle cell anemia are not entirely clear.

Data indicate an association between sickle cell trait and sudden death there is no direct evidence of cau-sation.

Dehydration, hyperthermia and acidosis associated with extreme physical exertion suggested

Results include rhabdomyolysis (muscle break-down), acute renal failure and coronary vasoconstriction

Sickle cell trait

Hydroxyurea (medication)

◦ Oral efficacy and low toxic effects

◦ Increase hemoglobin concentrations

◦ Decreasing platelet and white cell counts

◦ Changing expression of adhesion molecules

◦ Nitric oxide generation

Treatment

Red blood cell transfusion◦ Corrects anemia

◦ Decreases the percentage of sickled hemoglobin

◦ Suppresses sickle synthesis,

◦ Reduces polymerization.

◦ Necessary if the hemoglobin concentration is high, or if rapid decrease in sickled hemoglobin percent-age needed

Treatment

Hematopoietic stem cell transplantation

◦ AKA bone marrow

◦ The only cure for sickle cell disease

◦ First bone marrow transplantation for sickle cell in 1983 on 8-year-old patient with leukemia and sickle cell disease The bone marrow transplantation cured both dis-

eases

Treatment

Hematopoietic stem cell transplantation

◦ Indications1. Stroke or CNS event lasting longer than 24 hours2. Abnormal brain MRI3. Elevated transcranial Doppler4. Acute chest syndrome with recurrent hospital-

izations5. Two or more vaso-occlusive crises requiring hos-

pitalizations6. RBC alloimmunization

Treatment

Splenectomy

◦ The spleen is the organ most often affected by sickle cell disease.

◦ To prevent complication

◦ Also reduces patients’ need for transfusion

◦ Decreases splenic complications

◦ Further eliminates pain

Treatment

Acute pain - most common cause of hospital admission

Infection - major cause of morbidity and mortality

Stroke

Acute chest syndrome - second most common cause of hospital admis-sion

Pulmonary hypertension

Heart disease

Renal complications - almost inevitable, hemoglobin polymerize in the renal medulla, because of the low oxygen

Complications

About 90% of patients survive to age 20

Close to 50% survive beyond the fifth decade.

Prognosis

No methods to prevention sickle cell disease

Screening and diagnosing sickle cell in advance will help prevent complications in the future

Engaging and educating patients before complications begin are also good ways of preventing complications.

Prevention

A college football player with sickle cell trait (SCT) who col-lapsed minutes after running 16 successive sprints of 100 yards each at sea level.

The player, 19 year old, African American, was apparently healthy when running.

No exertional heat illness was present.

After collapsing, went into coma and developed fulminant rhab-domyolysis, profound lactic acidosis, acute myoglobinuric renal failure, refractory hyperkalemia, and disseminated intravascular coagulation.

Died about 15 hours after admission to hospital

Case study

Cause of death was acute exertional rhabdomyolysis as-sociated with SCT

appears that sickling can begin within 2-3 minutes of maximal exertion and can reach grave levels very soon

Being urged on by coaches can pose problem

Heat, dehydration, altitude, and asthma can increase the risk

Screening and simple precautions can prevent this unique syndrome and enable SCT athletes to thrive in their sports

Case study

1. Redding-Lallinger R, Knoll C. Sickle cell disease--pathophysiology and treatment. Current Problems In Pediatric And Adolescent Health Care. 2006;36(10):346–376.

2. Parrish M R, Morrison J C. Sickle cell crisis and pregnancy. Seminars in Perinatol-ogy. 2013;37(4):274–279. doi:10.1053/j.semperi.2013.04.006.

3. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018–2031. doi:10.1016/S0140-6736(10)61029-X.

4. Sheth S, Licursi M, Bhatia M. Sickle cell disease: time for a closer look at treat-ment options? British Journal Of Haematology. 2013;162(4):455–464. doi:10.1111/bjh.12413.

5. Apanah S, Rizzolo D. Sickle cell disease: Taking a multidisciplinary approach. JAAPA: Journal of the American Academy of Physician Assistants (Lippincott Williams & Wilkins). 2013;26(8):28–33. doi:10.1097/01JAA.0000432497.24151.d4.

6. Aloe A, Krishnamurti L, Kladny B. Testing of collegiate athletes for sickle cell trait: what we, as genetic counselors should know. Journal Of Genetic Counseling. 2011;20(4):337–340. doi:10.1007/s10897-011-9366-9.

7. Anzalone ML, Green VS, Buja M, Sanchez LA, Harrykissoon RI, Eichner ER. Sickle Cell Trait and Fatal Rhabdomyolysis in Football Training: A Case Study. Medicine & Science in Sports & Exercise. 2010;42(1):3–7.

References