Sickle cell disease is a genetic blood disorder caused by a mutation in the beta-globin gene. The mutation causes red blood cells to become rigid, sticky, and shaped like a sickle. During vaso-occlusive crises, these sickled cells can block small blood vessels, causing pain. Common clinical features of sickle cell disease include anemia, painful crises, infections, acute chest syndrome, and organ damage to tissues like the spleen, liver, and eyes. Laboratory tests can diagnose sickle cell disease through complete blood counts, peripheral smears showing sickle-shaped cells, and solubility tests.

1. Zera International College of
Health Sciences
DEPARTMENT OF CLINICAL MEDICINE
BIOMEDICAL SCIENCES
HEMATOLOGY
LECTURE 7: SICKLE CELL DISEASE
MRS N NG’ANDWE
BSC, BMS

2. Introduction
 Sickle cell disease is a group of haemoglobin disorders resulting from the
inheritance of the sickle β gene.
 Is a recessively inherited chronic hemolytic anemia.
 Caused by a single nucleotide substitution in the β globin gene on chromosome
11.
 Mutant hemoglobin polymerizes under low oxygen conditions and form bundles
that distort red cells into the classic sickle shape.

3. Pathophysiology
Deoxygenation
polymerization of hemoglobin
sickling of red cells
endothelial damage/activation
RBC and leukocyte adhesion to endothelium,
vasoconstriction
vascular occlusion, organ ischemia and end-
organ damage

4. Pathophysiology

5. Sickle cell Disease clinical features
 Clinical features are of a severe hemolytic anemia punctuated by crises
 Sickle cell crisis is a painful episode that may begin suddenly in a person who has SCD
 This occurs when sickled shaped blood cells clump together and block small blood vessels that
carry blood to certain organs, muscles and bones. It causes mild to severe pain
 The clinical expression of Hb SS is very variable.
 Some patients having an almost normal life free of crises Others develop severe crises even as
infants and may die in early childhood or as young adults.
 Crises may be vaso - occlusive, visceral, aplastic or haemolytic

6. Vaso occlusive crisis
 The vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and
restrict blood flow to an organ resulting in ischemia, pain, necrosis and often organ damage.
 These are the most frequent and are precipitated by such factors as
 Infection
 Acidosis
 Dehydration
 Deoxygenation (e.g. altitude, operations, obstetric delivery, stasis of the circulation, exposure to
cold, violent exercise).
 Infarcts causing severe pain occur in the bones (hips, shoulders and vertebrae).

7. Vaso occlusive crisis
 The ‘ hand – foot ’ syndrome (painful dactylitis caused by infarcts of the small bones) is frequently
the first presentation of the disease and may lead to digits of varying lengths.

8. Vaso occlusive crisis
 The swelling is caused by sickle-shaped red blood cells blocking blood flow to the hands
and feet.
 Soft tissues affected include the Lungs and the Spleen.
 The most serious vaso – occlusive crisis is of the brain (a stroke occurs in 7% of all patients) or
spinal cord.
 Painful crises are treated with hydration, analgesics and blood transfusion.
 These can be largely prevented by regular blood transfusions in these cases.

9. Visceral Sequestration Crises
 These are caused by sickling within organs and pooling of blood with a severe exacerbation of
anaemia
 Sickle cells can block the blood vessels leading out of the spleen.
 When this happens, blood stays in the spleen instead of flowing through it.
 This causes the spleen to get bigger and the blood counts to fall.
 Patients present with Dyspnea, Falling arterial PO2, Chest pain and Pulmonary infiltrates on chest X
- ray.
 Treatment is with analgesia, oxygen, exchange transfusion and ventilatory support if necessary.
 Hepatic and splenic sequestration may lead to severe illness requiring exchange transfusions

10. Visceral Sequestration Crises
 Hepatic and girdle sequestration crises and splenic sequestration may lead to
severe illness requiring exchange transfusions.
 Attacks tend to be recurrent and splenectomy is often needed.
 Splenic sequestration is typically seen in infants and presents with an enlarging
spleen, falling haemoglobin and abdominal pain.
 Treatment is with transfusion and patients must be monitored.

11. Aplastic Crises
 Aplastic crisis is a temporary shutdown of red cell production.
 Because of the shortened red cell lifespan in patients with sickle cell disease, a rapid drop in hemoglobin
occurs when the bone marrow is not producing red blood cells.
 Aplastic crisis is defined as a decrease in Hb ≥3g/dl with reticulocytopenia without evidence of hemolysis,
usually from parvovirus B19 infection.
 This occurs as a result of infection with parvovirus or from folate deficiency.
 Persons with decreased erythrocytes caused by conditions such as iron deficiency anemia, human
immunodeficiency virus (HIV), sickle cell disease, spherocytosis, or thalassemia are at risk of transient aplastic
crisis if infected with parvovirus B19. The virus causes a cessation of erythrocyte production
 Characterized by a sudden fall in haemoglobin, usually requiring transfusion.
 Also characterized by a fall in reticulocytes.

12. Hemolytic Crises
 These are characterized by an increased rate of hemolysis.
 Fall in Haemoglobin levels
 Rise in reticulocytes and usually accompany a painful crisis

13. Hepatobiliary complications
 The breakdown of red blood cells produces a substance called bilirubin. A high level of bilirubin in
your body can lead to gallstones.
 The liver can be affected by intrahepatic trapping of sickle cells.
 Episodes of cholestasis (A condition which impairs the flow of bile from the liver to the small
intestine by either slowing or stopping the flow) due to intrahepatic sickling can lead to liver failure
in rare instances.
 Pigmented gallstones are seen in two-thirds of patients.
 Patients with abdominal symptoms attributable to gallstones should undergo cholecystectomy

14. Pregnancy
 Painful episodes become more common in the last trimester.
 The incidence of pre-eclampsia is higher than normal in SCD patients and there is
a slight increase in maternal mortality.
 Risk to the fetus from abortion, stillbirth, low birth weight and neonatal death is
also increased.
 It is safe to use oral contraceptives for birth control in SCD.

15. Priapism
 Men with sickle cell anemia can have painful, long-lasting erections, a condition called priapism.
 As occurs in other parts of the body, sickle cells can block the blood vessels in the penis. This can
damage the penis and lead to impotence
 Priapism occurs in two-thirds of males with SCD, with a peak incidence in the second and third
decades.
 It is caused by vaso-occlusion leading to obstruction of venous drainage from the penis
 Episodes can be brief (stuttering) or prolonged, when they last for longer than 3 hours.

16. Ocular complications
 Tiny blood vessels that supply your eyes may become plugged with sickle cells. This can damage
the retina (the portion of the eye that processes visual images, leading to vision problems).
 Vaso-occlusion of retinal and other vascular beds in the eye can lead to grave complications
 Patients with SCD can develop:
 Abnormal conjunctival vessels
 Iris atrophy
 Retinal pigmentary changes and
 Retinal haemorrhages.

17. Leg ulcers
 Ulcers of the lower legs are common, as a result of vascular stasis and local ischaemia occurs

18. Laboratory diagnosis of SCD
1. Full Blood Count
 Reduced hematocrit, and red cell count.
 The reticulocyte count is always elevated
2. Peripheral Smear (During Crisis)
 During crisis episodes, the peripheral smear will show Many nRBCs (nucleated
RBCs), Presence of irreversible and reversible sickle cells

19. Peripheral blood smear (during crisis)

20. Laboratory diagnosis of SCD
3. Solubility test
 First-level screening procedures for adults
includes the solubility test.
Other supportive tests
 Bilirubin and LDH are increased.
 Haptoglobin (a protein present in blood
serum which binds to and removes free
haemoglobin from the bloodstream) is
decreased, indicating intravascular
hemolysis.
Solubility Test