Pathophysiology: 

Sickle Cell disease is a genetic, autosomal recessive disorder that results in abnormalities of the globin genes of the hemoglobin molecule of the RBC’s  The BbS gene is the gene and it is inherited in people of African decent and to a much lesser extent from the middle east and the Mediterranean.  This gene causes the hemoglobin molecule to be defective.

The sickle hemoglobin acquires a crystal like formation when exposed to low oxygen tension.  When exposed to low oxygen tension (hypoxemia) the Erythrocyte containing the BbS gene loses it’s round pliable biconcave shape of a normal RBC  and becomes deformed rigid and sickle shaped.  These sickle shaped cells can adhere to the endothelium of small vessels and when they adhere to each other they can block  or reduce the blood flow to any organ or region of the body.  If ischemia or infarction occurs the patient may have pain, welling and fever. Other causes are strenuous exercise or low O2 concentration during anesthesia, high altitude, decreased plasma volume, decreased blood pH or increased plasma osmolality as the result of dehydration.  The cold can aggravate the sickling process due to the vasoconstriction that can reduce blood flow.

Sickle Cell Crisis

There are four types of Sickle cell crisis:

• Vaso-occlusive Crisis – Most common- and is the result of sickling in the microcirculation that leads to vasospasm, thrombosis and local infection.
• Sequestration Crisis:  – infants between 8 and 24 months due to massive pooling of RBC’s in the liver and spleen.
• Aplastic crisis- Result from bone marrow depression and associated with viral infections.  This leads to a compensatory increase in RBC’s and RBC lysis.
• Hyperhemolytic crisis- rare- can result from certain medications or infections.

Signs and symptoms:

Result from chronic hemolysis or thrombosis.

• Sickle cells are rapidly hemolyzed and have shorter life span 10-12 days
• Anemia (always) Hb is usually 7-10 g.dl   (this patient Hb is 7.1 g/dl)
• Tachycardia (r/t chronic anemia), cardiac murmurs, cardiomegaly
• Jaundice in sclerae.
• Infection – commonly pneumonia and osteomylitis.
• Necrosis
• Hypoxemia
• Acute Chest Syndrome
  • Fever
  • Cough
  • Infiltrates on CXR.

Complications

• Infection
• Stoke
• Renal failure
• priapism / Impotence
• Pulmonary hypertension

• HCT/ Hb –  both low with sickle cells in blood smear (my patient 7.1/ 28.8)
• Diagnosis confirmed by hemoglobin electrophoresis –
  • Hemoglobin electrophoresis (also called Hgb electrophoresis), is a test that measures the different types of hemoglobin in the blood. The method used is called electrophoresis, a process that causes movement of particles in an electric field, resulting in formation of “bands” that separate toward one end or the other in the field. This will determine if there is BsB gene present.
• Other labs for associated problems, liver function (AST, ALT, Alk Phos, Bilirubin) , (Renal function creatinine, BUN, urinalysis) and x-rays of the chest.
• Immunoglobulins  IgG, IgM, IgA-  my patient has these checked. High  IgG (2.270) and IgA (373) but lower  IgM (50)  Globulin level of 40.These  can be increased in increased Significantly raised IgG but normal IgA and IgM – chronic stimulation of reticuloendothelial cells secondary to chronic hemolysis.
• Cardiac Markers  Troponin, CKMB for ischemia or infarct

Medical Treatment:

Preventive care is best.  However, if sickle cell crisis occurs the goals of treatment are symptom control and management of disease complications.

• Transfusion therapy- RBC transfusions are effective in acute anemia, prevention of complicatons or surgery and anesthesia, and in cases of acute chest syndrome.
• Pharmacological therapy-
  • Hydroxyurea- a chemotherapy agent is effective in increasing fetal hemoglobin in patients with sickle cell anemia. This decreases the formation of sickle cells.  Also lowers the incidence of crisis.
  • Arginine- has anti-sickling properties and enhances the availability of nitric oxide (vasodilator) for decreased pulmonary artery pressure. Has some use in Pulmonary hypertension and acute chest syndrome.
• Peripheral stem cell replacement- possible reveral of sickle cell anemia.  Must have a compatible donor.
• Supportive Therapy –
  • oral hydration or if not tolerated IV hydration with D5W or dextrose 5% in 0.25 NS
  • Supplemental oxygen.
  • management of pain-
    • Aspirin is good for mild or moderate pain diminishment, inhibits
    • platelet aggregation and diminishes inflammation.
    • NSAIDs for moderate pain with or without narcotic analgesics.
    • PCA pumps frequently used.