Sickle Cell Disease The Silent Crisis

  
  
  
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These patients are too young. That is always my first thought when  see the History and Physical. Sickle Cell Disease can be so destuctive to some patients. It can be a challanging managing these patients, since acurate diagnosis can be tricky with this disease. Sickle cell disease is a genetically transmitted autosomal recessive disorder in red blood cells. Instability of the hemoglobin molecule in the deoxygenated state, cuases red blood cells to change from the usual biconcave disc shape to an irregular sickled shape. The abnormal shape of these red blood cells and their propensity to adhere to the walls of blood vessels can occlude the vessels, preventing normal blood flow and decreasing the delivery of oxygen to organs and tissues, a condition known as crisis. The sickled cells are also extremely susceptible to hemolysis, causing individuals with sickle cell disease to have chronic anemia.  sickle cell anemia – support group.3.jpgsickle.jpg

Vaso-occlusive episodes are associated with dehydration, acidosis, and fever. Cold and systemic illnesses (eg, infections) commonly precipitate sickle cell crises. Sudden changes in altitude and travel in nonpressurized aircraft sometimes precede onset of a vasoocclusive crisis.

The skeletal manifestations of sickle cell disease are the result of changes in bone and bone marrow caused by the chronic tissue hypoxia that is exacerbated by episodic occlusion of the microcirculation by the abnormal sickle cells. The main processes that lead to bone and joint destruction in sickle cell disease are infarction of bone and bone marrow, compensatory bone marrow hyperplasia, secondary osteomyelitis, and secondary growth defects.

When the rigid erythrocytes jam in the arterial and venous sinusoids of skeletal tissue the resultant effect is intravascular thrombosis, which leads to infarction of bone and bone marrow. Repeated episodes of these crises eventually lead to irreversible bone infarcts and osteonecrosis especially in weight bearing areas. These areas of osteonecrosis (avascular necrosis/aseptic necrosis) become radiographically visible as sclerosis of bone with secondary reparative reaction and eventually result in degenerative bone and joint destruction.

 These painful crises, which occur in almost all patients at some point in their lives, can last hours to days, affecting the bones of the back, the long bones, and the chest. Some patients have one episode every few years, while others have many episodes per year. The crises can be severe enough to require admission to the hospital for pain control and intravenous fluids.

Repeated crises can cause damage to the kidneys, lungs, bones, eyes, and central nervous system.

 Infarction usually occurs in a segmental pattern that suggests damage to the large cerebral arteries. The most common abnormalities found on arteriography or magnetic resonance angiography (MRA) are marked narrowing or complete occlusion of the anterior cerebral arteries (ACA) and/or middle cerebral arteries (MCA). Multiple, bilateral vessel involvement is usual, even in patients who have unilateral neurologic signs. Vessel narrowing is the consequence of intimal and medial proliferation that is thought to be caused by endothelial damage from sickled red blood cells. The damaged, irregular endothelium can serve as a nidus for the adhesion of platelets and sickle cells, thereby resulting in thrombus formation. The stroke event occurs when narrowing is severe enough to compromise distal flow or the thrombus dislodges and causes distal embolization. Transient neurologic symptoms can result from vessel spasm. Intracranial hemorrhage can be intracerebral or subarachnoid and can result from rupture of an aneurysm of the circle of Willis. Intracerebral hemorrhage may also occur years later in patients who had prior cerebral infarction as a result of a rupture of fragile collateral vessels (moyamoya).

The SILENT STROKE

Silent Stroke Is Not Detected With a Standard Neurologic Examination. To evaluate the sensitivity and specificity of neurologic examinations for detecting silent stroke, a pediatric neurologist examined four groups of children: 1) children with stroke detected with MRI but without focal neurologic findings (silent stroke); 2) children with stroke detected with MRI with focal neurologic findings (overt stroke); 3) children with sickle cell disease but no evidence of stroke with MRI; and 4) normal sibling controls. The division found the neurologic examination was not a sensitive method to detect a silent stroke; 34% of children with stroke as defined by MRI exhibited no focal neurologic findings [Glauser, 1995]. All children with a silent stroke had abnormal neurocognitive scores [Glauser, 1995].Common symptoms include:

 

MRI is the best method for detecting early signs of osteonecrosis in patients with sickle cell disease and for identifying episodes of osteomyelitis

Nuclear scanning can also be used to detect early avascular necrosis. This modality also plays a role in detecting osteomyelitis. Likewise, indium leukocyte scanning has an important role in diagnosing osteomyelitis.

Patients with acute bone pain crises usually present with fever, leukocytosis, and warmth and tenderness around the affected joints. This process tends to affect the knees and elbows, mimicking rheumatic fever and septic arthritis. In adolescence and adulthood, the most prominent complication is osteonecrosis of 1 or more epiphyses, usually of the femoral or humeral heads. Chronic pain is often associated with later stages of osteonecrosis, particularly in the femoral head. Pain due to avascular necrosis is most notable with weight bearing on the joint. Patients often have pain associated with functional limitation of the affected joint.

Patients with sickle cell disease are prone to infection of the bone and bone marrow, or osteomyelitis, in areas of infarction and necrosis. Although Staphylococcus aureus is the most common cause of osteomyelitis in the general population, studies have shown that in patients with sickle cell disease the relative incidence of Salmonella osteomyelitis is twice that of staphylococcal infection

Treatment

Bone marrow transplant offers the only potential cure for sickle cell anemia. But very few people have a suitable donor for transplant.

As a result, treatment for sickle cell anemia is usually aimed at avoiding crises, relieving symptoms and preventing complications. If you have sickle cell anemia, you’ll need to make regular visits to your doctor to check your red blood cell count and monitor your health. You may also require treatment from specialists at a hospital or sickle cell anemia clinic. Treatments may include medications to reduce pain and prevent complications, blood transfusions and supplemental oxygen, as well as bone marrow transplant.

Risks and benefits of allogeneic bone marrow transplantation in children with complications of sickle cell disease.

Additional treatments may include:

  • Dialysis or kidney transplant for kidney disease

  • Drug rehabilitation and counseling for the psychological complications

  • Gallbladder removal (if there is significant gallstone disease)

  • Hip replacement for avascular necrosis of the hip (death of the joint)

  • Irrigation or surgery for priapism (persistent, painful erections)

  • Partial exchange transfusion for acute chest syndrome

  • Surgery for eye problems

  • Transfusions or surgery for brain problems, such as strokes

  • Wound care, zinc oxide, or surgery for leg ulcers

Medications

Medications used to treat sickle cell anemia include:

  • Antibiotics. Children with sickle cell anemia usually begin taking the antibiotic penicillin when they’re about 2 months of age and continue until they’re 5 years old. Doing so helps prevent infections, such as pneumonia, which can be life-threatening to an infant or child with sickle cell anemia. Antibiotics may also help adults with sickle cell anemia fight certain infections.

  • Pain-relieving medications. To relieve pain during a sickle crisis, your doctor may advise over-the-counter pain relievers and application of heat to the affected area. You may also need stronger prescription painkillers.

  • Hydroxyurea (Droxia, Hydrea). This prescription drug, normally used to treat cancer, may be helpful for adults with severe disease. When taken daily, it reduces the frequency of painful crises and may reduce the need for blood transfusions. It seems to work by stimulating production of fetal hemoglobin — a type of hemoglobin found in newborns that helps prevent the formation of sickle cells. There is some concern about the possibility that long-term use of this drug may cause tumors or leukemia in certain people. Your doctor can help you determine if this drug may be beneficial for you.

Blood transfusions

In a red blood cell transfusion, red blood cells are removed from a supply of donated blood. These donated cells are then given intravenously to a person with sickle cell anemia.

Blood transfusions increase the number of normal red blood cells in circulation, helping to relieve anemia. In children with sickle cell anemia at high risk of stroke, regular blood transfusions can decrease their risk of stroke.

Blood transfusions carry some risk. Blood contains iron. Regular blood transfusions cause an excess amount of iron to build up in your body. Because excess iron can damage your heart, liver and other organs, people who undergo regular transfusions must often receive treatment to reduce iron levels. In 2005, the Food and Drug Administration approved deferasirox (Exjade), the first oral medication that can reduce excess iron levels, for use in people older than the age of 2.

 

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