room with complaints of bilateral thigh and hip pain. The pain has
been present for 1 day and is steadily increasing in severity.
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Acetaminophen and ibuprofen have not relieved her symptoms. She
denies any recent trauma or excessive exercise.
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? She does report feeling fatigued and has been having burning withurination along with urinating frequently. She reports having similar
pain episodes in the past, sometimes requiring hospitalization.
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? On examination, she is afebrile (without fever) and in no acutedistress. No one in her family has similar episodes.
? Her conjunctiva and mucosal membranes are slightly pale in
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coloration.
? She has nonspecific bilateral anterior thigh pain with no abnormalities
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appreciated. The remainder of her examination is completely normal.? Her white blood cell count is elevated at 17,000/mm3, and her
hemoglobin (Hb) level is decreased at 7.1 g/dL. The urinalysis
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demonstrated an abnormal number of numerous bacteria.
Learning objectives
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? What is the most likely diagnosis?? What is the molecular genetics behind this disorder?
? What is the pathophysiologic mechanism of her symptoms?
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Hemoglobinopathies1. Group of genetic disorders caused by production of a structural y
abnormal hemoglobin molecule(Qualitative);
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2. Synthesis of insufficient quantities of normalhaemoglobin(Quantitative);
? or, rarely, both.
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Diagnosis of Case: Sickle cel Anemia
Molecular Mechanism
? Autosomal Recessive
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? GTG GAG at 6th position of globin chain.? The replacement of the charged glutamate with the nonpolar valine
on surface of globin chain
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? The intrinsic oxygen binding properties of HbA and HbS are the same,however, the solubility of deoxy HbS is reduced because of exposure
of Val-6 at the surface of the -chain.
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? Since hemoglobin is present at very high concentrations in the red
blood cell, deoxy HbS wil precipitate inside the cell.
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? The precipitate takes the form of elongated fibers because of theassociation of complementary hydrophobic surfaces on the - chains
of deoxy HbS.
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? At oxygen saturations found in arterial blood, the oxy HbS
predominates and HbS does not precipitate because Val-6 of the -
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chain is not exposed to the surfaceHydrophobic Sticky Patch of deoxy HbS
? At low oxygen tension, deoxyhemoglobin S polymerizes inside the
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RBC, forming a network of insoluble fibrous polymers that stiffen anddistort the cell, producing rigid, misshapen RBC. Such sickled cells
frequently block the flow of blood in the narrow capillaries
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Pathophysiologic Mechanism of Symptoms? This interruption in the supply of oxygen leads to localized anoxia
(oxygen deprivation) in the tissue, causing pain and eventually death
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(infarction) of cells in the vicinity of the blockage.
? Sickle cell crisis
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Pathophysiology of Sickle cel CrisisSymptoms of SCD
? Vaso-occlusive events result in tissue ischemia leading to acute and
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chronic pain as well as organ damage that can affect any organsystem, including the bones, spleen, liver, brain, lungs, kidneys, and
joints.
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? Dactylitis (pain and/or swelling of the hands or feet) is often the
earliest manifestation of SCD.
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? In children, the spleen can become engorged with blood cells in a"Splenic sequestration.".
Symptoms of SCD
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? The spleen is particularly vulnerable to infarction and the majority of
individuals with SCD who are not on hydroxyurea or transfusion
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therapy become functionally asplenic in early childhood, increasingtheir risk for certain types of bacterial infections.
? Acute chest syndrome is a major cause of mortality in SCD.
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? Chronic hemolysis can result in varying degrees of anemia, jaundice,cholelithiasis, and delayed growth and sexual maturation.
Bender MA1. Sickle Cel Disease. GeneReviews? [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
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2003 Sep 15 [updated 2017 Aug 17].
Possible selective advantage of the
heterozygous state
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? high frequency of the bS mutation among black AfricansDiagnosis
? Hemoglobin Electrophoresis
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? Ful blood count? Peripheral blood smear.
http://www.hematology.org/Fel ows/Case-Studies/725.aspx
Hb Electrophoresis
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Treatment
? Management of pain episodes includes hydration, anti-inflammatory
agents, and pain medication
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? Fever and suspected infection is treated with appropriate antibiotics
? Life-threatening or severe complications (e.g., severe acute chest
syndrome, aplastic crisis, and stroke) are often treated with red
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blood cell transfusion
? Splenectomy may be necessary for splenic sequestration
? Hydroxyurea can decrease the frequency and severity of vaso-
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occlusive processes, reduce transfusion needs, and increase life span.
Sickle Cell Disease.
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Bender MA.GeneReviews?[Internet]. updated 2017
Treatment
? Hydroxyurea(FDA Approved):
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By inhibiting the enzyme ribonucleotide reductase, hydroxyurea has
been shown to increase the levels of fetal Hb (HbF, 22) by
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mechanisms not fully understood.Increase in HbF concentrations has the effect of decreasing HbS levels
and its polymerisation in the red blood cell.
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? Glutamine has received FDA approval for the prevention of acute
complications in individuals with SCD age five years and
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older(antioxidant).? Stem cell transplantation may be an option in selected individuals
Summary and Discussion of the Case
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? This 15-year-old female's description of her pain is typical of a sickle
cell pain crisis.
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? Many times, infection is a trigger, most commonly pneumonia or aurinary tract infection. This case is consistent with a urinary tract
infection, indicated by her symptoms of urinary frequency, and
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burning with urination (dysuria). Her white blood cell count is
elevated in response to the infection.
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? The low hemoglobin level is consistent with sickle cell anemiaSummary
? Since she is homozygous (both genes coding for sickle hemoglobin),
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both her parents have sickle cell trait (heterozygous) and thus do nothave symptoms.
? The diagnosis can be established with hemoglobin electrophoresis.
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? The tendency for deoxy HbS to precipitate is why clinicalmanifestations of sickle cell anemia are brought on by exertion and
why treatment includes administration of oxygen.
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Thank You!