Sickle cell anemia

• • Hemolysis and anemia due to decreased deformability of RBCs due to crystallization of HbS under conditions of low O₂ tension

  • Comes from a point mutation, resulting in substitution of Val for Glu at the 6^th position of the -globin chain

  • Diagnosis from seeing sickled RBCs in peripheral smear (not too specific) and confirmed with a sickling test (put RBCs into O₂-poor test tube and look for sickling) and by looking for mobility of HbS on acidic Hb electrophoresis (HbD and HbG cannot be separated by either acidic or basic electrophoresis)

  • About 8% of American blacks are heterozygotes; they are asymptomatic unless exposed to severe hypoxia, as they have an [HbS] of about 40%

  • Homozygotes have most of their Hb as HbS

  • Deoxygenated HbS polymerizes, leading to the formation of drepanocytes (sickle cells); sickling of the cell causes membrane damage, chronic hemolysis, and occlusion of small vessels with ischemic tissue damage

  • Newborns won’t show the disease until 5-6 MOA, as HbS won’t polymerize with HbF (or with any other Hb for that matter; people who are heterozygous for HbS and another variant Hb have a much less severe anemia that those who are only heterozygous for HbS)

  • MCHC

    • Increasing MCHC (such as with dehydration) leads to increased sickling

    • Decreasing MCHC (as would occur with a co-existing thalassemia) lessen the severity of the anemia

  • Decreasing the pH increases the amount of deoxygenated Hb present, which encourages sickling

  • Sickling may at first be reversed with oxygenation, but as the amount of sickling an RBC is exposed to increases, the amount of membrane damage increases, leading to irreversibly sickled cells, which are sequestered and destroyed in the spleen (there may be some intravascular hemolysis from the mechanical fragility of the sickled cells)

  • Chronic hemolysis can lead to formation of pigment gallstones (from increased amounts of BR), and frequent transfusions can lead to iron overload (hemosiderosis)

  • If the RBCs are trapped in the liver, sickle cell “cirrhosis” may occur

  • The bone marrow is hypercellular from erythroid hyperplasia and there is peripheral reticulocytosis (if there is no reticulocytosis, be very afraid, because that means that the patient’s bone marrow has shut down)

  • Marrow expansion can lead to the “crew cut” look of the skull on X-Ray

  • Extramedullary hematopoiesis may be seen in the spleen and liver (“leukoerythroblastosis”)

  • Kids may have mild splenomegaly; chronic erythrostasis leads to splenic infarction, scarring, and eventually autosplenectomy

  • Infarctions from vessel occlusion may also be seen in the bones, brain, kidney, liver, lung, and retina; vascular stagnation in the sub-q tissues of adults leads to stasis ulcers

  • People with sickle cell anemia are very susceptible to blood borne infection and infection with encapsulated m/o (septicemia and meningitis from S. pneumoniae and H. influenzae are the 2 most common causes of death in kids with sickle cell anemia) due to splenic dysfunction

  • Patients are also very susceptible to Salmonella osteomyelitis (maybe because the bone pain from ischemia resulting from a sickling crisis may be hard to tell apart from the pain of osteomyelitis – sickling patients should be put on a course of prophylactic a/b)

  • Crises

    • Vasoocclusive crisis (painful crisis)

      • Come from things that favor sickling

      • Commonly involve bones, lungs, liver, brain, spleen, and penis (priapism)

      • Involvement of lungs may present with F, cough, chest, pain, and a pulmonary infiltrate (this is called acute chest syndrome and is hard to tell apart from pneumonia)

      • CNS hypoxia can cause stroke or seizures

    • Aplastic crises – marrow temporarily stops working; triggered by infections and/or nutritional deficiencies

    • Sequestration crisis

      • May be seen in kids with splenomegaly and in adults whose spleens haven’t undergone autoinfarction

      • Massive RBC sequestration leads to rapid splenomegaly, hypovolemia, and maybe shock

    • Any of these crises can be fatal, but they may be reversed with transfusion, rehydration, and treatment of infection

  • Can use hydroxyurea to induce the formation of HbF and lessen sickling

• Other variant Hbs (such as HbC, HbG, etc); can be separated by electrophoresis

• Unstable Hb variants, such as Heinz body hemolytic anemia

• Hbs with altered O₂ affinity

• Thalassemias
  

Category: Medical Subject Notes , Pathology Notes