Hem: Hemoglobinopathies

It has two alpha chains and two beta chains.
Each chain has a globin bound to an iron.

Alpha-globin comes from chromosome 16, and
beta-globin comes from chromosome 11.

Alpha2-gamma2 = HgF (fetal hemoglobin,)
Alpha2-delta2 = HgA2, and
Alpha2-beta2 = HgA

Cooperativity refers to conformational changes in hemoglobin that alter its affinity for oxygen.

P50 is the partial pressure of oxygen in which the hemoglobin is 50% saturated with oxygen.

Hemoglobin will have decreased affinity for oxygen and there will be a rightward shift on the dissociation curve.

Diseases where mutations either partially or completely inactivate production of either alpha or beta globin chains, resulting in globin chain imbalance.

Thalassemia minor (trait),
Thalassemia major (transfusion-dependent), and
Thalassemia intermedia (not transfusion-dependent)

Deficiency in one globin chain leads to excess in the other chain, causing
ineffective erythropoiesis (Heinz body hemolysis), and
destruction of produced RBCs.

Splenomegaly,
skeletal deformities due to marrow expansion (frontal bossing), and
iron overload (iron from transfusions and hyperabsorption in gut.)

Iron failure causes hypogonadism, pancreatic failure, liver failure, and heart failure.

B0 has no beta globin synthesis, B+ thalassemia has decreased beta globin synthesis.

Beta-thalassemia minor is when the patient has one normal beta chain and one abnormal (heterozygous.)

Smear shows hypochromia, microcytosis, target cells, and basophilic stippling.
Hemoglobin electrophoresis reveals increased A2.

Cooley's anemia.

1. the effects of severe and chronic anemia,
2. chronic hemolysis,
3. organ damage from iron overload, and rapidly expanding mass of bone marrow progenitors.
4.

Thalassemia intermedia.

1. Infants well at birth,
2. Skeletal changes ("hair on end" appearance of the skull, frontal bossing, shortening of limbs, compression fractures of spine)
3. Liver and gallbladder iron overload (hepatomegaly, premature bilirubin gallstone disease and biliary tract inflammation),
4. splenomegaly, and
5. endocrine and metabolic abnormalities (growth retardation, hypogonadism, glucose intolerance), and
6. cardiopulmonary complications (cardiac dilatation, cardiac hemosiderosis, cardiomyopathy, pulmonary hypertension.)

Teardrops, target cells, clumped inclusion bodies, and basophilic stippling.

Chronic transfusion and chelation for iron overload.
Also, spelectomy.

One gene deletion: typically silent, Hg normal.
Two gene deletion: mildly anemic, Hg normal.
Three gene deletion: Hemoglobin H disease (Hg H = B4 tetramers),
Four gene deletion: hydrops fetalis (Hg Barts = gamma4 tetramers.)

Bite cells

The sixth aa in the beta chain is changed from glutamate (charged) to valine (hydrophobic.)
Less soluble, polymerizes.

The sixth aa in the beta chain is changed from glutamate to lysine.
Increased cellular dehydration.

S-B0 thalassemia looks just like SS disease.
S-B+ thalassemia is a minor disease since some normal beta chains are being made.

Cycles of sickling/desickling leading to cells becoming irreversibly sickled.
Gardos channel activation leading to cellular dehydration.
Hemolysis of sickled cells and abnormal adhesion to endothelial cells.

Hemolysis,
anemia (if below baseline, think of other possibilities like Parovirus B19 aplastic crisis),
functional asplenia, and
thrombosis (venous clots.)

1. hemolytic crisis,
2. splenic sequestration crisis,
3. aplastic crisis, and
4. painful crisis.

1. profound anemia,
2. massive splenomegaly, and
3. hypovolemic shock.

Exercise, dehydration, infection, cold, stress, menstuation, surger-trauma, and pregnancy.

They have "autosplenectomy" from splenic infarct, so they have increased susceptibility to encapsulated organisms.

Osteomyelitis (salmonella osteomyelitis.)

1. hypoxemia,
2. new infiltrate on CXR, and
3. new fever, chest pain, dyspnea, or cough.

Antibiotics, oxygen, and transfusion (simple or exchange.)

Pulmonary hypertension.
No effective treatment.

5 years old.
Acute treatment: exchange transfusion.
Chronic treatment in children: regular transfusions.

Transcranial doppler.
Chronic regular transfusions will prevent the first instance of stroke.

Microscopic hematuria, and
Isosthenuria (inability to concentrate urine.)

Priapism is a prolonged painful erection caused by vasoocclusion.

Iron overload caused by transfusion.

Give patients blood that is negative for C, E, and Kell antigens.

It increases the amount of HbF, thus decreasing HbS.

1. increases baseline hemoglobin values,
2. reduces number of sickle crises,
3. reduces episodes of acute chest syndrome,
4. prevents pulmonary hypertension, and
5. reduces mortality.

Isosthenuria and
microscopic hematuria.

Microcytosis and target cells.
Splenomegaly.