10.10.18 Hemoglobinopathies Flashcards
genetically heterogeneous conditions resulting from imbalance between the amounts of alpha and beta globin chains that are synthesized
Thalassemia
How are thalassemia’s classified?
- Severity of clinical manifestations
- Major hemoglobin species formed
- Genotype
If a mutation causes absent beta globin synthesis
B0 thalassemia
If a mutation has decreased (but still present) beta globin synthesis
B+ thalassemia
What region is beta thalassemia most common in?
Southern Europe (Also SE Asia, Africa, Middle East)
What is the genotype for Cooley’s Anemia
In which population is it typically seen in?
How would you diagnose?
B0/B0; B Thalassemia major
Mediterraneans
Hb electrophoresis
What are the symptoms of homozygous beta thalassemias?
- Ineffective erthropoiesis
- Destruction of produced RBC
- Splenomegaly
- Skeletal deformaties
- Iron overload- transfusions; iron hyperabsorption
Hemolysis of red cell precursors inside the marrow
Intramedullary hemolysis
Heterozygoies state where one allele is normal and the other allele is Beta +; enough beta to pair with alpha so not so many a4 tetramers
Beta thalassemia minor (trait)
What are the lab findings in beta thalassemia?
- Microcytic
- May or may not be anemic (if present it is mild)
- RBC count elevated
- Normal RDW
- Higher HbA2 levels
Characteristics of this alpha thalassemia include:
- typically silent
- minimal microcytosis
- anemia not present
- electrophoresis normal
aa/a-
Characteristics of this alpha thalassemia include:
- Mildly anemic
- Microcytosis
- Hgb electrophoresis normal in adults; abnormal in newborns
aa/– and a-/a-
What population has aa/– and which population has a-/a-
a-/a- : AA
aa/–: Asians
Characteristics of this alpha thalassemia include:
- Hemoglobin H = B4 tetramers
- Heinz bodies –> bite cells –> hemolytic anemia
- Splenomegaly
- Low MCV and MCH, high RDW
a-/–
Characteristics of this alpha thalassemia include::
- Hydrops fetalis
- Hemoglobin barts = Gamma4 tetramers
- Intrauterine death; treated in utero
–/–
Disorder in which sixth aa in beta chain is changed from glutamate to valine; less soluble and polymerizes
Hemoglobin S
Disorder in which sixth aa in beta chain is changed from glutamate to lysine; leads to increased cellular dehydration and founnd in West African descent
Hemoglobin C
Under what conditions do HbS polymerize and cause cells to sickle?
Hypoxia and acidosis
How do multiple cycles of sickling/unsickling affect the cell?
Leads to cellular dehydration which reduces threshold for further sickling
What cells have abnormal adhesion to endothelial cells?
Sickle cells
What genotypes are classified as sickle cell disease vs anemia?
Anemia= homozygous SS
Disease= SC, S beta thalassemia
What are the types of sickle cell crises?
- Splenic sequestration crisis
- Aplastic crisis
- Painful (vaso-occulusive) crisis
In children, rapid and extensive trapping of RBC in spleen;
profound anemia, massive splenomegaly, hypovolemic shock
Splenic sequestration crisis
Parovirus B19 leads to marrow suppression with rapid development of anemia (but not so fast as in sequestration crisis)
Aplastic crisis
Most common type of sickle cell crises
Periodic episodes of acute vascular occlusion
Attacks of pain usually affecting bones and large joints
Painful (Vaso-occulusive) crisis
What are the hematologic manifestations of sickle cell?
- Anemia
- Leukocytosis
- Throbocytosis
- Functionally asplenic
- Thromboses- risk for venous clots
What are triggers of painful crisis?
- Exercise
- Dehydration
- Infection
- Cold
- Stress
- Menstruation
- Surgery/trauma
- Pregnancy
How do you manage painful crisis
- Treat underlying infection
- Treat pain
- Supplement oxygen
- Folate replacement
- Replace fluid if dehydrated
What are you at risk for infection with in sickle cell?
Encapsulated organisms
If undergoing iron chelation therapy in sickle cell what are you at risk for?
Yersinia or Vibrio organisms
What can cause osteomyelitis and septic arthritis?
Salmonella osteomyelitis
most common cause of death in patients with sickle cell disease
Hypoxemia, New infiltrate on CXR, New fever, chest pain, dyspnea or cough
Acute Chest Syndrome
What are respiratory complications associated with sickle cell?
- Acute Chest Syndrome
2. Pulmonary Hypertension
What are the causes of acute chest syndrome
- Infection with atypical organisms- chlamydia and mycoplasma
- Fat embolism from necrotic bone marrow
How do you treat acute chest syndrome?
Antibiotics, oxugen, Transfusion (simple or exchange)
Not due to atherosclerosis but because of disordered blood vessels; occurence at 5 yo
Stroke
How do you treat stroke acutely and chronically?
Acute- exchange transfusion
Chronic- chronic regular transfusion
This type of transfusion gives red cells
Simple
This type of transfusion takes old red cells out while putting new red cells in
Exchange
What are complications of transfusion in SCD?
- Iron overload
2. Allo-immunization
What organs are damaged with iron overload and how do you treat?
heart, liver, and endocrine
Treat with chelation
How do you prevent allo-immunization?
Transfuse with blood negative for C, E, and Kell groups
What are complications occur in SCD?
- Renal
- Leg ulcers
- Avascular Necrosis (AVN)
- Priapism
What should you treat SCD with?
Hydroxyurea
What are the effects of hydroxyurea?
- Increases baseline Hb
- Reduces sickle crises
- Reduce acute chest syndrome
- Prevents pulmonary hypertension
- Reduces mortality
What are hallmarks of Hb C Disease?
- Microcytosis
- Target cells
- Splenomegaly
