Heme/Onc1 Flashcards
Pyruvate kinase deficiency
autosomal recessive defect in pyruvate kinase –> decrease in ATP –> rigid RBCs
Classic findings in pyruvate kinase deficiency.
A neonate with an enlarged spleen and severe anemia
(splenic macrophages are consuming the RBCs, leading both to the anemia, and the large spleen.
What type of hemolytic anemia is pyrivate kinase deficiency (extravascular or intravascular)?
extravascular
What type of hemolytic anemia (extravascular or intravascular) is G6PD deficiency?
extravascular
Let’s say you are presented with an african american male patient who develops shortness of breath during a plane ride. Why might you suspect?
We would put sickle cell trait/disease on the differential. An airplane ride–or any activity at low pO2, can cause precipitation of the sickle hemoglobin (HbS), which results in anemia and vaso-occlusive disease.
What is the pathogenesis/risk factors for sickle cell anemia exacerbation?
(1) low pO2
(2) dehydration
(3) acidosis
The above three precipitate sickling (deoxygenated hemoglobin polymerizes), which results in anemia and vaso-occlusive disease.
Why has the sickle cell allele persisted in the population?
Because heterozygotes (sickle cell trait) have resistance to malaria
Why are newborns with sickle cell anemia initially asymptomatic?
Because the sickle allele is a variant of beta globin. When babies are born, initially HbF (which contains alpha and gamma globin units) is high, and HbS (which contains the alpha and sickle [beta] globin chains) is low
What is sickle cell anemia? (brief definition relating to genetics)
HbS is due to a single point mutation that results in a single amino acid substitution in the beta chain of hemoglobin (glutamic acid with valine at position 6)
What would we see on radiographic image in sickle cell anemia?
A “crew-cut” appearance on skull X-ray due to bone marrow expansion from increased erythropoiesis
(this is also seen in thalassemias)
How is sickle cell anemia diagnosed?
hemoglobin electrophoresis
What is the treatment for sickle cell anemia?
- -hydroxyurea (which increased the production of fetal hemoglobin)
- -bone marrow transplant
What is the function of heparin/how does it work?
Heparin is an anticoagulant that accelerates the activity of antithrombin III, thereby inactivating thrombin
What laboratory study is used to monitor the effect of heparin?
PTT (partial thromboplastin time)
Why is it important to monitor heparin with PTT?
You do not want the PTT (aPTT - activated PTT) to exceed 1.5-2 times the control value, because the risk for internal bleeding can increase substantially
Factor I
fibrinogen
Factor II
prothrombin
What measures would be used to measure the effect of warfarin?
PT or INR –both measure the extrinsic pathway (and common pathway) of the coagulation cascade
What is the most common inherited coagulation disorder?
vW Disease
How does vW Disease typically present?
with mild skin and mucosal bleeding.
vWF is essential for platelet adhesion in primary hemostasis
Why does vW Disease present with a prolonged PTT?
This is because vWF binds to circulating Factor VIII and protects it from degradation
How do you treat vW Disease?
with Desmopressin , an ADH analog, which increases the release of vWF from Weibel-Palade bodies of endothelial cells.
What is the function of fibronectin?
fibronectin is a serum protein that acts as an opsonin for phagocytic cells in clots. Fibronectin binds non-specifically to bacteria and other materials in the newly-formed clots and draws the cell membranes of phagocytes into close contact with these substances.
Patient with:
- -skin and mucosal bleeing (gums bleed after vigorous brushing of teeth; hematoma develops at IV injection site)
- -normal platelet count
- -normal PT
- -prolonged PTT
- -increased bleeding time
What is the likely diagnosis?
von Willebrand Disease
