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Flashcards in Heme/Onc1 Deck (56):

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)?



What type of hemolytic anemia (extravascular or intravascular) is G6PD deficiency?



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



Factor II



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


normal RBC count

male: 4.5-5.5 million/mcl
female: 4-5 million/mcl


normal Hb

male: 13.5-17.5
female: 12.0-15.5


normal Hct

male: 40-50
female: 35-45


normal WBC



normal platelets



how can you differentiate reticulocytes from RBCs in blood smear?

reticulocytes appear as slightly larger cells with blueish cytoplasm (due to residual RNA)


What is a normal reticulocyte count?

1-2% of total RBCs


What would be the reticulocyte response be to anemia if you have a properly functioning bone marrow?

the reticulocyte count would increase to >3%


Why would a reticulocyte count be falsely elevated in anemia?

The reticulocyte count is calculated as a percentage of total RBCs. A decrease in the total number of RBCs (as would be seen in anemia) would falsely elevate the precentage of reticulocytes


How do you correct the reticulocyte count?

by multiplying the reticulocyte count by Hct/45


What does a corrected reticulocyte count of >3% indicate?

This indicates a good marrow response and suggests peripheral destruction


What does a corrected reticulocyte count of <3% indicate?

This indicates a poor marrow response and suggests underproduction (i.e., a problem with the bone marrow)


What is meant by extravascular hemolysis (RBC destruction)/what does it involve?

extravascular hemolysis involves RBC destruction by the reticuloendothelial system (macrophages of the spleen, liver, and lymph nodes)


What are the breakdown products of hemoglobin?

(1) globin is broken down into amino acids
(2) heme is broken down into iron and protoporphyrin; iron is recycled
(3) protoporphyrin is broken down to unconjugated bilirubin, which is bound to serum albumin and delivered to the liver for conjugation and excretion into bile


What are the clinical and lab findings of extravascular hemolysis?

--Anemia with splenomegaly
--jaundice due to unconjugated bilirubin
--increased risk for bilirubin gallstones
--marrow hyperplasia with corrected reticulocyte count >3%


Why is unconjugated bilirubin (from the breakdown of hemoglobin and protoporphyrin, for instance) bound to serum albumin?

because unconjugated bilirubin is fat soluble. It will remain in the serum bound to albumin until the liver can take it, conjugate it, and then secrete it into the bile


What is meant by intravascular hemolysis (RBC destruction)/what does it involve?

intravascular hemolysis involves destruction of RBCs within vessels


What are the clinical and lab findings of intravascular hemolysis?

Early change: decreased serum haptoglobin
Next, during period of hemolysis:
Days later: hemosiderinuria


Why do we see a decrease in serum haptoglobin early in intravascular hemolysis?



Why do we see hemoglobinemia and hemoglobinuria in intravascular hemolysis?



Why do we see hemosiderinuria days later in intravascular hemolysis?



What is aplastic anemia?

Damage to hematopoietic stem cells, resulting in a pancytopenia (anemia, thrombocytopenia and leukopenia) with low corrected reticulocyte count


What is a classic lab finding of aplastic anemia?

A hypcellular, fatty bone marrow.

(hypocellularity of all cell lines to <25% of normal, normal cell architecture, and a predominance of fate and marrow stroma)


What are the classes of etiologies of aplastic anemia?

--chemicals/environmental toxins
--viral infections


What viral infections are associated with/linked to development of aplastic anemia?

--cytomegalovirus (CMV)


What chemicals/environmental toxins are associated with/linked to development of aplastic anemia?



What drugs are associated with/linked to development of aplastic anemia?

--anticonvulsant drugs (carbamazepine, phenytoin)


How do you treat aplastic anemia?

--discontinuation of causative drugs
--immunosuppressive medications (corticosteroids, cyclosporine, immune globulin)
--bone marrow transplant
--supportive care with transfusions and marrow-stimulating factors (GM-CSF, EPO, G-CSF)


What are ringed sideroblasts on Prussion blue stain characteristic of?

Siderblastic anemia


What would we see on bone marrow biopsy in multiple myeloma?

sheets of abnormal plasma cells


How does Parvovirus B19 affect hematopoiesis?

Parvovirus B19 can infect progenitor red cells and temporarily halt erythropoiesis, resulting in a pure red-cell aplasia.

This leads to significant anemia in the setting of preexisting marrow stress (e.g., sickle cell anemia and hereditary spherocytosis)


Why would we see a red-cell aplasia (anemia) following parvovirus b19 infection in someone with sickle cell anemia, but not in a healthy individual?

This is because a healthy individual has reserve capacity (of RBCs) However, a patient who is highly dependent on their reserve (such as a patient with sickle cell) would show signs even with a minimal knock-down of their production of RBCs