Heme/Onc2

Question 1

What is DIC?

Answer 1

Pathologic activation of the coagulation cascade, characterized by the consumption of both platelets and coagulation factors.
Widespread microthrombi result in ischemia and infarction.

Question 2

What are the clinical manifestations/presentation of DIC?

Answer 2

bleeding, especially from IV sites and mucosal surfaces (bleeding from body orafices). Almost always secondary to a stimulus/other disease process

Question 3

What are known triggers for DIC? (5)

Answer 3

(1) sepsis
(2) obstetric complications
(3) adenocarcinoma
(4) acute promyelocytic leukemia
(5) rattlesnake bite

Question 4

Why do obstetric complications trigger DIC?

Answer 4

tissue thromboplastin in the amniotic fluid activates coagulation.

If the amniotic fluid were to leak into the mother’s circulation, it could result in activation of the coag. cascase

Question 5

What is tissue thromboplastin?

Answer 5

Also known as tissue factor, or factor III. This is a potent activator of the extrinsic pathway of the coagulation cascade.

Question 6

Why do adenocarcinomas cause DIC?

Answer 6

Mucin (produced by the carcinoma) activates coagulation

Question 7

Why does a rattlesnake bite tigger DIC?

Answer 7

venom activates coagulation

Question 8

Why does acute promyelocytic leukemia cause DIC?

Answer 8

primary granules activated coagulation.

Question 9

Why does sepsis cause DIC? With what microbes is this seen?

Answer 9

The endotoxins from bacterial walls and cytokines (e.g., TNF and IL-1) induce endothelial cells to produce tissue factor.

The is seen especially in sepsis with E. coli or N. meningitidis

Question 10

What lab findings to we see in DIC? (5)

Answer 10

(1) decreased platelet count
(2) increased PT/PTT
(3) decreased fibrinogen
(4) microangiopathic hemolytic anemia
(5) elevated fibrin split products, particularly D-dimers

Question 11

What are D-dimers

Answer 11

Fibrin split products derived from the splitting of cross-linked fibrin.
**D-dimer is not produced from splitting fibrinogen

Question 12

What is the best screening test for DIC?

Answer 12

elevated D-dimer

Question 13

What is the treatment for DIC?

Answer 13

(1) addressing the underlying cause

(2) transfusing blood products and cryprecipitate as necessary

Question 14

Why would we want to give cryoprecipitate to someone with DIC?

Answer 14

cryoprecipitate contains coagulation factors, which are being consumed in DIC

Question 15

What test is used to measure prekallikrein?

Answer 15

PTT

Question 16

What test is used to measure high molecular weight kininogen?

Answer 16

PTT

Question 17

What test is used to measure fibrinogen?

Answer 17

TT (thrombin time)

Question 18

On what cells is myeloperixidase stain used, and for what?

Answer 18

Used on neutrophils to diagnose myeloperoxidase deficiency.

This disease is clinically similar to chronic granulomatous disease

Question 19

What is chromium-51 used to measure?

Answer 19

red cell survivial

Question 20

What might an anti-Epstein-Barr virus stain be useful for?

Answer 20

in helping to prove that atypical lymphocytes on peripheral blood smear are probably due to infectious mononucleosis.

Question 21

In what demographic group is hairy cell leukemia most often seen?

Answer 21

older men

Question 22

What should we think of if we observe a megaloblastic anemia in a person from the Great Lakes region after consuming poorly cooked fish?

Answer 22

Diphyllobothrium latum

Question 23

B12 deficiency with resulting megaloblastic anemia is specifically associated with what infection?

Answer 23

Diphyllobothrium latum

Question 24

What is the process of B12 absorption?

Answer 24

(1) salivary gland enzymes liberate vitamin B12, which is then bound by R-binder (also from the salivary gland) adn carried through the stomach to the small bowel
(2) pancreatic proteases in the duodenum detach B12 from R-binder
(3) B12 binds intrinsic factor in the small bowel; intrinsic factor-B12 complex is absorbed in the ileum.

Question 25

What is the difference in onset of folate deficiency versus B12 deficiency, and why?

Answer 25

B12 deficiency is less common than folate deficiency, and takes years to develop, whereas folate deficiency develops within months. This is because the body has minimal folate stores, whereas the body has large hepatic stores of B12

Question 26

What is the most common cause of B12 deficiency?

Answer 26

Pernicious anemia

Question 27

What is pernicious anemia.

Answer 27

Autoimmune destruction of gastric parietal cells (in the body of the stomach) leads to an intrinsic factor deficiency--> impaired B12 absorption. (The ileum recognizes/absorbs B12/IF complex, but not B12 alone. If the levels of IF decrease, the ileum will be unable to absorb B12--> deficiency.)

Question 28

Besides pernicious anemia, what are other causes of B12 deficiency? (3)

Answer 28

(1) pancreatic insufficiency (2) damage to the terminal ileum (e.g., Crohn disease, diphyllobothrium latum) (3) dietary deficiency--rare, except in vegans

Question 29

What are the clinical and lab findings in B12 deficiency? (6)

Answer 29

(1) macrocytic RBCs with hypersegmented neutrophils (2) glossitis (3) subacute combined degeneration of the spinal cord (4) decreased serum B12 (5) increased serum homocysteine (6) increased methylmalonic acid --> spinal cord damage

Question 30

A 7 month old boy with failure to thrive is brought to the physician for a follow-up examination. His Hb is 4.4 g/dL. The PBS shows very small RBCs with marked palloe. Further evaluation shows low levels of HbA with elevated fractions of HbA2 and HbF. What is the underlying mechanism responsible for the findings in this patient?

Answer 30

This patient likely has beta thalassemia. In beta thalassemia, a decrease in the production of globin --> a decrease in Hb --> microcytic anemia

Question 31

What is thalassemia?

Answer 31

A microcytic anemia due to decreased synthesis of the globin chains of Hb: decrease globin --> decrease Hb --> microcytic anemia

Question 32

Against what disease are carriers of thalassemia protected?

Answer 32

Carriers are protected against Plasmodium Falciparum malaria

Question 33

What would you see on peripheral blood smear with ß- thalassemia minor?

Answer 33

- -microcytic, hypochromic RBCs | - -targets cells

Question 34

What would Hb electrophoresis show in ß- thalassemia minor?

Answer 34

- -decreased HbA - -increased HbA2 - -increased HbF

Question 35

When would ß thalassemia major present, and why does it present at this specific time?

Answer 35

Beta+ thalassemia typically presents at around 6 months of age. This is because for the first six months of life, HbF is still predominant and protective. However, after about six months, the predominant Hb switches to HbA, at which point infants become markedly anemic.

Question 36

Why do we see increased HbA2 and HbF in ß-thalassemia major?

Answer 36

Production of these forms of hemoglobin increases to compensate for the diminished production of HbA

Question 37

When would we see antibodies against fetal blood cells?

Answer 37

These are generally produced by a mother who has been sensitized to fetal blood antigens by transfusion or a previous pregnancy

Question 38

What is the consequence of antibodies against fetal blood antigens?

Answer 38

Immune-mediated hemolysis--> intrauterine anemia and hydrops fetalis

Question 39

What is hereditary spherocytosis?

Answer 39

Inherited defect of RBC cytoskeletal MB proteins, leading to normocytic anemia with extravascular hemolysis.

Question 40

What is the basic pathogenesis of hereditary spherocytosis?

Answer 40

- -membrane blebs are formed and lost over time - -loss of membrane renders cells round (spherocytes) instead of disc shaped - -spherocytes are less able to maneuver through the splenic sinusoids and are consumed by splenic macrophages, resulting in anemia

Question 41

What do we see on PBS in hereditary spherocytosis? (3)

Answer 41

- -spherocytes with loss of central pallor - -increased RDW - -increased MCHC (mean corpuscular Hb concentration)

Question 42

What are the clinical findings in hereditary spherocytosis?

Answer 42

- -splenomegaly - -jaundice (inc. unconjugated bilirubin) - -increased risk for bilirubin gallstones - -anemia

Question 43

What complication are people with hereditary spherocytosis at increased risk for?

Answer 43

At increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors.

Question 44

How is hereditary spherocytosis diagnosed?

Answer 44

Diagnosed by osmotic fragility test This test reveals increased spherocyte fragility in hypotonic solution. (reduced MB and greater [Hb]--> greater cell swelling when placed in hypotonic solution)

Question 45

What is the treatment for hereditary spherocytosis? Why?

Answer 45

splenectomy. This removes the site of peripheral/extravascular destruction: the splenic macrophages. This will resolve the anemia

Question 46

What is the consequence of splenectomy in hereditary spherocytosis? (What will show up on PBS?)

Answer 46

Howell-Jolly bodies with appear on peripheral blood smear. These are fragments of nuclear material in RBCs that are normally removed by splenic macrophages.

Question 47

What cytoskeletal proteins are mostly commonly involved in hereditary spherocytosis?

Answer 47

- -spectrin - -ankyrin - -band 3.1

Question 48

A 3 month-old boy is brought to the emergency department by his parents because of yellowing of his skin. Physical examination shows pale palpebral conjunctiva, diffuse jaundice, and splenomegaly. A peripheral blood smear shows spherocytosis. The reticulocyte count is elevated. His parents state that two relatives have a similar condition. What is this boy's likely diagnosis? Which of the following is a complication? - -aplastic anemia - -gallstones - -hemorroids - -immunodeficiency - -renal stones

Answer 48

He has hereditary spherocytosis. He is at increased risk for bilirubin gallstones

Question 49

A 3 month-old boy is brought to the emergency department by his parents because of yellowing of his skin. Physical examination shows pale palpebral conjunctiva, diffuse jaundice, and splenomegaly. A peripheral blood smear shows spherocytosis. The reticulocyte count is elevated. His parents state that two relatives have a similar condition. Why is his reticulocyte count increased?

Answer 49

This boy has peripheral, extravascular destruction of his RBCs. However, he has no problem making RBCs. His bone marrow will respond by increasing RBC synthesis, which will lead to an increase in the corrected reticulocyte count to >3%.

Question 50

How can ITP be distinguished from HUS or TTP?

Answer 50

In all three disorders, the platelet count will be decreased, the bleeding time will be increased, and the PT and PTT will be unchanged. However, in TTP and HUS, you will see shistocytes (helmet cells) on PBS; these will be absent in ITP.