Pathology Ch 14: Red Blood Cell And Bleeding Disorders

Front 1

what does the RCDW measure

Back 1

red cell distribution width. a coefficent of variation in red cell volume

Front 2

what are some symptoms that are characteristic of anemia

Back 2

weakness, malaise, easy fatigability, and mild dyspnia on exertion

more extreme cases: fatty change of liver, myocardium and kidney

Front 3

how long from the onset of hypoxia and the release of erythropoietin from the kidney does it take CFU-E proenitors to mature and appear in the blood

Back 3

5 days. they appeat as reticulocytes

Front 4

leukocytosis, reticulocytosis, and thrombocytosis are often associated with

Back 4

blood loss anemias

Front 5

shortened blood cell lifespan (<120 days), elevated EPO levels, and accumulation of hemoglobin breakdown products are all hallmark signs of __________________

Back 5

hemolytic anemia

Front 6

what is the difference between intravascular and extravascular hemolysis

Back 6

extravascular hemolysis occurs when RBCs are destroyed within phagocytes, can lead to splenic and phagocytic hyperplasia, also jaundice and reduced haptoglobin

intravascular hemolysis is caused by mechanical injury, compliment fixation, and parasites, this is less common

Front 7

what rises as haptoglobin is used up?

Back 7

free hemoglobin in the blood is oxidized to methemoglobin (Fe+++ hemoglobin)

free iron is converted to hemosiderin and can accumulate in the kidneys

bilirubin accumulates and can cause jaundace

Front 8

is splenomegaly seen in extravascular hemolysis

is excess serum bilirubin conjugated

Back 8

no and no

Front 9

defecits in ankryin, band 3, spectrin, and band 4.2 cause what disorder?

Back 9

hereditary spherocytosis

Front 10

what anemia would you suspect if a patient presented with spleomegaly, and jaundace, as well as small dark staining hyperchromic red cells

Back 10

hereditary spherocytosis

Front 11

what can cause a sudden worsening of spherocytosis

Back 11

parvovirus infection

Front 12

what painful complication is associated with excessive bilirubin released into the GI tract

Back 12

gallstones derived from heme pigments

Front 13

what x linked recessive deficency associated with the hexose monophosphate shunt or glutathione metabolism reduces the ability of red cells to protect themselves from oxidative injuries

Back 13

Glucose 6 phosphate deficency

reduction of glutathione (which eliminates H2O2 radicals) is dependent of G6P

Front 14

What would worsen the anemia of a patient with G6P deficency

Back 14

increased oxidative stress, like that assiciated with infections

Front 15

what is a heinz body? what is a bite cell?

Back 15

dark inclusions within red cells associated with G6PD

macrophages in the spleen try to get the heinz bodies and take a bite out of the affected cells

Front 16

what causes the deficit that is responsible for sickle cell disease?

Back 16

point mutation (glutamate switches to valine) in the beta globin gene which causes polymerization of deoxygenated hemoglobin

Front 17

what is the composition of Hemoglobin A

Back 17

2 alpha and 2 beta chains

Front 18

what is the composition of HbS

Back 18

2 alpha chains and 2 beta-s chains

Front 19

what is the effect of increased HbF on sickle cell patients

Back 19

milder disease because HbF prevents sickling of HbS

Front 20

what is the effect on dehydration on MCHC in sickle cell patients? what does this cause?

Back 20

higher MCHC, more sickling

Front 21

how does the bhor effect relate to sickle cell disease?

Back 21

lower pH (as in higher CO2) causes lower affinity of hemoglobin for oxygen. this increases fraction of deoxy HbS and increases sickling

Front 22

why is the spleen a common site for sickle cell aggregation

Back 22

sluggish blood flow

Front 23

what is responsible for the most serious clinical features of sickle cell disease

Back 23

microvascular occlusions which cause hypoxia, further sickling, pain and infarct (vaso-occlusive crisis)

hand foot syndrome and acute chest syndrome are specific types of vaso occlusive crises

Front 24

why is hydroxyurea affective in treating sickle cell disease

Back 24

1. increases HbF

2. has an antiinflamatory effect

Front 25

what mutations are most often associated with B+ thalassemia

Back 25

splicing mutations

Front 26

what mutations are most commonly associated with B0 thalassemia

Back 26

chain terminator mutations (frameshifting) prevent any functional synthesis of hemoglobin B

Front 27

what would you see in a CBC of a patient with B-thalassemia

Back 27

hypochromic, microcytic red cells and less HbA due to imbalance in a/b globin synthesis

Front 28

what role does hepticidin play in thalassemia syndromes

Back 28

hepticidin is a negative regulator of iron absorbtion. ineffective erythropoesis results in excessive iron accumulation

Front 29

what genotypes are associated with transfusion dependent B thalassemia major

Back 29

B+/B+

Bo/Bo

B+/Bo

Front 30

what genotypes are associated with the beta thalessemia trait (minor)

Back 30

Bo/B

B+/B

Front 31

in what poplations is B thalassemia major the most common

Back 31

mediterranean, africa, SE asia

Front 32

when does b-thallasemia manifest

Back 32

6-9 months when HBF production swithes to HbA

Front 33

how many alpha globin genes are usually present?

Back 33

4. thalassemia severity depends on number of genes that are defective. deletion of a single gene results in a silent carrier state

Front 34

what are the genotypes associated with alpha thalassemia trait

Back 34

a/a -/- , a/- a/-

Front 35

which populations have a higher incidence of alpha thalassemia

Back 35

asians

Front 36

what is hemoglobin H disease

Back 36

deletion of 3 alpha globin genes. causes formation of tetramers of beta globin which have a very high affinity for oxygen and are not effective for oxygen transfer

Front 37

what is hydrops fetalis

Back 37

deletion of all 4 alpha globin genes. results in a lifelong dependence on transfusion for survival, hematopoetic stem cell transplant can be curative

Front 38

what is paroxysmal nocturnal hemoglobinuria

Back 38

anemia associated with membrane compliment regulatory proteins (PIGA).

rbcs deficent in this are susceptable to lysis by compliment mediated processes especially the C5-9 membrane attack complex

Front 39

what is warm antibody type immunohemolytic anemia

Back 39

idiopathic hemolytic anemia characterized by IgG attack of RBCs

often due to presence of antigenic drugs. will manifest 1-2 weeks after dose of dru is applied

Front 40

what is cold-agglutin type hemolytic anemia

Back 40

IgM attack of RBCs in low temperature settings. presents like reynaud phenemenon

Front 41

what is the most common hemolytic anemia associated with trauma to red cells

Back 41

cardiac valve replacements can cause turbulent flow

Front 42

what is a helmet cell

Back 42

red cell fragment associated with trauma to red blood cells due to sheer stress

Front 43

what are common themes aong megaloblastic anemias?

Back 43

impaired DNA synthesis

ineffective hematopoesis

abnormally large erythroid precursors and red cells

Front 44

what is the pathogenesis of pernicious anemia

Back 44

autoimmune gastritis decreases intrinsic factor which is required for B12 absorption. Decreased B12 causes megloblastic anemia.

type 1 antibodies block b12 from binding to intrinsic factor

type 2 antibodies prevent b12-IF from binding to ileal receptors for uptake

Front 45

what are the criteria for diagnosis of pernicious anemia

Back 45

1. megloblastic anemia (moderate to severe)

2. leukopenia

3. hypersegmented granulocytes

4. elevated homocystene/methylmalonic acid

Front 46

is anemia of folate deficency clinically different from B12 deficent anemia

Back 46

no not really

Front 47

what is the most common nutritonal deficency in the world?

Back 47

iron deficency

more common in women paricularly of childbearing age

Front 48

what carries iron in the blood?

Back 48

transferrin

Front 49

what levels of hepticidin do you expect to see in hemochromotosis

Back 49

low

Front 50

who is at highest risk for iron deficency

Back 50

infants

the impoverished

older adults

teenagers

Front 51

what is sprue

Back 51

impaired absorption can cause iron deficency

Front 52

what is the pathogenesis of iron deficency anemia

Back 52

hypochromic, microcytic anemia

lower serum iron and transferrin saturation

increased erythroid activity

reduced serum heptacidin

Front 53

what is the effect of sustained inflammation on anemia?

Back 53

can lead to anemia

IL-6 stimulates an increase in heptacidin production which reduces transport of ron from storage pool to erythroid precursors

Front 54

what is the most common cause of aplastic anemia

Back 54

exposure to chemicals, drugs, and irridation

Front 55

what is fanconi anemia

Back 55

autosomal recessive d/o that is caused by a defect in the DNA repair

accompanied by kidnek and spleen hypoplasia

Front 56

what is pancytopenia

Back 56

anemia

neutropenia

thrombocytopenia

Front 57

a patient presents with a moderate to severe anemia that is without splenomegaly. With only this information what type of anemia can you rule out

Back 57

aplastic anemia is almost never associated with enlargment of the spleen

Front 58

what is pure red cell aplasia and how does it differ from aplastic anemia

Back 58

only erythroid precursors are affected

leukocytes and platlets are unaffected

Front 59

what are acute and chronic causes of red cell aplasia

Back 59

acute- parvovirus B19

chronic- thyroma, antibodies that act against EPO

Front 60

what form of marrow failure is associated with space occupying lesions replacing normal marrow elements

Back 60

myelophtisic anemia

Front 61

what distinguishes absolute polycythemia from relative polycythemia

Back 61

relative is due to deyhdration

absolute can be primary (increase in progenitors) and secondary (increase in EPO)

Front 62

what is the most common cause of primary polycythemia

Back 62

polychthemia vera

mutations cause EPO independent RBC development

Front 63

what do PT and PTT measure?

Back 63

PT measures extrinsic and common coagulation pathways (V,VII,X, PT, fibrinogen)

PTT measures intrinsic and common coagulation pathways (V,VIII,IX,X,XI,XII, PT, fibrinogen)

Front 64

Scurvy and Ehlers-Danlos syndrome are both ossciated whith what type of anemia

Back 64

hemmorhagic diatheses associated with microvascular bleeding

Front 65

what serious hereditary blood disorder is associated with dilated, tortuous blood vessels with thin, easy bleeding walls and frequent nosebleeds

Back 65

hereditary hemorrhagic telangiectasia

Front 66

<100k platelets per microliter is associated with what bleeding dsorder,

Back 66

thrombocytopenia

Front 67

what an cause decreased platelet count

Back 67

aplastic anemia, leukemia, drugs, HIV, alcohol

Front 68

what is an alloantibody? how does it cause anemia?

Back 68

can cross placenta and attack platelets in newborn causing thrombocytopenia

Front 69

What causes chronic ITP? What are the clinical signs?

Back 69

autoantibody mediated destruction of platlets

adult women <40yo pinpoint petechiae with occasional progression to ecchymoses

PT/PTT normal

tx with glucocorticoids

Front 70

What is acute ITP who gets it

Back 70

autoantibodies to platelets occuring in childhood usually self limiting

tx with glucocorticoids if thrombocytopenia is severe

Front 71

What is HIT? Type 1? Type 2?

Back 71

Heparin which is an anticoagulant can cause low platlets in 2 patterns

1. Type 1 occurs rapidly after onset of therapy

2. Type 2 occurs 5-14 days after initial treatment and can cause life threatening thrombosis due to antibodies that recognize heparin and platlet factor 4.

Front 72

What is the most common hematologic manifestation of HIV infection

Back 72

thrombocytopenia

Front 73

A deficiency of plasma enzyme ADAMTS13 is associated with which bleeding disorder?

Back 73

TTP

ADAMS13 degrades high molecular weight vWF to a less coaguable form. without it you see aggregates of vWF in the plasma which can trigger activation of platelets and microthrombi

Front 74

What infection is associated with Hemolytic-Uremic Syndrome (HUS)

Back 74

E coli. A shinga like toxin from E Coli can be absorbed from gastric mucosa and enter peripheral circulation where it promotes formation of microthrombi

Front 75

what disorder causes abnormal platelet adhesion due to inherited deficits of glycoprotein complexes on the platelet membrane?

Back 75

bernard souiler syndrome

Front 76

what is a consequence of excess asprin and NSAID

Back 76

asprin irreversibly binds COX which forms prostoglandins some of which are important mediators of platelet activation

Front 77

what are the 2 most common inherited disorders of bleeding

Back 77

hemophelia A and vWF disease

Front 78

what does factor 8 do?

Back 78

binds to vWF which stabilizes it and allows it to survive in the blood where it activates IX which activates X and propagates the clotting cascade.

Front 79

What is type 1,2,3 vWF disease

Back 79

1- dominant D/O, mild to moderate vWF deficit (70%) of cases

3- worse version of 1

2- qualaitative defects in vWF

Front 80

how does vWF disease affect PT, PTT ?

Back 80

PT normal

PTT prolonged

Front 81

how would you distinguish hemophilia A from hemophilia B?

Back 81

Trick question! VIII (A) activates IX (B) so they are virtually indistinguishable clinically

you will see prolonged PTT and normal PT in patients with A and B

Front 82

release of tissue factor into circulation and widespread injury to endothelial cells are two triggering mechanisms for what life threatening disease?

Back 82

DIC

Front 83

What mediator of endothelial injury is often implicated in DIC occuring with sepsis

Back 83

TNF which induces endothelial cells to express tissue factor, decrease thrombomodulin expression, also upregulates adhesion molecules on endothelial cells promoting leukocyte adhesion and ROS release

Front 84

What is most often associated with DIC

Back 84

obstetric complications, sepsis major trauma and certain cancers

Front 85

patients with a deficit in ____________ are prone to severe potentially fatal allergic reactions with transfusions

Back 85

IgA

Front 86

What is TRALI?

Back 86

transfusion related acute lung injury associated with transfusions triggering neutrophilia in the lung microvasculature