Path 14 Rbc, Bleeding Disorders

Front 1

common sxs of anemia?

Back 1

pallor, weakness, malaise, easy fatigability

Front 2

causes of microcytic, hypochromic anemia (MCV<80)?

Back 2

iron def
alpha- and beta-thalassemia
lead poisoning
sideroblastic anemia

Front 3

causes of megaloblastic anemia?

Back 3

folate deficiency
B12 deficiency

Front 4

causes of non-megaloblastic macrocytic anemia?

Back 4

liver dz
alcoholism
reticulocytosis
metabolic disorder (congen def of purine/pyrimidine synthesis)
drugs (5-FU, AZT, hydroxyurea)

Front 5

causes of nonhemolytic normocytic, normochromic anemia?

Back 5

anemia of chronic dz
aplastic anemia
kidney dz

Front 6

causes of intrinsic hemolytic anemia?

Back 6

hereditary spherocytosis
G6PD def
pyruvate kinase def
SCA
HbC defect
parxoysmal nocturnal hemoglobinuria

Front 7

causes of extrinsic hemolytic anemia?

Back 7

autoimmune
microangiopathic (eg DIC, TTP-HUS)
infectious

Front 8

causes of intravascular hemolysis?

Back 8

paroxysmal nocturnal hemoglobinuria
autoimmune (cold agglutinins)
mechanical (AO stenosis, prosthetic valve)

Front 9

causes of extravascular hemolysis?

Back 9

Hereditary spherocytosis
G6PD def
Pyruvate kinase def
SCA
HbC defect
Autoimmune (warm agglutintins)
Microangiopathic (eg DIC, TTP-HUS)

Front 10

Types of normochromic, normocytic anemias?

Back 10

nonhemolytic
Intrinsic hemolytic
Extrinsic hemolytic
Intravascular hemolysis
Extravascular hemolysis

Front 11

why does acute blood loss result in anemia?

Back 11

blood volume lost is restored by intravascular shift of water from interstitial fluid compartment, resulting in hemodilution and lowering of HCT

Front 12

What changes in peripheral blood are seen after significant blood loss?

Back 12

low HCT
reticulocytosis
leukocytosis
thrombocytosis

Front 13

when does chronic blood loss result in anemia?

Back 13

when rate of loss exceeds regenerative capacity of marrow
or
when iron reserves are depleted, results in iron deficiency anemia

Front 14

which anemia is characterized by splenomegaly and jaundice?

Back 14

extravascular hemolytic anemia

Front 15

which anemia is manifested by hemoglobinemia, hemoglobinuria, hemosiderinuria, and jaundice?

Back 15

intravascular hemolytic anemia

Front 16

common non-hematologic complication of chronic hemolytic anemia

Back 16

pigment gallstones

Front 17

normocytic, normochromic anemia w/ reticulocytosis

Back 17

hemolytic anemia

Front 18

anemia resulting in hemosiderosis of spleen, liver, and bone marrow

Back 18

hemolytic anemia

Front 19

most prevalent inheritance pattern in spherocytosis?

Back 19

autosomal dominant (75%)

(25% have more severe form caused by two different defects)

Front 20

PBS shows small, hyperchromic RBCs lacking central pallor. Dx?

Back 20

spherocytosis

Front 21

Howell-jolly bodies indicate what?

Back 21

splenic dysfunction or splenectomy (esp in setting of spherocytosis)

Front 22

what causes spherocytosis?

Back 22

mutations lead to insufficiency of RBC membrane components and progressive loss of membrane fragments

Front 23

what are the RBC membrane skeletal components?

Back 23

ankyrin, band 3, spectrin, band 4.2

Front 24

what usually triggers aplastic crises in spherocytosis?

Back 24

parvovirus infxn
(kills RBC progenitors)

Front 25

treatment for spherocytosis?

Back 25

splenectomy and/or transfusion

Front 26

CBC findings in spherocytosis?

Back 26

anemia, inc MCHC, inc RDW

Front 27

abnormalities in hexose monophosphate shunt or glutathione metabolism are the basis of what disease?

Back 27

G6PD-deficiency (hemolysis)

Front 28

inheritance pattern of G6PD-def?

Back 28

X-linked (males at higher risk)

Front 29

PBS shows RBCs with Heinz bodies and bite cells. Dx?

Back 29

G6PD-def

Front 30

what triggers hemolysis in G6PD-deficient patients?

Back 30

oxidant stress, e.g. infxn, drugs (primaquine, chloroquine, sulfonamides), fava beans

Front 31

in what diseases are Heinz bodies found?

Back 31

G6PD-def, alpha thalassemia

Front 32

what causes Heinz bodies?

Back 32

exposure of RBC to high levels of oxidants cross-links globin chains which become denatured

Front 33

what causes bite cells?

Back 33

macrophages in splenic cords attempt to remove Heinz bodies and damage membrane

Front 34

why is spherocytosis is self limited?

Back 34

only old RBCs are at risk for lysis

Front 35

disease associated with a mutation that replaces glutamate in beta globin with valine

Back 35

sickle cell disease

Front 36

sickle cell trait vs. disease?

Back 36

heterozygosity for HbS

Front 37

composition of HbA?

Back 37

alpha2beta2

Front 38

composition of HbA2?

Back 38

alpha2 delta2

Front 39

composition of HbF

Back 39

alpha2 gamma2

Front 40

composition of HbS

Back 40

alpha2 beta(sickle)2

Front 41

what disorders confer immunity to malaria?

Back 41

sickle cell trait
G6PD-deficiency

Front 42

when does SCA start in child that has inherited the disease?

Back 42

6-7 mo (persistence of HbF)

Front 43

what other disease, when coexistent with homozygous HbS, leads to milder disease?

Back 43

a-thalassemia

Front 44

"crew cut" skull x-ray from marrow expansion from inc erythropoiesis?

Back 44

SCA and thalassemias

Front 45

what precipitates sickling in SCA?

Back 45

low O2 or RBC dehydration

Front 46

complications in SCA homozygotes?

Back 46

- aplastic crisis (B19 infxn)
- Autosplenectomy --> infxn w/ encapsulated organisms
- salmonella osteomyelitis
- vaso-occlusive crises
- renal papillary necrosis
- splenic sequestration crisis

Front 47

tx for SCA?

Back 47

hydroxyurea (inc HbF), BM txp

Front 48

what causes target cells?

Back 48

RBC dehydration
(SCA, HbC dz, asplenia, liver dz, thalassemias)

Front 49

what causes autosplenectomy in SCA?

Back 49

chronic erythrostasis leads to splenic infarction, fibrosis and shrinkage

Front 50

what is the genetic difference in the alpha and beta chains for HbA?

Back 50

α-globins are encoded by a pair of genes on chromosome 16 whereas β-globins are encoded by a single gene on chromosome 11

Front 51

cause of anemia prevalent in Mediterranean populations

Back 51

β thalassemia

Front 52

most common genetic cause of β+ thalassemia

Back 52

promoter region mutations

Front 53

most common genetic cause of β0 thalassemia

Back 53

chain terminator mutations

Front 54

genotype of thalassemia major?

Back 54

β0/β0 (HbA absent), β+/β+ or β0/β+ (HbA reduced)

Front 55

genotype of thalassemia minor?

Back 55

heterozygous carriers of one β+ or β0 allele

Front 56

how does α-thalassemia manifest in newborns?

Back 56

excess unpaired γ-globin (from HbF) clump together forming Hb-Barts leading to hydrops fetalis (fatal)

Front 57

how does α-thalassemia manifest in older children and adults?

Back 57

excess unpaired β-globin (from HbA) forms HbH tetramers --> HbH disease (tissue hypoxia and moderately severe anemia)

Front 58

in what population is HbH disease common?

Back 58

Asians

Front 59

genotype of silent carrier of α-thalassemia?

Back 59

-/α α/α

Front 60

genotype of α-thalassemia trait?

Back 60

-/- α/α (Asian), -/α -/α (African)

Front 61

genotype of HbH disease?

Back 61

-/- -/α

Front 62

genotype of hydrops fetalis?

Back 62

-/- -/-
(no α alleles)

Front 63

pathogenesis of paroxysmal nocturnal hemoglobinuria?

Back 63

acquired mutations in phosphatidylinositol glycan complementation group A gene (PIGA - makes surface proteins that inhibit complement-mediated lysis)
-->
complement lysis of RBCs, PLTs, WBCs

Front 64

why is PNH more active at night?

Back 64

low resp --> mild acidosis --> increase activity of complement

Front 65

abnml lab finding in PNH?

Back 65

hemosiderinuria

Front 66

difference between direct and indirect Coombs test?

Back 66

Direct: anti-Ig Ab added to pt's RBCs clumps if serum has anti-RBC surface Ig

Indirect: normal RBCs added to pt's serum, clump if serum has anti-RBC surface Ig

Front 67

anemia characterized by IgG-mediated membrane damage of RBCs; esp assoc'd with α-methyldopa, and large IV doses of penicillins and cephalosporins

Back 67

warm agglutinin autoimmune hemolytic anemia

Front 68

anemia associated with IgM-mediated hemolysis after infxn by Mycoplasma pneumoniae, EBV, CMV, influenza, HIV

Back 68

cold agglutinin autoimmune hemolytic anemia

Front 69

causes of microangiopathic hemolytic anemia?

Back 69

prosthetic valves or AS
DIC, TTP-HUS
SLE
malignant HTN

Front 70

schistocytes, burr cells, helmet cells and triangle cells on PBS indicate what class of anemias?

Back 70

microangiopathic hemolytic anemia

Front 71

causes of microcytic, hypochromic anemia?

Back 71

iron def
thalassemias
lead poisoning
sideroblastic anemia

Front 72

causes of macrocytic anemia?

Back 72

-folate or B12 def (megaloblastic)
-liver dz
-alcoholism
-reticulocytosis
-metabolic disorders (def of purine or pyrimidine synthesis
-drugs (5-FU, AZT, hydroxyurea)

Front 73

causes of nonhemolytic normocytic anemia?

Back 73

- ACD
- aplastic anemia
- kidney dz

Front 74

causes of intrinsic hemolytic anemia?

Back 74

- spherocytosis
- G6PD-def
- pyruvate kinase def
- SCA
- HbC defect
- PNH

Front 75

causes of extrinsic hemolytic anemia?

Back 75

- autoimmune hemolytic anemia (warm/cold agglutinins)
- microangiopathic anemia (RBC trauma)
- infections

Front 76

anisopoikilocytosis, low retic, large, hyper-segmented neutrophils. Dx?

Back 76

megaloblastic anemia

Front 77

pathogenesis of pernicious anemia?

Back 77

autoimmune gastritis --> loss of parietal cells --> dec IF --> dec abs of B12 --> folate trapped in intermediate form --> dec DNA synthesis

Front 78

why are both B12 and folate essential for DNA synthesis?

Back 78

B12 takes Me from N-methylFH4 and turns homocysteine into methionine and frees folate to convert dUMP to dTMP --> DNA

Front 79

causes of B12 deficiency?

Back 79

malnutrition (alcoholics)
malabsorption (Crohns)
pernicious anemia
Diphyllobothrium latum infxn

Front 80

causes of neuro sxs of B12 def?

Back 80

B12 used to convert methylmalonyl CoA to succinyl CoA; deficiency --> methylmalonate and propionate buildup --> incorporation of abnml fatty acids into neuronal lipids

Front 81

findings in B12 def?

Back 81

-inc homocysteine
-inc methymalonic acid
-hypersegmented neut
-glossitis

Front 82

causes of folate def?

Back 82

- malnutrition (alcoholics)
- malabsorption
- impaired metabolism (methotrexate, TMP)
- inc requirement (preg, hemolytic anemia)

Front 83

difference in lab findings of B12 and folate def?

Back 83

B12 = inc Hcy and methylmalonate

Folate = inc Hcy but normal methylmalonate

Front 84

what drugs interfere with the absorption of folate?

Back 84

phenytoin and oral contraceptives

Front 85

what drugs interfere with the metabolism of folate?

Back 85

folic acid antagonists (methotrexate, TMP)

Front 86

what stain detects hemosiderin deposits?

Back 86

Prussian blue stain

Front 87

function of hepcidin?

Back 87

inhibits iron transfer from enterocyte to plasma; suppresses iron release from macrophages

Front 88

MCC of iron deficiency in developed countries?

Back 88

GI blood loss

Front 89

what causes koilonychia, alopecia, atrophy of tongue and gastric mucosa, pica, and intestinal malabsorption?

Back 89

severe, chronic iron deficiency

Front 90

Plummer-Vinson syndrome?

Back 90

esophageal webs, microcytic hypochromic anemia, and atrophic glossitis

Front 91

iron deficiency anemia:
serum iron?
TIBC?
Ferritin?
% sat?

Back 91

iron LOW
TIBC HIGH
Ferritin LOW
% sat VERY LOW

Front 92

ACD:
serum iron?
TIBC?
Ferritin?
% sat?

Back 92

iron LOW
TIBC LOW
Frtn HIGH
% sat NORMAL

Front 93

Hemochromatosis:
serum iron?
TIBC?
Ferritin?
% sat?

Back 93

iron HIGH
TIBC LOW
Frtn HIGH
%sat VERY HIGH

Front 94

Pregnancy/OCP use:
serum iron?
TIBC?
Ferritin?
% sat?

Back 94

iron NORMAL
TIBC HIGH
Frtn NORMAL
%sat LOW

Front 95

causes of ACD?

Back 95

- chronic microbial infxn (osteomyelitis, bact endocarditis, lung abscess)
- chronic immune disorders (RA, regional enteritis)
- Neoplasms (lung and breast carcinoma, Hodgkin lymphoma)

Front 96

pathogenesis of ACD?

Back 96

inflammatory mediators (IL-6) stimulate inc hepatic production of hepcidin which causes macrophage sequestration of iron;
No retics d/t low EPO levels

Front 97

MCC of aplastic anemia?

Back 97

exposure to chemicals and drugs (cancer chemo, benzene, chloramphenicol, gold salts)

Front 98

Fanconi anemia?

Back 98

autosomal recessive, defects in multiprotein complex required for DNA repair lead to aplastic anemia