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Flashcards in aplastic + hemolytic anemia Deck (83):
1

Aplastic anemia - definition

pancytopenia of unclear etiology

2

main causes of aplastic anemia

any infection or cancer can invade the bone marrow, causing production or hypoplasia

3

other causes of aplastic anemia

1. radiation and toxins
2. drugs
3. SLE
4. Paroxysmal nocturnal hemoglobinuria
5. infections
6. B12 and folate def
7. thyroid inhibiting medications (PTU) and methimazole

4

toxins that cause aplastic anemia

1. toluene
2. insecticides (DDT)
3. benzene

5

drugs that cause aplastic anemia

1. sulfa 2. phenytoin 3. carbamazepine
4. chloramphenicol 5. alcohol 6. chemotherapy
7. thyroid inhibiting medications

6

aplastic anemia - presentation

1. fatique (anemia)
2. infections (low WBCs)
3. bleeding (thrombocytopenia)

7

aplastic anemia - confirmation

by excluding all the causes of pancytopenia

8

aplastic anemia - most accurate test

bone marrow biopsy

9

autoimmune disorder - aplastic anemia (mechanism and treatment)

- T cells attack the patient's own marrow
- treatment is based on medications like cyclosporine that inhibit T cells --> this brings the marrow back to life

10

aplastic anemia - symptomatic treatment

1. transfusion for anemia
2. antibiotics for infection
3. platelets for bleeding

11

aplastic anemia - treatment beside symptomatic treatment

- treat underlying cause
- a true aplastic anemia is treated with allogeneic bone marrow transplantation (BMT) if the patient is young enough and there is a matched donor
- when too old for BMT (above 50) or no matched donor --> antithymocyte globulin and cyclosporine

12

alternative to cyclosporine in aplastic anemia

tacrolimus

13

alemtuzumab - mechanism of action

anti-CD52 that suppresses T-cells

14

hemolytic anemia - all forms can lead to

1. sudden decrease in HcT
2. increased levels of LDH, indirect bil, and reticulocytes
3. decreased haptoglobin levels
4. sligh increase MCV (reticulocytes)
5. hyperkalemia (breakdown)
6. folate def (increased production)

15

Chronic hemolysis is associated with ...

bilirubin gallstones

16

sickle cell anemia (SCA) is caused by

point mutation at position 6 of the beta globulin chain:
valine replaces glutamic acid

17

SCA - acute painful vasooocclusive crisis is caused by

1. hypoxia 2. dehydration 3. infection/fever
4. cold temperatures

18

SCA - acute painful vasooocclusive crisis - presentation / epidimiology

look for an African american patient with sudden, severe pain in the chest, back and thighs that may be accompanied by fever
IT IS rare for an adult to present with an acute crisis without a clear history of SCA

19

beside acute painful vasooocclusive crisis, other common manifestations of SCA

1. bilirubin gallstone (from chronically elevated bilirubin)
2. increased infection from autosplenectomy (esp encapsulated orgnaims)
3. osteomyelitis (MC salmonella)
4. retinopathy
5. stroke
6. enlarged heart with hyperdynamic features and systolic murmur
7. lower extremity skin ulcers
8. avascular necrosis of the femoral head)
9. dactylitis (inflammation of fingers)
10 papillary necrosis of the kidney (from chronic kidney damage)

20

avascular necrosis of femoral test - best initial and most accurate test

best initial: x-ray
most accurate: MRI

21

children with SCA present with

dactylitis

22

SCA - best initial test

peripheral smear
TRAIT does not give sickled cells

23

SCA - most accurate test

Hb electrophoresis

24

what else can be found in smear in SCA

howell-jolly bodies (seen in functional or structural aspenia) --> basophilic nuclear remants in RBCs
normally removed by splenic macrophages

25

what lowers mortality in SCA

1. hydroxyurea (increases HbF)
2. antibiotics for fever

26

SCA treatment

1. begin with O2/hydration/analgesia
2. if fever or higher than usual WBCs --> antibiotics
3. folic acid in chronic basis
4. pneumococcal vaccination
5. hydroxyrurea prevents reccurences

27

SCA treatment which antibiotics / when to start

- ceftriaxone, levofloxacin or moxifloxacin
- do not wait for results to start if there is fever. the absence of a functional spleen leads to overwhelming infection

28

SCA - exchange transfusion

it is used if there is severe vasoocclusive crisis presenting with:
1. acute chest syndrome
2. priapism
3. stroke
visual disturbance from retinal infraction

29

sudden drop of Hct in patient with SCA - next step (expain)

reticulocyte count
usually high in SCA. Parvovirus B19 can cause aplastic crisis (freezes the marrow)
nothing visible in blood smear
the bone marrow will show giant PRONORMOBLASTS but this is not done routinely

30

first clue to parvovirus

sudden drop in reticulocyte levels

31

most accurate test for B19

PCR fr dna
more accurate than IgM

32

best initial treatment for B19

IV Ig

33

Sickle cell trait - definition / treatment

heterocyzgus for sickle gene (AS)
no treatment is needed

34

Sickle cell trait - manifestations

the only manifestation is defect in the ability to concentrate the urine or isosthenuria
clinically asymptomatic and habe both normal CBC level and normal smear results
sometimes hematuria

35

Hereditary Spherocytosis - etiology

defect in cytoskeleton of RBCs leadin to an abnormal round shape and loss of the normal flexibility characteristic of biconcave disc that allows red cells to bend in spleen

36

Hereditary Spherocytosis - manifestation

1. reccurent episode of hemolysis
2. intermittenr jaundice
3. splenomegaly
4. family history f anemia or hemolysis
5. bilirubin gallstones

37

Hereditary Spherocytosis - diagnostic tests (which is the most accurate)

1. Low MCV
2. increased mean corpuscular hb concentration (MCHC)
3. negative Coombs test
4. osmotic fragility (MOST ACCURATE)

38

Hereditary Spherocytosis - osmotic fragility

when cells are placed in a slightly hypotonic solution, the increased swelling of the cells leads to hemolysis

39

Hereditary Spherocytosis - treatment

1. chronic folic acid replacement (to support red cell production)
2. splenectomy (stop hemolysis but does not eliminate spherocytes)

40

autoimmune hemolysis - types

1. Warm (IgG)
2. cold (IgM)

41

autoimmune hemolysis IgG (warm) - etiology

50% of cases have no identified etiology. clear causes are:
1. CLL
2. lymphoma
3. SLE
4. Drugs

42

drugs that cause autoimmune hemolysis IgG (warm)

penicillin, a-methyldopa, rifampin, phenytoin

43

spherocyte RBCs are seen in

1. hereditary spherocytosis
2. autoimmune hemolysis

44

autoimmune hemolysis IgG (warm) - diagnostic test - most accurate

Coombs test: detects IgG antibody on the surface of the RBCs

45

autoimmune hemolysis IgG (warm) - direct vs indirect Coombs tests regarding the results

same thing
the indirect is associated with a greater amount of antibody

46

autoimmune hemolysis IgG (warm) - mechanism of spherocytes formation

autoantibodies remove small amounts of red cell membrane and lead to smaller membrane, forcing the cell to become round. Biconcave dics need a greater surface than a sphere. Autoimmune hemolysis is associated with microspherocytosis

47

autoimmune hemolysis IgG (warm) - destruction on smear

smear does not show fragmented cells because the red cell destruction occurs in hte spleen or liver

48

autoimmune hemolysis IgG (warm) - treatment (which is the best initial)

1. glucocorticoids such as prednisone (best initial)
2. reccurent episodes resont to splenectomy
3. severe acute not responding to prednisone --> IVIG
4. Rituximab, azathioprine, cyclophosphamide, mycophenolate or cyclosporine when splenectomy does not control

49

autoimmune hemolysis IgG (warm) - when IVIG

severe acute not responding to prednisone

50

autoimmune hemolysis IgG (warm) - when immunosuppresants

when splenectomy does not control
OR to diminish the need for steroids

51

autoimmune hemolysis IgM (cold) - etiology . definition

1. EBV
2. Mycoplasma pneumoniae
3. Waldestrom macroglobulinemia
definition: IgM antibodies against RBCs

52

autoimmune hemolysis IgM (cold) - presentation

- symptoms occur in colder parts of the body suc as numbness or mottling of the nose, ears, fingers, toes
- symptoms resolve on warming up the body of the part

53

autoimmune hemolysis IgM (cold) - diagnostic tests (which is most accurate)

1. direct coombs is (+) only for complement
2. The smear is normal, or may show spherocytes
3. Cold agglutinin (most accurate)

54

autoimmune hemolysis IgM (cold) - treatment

1. stay warm
2. administer rituximab and sometimes plasmapheresis
3. cyclophospamide, cyclosporine, or other immunosuppressive agents stop the production of the antibody

55

most wrong answers in autoimmune hemolysis IgM (cold) treatment

Prednisone and splenectomy

56

Cryoglobulins vs autoimmune hemolysis IgM (cold)

cryoglobulins are often mixed up with cold agglutinins. Although both are IgM and do not respond to steroids, cryoglobulins are associated with:
1. hep c
2. joint pain
3. glomerulonephritis

57

Cryoglobulins are associated with

1. hep c
2. joint pain
3. glomerulonephritis

58

autoimmune hemolysis IgM (cold) is aka

cold agglutinin disease

59

G6PD - etiology

XR (almost exclusively in men) disorder leading to an inability to generate glutathione reductase and protect the red cells from oxidant stress
(extravascular + intravascular hemolysis)

60

G6PD - the most common oxidant stress is

infection

61

G6PD - causes of stress

1. infection (MC)
2. Dapsone 3. quinidine 4. primaquine
5. nitrofurantoin 6. fava beans

62

G6PD - epidimiology

african american or mediterranian men

63

G6PD - presentation

sudden anemia and jaundice
normal spleen with an infection or using of specific drugs

64

G6PD - treatment

Nothing reverses the hemolysis
AVOID OXIDANT STRESS

65

G6PD - best initial test

Heinz bodies (on methylene blue) and bite cells

66

G6PD activity levels after hemolytic even

normal

67

G6PD - most accurate test

G6PD activity levels 1-2 months after an acute episode of hemolysis

68

Hemolytic uremic syndrome (HUS) vs thrombotic thrombocytopenic purpura (TTP)

different versions of the same basic disease caused by deficiency of MMP ADAMTS 13

69

HUS vs TTP regarding their associations

HUS --> E.Coli O157:H7
TTP --> ticlopidine, clopidogrel, cyclosporine, AIDS, SLE

70

both HUS and TTP are characterised by (manifestations)

1. intravascular hemolysis with fragmented red cells (schistocytes)
2. thrombocytopenia
4. renal insuficiency
TTP is also associated with neurological disorders and fever

71

TTP vs HUS regarding age

TTP --> more common in adults
HUS --> more common in children

72

TTP - neurological disorders

1. confusion
2. seizures

73

TTP + HUS - treatment

Severe cases are treated with plasmapheresis or plasma exchange. (if delay to plasmapheresis --> FFP)
Cases not related to drugs or diarrhea can be treated with steroids
NEVER PLATELET TRANSFUSION (worse it)

74

HUS/TTP - labs

both have normal PT/aPTT and negative Coombs test

75

Paroxysmal nocturnal hemogglobinuria - mechanism

clonal stem cell defect with increased sensitivity to ced cells to complement in acidosis. It is a form deficiency of the complement regulatory proteins CD55 + 59 (aka decay accelerating factors. The gene for phosphatidylinositol class A (PIG-A) is defective (the anchor) --> overactivation of the complement (this does nothing to unaffected person, but in PNH causes hemolysis + thrombosis)

76

Paroxysmal nocturnal hemogglobinuria - presentation

1. episodic dark urine
2. pancytopenia
3. iron def anemia
4. clots in unusual places (not just DVT or PE)

77

Paroxysmal nocturnal hemogglobinuria - MCC of death

thrombosis

78

Paroxysmal nocturnal hemogglobinuria - complications

1. aplastic anemia
2. myeolodysplasia
3. acute leukemia

79

Paroxysmal nocturnal hemogglobinuria - diagnosic tests (which is the most accurate)

1. CBC: pamcytopenia in additon to anemia
2. decreased level of CD55/59 - flow cytometry (most accurate)
3. Ham test and sucrose hemolysis test (obsolete)

80

Paroxysmal nocturnal hemogglobinuria - treatment

1. prednisone - best initial therapy for hemolysis
2. allogenic bone transplant (the only to cure)
3. eculizumab
4. give folic acid and replacement with transfusion as needed

81

Paroxysmal nocturnal hemogglobinuria - best initial test

prednisone

82

Paroxysmal nocturnal hemogglobinuria - cure?

allogenic bone transplant

83

Paroxysmal nocturnal hemogglobinuria - eculizumab

inactivates C5 in the complement pathway and decreases red cell destruction (complement inhibitor)
FOR HEMOLYSIS AND THROMBOSIS