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pr3154 > ic7 - anemia and drug induced hematological disorders > Flashcards

ic7 - anemia and drug induced hematological disorders Flashcards

1
Q

how do you classify the different types of anemia

A
  1. hypoproliferative (marrow damage, Fe deficiency, decr stimulation due to diseases or inflamm)
  2. maturation disorders (cytoplasmic defects and nuclear maturation defect)
    [cytoplasmic defects incl thalaseemia, Fe deficiency, sideroblastic] [nuclear maturation Fe defect incl folate and vB12 deficiency, refractory anemia]
  3. hemorrhage/ hemolysis (blood loss, intravascular hemolysis, autoimmune disease, hemoglobinopathy, metabolic/ membrane defect)
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2
Q

why would CKD patients have anemia

A

CKD pts have decr production of EPO thus decr production or RBC

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3
Q

what is thalassemia

A

inherited disorder of Hb chain synthesis

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4
Q

what is sideroblastic anemia and what are its common causes

A

result from acquired congenital defects in heme synthesis

common causes include lead poisoning, alcohol abuse, copper deficiency, medications like isoniazid and linezolid

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5
Q

what are the most common causes of anemia

A

Fe deficiency
vitB12 deficiency or folic acid deficiency
anemia of chronic disease/ anemia of inflamm
drug induced anemia

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6
Q

what are the types of mechanisms of Fe deficiency and list conditions that causes these mechanisms

A

decr Fe absorption (atrophic gastritis, PPI, other medications that decr gastric acidity, H pylori infection, gastric bypass, Ca rich food)

blood or Fe loss (pulmonary hemosiderosis, intravascular hemolysis, hematuria or hemoglobinuria)

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7
Q

where is Fe absorbed in in the body

A

stomach

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8
Q

what tx should be given for Fe deficiency (what agents for Fe supplementation) and how long would tx last

A

1000-1500mg of elemental Fe for complete supplementation for 3-6m for Fe stores to replete

ferrous gluconate (sangiobion) if not that deficient -> contains 30mg of elemental iron per tablet

iron polymaltose drops or tablets (maltofer) if CKD or early CKD -> contains 50mg/ml or 100mg of elemental iron

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9
Q

why might CKD patients be given Fe supplementation

A

CKD patients likely given EPO which requires Fe as a substrate to produce more EPO to produce more RBC

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10
Q

what are the conditions that can cause anemia of chronic disease/ anemia of inflamm and why would a chronic disease cause anemia

A

chronic inflamm states incr chemical hepcidin which is a hormone that regulates how our body uses Fe and when there is incr hepcidin, it inhibits intestinal Fe absorption

malignancy, HIV, rheumatologic disorders, IBS, castleman disease, HF, renal insufficiency, COPD

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11
Q

what is the steps to take when approaching a pt to diagnose anemia

A

hx taking: any blood loss, duration of anemia, genetic or aquired, assoc features due to infection or malignancy, any comorbs known to cause anemia

physical examination: pallor, jaundice, others which are RED FLAGS (lymphadenopathy, hepatosplenomegaly, bone tenderness, petechiae, ecchymoses)

lab evaluation (draw out flow chart): FBC (Hb count), reticulocyte count, peripheral smear

path 1 -> MCV, serum ferritin, TIBC
path 2 -> MCV, vitB12 and folate levels
path 3 -> MCV, reticulocyte count, WBC and PLT count

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12
Q

what is the Hb cut off to diagnose anemia

A

<11 for males, <13 for females

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13
Q

what does peripheral smear show

A

it can show:

microcytic (smaller nucleus than mature RBC)

hypochromic (more than 1/3 cell central pallor)

poikilocytosis (RBCs of different shapes)

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14
Q

what is petechiae and ecchymoses

A

petechiae is purple spots on skin

ecchymoses is small bruise resulting from blood leaking from broken blood vessels into skin tissues or mucus membranes

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15
Q

what is serum ferritin indicative of

A

Fe stores in body

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16
Q

what is TIBC

A

total Fe binding capacity which refers to the capacity of the body to carry Fe stores to sites for RBC production

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17
Q

what is TSAT

A

transferrin saturation which is ratio of serum Fe to TIBC

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18
Q

compare levels of ferritin, Fe and TIBC between Fe deficient anemia and anemia of chronic diseases

A

Fe deficient anemia: low Fe, low ferritin, high TIBC

anemia of inflamm: normal or decr ferritin, decr Fe, decr TIBC

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19
Q

what are megaloblasts and macrocytes

A

megaloblasts are large nucleated RBC precursors with non condensed chromatin due to impaired DNA synthesis

macrocytes are enlarged RBCs with increased MCV

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20
Q

what are the possible causes of vitB12 deficiency

A

causes of pernicious anemia incl decreased absorption (lack of intrinsic factor or gastric disruption), nutritional deficiencies (vitB12 found exclusively in meats), other causes (PPI and H2RA which increases gastric pH but acidic pH req for B12 and Fe absorption, and H pylori infection)

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21
Q

what is the tx for pernicious anemia

A

parenteral (IM or SQ) vitB12 given 1000mcg daily for 1w f/b 1000mcg q1w for 4w f/b 1000mcg q1m for life

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22
Q

how is PO vitB12 absorbed

A

by mass action and not reliant on action of intrinsic factor but PO often insufficient

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23
Q

what is vitB9

A

folate

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24
Q

what are the possible causes of folate deficiency

A

nutritional

25
Q

what is the tx for folate deficiency

A

1mg/d of folate for 1-4m until hematologic recovery as seen from normalising Hb

26
Q

what are the drug induced hematologic disorders

A

aplastic anemia

drug induced neutropenia/ agranulocytosis

hemolytic anemia

megaloblastic anemia

thrombocytopenia

27
Q

how to determine what kind of drug induced hematological disorder

A

link based on which cell line the hematopoietic stem cell differentiates into

agranulocytosis: from myeloblasts -> metamyelocyte -> neutrophil

hemolytic anemia: from proerythroblasts -> normoblast -> RBC

thrombocytopenia: from megakaryoblast -> megakaryocyte -> PLTs

28
Q

what are the drugs assoc with aplastic anemia

A

drugs that cause bone marrow failure (chemotx, radiation tx)

CBZ, PHT, sulfonamides, NSAIDs, PB, aspirin, chloramphenicol, dapsone, ticlopidine

29
Q

what is the diagnostic criteria for aplastic anemia

A

any two of the following

WBC 3500 cells/mm3 and below (3.5x10^9)
PLT 55000 cells/mm3 and below (55 x10^9)
Hb 10 g/dL and below AND reticulocyte count 30000 cells/mm3 and below (30x10^9)

30
Q

what are the types of aplastic anemia

A

inherited: fanconi’s, blackfan diamond

acquired: drugs, viruses (may present with pancytopenia), chemical exposure (may present with pancytopenia)

31
Q

what is pancytopenia

A

lower than normal RBC, WBC and PLT count

32
Q

what is the tx for aplastic anemia

A

step 1: withhold offending drug

step 2: manage risk for infections -> prophylactic abs and antifungal agents when neutrophil count <500cells/mm3 (0.5x10^9), if febrile neutropenia aka presenting with fever then give broad spectrum abx

step 3: manage risk for bleeding (due to low PLT) -> transfusion support with erythrocytes and PLT

step 4: consider HSCT and immunosuppressive tx using ciclosporin

33
Q

what happens if heavily transfused with erythrocytes and PLT and what should the next step be

A

overtransfusion can lead to Fe toxicity

iron chelation therapy by using IV deferoxamine or PO defasirox

34
Q

what are the goals of tx for aplastic anemia

A

to improve peripheral blood counts, limit the requirement for transfusions and minimise risk of infection

35
Q

how do you define neutropenia and agranulocytosis based on absolute neutrophil count (ANC)

A

neutropenia is when ANC is <1500/mcL (1.5x10^9)
agranulocytosis is when ANC = 0 aka absence of granulocytes but also loosely defines severe neutropenia when ANC <100, 200, 500/ mcL

36
Q

what is ANC

A

ANC is absolute neutrophil count which is numerically equal to the product of WBC and fraction of polymorphonuclear cells and band forms noted on the differential analysis

37
Q

what are the drugs assoc with neutropenia/ agranulocytosis and how and how fast do these drugs result in neutropenia/ agranulocytosis

A

antipsychotics, abx, antithyroid

antipsychotics like clozapine and other phenothiazines show effect 2-15w after initiation (peak onset 3-4w) which is slightly faster than antithyroid

antithyroid causes it via unknown mechanism but genomics may be involved (HLAB38:02 and HLADRB108:03 in chinese, HLAB*27:05 in white), more freq in >40yo and within 2m after initiation

abx has rapid onset of sx and is dose related likely due to accumulation of drug to toxic conc

38
Q

what should pts look for for indications of neutropenia

A

fever, cough, sob, sore throat, chills and sweat (think infection sx)

39
Q

what is the tx for neutropenia/ agranulocytosis

A

step 1: withhold drug

step 2: note that blood cell counts typically normalise within 2-4w depending on which cell line affected bc each have their own half life and own production path

step 3: give SQ filgrastim 300mcg/d if neutrophil nadir <100cells/mm3 (0.1x10^9)

step 4: unlikely to restart offending drug unless penicillin then maybe restart at lower dose if necessary

40
Q

what is nadir

A

lowest point

41
Q

how do you diagnose hemolytic anemia

A

through direct and indirect coomb’s test

42
Q

what are the types of hemolytic anemia

A

immune (IgG and IgM mediated RBC destruction, drug or non drug dependent)

metabolic (G6PD deficiency, Hb oxidation causing hemolysis)

43
Q

what are the drugs assoc w hemolytic anemia

A

methyldopa, quinidine, quinine, penicillin, cephalosporin, streptomycin

44
Q

what are the drugs assoc w oxidative hemolytic anemia

A

dapsone, metformin

45
Q

how to classify degree of G6PD deficiency and which are of clinical significance and differentiate between each

A

class I, II or III are of clinical significance

class I variants have severe enzyme deficiency (<10% of normal) and assoc w chronic hemolytic anemia

class II variants also have severe enzyme deficiency but usually only intermittent hemolysis typically on exposure to oxidant stress

class III variants have moderate enzyme deficiency (10-60% of normal) with intermittent hemolysis typically assoc w significant oxidant stress

46
Q

what is the role of G6PD

A

G6PD protects RBC from oxidative damage

47
Q

what are the drugs and substances unsafe in moderate to severe G6PD deficiency

A

fluoroquinolones (ciprofloxacin), quinine and primaquine and tafenoquine for malaria tx, sulfonylureas (glipizide), fava beans, henna compounds, naphthalene in moth balls and lavatory deodorant)

48
Q

what is megaloblastic anemia

A

characterised by very large RBC and very few RBC

49
Q

what are the drugs assoc w megaloblastic anemia and what should be done for each drug

A

antimetabolite (MTX for chemotx) -> hold off and give alternative

co-trimoxazole -> (esp when vitB12 or folate deficiency) give folinic acid 5-10mg up to QDS

ASM (PHT, PB) -> inhibits folate absorption or catalyse folate catabolism, give folic acid 1mg/d (but controversial bc may decr efficacy of PHT for some thus can just switch to another ASM)

50
Q

how to diagnose thrombocytopenia

A

any of the following:

PLT count 100,000 cells/mm3 or less (100x10^9) or greater than 50% reduction from baseline

51
Q

how fast are onset of sx indicating thrombocytopenia

A

1-2w after new drug initiated or immediately if agent used intermittently in past (eg. UFH) or rapid onset for GPIIb/IIIai (eg. eptifibatide)

52
Q

what are the drugs assoc w thrombocytopenia

A

ASM (PHT, CBZ, VPA, PB) and abx

heparin, GPIIb/IIIai

53
Q

what are the types of heparin induced thrombocytopenia

A

HIT I and HIT II

HIT I is not significant

54
Q

what to note if there is HIT

A

cross reactivity with LMWH

55
Q

for what types of pts is heparin commonly used for

A

for dialysis, heparin used to flush catheter

for PCI, bolus UFH given

56
Q

what class of drugs can be used for managing HIT

A

DOACs (eg. dabigatran)

57
Q

what is the tx for thrombocytopenia

A

step 1: withhold offending drug

step 2: recovery begins 1-2d after discontinuation of drug and is likely to be done after 1w (bc of PLT half life) but Ab likely to persist indefinitely thus unlikely to reinitiate offending drug (eg. pts who experienced HIT may have PF4 Ab)

58
Q

how to predict probability of HIT

A

using 4T score, if score = 6 then high probability

thrombocytopenia
timing of PLT count fall
thrombosis or other sequelae
other causes for thrombocytopenia

thrombocytopenia: PLT fall >50% and PLT count nadir 20 and above [2] PLT fall 30-50% or PLT nadir 10-19 [1] PLT fall <30% or PLT nadir <10 [0]

timing of PLT fall: clear onset between days 5-10 or PLT fall in 1 or less days with prior heparin exposure within 30d [2] consistent with days 5-10 fall but not clear/ onset after day 10 or fall in 1 or less days with prior heparin exposure 30-100days [1] PLT count fall <4 days without recent exposure [0]

thrombosis or other sequalae: new thrombosis/ skin necrosis, acute systemic rxn postIV UFH bolus) [2] progressive or recurrent thrombosis/ non necrotising skin lesions/ suspected thrombosis [1] none [0]

other causes for thrombocytopeia: none [2] possible [1] definite [0]

58
Q

how to predict probability of HIT

A

using 4T score, if score = 6 then high probability

thrombocytopenia
timing of PLT count fall
thrombosis or other sequelae
other causes for thrombocytopenia

thrombocytopenia: PLT fall >50% and PLT count nadir 20 and above [2] PLT fall 30-50% or PLT nadir 10-19 [1] PLT fall <30% or PLT nadir <10 [0]

timing of PLT fall: clear onset between days 5-10 or PLT fall in 1 or less days with prior heparin exposure within 30d [2] consistent with days 5-10 fall but not clear/ onset after day 10 or fall in 1 or less days with prior heparin exposure 30-100days [1] PLT count fall <4 days without recent exposure [0]

thrombosis or other sequalae: new thrombosis/ skin necrosis, acute systemic rxn postIV UFH bolus) [2] progressive or recurrent thrombosis/ non necrotising skin lesions/ suspected thrombosis [1] none [0]

other causes for thrombocytopeia: none [2] possible [1] definite [0]

pr3154 (20 decks)

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