IC7

Question 1

aplastic anemia criteria

Answer 1

presence of two of the following:

WBC ≤3500cells/mm3 (3.5 x 10^9/L)

Platelet count ≤55,000 cells/mm3 (55 x 10^9/L)

Hb value ≤10g/dL (100g/L; 6.21mmol/L) + reticulocyte count ≤30,000 cells/mm3 (30 x 10^9/L)

Question 2

treatment for aplastic anemia

Answer 2

**infections: **
- prophylactic antibiotic and antifungal agents when neutrophil counts <500 cells/mm3 (0.5 x 10^9/L)

• febrile neutropenia: start broad-spectrum antibiotics

**bleeding **
- transfusion support with erythrocytes and platelets
- if heavily transfused, iron chelation therapy with deferoxamine or deferasirox may be necessary (avoid iron overload)

**may also require allogenic HSCT and immunosuppressive therapy (ciclosporin) **

Question 3

what are the drugs associated with aplastic anemia

Answer 3

any drug that causes bone marrow failure will likely be associated with aplastic anemia
- radiotherapy, chemotherapy
other important drugs:
- nsaids
phenytoin, carbamazepine
chloramphenicol

Question 4

what are the goals of therapy for aplastic anemia

Answer 4

minimise infection risk
limit requirement for transfusions
improve peripheral blood counts

Question 5

criteria for drug-induced neutropenia or agranulocytosis

Answer 5

neutropenia: absolute neutrophil count (ANC) < 1500/uL

agranulocytosis: ANC = 0 (can also be <100-500/uL)

Question 6

drugs commonly associated with neutropenia/agranulocytosis

Answer 6

antibiotics, antipsychotics, antithyroid

beta lactam abx
methimazole
sulfonamides
clozapine
propylthiouracil

Question 7

what are the three prototype drug classes causing agranulocytosis?

Answer 7

antithyroid agents

clozapine and other phenothiazines

penicillins

Question 8

how do antithyroid agents cause agranulocytosis?

Answer 8

mOA unknown

common in >40y/o and within 2 months of initiation

may be asc with HLA38:02 and HLADRB108:03 in ethnic Chinese

Question 9

how do clozapine and other phenothiazines cause agranulocytosis?

Answer 9

2-15 wks after initiation
peak at 3-4weeks

require strict monitoring

Question 10

how do penicillins cause agranulocytosis

Answer 10

rapid onset
dose related = accumulation to toxic concentrations

Question 11

goals of therapy for agranulocytosis

Answer 11

improving mortality

elderly, renal failure, bacteraemia, shock more at risk of mortality.

Question 12

what is the management plan for agranulocytosis

Answer 12

blood cell count should return within 2-4 weeks (usually 4-24 days)

if neutrophil <100cells/mm3 = initiation filgrastim sq 300mcg/day

DO NOT RESTART offending agent
- possible to restart penicillin but at lower doses and after resolving neutropenia

Question 13

what are medicines likely to be unsafe in mod to severe g6pd def? = causing hemolytic anemia

Answer 13

DRUG
fluroquinolones (floxacins)
primaquine and tafenoquine (anti-malarial agents)
sulfonylureas (glipizides, glibenclamide)

FOOD/CHEMICALS
fava beans
henna compounds
naphthalene

Question 14

what is g6pd def

Answer 14

3 classes that have varying enzyme deficiency associated with hemolytic anemia (with or without exposure to certain drugs, food, chemicals)

class i associated with chronic hemolytic anemia.

Question 15

what are some drugs that are now probably safe with hemolytic anemia?

Answer 15

chloroquine
hydroxychloroquine

contradicting data: bactrim

Question 16

what are drugs associated with megaloblastic anemia?

Answer 16

antimetabolites: methotrexate
(most common) = hold off

cotrimoxazole
= esp if folate/vitb12 def, manage with folinic acid 5-10mg QDS

phenytoin, phenobarbital
= inhibit folate absorption or catalyse folate catabolism.
= manage with folic acid 1mg/day (controversial)

Question 17

what is the diagnosis for thrombocytopenia

Answer 17

PLC ≤100,000 cells/mm3 (100x10^9/L) OR more than 50% reduction from baseline values

Question 18

onset of thrombocytopenia?

Answer 18

typically 1-2 weeks after initiation
or
immediate if agent used in the past (eg UFH)
or
rapid onset (gp2b-3a)

Question 19

management of thrombocytopenia?

Answer 19

stop offending drug

recovery should occur 1-2 weeks after discontinuation of offending agent
complete at 1 week

atb may still persist for years = advise against using

Question 20

explain heparin induced thrombocytopenia?

Answer 20

two types: type1 insignficant

may actually be (paradoxically) associated with thrombosis = risk of stroke?

note cross reactivity with LMWH

Question 21

what is the scoring for HIT?

Answer 21

4Ts
Thrombocytopenia
(2) plc >50% decrease and 20x10^9/L
(1) plc 30-50% decrease and 10-19x10^9/L

Timing of PLC fall
(2) day 5-10 or ≤1 day with history of exposure within 30days
(1) >day 10 or timing uncler or ≤1 day with history of exposure within 30-100 days

Thrombosis or other sequelae
(2) proven new thrombosis, skin necrosis, acute systemic reaction after iv bolus
(1) prog or recurrent thrombosis, erythematous skin lesions, suspected thrombosis

Other causes for thrombocytopenia
(2) none
(1) possible

6-8 = high, 4-5 = int, 0-3 = low

Question 22

approach to suspected HIT

Answer 22

4-8 POINTS = stop heparin and start non heparin anticoauglant
= conduct pf4/heparin immunoassay = if positive = functional assay = positive = HIT

if negative pf4/heparin immunoassay = continue heparin and consider other causes, exclude HIT

Question 23

questions to ask in view of falling hb and PLC?

Answer 23

PMH: LOTAARRRP
ONSET
- duration?
ASSOCIATING
- any blood loss?
- associated features
PRECIPITATING?
- malignancy?
- comorbidities? (anemia of inflammation/anemia of chronic disease) renal failure, rheumatoid arthritis, IBD
- ethnicity?

PHYSICAL EXAM
- pale?
- jaundice (breakdown = bilirubin)

LABS
- FBC = haemoglobin? (male: 14-18, female: 12-16)
- reticulocyte count (0.73 – 2.14 % (Adults))
- peripheral smear = size shape, colour

Question 24

diagnosis of anemia based on lab?

Answer 24

refer to ic7 slide 12 (live)

Question 25

maangement of IDA?

Answer 25

prompt: further investigations, scopes
address: underlying etiology
treat: with iron for 3-6months at least 1000mg to 1500mg of elemental iron

iron polymaltose 100mg tab: treatment 100-300 mg daily as a single dose or in divided doses for approx 3-5 months until normalisation of Hb level is attained.

ferrous sulphate: appx 32% iron

Question 26

what are the causes of IDA?

Answer 26

IRON DEFICIENT ANEMIA
1) decrease absorption of iron
- likely gi condition: atrophic gastritis, celiac disease, hpylori infection, ppi…

2) blood/iron loss
- pulm hemosiderosis (iron storage), hemolysis, hematuria (blood in urine), hemoglobinuria

Question 27

difference between IDA and anemia of chronic disease

Answer 27

Ferritin:
should be increased or normal in chronic disease
(iron retained in the cells)
BUT
low in IDA
(low iron storage due to lack of iron)

HOWEVER,, (tibc = transferrin)
TIBC should be decreased in chronic disease
INCREASED in IDA to bind more iron.

Question 28

common cause of vitb12 deficient anemia

Answer 28

vit b12 deficient anemia

• reduce absorption (lack of intrinsic factor or gastric disruption)
• nutritional (b12 found in meat)
• others: ppi, h2ra, hpylori infection

Question 29

management of pernicious anemia

Answer 29

autoimmune condition related to intrinsic factor, cannot use oral as insufficient

treatment: Pernicious anemia: Parenteral (IM or SQ) vitamin B12, given 1000 𝝻g daily for 1 week followed by 1000 𝝻g weekly for 4 weeks followed by 1000 𝝻g monthly for life (PO often insufficient). Vitamin B12, 1000 𝝻g orally given daily, is absorbed by mass action, not relying on the action of intrinsic factor.

Question 30

management of vitb12 def

Answer 30

Cobalamin deficiency due to other causes is treated with 1000 𝝻g or 2000 𝝻g daily or oral Vit B12

Question 31

maangement of folate def

Answer 31

vit b9
1 mg/d of folate for 1 to 4 months or until hematologic recovery is achieved.