IC7 Flashcards
aplastic anemia criteria
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)
treatment for aplastic anemia
**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) **
what are the drugs associated with aplastic anemia
any drug that causes bone marrow failure will likely be associated with aplastic anemia
- radiotherapy, chemotherapy
other important drugs:
- nsaids
phenytoin, carbamazepine
chloramphenicol
what are the goals of therapy for aplastic anemia
minimise infection risk
limit requirement for transfusions
improve peripheral blood counts
criteria for drug-induced neutropenia or agranulocytosis
neutropenia: absolute neutrophil count (ANC) < 1500/uL
agranulocytosis: ANC = 0 (can also be <100-500/uL)
drugs commonly associated with neutropenia/agranulocytosis
antibiotics, antipsychotics, antithyroid
beta lactam abx
methimazole
sulfonamides
clozapine
propylthiouracil
what are the three prototype drug classes causing agranulocytosis?
antithyroid agents
clozapine and other phenothiazines
penicillins
how do antithyroid agents cause agranulocytosis?
mOA unknown
common in >40y/o and within 2 months of initiation
may be asc with HLA38:02 and HLADRB108:03 in ethnic Chinese
how do clozapine and other phenothiazines cause agranulocytosis?
2-15 wks after initiation
peak at 3-4weeks
require strict monitoring
how do penicillins cause agranulocytosis
rapid onset
dose related = accumulation to toxic concentrations
goals of therapy for agranulocytosis
improving mortality
elderly, renal failure, bacteraemia, shock more at risk of mortality.
what is the management plan for agranulocytosis
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
what are medicines likely to be unsafe in mod to severe g6pd def? = causing hemolytic anemia
DRUG
fluroquinolones (floxacins)
primaquine and tafenoquine (anti-malarial agents)
sulfonylureas (glipizides, glibenclamide)
FOOD/CHEMICALS
fava beans
henna compounds
naphthalene
what is g6pd def
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.
what are some drugs that are now probably safe with hemolytic anemia?
chloroquine
hydroxychloroquine
contradicting data: bactrim
what are drugs associated with megaloblastic anemia?
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)
what is the diagnosis for thrombocytopenia
PLC ≤100,000 cells/mm3 (100x10^9/L) OR more than 50% reduction from baseline values
onset of thrombocytopenia?
typically 1-2 weeks after initiation
or
immediate if agent used in the past (eg UFH)
or
rapid onset (gp2b-3a)
management of thrombocytopenia?
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
explain heparin induced thrombocytopenia?
two types: type1 insignficant
may actually be (paradoxically) associated with thrombosis = risk of stroke?
note cross reactivity with LMWH
what is the scoring for HIT?
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
approach to suspected HIT
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
questions to ask in view of falling hb and PLC?
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
diagnosis of anemia based on lab?
refer to ic7 slide 12 (live)
maangement of IDA?
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
what are the causes of IDA?
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
difference between IDA and anemia of chronic disease
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.
common cause of vitb12 deficient anemia
vit b12 deficient anemia
- reduce absorption (lack of intrinsic factor or gastric disruption)
- nutritional (b12 found in meat)
- others: ppi, h2ra, hpylori infection
management of pernicious anemia
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.
management of vitb12 def
Cobalamin deficiency due to other causes is treated with 1000 𝝻g or 2000 𝝻g daily or oral Vit B12
maangement of folate def
vit b9
1 mg/d of folate for 1 to 4 months or until hematologic recovery is achieved.
