ic7 - anemia and drug induced hematological disorders Flashcards
how do you classify the different types of anemia
- hypoproliferative (marrow damage, Fe deficiency, decr stimulation due to diseases or inflamm)
- 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] - hemorrhage/ hemolysis (blood loss, intravascular hemolysis, autoimmune disease, hemoglobinopathy, metabolic/ membrane defect)
why would CKD patients have anemia
CKD pts have decr production of EPO thus decr production or RBC
what is thalassemia
inherited disorder of Hb chain synthesis
what is sideroblastic anemia and what are its common causes
result from acquired congenital defects in heme synthesis
common causes include lead poisoning, alcohol abuse, copper deficiency, medications like isoniazid and linezolid
what are the most common causes of anemia
Fe deficiency
vitB12 deficiency or folic acid deficiency
anemia of chronic disease/ anemia of inflamm
drug induced anemia
what are the types of mechanisms of Fe deficiency and list conditions that causes these mechanisms
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)
where is Fe absorbed in in the body
stomach
what tx should be given for Fe deficiency (what agents for Fe supplementation) and how long would tx last
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
why might CKD patients be given Fe supplementation
CKD patients likely given EPO which requires Fe as a substrate to produce more EPO to produce more RBC
what are the conditions that can cause anemia of chronic disease/ anemia of inflamm and why would a chronic disease cause anemia
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
what is the steps to take when approaching a pt to diagnose anemia
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
what is the Hb cut off to diagnose anemia
<11 for males, <13 for females
what does peripheral smear show
it can show:
microcytic (smaller nucleus than mature RBC)
hypochromic (more than 1/3 cell central pallor)
poikilocytosis (RBCs of different shapes)
what is petechiae and ecchymoses
petechiae is purple spots on skin
ecchymoses is small bruise resulting from blood leaking from broken blood vessels into skin tissues or mucus membranes
what is serum ferritin indicative of
Fe stores in body
what is TIBC
total Fe binding capacity which refers to the capacity of the body to carry Fe stores to sites for RBC production
what is TSAT
transferrin saturation which is ratio of serum Fe to TIBC
compare levels of ferritin, Fe and TIBC between Fe deficient anemia and anemia of chronic diseases
Fe deficient anemia: low Fe, low ferritin, high TIBC
anemia of inflamm: normal or decr ferritin, decr Fe, decr TIBC
what are megaloblasts and macrocytes
megaloblasts are large nucleated RBC precursors with non condensed chromatin due to impaired DNA synthesis
macrocytes are enlarged RBCs with increased MCV
what are the possible causes of vitB12 deficiency
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)
what is the tx for pernicious anemia
parenteral (IM or SQ) vitB12 given 1000mcg daily for 1w f/b 1000mcg q1w for 4w f/b 1000mcg q1m for life
how is PO vitB12 absorbed
by mass action and not reliant on action of intrinsic factor but PO often insufficient
what is vitB9
folate
what are the possible causes of folate deficiency
nutritional
what is the tx for folate deficiency
1mg/d of folate for 1-4m until hematologic recovery as seen from normalising Hb
what are the drug induced hematologic disorders
aplastic anemia
drug induced neutropenia/ agranulocytosis
hemolytic anemia
megaloblastic anemia
thrombocytopenia
how to determine what kind of drug induced hematological disorder
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
what are the drugs assoc with aplastic anemia
drugs that cause bone marrow failure (chemotx, radiation tx)
CBZ, PHT, sulfonamides, NSAIDs, PB, aspirin, chloramphenicol, dapsone, ticlopidine
what is the diagnostic criteria for aplastic anemia
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)
what are the types of aplastic anemia
inherited: fanconi’s, blackfan diamond
acquired: drugs, viruses (may present with pancytopenia), chemical exposure (may present with pancytopenia)
what is pancytopenia
lower than normal RBC, WBC and PLT count
what is the tx for aplastic anemia
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
what happens if heavily transfused with erythrocytes and PLT and what should the next step be
overtransfusion can lead to Fe toxicity
iron chelation therapy by using IV deferoxamine or PO defasirox
what are the goals of tx for aplastic anemia
to improve peripheral blood counts, limit the requirement for transfusions and minimise risk of infection
how do you define neutropenia and agranulocytosis based on absolute neutrophil count (ANC)
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
what is ANC
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
what are the drugs assoc with neutropenia/ agranulocytosis and how and how fast do these drugs result in neutropenia/ agranulocytosis
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
what should pts look for for indications of neutropenia
fever, cough, sob, sore throat, chills and sweat (think infection sx)
what is the tx for neutropenia/ agranulocytosis
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
what is nadir
lowest point
how do you diagnose hemolytic anemia
through direct and indirect coomb’s test
what are the types of hemolytic anemia
immune (IgG and IgM mediated RBC destruction, drug or non drug dependent)
metabolic (G6PD deficiency, Hb oxidation causing hemolysis)
what are the drugs assoc w hemolytic anemia
methyldopa, quinidine, quinine, penicillin, cephalosporin, streptomycin
what are the drugs assoc w oxidative hemolytic anemia
dapsone, metformin
how to classify degree of G6PD deficiency and which are of clinical significance and differentiate between each
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
what is the role of G6PD
G6PD protects RBC from oxidative damage
what are the drugs and substances unsafe in moderate to severe G6PD deficiency
fluoroquinolones (ciprofloxacin), quinine and primaquine and tafenoquine for malaria tx, sulfonylureas (glipizide), fava beans, henna compounds, naphthalene in moth balls and lavatory deodorant)
what is megaloblastic anemia
characterised by very large RBC and very few RBC
what are the drugs assoc w megaloblastic anemia and what should be done for each drug
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)
how to diagnose thrombocytopenia
any of the following:
PLT count 100,000 cells/mm3 or less (100x10^9) or greater than 50% reduction from baseline
how fast are onset of sx indicating thrombocytopenia
1-2w after new drug initiated or immediately if agent used intermittently in past (eg. UFH) or rapid onset for GPIIb/IIIai (eg. eptifibatide)
what are the drugs assoc w thrombocytopenia
ASM (PHT, CBZ, VPA, PB) and abx
heparin, GPIIb/IIIai
what are the types of heparin induced thrombocytopenia
HIT I and HIT II
HIT I is not significant
what to note if there is HIT
cross reactivity with LMWH
for what types of pts is heparin commonly used for
for dialysis, heparin used to flush catheter
for PCI, bolus UFH given
what class of drugs can be used for managing HIT
DOACs (eg. dabigatran)
what is the tx for thrombocytopenia
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)
how to predict probability of HIT
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]
how to predict probability of HIT
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]
