-
symptoms if plt count 30-50,000/mm3
excessive bruise with minor trauma
-
symptoms if plt count 10-30,000/mm3
- petechiae
- ecchymoses spontaneous
-
symptoms if plt count <10,000/mm3
risk of internal bleeding spontaneously
-
thrombocytopenia can occur b/c of impaired production of plt. what kind of disorders can cause this?
- disorders that damage stem cell or impair stem cell proliferation.
- i.e. marrow aplasia, fibrosis, malignant infiltration, cytotoxic chemotherapy
-
drugs that can cause thrombocytopenia. do they persist after d/c? (s40)
- thiazide diuretic, ethanol, estrogen, linezolid (>2wk)
- persist for months after drug d/c
-
___ sequestration can cause thrombocytopenia. it includes these two conditions. (s41)
- splenic
- portal hypertension, malignant splenic infiltration
-
heparin induced platelet clumping can yield undercount of plt. effect is mild and early in tx. this is immune or non-immune effect?
non-immune direct effect on platelet
-
pathophys of immune thrombocytopenia
- immune response with Ab targeting platelet for destruction by either -->
- hapten type rxn
- innocent bystander
-
onset of immune thrombocytopenia
- 6-12d of heparin (variable with other agents)
- if prior heparin exposure, onset is in 1-4d (esp if in the last 100 days)
-
how to you manage immune thrombocytopenia
- drug withdrawal leads to plt count recovery (7-10d generally)
- but if drug deposits in the body, it takes longer
-
which one is exposure dependent, not concentration dependent, for thrombocytopenia?
(the other three are conc dep)
A) heparin
-
petechiae is pinpoint hemorrhage that is ___mm in diameter. purpura is __mm in diameter.
-
Reversible?
a) type I (HAT)
b) type II (HIT)
a) type I (HAT)
-
transient within few days of starting heparin
a) type I (HAT)
b) type II (HIT)
a) type I (HAT)
-
onset is 1-4 days
a) type I (HAT)
b) type II (HIT)
a) type I (HAT)
-
may not require stopping heparin
a) type I (HAT)
b) type II (HIT)
a
-
platelet level is ~100,000/mm3
a) type I (HAT)
b) type II (HIT)
a
-
delayed and serious
a) type I (HAT)
b) type II (HIT)
b
-
platelet <100,000 or >50% decrease.
a) type I (HAT)
b) type II (HIT)
b
-
requires d/c of heparin
a) type I (HAT)
b) type II (HIT)
b
-
onset 5-12 d, sooner if prior use of heparin
a) type I (HAT)
b) type II (HIT)
b
-
immune mediated: IgG and IgM antibody against heparin-platelet factor I complex.
a) type I (HAT)
b) type II (HIT)
b
-
check antibody b/c this is an autoimmune process.
a) type I (HAT)
b) type II (HIT)
b
-
may react with endothelial bound plt factor 4 leading to plt aggregation. clotting.
a) type I (HAT)
b) type II (HIT)
b
-
hep-induced thrombo:
does LMWH cross react with heparin? what else can you use?
- yes
- danaparoid (inhibit activated factor x)
-
hep-induced thrombo:
can you switch to lovenox if hep-ind thromb?
-
if severe, can heparin be used in central line and peripheral line flushes?
nopeee
-
when do you support with platelet if hep-ind thrombocytopenia?
when bleeding or platelet <10,000.
-
what to do in continued anticoagulation in HIT?
tx of choice?
- d/c heparin and LMWH
- could start warfarin (only when plt is normal)
- tx: lepirudin, argatroban, fondaparinux
-
LEPIRUDIN
brand name.
pharmacological class.
target and monitor.
important to remember.
- Refludan
- direct thrombin inhibitor
- aPTT 1.5-2 nl (can adjust q4h)
- monitor platelet, PTT, renal fx, bleeding, allergy, fever, liver fx.
- RENALLY adjusted
-
ARGATROBAN
pharmacological class
cautions
when to adjust dose?
how to monitor aPTT? when does it normalize?
what else to monitor?
SEs
- reversible thrombin inhibitor
- caution in LP, severe htn, major surgery
- adjust dose when hepatic issue
- monitor q2h, adjust to 1.5-3 x nl. normalize w/i 2h of d/c drug
- monitor platelet, apTT
- SE bleed, hotn, allergy, GI
-
FONDAPARINUX
brand name.
pharm class.
MoA.
when to dose adjust.
contraindication.
monitor.
SE.
- Arixtra
- synthetic pentasaccharide
- bind to antithrombin III, potentiate factor Xa neutralization and inhibit thrombin formation. (3 and 10)
- dose adjust when renal
- CI when CrCl<30 and antiplatelet Ab present.
- monitor platelet and anti-factor Xa
- SE bleed, fever, rash
-
DANAPAROID
pharm class
pharm action
indications
SE
does it cross react?
- LMWH
- inhibit thrombin via anti Xa and anti IIA (2 and 10)
- indicated for subacute and acute event tx of venous or arterial thromboembolism.
- SE bleed, fever, NV, constipation, rash
- cross react 10-30%
-
check aPTT in 2 h -->
check aPTT in 4 h -->
match.
a) argatroban
b) lepirudin
-
renal dysfx use -->
hepatic dysfx use -->
match.
a) argatroban
b) lepirudin
- renal: use argatroban
- hepatic: lepirudin (Liver for Lepi)
-
what to monitor in both argatroban and lepirudin?
- goal apTT (1.5-3 x baseline for arga and 1.5 - 2.5 x baseline for lepi)
- platelet
-
define leukopenia.
WBC <3000 cells/mm3
-
define granulocytopenia
- granulocyte <1500 cells/mm3
- (includes neutrophil, basophil, eosinophil, bands)
-
define agranulocytosis.
granylocyte <2000 cells/mm3
-
define neutropenia.
- ANC < 500 cells/mm3
- or ANC of 1000 cells/mm3 with expected decline of <500 cells/mm3
-
risks for neutropenia
- renal fail
- autoimmune disease
- genetic
-
another name for "segs"?
neutrophil!
-
calculate ANC.
WBC 1.4
segs 16%
bands 20%
lymph 60%
eos 2%
baso 2%
- ANC = WBC x (% of seg + band)
- 1400 x (0.16 + 0.20) = 504
- this is not severe. severe is <500.
-
onset of neutropenia and resolution time.
what to do if not resolve?
- 7-14 d onset
- 10-14 d resolve
- bone marrow aspirate and biopsy
-
most common cause of neutropenia is...
chemotherapy
-
drugs for drug induced neutropenia?
- clozapine (need to register w/ company. check q2w)
- carbamazepine
- chemotx
- (also chloramphenicol, sulfa, sulfonylurea, phenylbutazone, felbamate, colchcine, dapsone, ganciclovir, methimazole, gold salts, isoniazid)
-
S&S of neutropenia
- FEVER!!!
- usually blunted, malaise, chill, sore throat, pharyngitis, mouth ulcer, oral thrush, vaginal yeast infxn, diarrhea, infxn (bacteremia, sepsis, pna, cellulitis, uti)
-
if ANC is < ___, whether you have fever or not you MUST treat.
- 500
- if 500-1500, just monitor. treat if fever present
-
2 mechanisms of neutropenia
- immune mediated
- direct toxic effect on bone marrow
-
5 agents that cause immune mediated neutropenia.
- this is Ig induced peripheral destruction of cells.
- carbamazepine, clozapine, chlorpropamide, methimazole, PTU
- (CCCMP)
-
5 agents that cause neutropenia by direct toxic effect on the bone marrow.
chemo, cimetidine, quinidine, ticlopidine, sulfonamide
-
2 agents that cause neutropenia via both mechanisms (immune-med and direct tox)
-
how to manage neutropenia
- d/c suspected agent
- avoid sick ppl, fresh fruit/flower; barrier
- face mask not necessary
- wash hands
-
neutropenic fever (NF) is medical emergency!
how to manage?
- broad spectrum pseudo
- vanco only if G+ infxn
- add fungal if no improve after 5-7d
-
if you expect long course or high risk of neutropenia management, what to use? when are these indicated (ANC level).
- Colony stimulating factor:
- Filgrastim (Neupogen) 5mcg/kg/d sq
- Peg-filgrastim (Neulasta) 6mg q14-21d sq
- Sargramostim (Leukin) 250mcg/kg/d sq
-
what to monitor for neutropenia?
- temp
- CBC w/ differential
- S&S of infxn
- SE of treatment
-
aplastic anemia. what does BM bx show?
decreased cellularity
-
what is aplastic anemia?
combo of 2 or more of neutropenia, thrombocytopenia or anemia
-
S&S of aplastic anemia
- fever, fatigue
- malaise, chill, thrush, vaginal yeast infxn, mouth ulcer, diarrhea, infxn (b/c neutropenia), SOB (b/c lack of Hgb), dyspnea on exertion, weak, pallor, petechia, bruise (b/c low platelet), bleed
-
drugs that induce aplastic anemia.
- NSAID (indomethacin, diclofenac, aspirin)
- beta lactam abx
- phenytoin, felbamate, phenobarb
- chlorpromazine, lithium
- interferon
- chlormaphenicol, chloroquine, sulfonamide (furosemide), captopril, enalaprin, methyldopa, quinidine
-
what med to give when MS? how often monitor? impt blood disorder SE?
- interferon
- monitor q month for CBC, WBC
- aplastic anemia
-
how to manage aplastic anemia?
- treat NF
- immunosuppression
-
current therapy of choice for aplastic anemia
- stem cell transplant
- ATGAM 40mg/kg/d IV x 4d
- CSA 12mg/kg/d for adults div bid
- methylprednisolone 1mg/kg IV qd
- (+/- colony stimulating growth factor filgrastim 5mcg/kg sq qd)
-
dosage of ATGAM for immunosuppression in aplastic anemia.
- test dose required: 0.1ml intradermal of 1:1000 dilution
- option 1: 10-20mg/kg/d IV qd x8-14d (long course)
- option 2: 40mg/kg/d IV x 4d (preferred; short)
-
how to decrease serum sickness when using ATGAM for aplastic anemia? what is serum sickness
- use methylprednisolone 1mg/kg IV qd (minimum of 40mg) (3-5d)
- fever, hypotension
-
prednisone:methylprednisolone = __mg:__mg
5:4
-
ATGAM (for aplastic anemia) stands for
antithymocyte globulin
-
ATGAM toxicity (this is for aplastic anemia)
- anemia, thrombocytopenia, neutropenia
- hypersensitivity rxn (thus need test dose; anaphylaxis, serum sickness, HA, chill, arthralgia, fever, rash, edema, joint pain, hotn, infxn, resp distress)
-
MoA of cyclosporine A (this is for aplastic anemia)
inhibit lymphocyte fxn from bone marrow
-
dose for cyclosporine for immunosuppression in aplastic anemia.
- 12mg/kg/d for adults
- 15mg/kg/d for children (higher)
-
what to monitor for cyclosporine (aplastic anemia)
whole blood level 200-400 ng/ml
-
toxicity of cyclosporine (this is for aplastic anemia)
- renal tox
- htn
- cns
- Mg loss (thus ALL needs Mg supple)
-
which agents increase CSA level?
- 3A4 inhibitors:
- fluconazole, macrolides, metoclopramide, amiodarone, danazle, testosterone, CCB, oral contraceptive
-
which agents decrease CSA level?
- 3A4 inducers:
- carbamazepine, phenobarbital, phenytoin
- rifampin, rifabutin
- bactrim
- ketoconazole
- imipenem
-
what to evaluate in anemia?
- Hgb/Hct
- MCV, MCH, MCHC
- as indicated: iron, B12, folate panel
- as indicated: Coomb's test
-
what's Coomb test? what is direct vs. indirect
- to see if antibody is attacking RBC
- indirect: see if antibody to RBC; done before blood transfusion
- direct: see if antibody on RBC surface; to check if hemolytic anemia.
-
what happen to Hgb and Hct if a lot of reticulocyte (immature RBC)?
hgb and hct low
-
when do you adjust for reticulocyte? what's the formula of corrected reticulocyte?
- should be adjusted if low hematocrit and reticulocyte is >1%
- corrected reticulocyte(%) = (observed reticulocyte count) x (patient's hct/ normal hct)
-
etiology of anemia
- decreased production: bone marrow injury, nutrition deficiency, endocrine dysfunct (hypothyroidism)
- increased destruction, loss: hemorrhage, hemolytic anemia
- hereditary: thalassemia, sickle cell anemia
- deficient synthesis: hepatic insufficiency, chronic disease (CKD)
- damage to RBC: spleen sequestration
-
mechanism of immune hemolytic anemia
- destruction of RBC by antibody to antigen on erythrocyte membrane: drug depdent and independent antibody, non-immunologic protein adsorption
- mediated by either IgG or IgM (antibodies)
-
immune hemolytic anemia signs and symptoms
- pale, fatigue, SOB, dark urine, inc HR
- inc: bili (yellow), haptoglobin, reticulocyte count, K+
- dec: hgb, hct
- hemolysis
- (+) coomb test (esp direct)
-
drugs that cause hemolytic anemia
- cephalosporin
- methyldopa (alpha agonist)
- NSAIDs
- sulfonamides (bactrim, sulfasalazine)
- quinidine
-
immune hemolytic anemia:
mechanism of this anemia? when do symptoms occur?
what to do??
- generate drug-independent auto-ab --> stick to RBC then lysis.
- 3-6 mo , usually mild
- d/c meds!
-
fludarabine can have auto-immune hemolytic anemia. how to decrease risk?
combine with rituxumab and cyclophosphamide
-
quinidine:
what anemia?
mechanism?
management?
- hemolytic anemia
- formation of immune complexes
- bind to RBC membrane at allo-antigen site --> antigen-drug complex (neoantigen) activates complement --> rapid, acute, severe hemolysis
- d/c drug, supportive care (transfusion, prednisone, immunosupp, IVIg, dialysis)
-
drugs that cause hemolytic anemia via "drug adsorption" mechanism.
pcn, cephalo, tetracycline
-
what blood disorder do pcn, cephalo and tetracycline cause?
mechanism?
- hemolytic anemia
- drug adsorption: direct, covalent adsoprtion to RBC membrane --> splenic sequestration or direct lysis
- stop drug or reduce dose (b/c usually mild and happens at high dose)
-
methyldopa.
what kind of anemia?
- drug independent auto-ab
- hemolytic anemia
- could persist even after d/c drug
-
cephalosporin:
what kind of anemia
hemolytic anemia (drug adsorption and non-immune drug adsorption)
-
what drug causes hemolytic anemia via non-immune drug adsorption?
mechanism?
how to manage
- cephalosporin
- bind to RBC membrane --> bind to other protein
- no hemolysis
- no treatment needed
-
G6PD deficiency causes immune or non-immune hemolytic anemia?
non-immune
-
G6PD deficiency is common in which population?
- African blacks
- mediterranean (greek)
- sephardic jews
- chinese
- these ppl don't have the enzyme so RBC destroyed
-
in G6PD def, what condition can exacerbate hemolysis?
oxidative environmental stress
-
what to do for G6PD deficiency?
- d/c drug
- screen carefully - go for G6PD test
- epoetin if hgb too low (<8)
- hydration
-
what drugs can induce G6PD hemolysis?
- bactrim, sulfasoxazole
- dapsone
- pyridium (phenazopyridine)
- nitrofurantoin
-
once HIT is resolved, what would you start?
warfarin
-
if HIT type II, what should you check?
- HIT antibody!
- this is autoimmune dz
- antibody to system and bind to platelet to destroy
-
if warfarin is started before HIT/thrombocytopenia is resolved, what happens?
venous gangrene
-
what to monitor in hemolytic anemia?
hgb, hct, haptoglobin, bili
-
what should you NOT eat if you have G6PD def?
fava beans (derr.?)
-
normal platelet?
150,000-400,000
-
normal hgb
- men: 13.5 - 17.5 g/dL
- women: 11.5 - 15.5 g/dL
-
normal haptoglobin. what is it?
- protein that binds to free hgb
- 41-165 mg/dL
-
what to consider in aplastic anemia (general management)
- d/c drug!
- broad spectrum abx (check PCN allergy and cx!! zosyn, aztreonam+gent, vanco)
- neutropenic fever: tylenol
- oral thrush and mouth sore: antifungal (nystatin, fluconazole, clotrimazole; no chlorexidine!)
- ATGAM (test dose, methylprednisolone for serum sickness, tylenol, H1 or 2 blocker), or cyclosporine (check drug interaction)
- transfuse blood if hgb <8
- neupogen if ANC <500 (severe)
- if young pt, allo SCT may help
-
how to manage hemolytic anemia?
- d/c agent
- adequate hydration (NS 125-150ml/hr iv), may alkalinize urine (bicarbonate to IV fluid)
- blood prodruct support if necessary (avoid if autoimmune hemolytic anemia) (only for severe, hgb <8 or sev sympt)
-
when to avoid blood transfuse?
when to give?
- avoid if autoimmune dz (blood may hemolyze due to anti-RBC antibody b/c antibody still in the body)
- give when severe sympt or hgb <8
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