Hematology/Oncology Flashcards
Heparin to Warfarin bridge
Prot C and S w/ shorter t1/2
II, VII, IX, X longer t1/2
Transient paradoxic hypercoag before anticoag
Heparin vs LMWH
Heparin: activ antithromb; ↑PTT
Antidote: protamine sulfate
LMWH: esp inhib Xa; No eff on PTT
No eff of prot sulf
Warfarin
Inhib synth vitK-dep coag fact
↑PT
Reversal: rapid w/ FFP; slow vitK
! teratogen
tPA
Help conv plasminog to plasmin (breaks fibrin)
↑PT; ↑PTT
If toxicity, give aminocap acid
Factor Xa inhibitors
Factor IIa inhibitors
No monitoring (PT, PTT) No reversal agent
Hemophilia (PE)
X-linked; A=VIII; B=IX; C=XI Rare acquir (autoimm, post-part)
Young boy; spont hge tissue/joint (intracereb/GI/…)
Hge after surg, trauma, dental proced
If not ttt, arthropathy/joint destruction
Hemophilia (dg, ttt)
Dg: ↑PTT; normal PT/BT
Mixing study (#1): correct PTT
Specific fact assay (accur)
ttt: if sever bld or fact ≤1% (immediat transfu missing fact; cryoprecip)
If not sev and >1% (DDAVP releases VIII from endoth C)
von Willebrand disease (PE)
AD; #1 inherit bld ds
Defect or deficiency in vWF + ↓VIII
Types: 1 (mild-mod defic); 2 (qualit defect); 3 (No funct)
Child; recurr + prolong mucosal bld + bld after proced
⊕ fam Hx; sympt worse w/ ASA
von Willebrand disease (dg, ttt)
Dg: ↑BT; may ↑PTT (by ↓VIII); normal PT/PC
Accur: Ristocetin cofact assay + vWF Ag level
ttt: DDAVP (mild-mod); OCPs (if menorrhg); Avoid ASA and plt fct inhib
Bernard-Soulier syndrome
Glanzmann thrombasthenia
B-S: def GpIb (binds plt to endoth vWF)
G-T: def GpIIb/IIIa (binds 2 plts by fibrinogen)
ADP receptor inhibitors
GpIIb/IIIa inhibitors
ADP-R inh: clopidog/prasug/ticlopidine
No externaliz of GpIIb/IIIa
GpIIb/IIIa inh: abciximab/eptifibatide/tirofiban
Hypercoagulable states (etiologies)
Thrombophilias or prothrombotic states
Genet, acquir, physiol
3 main causes but same PE
- F.V Leiden: f.V resist to inactiv by activ prot C (#1 hered thromboemb ds)
- HIT: immuno react to heparin; Ab activates plt; bld clots + rapid ↓50% PC
- APS: ass w/ SLE/RA; art+ven thrombi; spont abort
Hypercoagulable states (PE, dg)
Recurr thromb (DVT, PE, art thromb, MI, stroke, abort)
HIT: hospit ptt on anticoag then ↓PC
F.V.L: young caucas + pers/fam Hx thromb
APS: middle-age women + recurr miscarr/thromb
Dg: r/o acqu causes before hered workup
Hered: 2 abNl values while asympt/unttt + similar values in 2 fam memb
HIT: PF4 Ab + serotonin release assay
APS: lupus anticoag + anticardiol Ab
Hypercoagulable states (ttt)
DVT/PE: heparin then 3-6mo warfarin (1st epis); 6-12mo (2nd); lifelong (next)
If anticoag CI (hge, sev HTN, recent trauma) or refract: IVC filter
HIT: !d/c hep; start argatroban/lepirudin
F.V.L: avoid OCPs
Protein C or S deficiency (PE)
Skin or tissue necrosis after Warfarin
Disseminates intravascular coagulation (RF)
Acquir; deposit of fibrin in Vx → thromb + end-org dam
Deplet coag fact + plts → bleed
Ass w/ obstetr complic; sepsis; neopl; ApML; pancreatitis; massiv trauma; drug react; ARDS; …
Disseminates intravascular coagulation (PE, dg, ttt)
Acute: bld from venipunct/in org; ecchym, petech
Chronic: bruis, mucos bld; thrombophleb; renal dysfct; neuro sympt
Dg: clinic+lab; #dg liv ds (but DIC w/ VIII is depressed)
ttt: underl cause; transfuse RBCs/plts/FFP; manage shock
Thrombotic thrombocytopenic purpura (PE)
Inherit or acquir (after inf)
vWF-cleav enz def (ADAMTS-13 def) → large vWF → plts microthrombi → end-org dam
RBCs fragm by microT → hemolysis
TTP if 3/5⊕: ↓PC; microang hemol anemia; neuro chang; impair renal fct; fever
Thrombotic thrombocytopenic purpura (dg, ttt)
Dg: schistoc + ↓PC + ↑creat
HUS: simil to TTP; child w/ EcoliO157H7; renal fail, hemol anemia, ↓PC, No neuro sympt
ttt: #1 plasma exchange; steroids to ↓thromb
CI for plt transfu
3 causes of microangiopathic hemolytic anemia
HUS
TTP
DIC
Idiopathic thrombocytopenic purpura (PE, etiologies)
IgG against plts → plt/Ab complex destr by spleen → ↑plt prod by BM
#1 immuno ds in middle-age women
Ass w/ leukemia/lymphoma/SLE/HIV/HCV
Acute (aft viral inf; 2-6yo) or chronic (20-40yo, esp women)
Asympt; minor mucocut bld, easy bruis, petech, hematuria, melena
Idiopathic thrombocytopenic purpura (dg, ttt)
Dg: of exclusion; r/o causes of thrombocytop then labs (Nl RBC morpho) BM biopsy (only if atyp or >60yo): ↑megakaryoc
ttt: No ttt (if plt >30K + no bld)
CS or IVIG: if plt <30K or bleed/sympt
If refract: splenectomy +/- rituximab +/- TPO recept agonist
9 #dg of thrombocytopenia
HIT HUS TTP ITP Medications Splenomegaly Hereditary (Wiskott-Aldrich sd) Chemotherapy Other (malignancy)
Iron deficiency anemia (etiologies, PE)
Normocytic then microcytic An
↑demand (pgncy, growth) or ↓iron (malnutr/malabs, bleed)
Esp toddlers, ado girls, women of childB age
Fatig, dyspn, tachycard, pica; asympt if slowly
Glossitis; conj pallor; cheilosis; koilonychia
Iron deficiency anemia (dg, ttt)
Dg: CBC; ↓iron, ↑TIBC/transferrin, ↓ferritin, ↑RDW; periph bld smear (hypochromic+microc w/ ↓reticulocyte count)
ttt: oral iron x4-6mo (!N, abdo pain, const/diarr)
CI antacids w/ iron
IV iron dextran (! anaphylaxis)
Anemia of chronic inflammation/disease
Chronic infl, inf, malign, RA, SLE
Body hides iron (limit bact prolif)
Normocytic then microcytic An
Dg: ↓iron, ↓TIBC/transf, ↑ferritin
Sideroblastic anemia
Microcytic An
Def in heme metab (hered; alcoh, lead poison, chloramph, INH, malign)
Dg: ↑iron; basoph stippl (periph smear); ringed sideroblasts (BM)
Megaloblastic anemia (etiologies, PE)
Macrocytic anemia
Impaired DNA synth (vitB9 def, vitB12 def, MTX, 6-MP)
-B12: intest malabs (Crohn/celiac/gastrect/panc insuff), pernicious An, vegetarian, Diph latum
-B9: alcoh, ↓diet folate, malabs, phenytoin
Fatig, pallor, diarr, ↓appet, headac
B12: demyelin (subacute comb degen of cord)
Megaloblastic anemia (dg, ttt)
Dg: CBC, smear w/ hypersegm neutroph (≥6 lobes)
MMA+homocysteine (↑both in B12 but MMA Nl in B9)
BM (giant+hyperseg neutro); Schilling test (for B12)
ttt: underl cause
Hemolytic anemia (etiologies)
Normocytic An
BM unable to compens for ↑destruc
- Intrinsic: memb def (spheroc), enz def (G6PD def), HbC, SCD, parox noct hemoglobinuria
- Extrinsic: autoimm, microangiop (HUS/TTP/DIC), macroangiop (mechan heart valv), inf (malaria), hypersplenism
Hemolytic anemia (PE, dg, ttt)
Pallor, fatig, tachycard, tachypn
Dg: jaund, ↑ind bili, ↑reticuloc, ↑LDH, ↓haptogl
ttt: underl cause; CS in immuno; iron to replace loss
If severe, splenectomy or transfusions
G6PD deficiency
X-linked; hemolyt An after oxidant stress
Episod dark urin + jaund
Trigger: sulfa drug, antimalar, inf, fava beans, metab acid
Dg: CBC, smear (bite cell, Heinz); G6PD level after 1mo
ttt: avoid trigg
Paroxysmal nocturnal hemoglobinuria
Def in GPI-anchor molec → No CD55/CD59 on RBCs → No protec ag complem-med hemolysis
Dg: An, dark urin, venous thromb, abdo pain; flow cytom w/o CD55/59 (accur)
Hereditary spherocytosis
AD def in spectrin/ankyrin
Spherical RBCs destroyed by spleen (extravasc hemol)
Dg: CBC + smear; osmotic fragil test (accur)
ttt: splenectomy (+pneumo/meningo/haemo vacc before)
Sickle cell disease (PE, complications)
AR; beta chain has Val (not Glu)
Trigg: dehydr, deoxyg, high altit, inf, cold
Dactylitis (child); An, jaund, pigm cholelith, ↑CO (CHF), delayed growth
- Vaso-occlusion: isch org dam, splen infarc, acute chest sd, avasc hip necr, priapism, stroke
- Splenic sequestr: hypovol; Nl/↑ plts
- Aplastic crisis: by parvoB19; ↓plts
Sickle cell disease (dg, ttt)
Dg: CBC w/ smear (sickle C, Howell-Jolly); Hb electroph (accur)
ttt: hydroxyurea (↑fetal Hb); if ineff, chronic transfu
Cholecystec if lithias; folate suppl; vaccines; penicill in <5yo
-VasoO crisis: pain manag, O2, IV hydr, AB
-Acute chest sd: aggr hydr, spirom, transfu
Autoimmune hemolytic anemia
AutoAb: warm (IgG ass w/ SLE, CLL, drugs) and cold (IgM ass w/ EBV, mycopl)
Dg: direct Coombs
ttt: no ttt (mild); steroids (severe warm); avoid cold+/-Rituximab (severe cold)
Aplastic anemia
BM cells destruc → No bld cells
Hered (Fanconi An); autoimm; viral (HIV, parvoB19); toxins; radiation; drugs
Pancytop: pallor, weak, ↑inf, petech, bruis, bleed
Dg: CBC; BM biopsy w/ hypocell + fat (accur)
ttt: transfu + SCT; ttt inf aggress; if no donor, immunosupress to prevent autoimm BM destr
Thalassemias (etiologies, PE)
Heredit; ↓/No prod of nl globin
Alpha: mut of ≥1 of 4 genes for alpha-Hb
Beta: mut of ≥1 of 2 genes for beta-Hb
Africa, middle east, Asia
PE depends on nb of genes; asympt; fatig w/ microcyt An + Nl iron studies
Thalassemias (dg, ttt)
Dg: Hb electroph and DNA studies
ttt: most, no ttt
Beta-T major (0/2 beta) and HbH ds (1/4 alpha): transfu-dep + iron chelator
Polycythemias (etiologies, PE)
Erythrocytosis: -absolute (↑RBC prod: hypoxia, lung ds, smok, altit; neopl, EPOtumor; PCV) or relative (↓plasma, hypovol and hemoconcentr)
↑Ht; ↓tissu bld flow+O2; ↑card work
Hyperviscosity sd: easy bleed/bruis; blurred vis*; neuro def; prurit aft warm bath; thromb; CHF; HSM
Polycythemias (dg, ttt)
Dg relative erythro: ↑Ht, ↑/Nl EPO, O2 often ↓ compared to PCV
ttt relative eryth: underl cause; phlebotomy (↓sympt)
Polycythemia vera
Clonal prolif of a pluripotent marrow stem cell
All marrow cell lines ↑, esp RBCs
Older ptt
Dg: CBC, ↑RBCs, ↑WBCs, ↑plts; ↓EPO, Nl O2, ↑Ht >60%
JAK2 mutation⊕
ttt: phlebotomy + aspirin (↓sympt + prev thromb); hydroxyurea + IFN (↓cells)
Febrile nonhemolytic transfusion reaction
Cytokine format* in storage
Fever/chill, malaise; aft 1-6h
ttt: stop transfu + give acetamino
Allergic transfusion reaction
Ab ag donor prot; usual aft plasma-contain prod
Prominent urticaria
ttt: antihist; if severe, stop transfu + give epinephrine
Hemolytic transfusion reaction
Preformed (acute) or formed (delayed) Ab ag donor RBCs
ABO mismatch; Rh and Duffy Ag
Fever/chilld, N, flush, burn at IV site, tachycard, hypoTN direcly aft transfu
ttt: stop transfu immediately + vigorous IV fluids + monitor urine
Porphyria (etiologies, dg, ttt)
Inherit ds, abNl heme prod
Accumul of porphyrins
Acute intermitt porph; erythropoietic porph; porphyria cutanea tarda
Dg: urin+plasm porphyrin lev; mutat*/enz analysis (accur)
ttt: avoid trigg; sympt ttt in attacks + high dose glucose
Porphyria (PE)
Photodermatitis, neuropsych, visceral sympt (colic abdo pain), seizures
Tachycard, skin erythema, blisters, areflexia
-Erythrop porph: hemolyt An, urine pink/black
Attacks ass w/ ↑heme synthesis (fasting, chemic expo, alcoh, barbit, OCPs)
-Acute interm porph: abdo pain, red urin, polyneurop, psychol disturb; by CYP450 inducers/alcoh/fasting
Acute leukemias (PE)
Clonal disord of blasts → unregul WBCs in BM
BM overwhelmed → anemia/fatig, inf, hge/petech/purpu
DIC (AML); bone pain (ALL)
Child + adult; rapid onset+progr
Leukemic infiltr: HSM; swoll/bld gums; skin; CNS
Acute leukemias (dg)
Dg: CBC w/ smear (AML: myeloblasts; ALL: lymphoblasts); BM biopsy (accur) + flow cytom
AML: Auer rods, myeloperoxidase ⊕
↑WBCs but dysfct or neutropenia
If WBCs >100K, leukostasis (vaso-occl)
Acute leukemias (ttt)
AML/ALL: chemotherapy; if unfavor genetics, BMT
Leukostasis sd: hydroxyu +/- leukapheresis
Poor pg: -ALL (<1 or >10yo; WBC>50K; t(9:22); CNS)
-AML (>60yo; ↑LDH; complex karyotype)
CLL (PE)
Dysfct lymphocytes in BM/bld/LN/spleen/liv Older adults (65yo; M=2F)
Asympt; fatig, malaise, inf
Lymphadenopathy; SMG
CLL (dg)
Dg: CBC+diff; smear (lymphocytosis + smudge cells)
Flow cytom w/ CD5 on B cells (accur)
Granulocytop, anem, thrombocytop, hypogammaglobulin
Rarely BM done
CLL (ttt)
Palliative; ttt given when symptomatic (recurr inf/sev LNpathy/SMG/An/thrombocytop)
Chemoth: fludarabine + chlorambucil
No cure; ds-free intervals w/ adequate ttt
CML (PE)
Clonal prolif myeloid progen cells + BCR-ABL transloc
Philad chrm t(9,22); middle-aged ptt
↑granulocytes and basophils; maybe ↑RBCs and plts
Asympt; anem, SMG w/ LUQ pain, anorex/fev/chil/↓weight
3 phases: chronic, accelerated, blast crisis
CML (dg)
Philad chrm (accur) by PCR/FISH
CBC (WBCs >100K to 500K); ↓LAP
↑ LDH, uric ac, B12
#dg: leukemoid reaction (↑neutro w/ left shift; ↑LAP)
CML (ttt)
Chronic: imatinib (Gleevec)
Young ptt: allogen SCT
Blast crisis: chemotherapy; dasatinib + SCT
Leukemia based on age (~)
<13yo: ALL
13-40yo: AML
40-60yo: CML
>60yo: CLL
Hairy cell leukemia (PE)
Ds of well-diff B lymphoc
Older men
Pancytop, BM infiltr, SMG Weak, fatig, petec, bruis, ing, abdo pain, ↓weight Rare LNpathy (#CLL)
Hairy cell leukemia (dg, ttt)
Dg: CBC w/ smear (hairy C w/ TRAP stain) Flow cytom (accur)
ttt: cladribine; splenectomy; IFN-alpha
Non-Hodgkin lymphoma (PE)
1 hematopoietic neopl
Group of mature B (85%) and T cell neopl
>50yo; aggress in child
Painless periph LNpathy + extranodal (#HL) B sympt (fev, night swt, ↓weight)
Non-Hodgkin lymphoma (dg, ttt)
Dg: excisional LN biopsy; Ann Arbor staging
CSF exam if HIV, neuro sympt, 1*CNS lymphoma
ttt: based on histopath (not stage) → radioth, chemoth, x2
Low grade: palliative
High-grade: aggress ttt
4 types of B cell NHL
- Follic: adult; low grd; painless wax/wan LN; radioth if local
- DLBC: middle-age/elder; interm grd; single rapid grw mass; R-CHOP ttt
- Burkitt: child/ado; high grd; starry sky; jaw/Afr; abdo/USA; EBV; t(8;14); aggress ttt
- Mantle cell: elder men; rare
2 types of T cell NHL
- Adult T-cell: adult; high grd; progr to ALL; cutan les*; by HTLV; ass w/ IVDA
- Mycosis fungoides: adult; skin; eczema-like + prurit; cerebriform cells; progr to Sezary sd (leukemia)
Tumor lysis syndrome
Hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalemia; renal insuff
Prevent: gd hydrat + allopur or rasbur
Hodgkin lymphoma (PE)
Predomin B-cell; ass w/ EBV
Bimodal age: 30yo (nodular sclerosing type); 60yo (lymphocyte-depleted type)
Above diaphragm (cervic LNpathy); if under D = dissem
Systemic B symptoms, prurit, HSMG
Rare: Pel-Ebstein fevers and alcohol-induced pain
Hodgkin lymphoma (dg, ttt, pg)
Dg: excisional LN biopsy (Reed-Sternb C = giant B C)
Stage: nb of nodes, if B sympt, if both sides of diaph
ttt: stage-dep; chemoth and radiation
5-yr pg: stage I/II 90%; III 84%; IV 65%
Lymphocyte-predomin HL: best pg
Multiple myeloma (RF, PE)
Clonal prolif of plasma C w/ excess monoclon Ig (A/G) or Ig fragm (kappa/lambda light chains)
Elder
RF: radiation; MGUS; petrolium; pesticides
Bone pain/pathol fx; anem; hyperCa; renal abnl
Inf (monoclon Ig ineffect); ↑monoclon M prot
Multiple myeloma (dg, ttt)
Dg: serum prot electroph (IgG/IgA spike)
BM biop (>10% monoclon CD138+ plasma cells)
CBC w/ smear (rouleaux); ↑prot:album
Urinal (Bence Jones prot); skeletal survey
ttt: autolog BMT (if <70yo); melphalan+prednis (if >70yo)
Cryoglobulinemia vs cold agglutinins
IgM Ab
Cryog: in HCV, joint pain, renal involv
Cold agg: in EBV, mycoplasma, Waldenstrom macroglob; numbness on cold expo,
Waldenstrom macroglobulinemia (PE)
B cells; malign monoclonal gammopathy
↑IgM; hyperviscosity sd
Coag abNl, cryoglobul, cold agglutinin ds, amyloidosis
Lethargy, ↓weight, Raynaud phen, neuro prob, organomeg, org dysfct
MGUS is precursor
Waldenstrom macroglobulinemia (dg, ttt)
Dg: BM biopsy/aspirate (abNl plasma cells w/ Dutcher bodies); prot electroph+immunofixation; ↑ESR, uric ac, LDH, ALP
ttt: chemo; plasmapheresis
Amyloidosis (PE)
Extracell deposit of amyloid prot fibrils
Elder
PE: dep on type, amount, distrib (esp kidney, heart, liv)
Alzheimer ds: deposit just in brain
Amyloidosis (dg, ttt)
Dg: tissue biopsy w/ Congo red (apple green birefr) (accur)
Immunohistochemistry
ttt: 1* amyl: experimental chemoth + autologous SCT
2* amyl: underl cause
5 types of amyloidosis
- AL: monoclonal light-chain fragm; ass w/ MM + Walden macroglob
- AA: amyloid A; ass w/ chron infl ds/inf/neopl
- Dialysis related: Beta2-microglobulin, pt on long-term dialysis
- Heritable: deposit of abnl gene prod (transthyretin)
- Senile-systemic: deposit of Nl transthyretin
Neutropenia (etiologies)
ANC <1500/mm3
Acquired or intrinsic
↓prod; migrat* from Vx; ↑destruct; utilization
Adult: #1 by inf; #2 by drugs; leuk/lymph; aplast anem; B12/B9 def
Neutropenia (PE)
↑R of inf
Acute: S aureus; Pseudom; E coli; Proteus; Klebs sepsis
Chron + AI: recurr sinusitis; stomatitis; gingivitis; perirectal ing
+/- SMG
Neutropenia (dg)
Dg: CBC w/ smear; Hx (drug/toxin/ing/AI/neopl)
Follow w/ CBC+ANC
If ↓plts/RBCs, BM biopsy/aspirate
Immuno eval; ANA lev; collagen vasc ds
Neutropenia (ttt)
ttt inf
Neutropenic fever = emergency; broad AB (cefepime) +/- antifungal
G-CSF shortens durat* of neutrop
Rare: IVIG; allogen BMT
Eosinophilia (etiologies, PE)
AEC >350/mm3
Trigg: overprod of cytokines/chemokines
1* or 2* to allergy, parasitic inf
Hx travel, med, atopic, leuk/lymph, diet
Hypereosino sd: fever, anem, cardiac findings), other org
Eosinophilia (dg, ttt)
Dg: CBC w/ diff
CSF w/ eosino: drug react* or inf (coccidio, helminth)
Hematuria w/ eosino: schistosom
ttt: cardiac find, eos >100K, drug react w/ systemic sympt → early dg + steroids + stop off agent
3 types of tissue transplantation
- Autologous: ptt to him/herself
- Allogenic: donor to genet diff ptt; ABO and HLA match; but match + immsuppr and still get rejection
- Syngeneic: btw/ identical twins (genet identical)
3 types of solid organ transplant rejection
-Hyperacute: min; preform Ab; Vx thrombi; tissu isch
Prevent (check ABO); ttt (cytotoxic agent)
- Acute: 5d-3mo; T-cell med; tissu destr (↑GGT/ALP/LDH/ BUN/creat); No prevent; confirm w/ biopsy then ttt (CS, OKT3, tacrolimus, MMF)
- Chronic: mos-ys; imm react* to fibrosis; gradual loss of fct; No prevent; No ttt (biopsy to r/o treatable acute react*)
GVHD
Specif to allogeneic BMT
Donor T cells attack host tissues
Acute (<100d) or chronic (>100d)
Esp skin, liv, GI (by minor histocomp Ag)
Skin changes, cholest liv dysfct, obstr lung ds, GI probl
ttt: high-dose CS
Typical posttransplant immunosuppression and infection prophylaxis
Imm: prednisone, MMF, tacrolimus
Proph: TMP-SMX, ganciclovir, ketoconazole
