Heme/Onc Flashcards
Anemia of Chronic Disease: Normocytic definition, sx, dx, tx
Anemia due to decreased RBC production in the setting of chronic disease
Etiologies: chronic inflammatory conditions – chronic infection, inflammation, autoimmune disorders, malignancy
sx
PATHO: 3 main factors decrease serum iron
*↑ hepcidin: blocks release of iron from macrophages & reduces GI absorption
*↑ ferritin: sequesters iron into storage
*erythropoietin inhibition
dx
CBC:
*mild normocytic normochromic anemia
*↓ reticulocytes, normal/↑ RDW
Iron studies:
*normal/↑ ferritin
*↓ TIBC, ↓ serum iron
tx
Treat the underlying disease
Erythropoietin-alpha if renal disease or low EPO levels
B12 Deficiency definition, sx, dx, tx
Macrocytic
Sources: meats, eggs, dairy
Absorption: combines w/ intrinsic factor, absorbed mainly in distal ileum
PATHO: deficiency causes abnormal DNA synthesis
Etiologies:
*decreased absorption: pernicious anemia, Crohn disease, chronic ETOH use, H2 blockers/PPIs, metformin
*decreased intake: vegans
sx
Hematologic: fatigue, exercise intolerance, pallor
Epithelial: glossitis, diarrhea, malabsorption
Neuro sxs:
*symmetric paresthesias MC initial symptom
*lateral & posterior spinal cord demyelination & degeneration: ataxia, weakness, vibratory, sensory, & proprioception deficits, ↓ DTRs
dx
CBC w/ peripheral smear:
*megaloblastic anemia: hypersegmented neutrophils, macro-ovalocytes, mild leukopenia &/or thrombocytopenia
*low reticulocytes
↓ B12, ↑ LDH, ↑ homocysteine
↑ methylmalonic acid (distinguishes from folate deficiency)
tx
IM B12 – IM cyanocobalamin
- weekly until corrected 🡪 monthly
- can switch to PO once resolution of sxs
- pts w/ pernicious anemia need lifelong monthly injections
Folate Deficiency definition, sx, dx, tx
Macrocytic
PATHO: deficiency causes abnormal DNA synthesis
Etiologies:
*inadequate intake (MC): alcoholics, unbalanced diet
*increased requirements: pregnancy
*impaired absorption
*impaired metabolism: methotrexate, trimethoprim
*loss: dialysis
sx
NO NEURO SXS!
Hematologic: fatigue, exercise intolerance, pallor, chlorosis (pale, faintly green complexion – extremely rare)
Epithelial: glossitis, aphthous ulcers, diarrhea, malabsorption
dx
CBC w/ peripheral smear:
*megaloblastic anemia (hypersegmented neutrophils, macro-ovalocytes)
*low reticulocytes
↓ B12, ↑ LDH, ↑ homocysteine
NORMAL methylmalonic acid (distinguishes from B12 deficiency)
tx: PO folic acid
Factor V Leiden mutation Definition, sx, dx, tx
MC inherited cause of hypercoagulability (thrombophilia)
PATHO: mutated factor V is resistant to breakdown by activated protein C, leading to increased hypercoagulability
sx
Increased incidence of DVT, PE, hepatic vein, or cerebral vein thrombosis
Increased risk of miscarriages during pregnancy
dx
*activated protein C resistance assay
(+) 🡪 confirm w/ DNA testing
*DNA testing: mutation analysis
tx: indefinite anticoagulation
Protein C or S Deficiency definition, sx, dx, tx
Proteins C & S are vitamin K-dependent anticoagulant proteins produced by the liver that stimulate fibrinolysis & inactivate factors V & VIII
*decreased protein C or S leads to hypercoagulability
Etiologies:
*inherited: autosomal dominant (C MC)
*acquired: ESLD, severe liver disease w/ synthetic dysfunction, early warfarin admin.
sx
Increased incidence of DVT/PE
Warfarin-induced skin necrosis
dx
*protein C & S functional assay, plasma protein C & S antigen levels
tx
Thrombosis:
- protein C concentrate
- indefinite anticoagulation
Warfarin-induced necrosis:
- immediate D/C warfarin
- admin. IV vitamin K, heparin, protein C concentrate, or FFP
Antithrombin III Deficiency definition, sx, dx, tx
PATHO: antithrombin normally inhibits coagulation by neutralizing the activity of thrombin (factors IIa, IXa, & Xa); decreased levels lead to increased risk of clotting
Etiologies:
*inherited: autosomal dominant
*acquired: liver disease, nephrotic syndrome, DIC, chemo
sx: Increased incidence of DVT, PE
dx: antithrombin III assays
tx
Asymptomatic:
- anticoagulation only before surgical procedures
Thrombosis:
- high-dose IV heparin
- PO anticoagulation indefinitely
Hemophilia definition, sx, dx, tx
x-linked recessive disorder occurring almost exclusively in males
*A = factor VIII deficiency (MC)
*B = factor IX deficiency *Christmas disease
*C = factor XI deficiency *Ashkenazi jews
sx
Hemarthrosis: delayed bleeding or swelling in weight-bearing joints (MC ankles)
Excessive hemorrhage due to trauma & surgery or incisional bleeding
*epistaxis, bruising, GI or urinary tract hemorrhage
dx
*prolonged aPTT
Mixing studies: PTT corrects w/ mixing studies
A = low factor VIII
B = low factor IX
C = low factor XI
tx
- A: factor VIII infusion; desmopressin (DDVAP)
- B: factor IX infusion
- C: factor XI infusion
Von Willebrand Disease definition, sx, dx, tx
Autosomal dominant disorder associated w/ ineffective platelet adhesion due to deficient or defective vWF
MC hereditary bleeding disorder
sx
Mucocutaneous bleeding: epistaxis, bleeding gums, petechiae, purpura, bruising, menorrhagia, prolonged bleeding time after minor cuts
dx
*prolonged PTT & bleeding time (worse w/ aspirin)
Ristocetin-induced platelet aggregation (gold standard)
tx
- DDVAP
- factor VIII concentrates
- VWF-containing products
Antiphospholipid Syndrome (APS) definition, sx, dx, tx
*autoimmune disorder
*arterial/venous thromboembolic events
*recurrent pregnancy loss
*persistent antiphospholipid antibodies
PATHO: antiphospholipid antibodies induce cellular activation resulting in multiple procoagulant/inflammatory effects & activation of complement = thrombosis
sx
HALLMARK: thrombotic events (venous > arterial)
– MC venous site: lower extremity DVT
*superficial vein thrombosis, PE
– MC arterial site: cerebral (i.e., stroke or TIA)
HALLMARK: pregnancy complications
– 1+ fetal death >10wks gestation
– premature birth d/t preeclampsia/placental insufficiency
– 3+ unexplained embryonic losses (<10wks gestation)
*thrombocytopenia, livedo reticularis
*valvular disease
dx
LABS: CBC, CMP, UA
Antiphospholipid Antibody Testing:
*anticardiolipin antibodies (aCL), IgG/IgM (ELISA)
*false⊕ RPR
*anti-β2 glycoprotein I (aβ2GPI) antibodies, IgG/IgM (ELISA)
*lupus anticoagulant (LA) functional coagulation assay
– dilute Russell viper venom time (dRVVT), aPTT
tx
Acute thrombosis:
*anticoagulate w/ Warfarin (INR 2-3)
*preferred vs DOACs
Secondary thrombosis prevention:
*VTE: Warfarin *lifelong
*Arterial: Warfarin + ASA *lifelong
Pregnancy: LMWH *NO WARFARIN
Polycythemia Vera (PV) definition, sx, dx, tx
*acquired clonal myeloproliferative disorder
*overproduction of all 3 hematopoietic cell lines
*most prominently RBCs
*MCC of primary erythrocytosis
PATHO: JAK2 mutation
*erythroid production independent of EPO
RF: 60yo is median age at diagnosis, men
sx
Expanded blood volume & ↑ blood viscosity:
*HA, dizziness, tinnitus, blurred vision, fatigue
Aquagenic pruritis (pruritis after warm bath/shower)
*histamine release from excess basophils
Erythromelalgia
*burning pain in hands/feet w/ erythema, pallor, or cyanosis
Thrombosis (e.g., CVA, MI, DVT, PE, superficial)
*Budd-Chiari syndrome (triad of abdominal pain, ascites, & hepatosplenomegaly)
Hemorrhage (e.g., epistaxis d/t mucosal engorgement & platelet dysfunction)
*facial plethora (constant blush, “ruddy cyanosis”)
*engorged retinal veins, gout, splenomegaly, HTN
dx
LABS: ↑ WBC >10,500/µL,↑ platelets >450,000/µL,
↑ LDH, ↑ B12, ↑ uric acid
⊕PV DX: all 3 major criteria or (first 2 major + minor)
tx
Low-risk (≤60yo, ⊖hx of thrombosis):
*phlebotomy to maintain Hct <45%
*ASA 81mg
*NO iron supplementation
*encourage low-iron diet
High-risk (>60yo, ⊕hx of thrombosis):
*phlebotomy to maintain Hct <45%
*ASA 81mg
*cytoreductive therapy w/ Hydroxyurea
Refractory Symptoms:
*pruritis – avoid triggers, antihistamines
*gout – allopurinol
Refractory to Hydroxyurea:
*pegylated interferon, Busulfan
PROGNOSIS: median survival 15y
Sickle Cell Anemia definition and sx
SCD – group of inherited hemoglobinopathies secondary to the production of abnormal Hgb complicated w/ an associated hemolytic anemia & vaso-occlusion
Genetic mutation in both beta-globulin genes, w/ at least 1 mutation resulting in HbS – homozygous SS MC form & most severe (MC in AA)
sx
Painful episodes: vaso-occlusive event resulting in acute onset of severe pain commonly in back, check, & extremities
*swelling of hands/feet in infants (dactylitis)
Fever (>38.5C): more susceptible to bacterial infections because of functional asplenia; highest risk for sepsis from encapsulated organisms such as S. penumoniae, N. meningitidis, & Salmonella
Splenic sequestration: intrasplenic trapping of RBCs & platelets – decrease in Hgb & often platelets w/ an acute enlargement of spleen that can lead to life-threatening anemia (often associated w/ acute viral/bacterial illnesses)
Acute chest syndrome: fever, respiratory sxs, new pulmonary infiltrate on CXR
*causes: bacterial (M. pneumoniae, C. pneumoniae, S. aureus, S. pneumoniae, H. flu), viral, fat emboli, in situ vaso-occlusion, pulmonary edema, thromboembolism
Aplastic crisis: marked anemia w/ reticulocytopenia, frequently secondary to parvovirus infection that causes a maturation arrest of RBC production in bone marrow for 1-2wks
*increased fatigue, pallor, fever
*reticulocytopenia begins ~5d after exposure & lasts 7-10d
Sickle Cell Anemia dx and tx
Peripheral smear:
*target cells, sickled erythrocytes, ↓ H/H
*Howell-jolly bodies indicates functional asplenia
Hgb electrophoresis: 90% HbS, 8% HbF
Fever: all pts w/ SCD + fever need urgent evaluation w/ PE, blood culture, CBC w/ diff, reticulocyte count; consider urine culture, CXR
Stroke: head MRI, CBC w/ reticulocyte count, Hgb electrophoresis for HbS %, type & screen
*prevention: routine transcranial Doppler
tx
Painful episodes:
*outpatient: PO meds (anti-inflammatories w/ or w/o opioid) & hydration
*inpatient: combo of ibuprofen or ketorolac w/ an opioid & IV hydration
Fever: ceftriaxone or high-dose ampicillin + observation
Splenic sequestration: follow Hgb & spleen size closely; fluid admin in stable pts w/ mild decrease in Hgb
*hypoxia, tachypnea, tachycardia: transfuse 5-10mL/kg RBCs, then reassess
Acute chest syndrome: ampicillin or 3rd gen cephalosporin (cefotaxime, ceftriaxone) + macrolide (erythromycin, azithromycin, clarithromycin) + oxygen if hypoxic; pain control; incentive spirometry
*respiratory/hemodynamic instability requires RBC transfusion
Aplastic crisis: PRBC transfusion if pt is symptomatic
Preventative Management:
*Penicillin prophylaxis, folic acid supplementation, hydroxyurea for pts >9mo
G6PD Deficiency definition, sx, dx, tx
x-linked recessive enzymatic disorder of RBCs that may cause episodic hemolytic anemia
Risk Factors: males, AA males
PATHO: decreased G6PD activity during oxidative stress results in an oxidative form of Hb (methemoglobin); the denatured hemoglobin precipitates as Heinz bodies
Exacerbating factors:
*infection MC cause, fava beans
*dapsone, methylene blue, primaquine, nitrofurantoin, phenazopyridine
sx
*neonatal jaundice
For milder forms pts are clinically & hematologically normal until they have an “oxidative challenge”
Severe forms can have a baseline hemolytic anemia
6-24h after exposure to oxidative agent: dark urine, jaundice, pallor, tachycardia, nausea, abdominal pain
24-48h: low-grade fever, irritability, listlessness, splenomegaly, hepatomegaly
dx
Peripheral smear:
*normocytic hemolytic anemia only during crises
*schistocytes (“bite” cells), anisocytosis, blister cells
*(+) Heinz bodies hallmark
Hemolytic anemia:
↑ reticulocytes, indirect bilirubin
↓ haptoglobin
Enzyme assay for G6PD: fluorescent spot test; DNA testing; usually performed after episodes
tx
Usually self-limited; avoid offending foods & drugs
*Hgb returns to normal within 3-6wks
Hgb >7mg/dL + clinically stable + no hemoglobinuria: observe for 24-48h
Hgb <7mg/dL or Hgb 7-9mg/dL w/ continued brisk hemolysis (persistent hemoglobinuria): consider PRBC transfusion
Neonatal jaundice: phototherapy
Iron Deficiency Anemia definition, sx, dx, tx
MC cause of anemia
Microcytic anemia w/ ↓ reticulocyte count & ↑ RDW due to a deficiency of iron
Etiologies:
*chronic blood loss (MC in US): excessive menstruation, GI blood loss (colon cancer)
*decreased absorption: diet (MC worldwide), celiac, bariatric surgery, H. pylori
PATHO: decreased RBC production due to lack of iron & decreased iron stores (decreased ferritin); normally, iron is stored in ferritin in bone marrow, liver, & spleen
sx
Classic sxs of anemia: fatigue, SOB, HA
CNS: irritability, difficulty sleeping
Pagophagia: craving for ice
Pica: craving for non-food substances
PE:
*koilonychia: spooning of the nails
*angular cheilitis: inflammation of one or both corners of the mouth
*tachycardia, glossitis (smooth tongue)
*signs of anemia (pallor)
*hx of drinking >24oz of cow’s milk a day or transition to cow’s milk <12mo old is common
dx
CBC:
*microcytic hypochromic anemia
*↑ RDW
*anisocytosis
*↓ reticulocytes
*may have thrombocytosis & poikilocytosis
Smear: hypochromic microcytic RBC w/ pencil forms
Iron studies:
↑ TIBC
↓ ferritin, transferrin saturation, serum iron
Bone marrow: absent iron stores
tx
Iron replacement: Ferrous sulfate – 4-6mg/kg/d divided in 2-3 doses
Take w/ vitamin C, w/ water or orange juice, & on an empty stomach for ↑ absorption
ADRs: GI (N/V/D/C, flatulence, dark stool)
Severe, life-threatening anemia: RBC transfusion
Alpha Thalassemia definition, sx, dx, tx
Microcytic
(-a/aa): silent carrier; clinically normal
Trans (-a/-a) or cis (–/aa): trait; trans common in pts of African descent
(-a/–): HbH disease; Heinz bodies
(–/–): hydrops fetalis; stillbirth or death shortly after
*Hgb Barts: gamma tetramers (γγγγ)
sx
Trait: mild microcytic anemia, asymptomatic
HbH: moderate hemolytic anemia, jaundice, hepatosplenomegaly, gallstones, occasional need for transfusion during illness
dx
Trait: mild microcytic anemia
*normal levels of HbA, HbA2, & HbF
*+Hb Barts (gamma-chain tetramer) on newborn screen
HbH: moderate hypochromic, microcytic anemia (Hgb 7-10g/dL)
*variation in RBC shape/size on peripheral blood smear & other findings of chronic hemolysis
*reticulocytosis
*HbH on electrophoresis
*newborn screen >25% Hb Barts
tx
Trait: no intervention
HbH: folic acid supplementation
Stem cell transplant: curative
Beta Thalassemia definition, sx, dx, tx
Microcytic
β,β – normal
β,βo or β,β+ – MC; minor; trait; heterozygous, mild reduction in beta-chain synthesis w/ a resultant mild microcytic anemia
β+,β+ or β0,β+ – intermedia (mild); homozygous, markedly reduced beta-chain synthesis & moderate anemia that will occasionally require transfusion
β+,β+ or β0,β0 – major (Cooley’s Anemia); homozygous, no detectable to severely reduced beta-chain production, severe microcytic hypochromic anemia that requires lifelong RBC transfusions
sx
Trait: mild microcytic anemia, asymptomatic
Intermedia (β+,β+ or β0,β+): moderate hemolytic anemia (Hgb >7g/dL)
*splenomegaly, intermittent transfusion requirement
Major (β+,β+ or β0,β0):
*massive hepatosplenomegaly, growth retardation
*bony deformities – frontal bossing, maxillary prominence from extramedullary hematopoiesis (all preventable w/ aggressive transfusion therapy)
dx
Trait: mild microcytic anemia
*HbA2 level 3.5-8%
*HbF level 1-5%
*significant variability depending on type of mutation; may not be detected on newborn screen
Intermedia: clinical designation based on having a moderate microcytic anemia (Hgb >7g/dL) – only necessitates transfusion w/ normal growth
Major (Cooley’s): clinical designation w/ a resultant severe anemia (Hgb 3-7g/dL)
*reticulocytosis
*HbF 30-100%, HbA2 2-7%
*MCV 50-60fL
*NB screen will demonstrate only HbF in pts w/o any beta-chain production
tx
Trait: no intervention
Major: chronic transfusion therapy may be required as early as 2mo, but necessary by 2y
*10-15mL/kg of PRBCs required q3-4wks
*goal pretransfusion Hgb 9-10g/dL
Chelation therapy for chronically transfused pts w/ iron overload – PO/SC/IV chelators available & necessary 5-7d/wk
In pts receiving chronic transfusion, ferritin levels should be monitored to screen for iron overload, but annual MRI should be used to more accurately assess cardiac/liver iron concentrations & guide chelation therapy
Stem cell transplant: curative
Immune Thrombocytopenic Purpura (ITP) definition, sx, dx, tx
PATHO: autoimmune-antibody reactions vs. platelets w/ splenic platelet destruction 🡪 consumptive thrombocytopenia
Incidence:
*young children 2-4yrs; often 1-3wks following acute viral infection (often self-limited)
*adults: young women <40; idiopathic, often recurrent
sx
Often asymptomatic
Mucocutaneous bleeding: petechiae, bruising, purpura, bullae, bleeding of tooth/gums, menorrhagia
dx
Isolated thrombocytopenia
Normal coagulation tests
tx
Children: observation; 80% resolve w/o tx within 6mo
- +/- IVIG
Adults:
- steroids
- IVIG
- splenectomy (refractory)
Thrombotic Thrombocytopenic Purpura (TTP) definition, sx, dx, tx
PATHO: auto-ab vs. ADAMTS13 (vWF-cleaving protease) 🡪 unusual large vWF multimers 🡪 micro thrombosis of small vessels 🡪 thrombocytopenia (consumptive) & hemolytic anemia
Incidence:
*young adults 20-50yrs
*MC women
sx
PENTAD: “FAT RN”
*fever
*anemia: microangiopathic hemolytic anemia
*jaundice
*thrombocytopenia: bruising, purpura, bleeding
*renal failure/uremia
*neuro sxs: HA, CVA, AMS
dx
Thrombocytopenia
Hemolytic anemia:
*peripheral smear: ↑ reticulocytes, schistocytes (bite or fragmented cells)
*LFTs: ↑ indirect bilirubin, ↓ haptoglobin
Normal coagulation tests
tx
- plasmapheresis: removes Ab & adds ADAMTS13
- immunosuppression: steroids, cyclophosphamides
Hemolytic Uremic Syndrome (HUS) definition, sx, dx, tx
PATHO: exotoxins (shiga-like & shiga toxins) damages vascular endothelium, activating platelets 🡪 microthrombosis of small vessels 🡪 consumptive thrombocytopenia & hemolytic anemia
*ADAMTS13 normal
Incidence:
*predominantly seen in children w/ diarrhea prodrome: Enterohem. E coli O157:H7 (80%), Shigella, Salmonella
*adults: seen w/ HIV, SLE, & antiphospholipid syndrome
sx
TRIAD: “RAT”
*renal failure/uremia (predominant symptom)
*anemia: microangiopathic hemolytic anemia
*jaundice
*thrombocytopenia: bruising, purpura, bleeding
dx
Thrombocytopenia
Hemolytic anemia:
*peripheral smear: ↑ reticulocytes, schistocytes (bite or fragmented cells)
*LFTs: ↑ indirect bilirubin, ↓ haptoglobin
↑ BUN/creatinine
Normal coagulation tests
tx
- observation in most children (usually self-limited)
- plasmapheresis
- +/- FFP if severe
*NO ABX – may worsen the disease
Disseminated Intravascular Coagulation (DIC) definition, sx, dx, tx
PATHO: pathologic clotting cascade activation 🡪 widespread thrombi 🡪 consumption of platelets 🡪 diffuse bleeding
Incidence:
*MC in young or elderly
*MC gram negative species
*OB emergencies, malignancy, massive tissue trauma
sx
Diffuse hemorrhage: venipuncture sites, mouth, nose; extensive bruising
Thrombosis: renal failure, gangrene (as clots block circulation)
Pts usually acutely ill
dx
Hemolytic anemia:
*peripheral smear: ↑ reticulocytes, schistocytes (bite or fragmented cells)
*LFTs: ↑ indirect bilirubin, ↓ haptoglobin
*abnormal coagulation tests
↓ fibrinogen
↑ D-dimer, PT, & PTT
Severe thrombocytopenia
tx
Reversal of the underlying cause mainstay of tx
- +/- platelet transfusion (if <20,000)
- +/- FFP
- +/- heparin in select cases
Heparin Induced Thrombocytopenia (HIT) definition, sx, dx, tx
Acquired thrombocytopenia esp. within the first 5-10d of the initiation of heparin
Risk Factors:
*UFH > LMWF, surgical > medical, F > M
PATHO: autoantibody formation to the hapten of heparin + platelet factor 4 causes platelet activation & consumption, leading to thrombocytopenia & thrombosis
sx
Thrombocytopenia – bleeding
Thrombosis – venous thrombosis, gangrene, organ infarction, skin necrosis
dx
*thrombocytopenia
*timing of platelet drop (>50%)
*thrombosis
Gold standard: 14-C-serotonin release assay
tx
Immediate D/C of all heparin + initiation of non-heparin anticoagulants
*direct thrombin inhibitors (argatroban, lepirudin)
*fondaparinux
*DOAC (apixaban, edoxaban, rivaroxaban)
Myelodysplastic Syndrome definition, sx, dx, tx
Heterogenous preleukemic disorders characterized by abnormal differentiation of cells of the myeloid cell line (hypercellular bone marrow), resulting in ineffective hematopoiesis in the bone marrow (pancytopenia)
Risk Factors: >65yrs, radiation, chemo, benzene exposure, tobacco smoke, mercury or lead exposure
Sxs of pancytopenia: easy bruising, bleeding, frequent infections, fatigue
dx
CBC w/ peripheral smear:
*↓ number of one or more myeloid cell lines (platelets, neutrophils, RBCs)
*hyposegmented neutrophils, normocytic or macrocytic anemia
Bone marrow bx:
*dysplastic bone marrow is hallmark
-↑ myeloblasts but <20%
-ringed sideroblasts
-pseudo-Pelger-Huet cells (hyposegmented/granulated
neutrophils)
tx
Supportive
- intermittent blood/platelet transfusions
- EPO
Systemic:
- pyrimidine analogs (5-Azacitidine)
- lenalidomide
Allogenic stem cell transplant only effective cure
Multiple Myeloma definition, sx, dx, tx
*cancer associated w/ proliferation of a single clone of plasma cells, leading to increased production of ineffective monoclonal antibodies (esp. IgG & IgA)
MC primary bone malignancy in adults
Risk Factors: elderly >65, AA, men, benzene exposure
PATHO: plasma cells accumulate in the bone marrow, interrupting bone marrow’s normal cell production; protein accumulation causes kidney injury
sx
“BREAK”
Bone pain: MC!
*vertebral involvement MC, ribs
*osteolytic lesions, pathogenic osteopenic fractures
*spinal cord compression, radiculopathy
Recurrent infections
*d/t leukopenia & ineffective IgG production; hyperviscosity
Elevated calcium
*d/t osteoclast activating factor from plasma cells, leading to bone destruction
Anemia: fatigue, pallor, weakness, weight loss, HSM
Kidney injury: d/t light chain protein antibody deposition in kidneys
*increased BUN & creatinine
dx
Serum protein electrophoresis:
*monoclonal protein spike – IgG MC
Urine protein electrophoresis:
*Bence-Jones proteins (kappa/lambda light chains)
CBC: Rouleaux formation
*RBCs w/ a “stack of coins” appearance d/t ↑ plasma protein (increased ESR)
Skull x-ray: “punched out” lytic lesions
Bone marrow aspiration:
*plasmacytosis >10% - definitive diagnosis
tx
Autologous stem cell transplant most effective
Chemo, radiation, bisphosphonates
Hodgkin Lymphoma (HL) definition, sx, dx, tx
HL: malignant lymphoma typically of B-cell origin ▪︎⊕Hodgkin/Reed-Sternberg (HRS) cells: classic RS cells
Classical Hodgkin Lymphoma (cHL)
* Nodular sclerosis * Mixed cellularity * Lymphocyte rich/depleted
o Nodular lymphocyte predominant
A 3x ↑ risk in young adults with prior history of serologically
confirmed infectious mononucleosis
sx
“B” symptoms present in approx. 30% of cases.
o Fever > 38°C (100.4°F)
o Drenching night sweats
o Weight loss (>10% of body weight) * Generalized pruritus * Single LN group and spreads to contiguous areas
* Late disseminated * Pain in involved lymph nodes immediately after the ingestion of
alcohol
Diffuse/puffy swelling rather than a discrete mass may be apparent in the
supraclavicular, infraclavicular, or anterior chest wall regions
* ~70% cervical node involvement
dx
LABS: CBC, kidney/liver function (CMP), albumin, electrolytes, ESR, HIV testing
Imaging: CXR, PET-CT (staging)
Confirmatory ⇢ tissue BX: excisional/incisional peripheral lymph node biopsy preferred
» ⊕HRS cells (classic RS/variants)
Classic Reed-Sternberg cell:
▪︎at least 2 nucleoli in separate nuclear lobes
▪︎characteristic “owl’s eye” appearance
tx
Limited Stage (I & II): chemo + RT
▪︎MC used chemotherapy ⇢ ABVD
» Adriamycin (doxorubicin)
» bleomycin
» vinblastine
» dacarbazine
Advanced Stage (III & IV):
▪︎3 possible treatment options
➀ ABVD
➁ Stanford V
➂ BEACOPP (bleomycin, etoposide,
Adriamycin, cyclophosphamide,
oncovin, procarbazine, prednisone)
Refractory/relapse: high-dose chemo, autologous stem cell transplant
Non-Hodgkin Lymphoma (NHL) types
▪︎B-cell lymphomas MC (85%)
Indolent (slow growing)
➀ Follicular Lymphoma ⇢ MC low-grade lymphoma in adults
PATHO: t(14;18) ⇢ IGH/BCL2 fusion gene ⇢ overexpression of BCL2 (blocks apoptosis) causes prolonged cell survival
➁ Hairy Cell Leukemia (HCL) ⇢ MC in middle-aged men
PATHO: late, activated memory B-cell w/ a BRAF V600E mutation
➂ Small lymphocytic Lymphoma (SLL): identical to CLL
▪︎CLL ⇢ disease manifests primarily in the blood
➃ Marginal Zone Lymphomas (MZLs)
▪︎post-germinal center memory B cells w/ capacity to differentiate into marginal zone cells & plasma
Aggressive
➀ Diffuse Large B-cell (DLBCL) ⇢ MC NHL overall**
▪︎mutations: BCL6 (MC), TP53, BCL2; MYC overexpression
▪︎AIDS-defining malignancy, associated w/ EBV
➁ Mantle Cell Lymphoma (MCL) ⇢ nodal & non-nodal MCL
▪︎express cyclin D1, BCL2, & CD5⊕; CD23⊖
PATHO: t(11;14) ⇢ translocation of CCND1 w/ Ig genes
➂ Burkitt Lymphoma (BL) ⇢ MC in children
PATHO: translocation/deregulation of MYC gene
Non-Hodgkin Lymphoma sx, dx, tx
sx
S/SXS: MC ⇢ painless lymphadenopathy +/- noncontiguous LNs
▪︎Indolent: insidious, slowly growing or waxing/waning LAD, obstruction
▪︎Aggressive: rapidly growing mass, ⊕B SXS
dx
LABS: anemia MC +/- lymphocytosis, ⇡ LDH
Imaging: CXR, PET-CT (staging)
Confirmatory ⇢ tissue BX: excisional/incisional peripheral lymph node biopsy of unfixed tissue
▪︎B-cell lymphomas CD19⊕, CD20⊕, CD79a⊕
▪︎T-cell lymphomas CD3⊕
Microscopy ⇢ Burkitt lymphoma: “starry sky”
▪︎benign histiocytes (“stars”) w/ abundant clear
cytoplasm dispersed throughout neoplastic tumor
cells (“sky”
tx
Indolent: highly treatable, but not reliably curable
▪︎asymptomatic ⇢ monitor
▪︎regional radiation therapy
Aggressive: responsive to chemo & often curable ⇢ R-CHOP
» rituximab
» cyclophosphamide
» hydroxydaunorubicin (doxorubicin)
» oncovin (vincristine)
» prednisone
CNS prophylaxis ⇢ MTX
Hairy Cell Leukemia:
▪︎cladribine or pentostatin
Acute Leukemias (AML & ALL)
S/SXS ⇢ sudden symptom onset & rapid progression
▪︎anemia: fatigue, pallor, weakness
▪︎thrombocytopenia: epistaxis, bleeding
types
Acute Myelogenous Leukemia (AML): ▪︎MC acute leukemia in adults, peak incidence 65yo AML S/SXS:
AML w/ minimal granulocyte maturation
▪︎skin infiltration ⇢ leukemia cutis (most often involves the face)
M2 AML w/ granulocyte maturation » papules/nodules, may be erythematous, violaceous, gray-blue
M3 Acute promyelocytic leukemia (APL)
▪︎M5 (monocytic): gingival infiltration ⇢ gingival hyperplasia
» t(15;17), ⊕Auer rods, MPO⊕ ▪︎bone pain & CNS involvement uncommon*
Acute Lymphocytic Leukemia (ALL): ▪︎MC childhood malignancy, peak incidence 2-5yo, ♂︎ > ♀︎
B-ALL B-lymphoblastic leukemia (MC, 80-85%) ALL S/SXS:
» CD19⊕, CD22⊕, CD79a⊕ ▪︎fever, night sweats, unexplained weight loss, painless LAD
T-ALL T-lymphoblastic leukemia (CD3⊕)
▪︎bone pain (limping/refusal to bear weight), hepatosplenomegaly
» mediastinal/thymic infiltration
▪︎CNS/meningeal infiltration (common): cranial nerve palsies, HA,
Acute Leukemias (AML & ALL) dx and tx
LABS: thrombocytopenia, anemia
Tumor lysis syndrome: ⇡ phosphate, ⇡ K, ⇣ calcium,
⇡ uric acid, ⇡ LDH
DX: bone marrow aspiration/BX, peripheral smear
AML DX: >20% myeloblasts, ⊕Auer rods
▪︎cytogenetic abnormalities:
» t(8;21), inv(16), t(16;16), trisomy 8
▪︎immunophenotype:
» MPO⊕, TdT⊖, PAS⊖
» CD13⊕, CD33⊕, CD34⊕, CD117⊕
▪︎Acute promyelocytic leukemia (APL)
» t(15;17)/PML-RARA
ALL DX: >20% lymphoblasts, ⊘Auer rods
▪︎cytogenetic abnormalities:
» childhood ⇢ t(12;21), high hyperdiploidy
» adults ⇢ t(9;22)/BCR-ABL1 (Philadelphia
chromosome, Ph⊕)
▪︎immunophenotype: MPO⊖, TdT⊕, PAS⊕
tx
Remission:
▪︎<5% blast cells in bone marrow
▪︎ANC >1000/mcL
AML TX:
▪︎cytarabine + idarubicin
▪︎APL ⇢ all-trans retinoic acid (ATRA)
» matures blasts cells
ALL TX:
▪︎doxorubicin, cyclophosphamide
▪︎vincristine, MTX, prednisone
▪︎Ph⊕ ⇢ add TKI (e.g., imatinib)
CNS prophylaxis: intrathecal MTX, cytarabine, & hydrocortisone
Chronic Myelogenous Leukemia (CML) definition, sx, dx, tx
CML: proliferation of mature myeloid cells ▪︎peak incidence 50-60yo, ♂︎ > ♀︎
PATHO: t(9;22) causes fusion between ABL1 gene (chromosome 9) & BCR gene (chromosome 22) & gives rise to the Philadelphia chromosome (Ph) which inhibits apoptosis & ⇡ miotic rate, resulting in uncontrolled proliferation of mature myeloid cells
S/SXS ⇢ 3 phases
➀ Chronic Phase (<10% blasts): MC clinical presentation at diagnosis (85% of patients)
▪︎often asymptomatic early on w/ insidious onset of nonspecific symptoms
▪︎fatigue, weight loss, excessive sweating, bleeding episodes d/t platelet dysfunction
▪︎abdominal fullness, splenomegaly w/ LUQ pain, gouty arthritis (overproduction of uric acid)
➁ Accelerated Phase (10-19% blasts):
▪︎ worsening splenomegaly, worsening cytopenias (anemia, infection/fever)
▪︎genetic instability (e.g., additional chromosomal abnormalities)
➂ Blast Phase/Crisis (≥20% blasts):
▪︎manifests as an acute leukemia, resembles AML (e.g., night sweats, weight loss, bone pain, bleeding)
▪︎leukostasis (hyperleukocytosis): dyspnea, visual changes, HA, tinnitus, priapism, fever
dx
Peripheral smear:
▪︎leukocytosis, median white count ~100,000/µL
▪︎differentiation ⇢ all cells of neutrophilic series
» myeloblasts, myelocytes, mature neutrophils
▪︎LOW leukocyte alkaline phosphatase (LAP)
» excludes leukemoid reaction
▪︎basophilia, eosinophilia
▪︎thrombocytosis (platelet count >600,000/µL)
Bone marrow BX: granulocytic hyperplasia
Confirmatory ⇢ cytogenetic testing:
» ⊕Ph chromosome &/or BCR-ABL1 fusion gene
TX: tyrosine kinase inhibitors (TKIs)
▪︎imatinib, dasatinib, nilotinib
Leukocytosis ⇢ hydroxyurea
Allogenic stem cell transplant
▪︎TKI-resistant CML, advanced phases
Chronic Lymphocytic Leukemia (CLL) definition, sx, dx, tx
CLL: proliferative mature B-cell malignancy
S/SXS: asymptomatic lymphocytosis MC (B SXS in 5-10%), fatigue
▪︎MC leukemia in adults, median onset 70-72yo
▪︎painless LAD (MC) ⇢ cervical, supraclavicular, axillary
▪︎RF: men, ⇡ age ▪︎splenomegaly (2nd MC), usually painless & nontender to palpation
▪︎leukemia cutis (rare), neutropenia, anemia, thrombocytopenia
LABS:
▪︎lymphocytosis >5,000/µL (threshold)
» often as high as 100,000/µL
▪︎hypogammaglobulinemia common
dx
Peripheral smear:
▪︎lymphocytosis (small mature lymphocytes)
▪︎⊕smudge cells ⇢ lymphocytes are mechanically
disrupted & smear out when being spread on slide
Immunophenotype:
▪︎CD5⊕, CD19⊕, CD20⊕ (dim), CD23⊕, CD10⊖
Markers of good prognosis:
▪︎CD38⊖, ZAP-70⊖
Markers of poor prognosis:
▪︎CD38⊕, ZAP-70⊕, del(11q)⊕, del(17p)⊕
tx
Low-risk (Rai 0, Binet A):
▪︎observation w/ regular f/u
Intermediate/high-risk, symptomatic or progressive ⇢ chemotherapy
▪︎ibrutinib, rituximab, alemtuzumab
▪︎fludarabine, cyclophosphamide
Curative ⇢ allogenic stem cell transplant (not routinely performed)
