Step 1 - HemeOnc 2

denniskwinn's version from 2015-04-25 16:02


Question Answer
Warm agglutinin anemia (2)(extrinsic hemolytic normocytic)
2. Chronic anemia seen in SLE, CLL or with certain drugs (alpha-methyldopa)
Cold agglutinin anemia (3)(extrinsic hemolytic normocytic)
1. IgM
2. Acute anemia triggered by cold
3. Seen with mycoplasma pneumoniae or infectious mononucleosis
Erythroblastosis fetalisseen in newborns due to Rh or other blood antigen incompatibility - - mother’s antibodies attack fetal RBCs
Direct Coombs’ test anti-Ig antibody added to patient’s RBCs agglutinate if RBCs are coated with Ig
Indirect Coomb’s test normal RBCs added to patient’s serum agglutinate if serum has anti-RBC surface Ig
Microangiopathic anemia (4)1. RBCs are damaged when passing through obstructed or narrowed vessel lumina
2. Seen in DIC, TTP-HUS, SLE and malignant HTN
3. Schistocytes (helmet cells) are seen on blood smear due to mechanical destruction of RBCs.
4. Prosthetic heart valves may cause
Infections that cause extrinsic hemolytic normocytic ↑ destruction of RBCs (malaria, babesia)
Lab values in Iron deficiency anemiaserum iron (primary), ⇡ transferrin/TIBC , ⇣ ferritin, ⇣⇣ % saturation
Lab values in chronic disease anemia⇣ serum iron, ⇣transferrin/TIBC, ⇡Ferritin (primary)
(body tries to keep iron from enemy)
Lab values in hemochromatosisserum iron (primary), ⇣ transferrin/TIBC, ⇡ Ferritin, ⇡⇡ % saturation
Lab values in pregnancy/OCP use⇡Transferrin/TIBC (primary)= bc estrogen , ⇣% saturation, serum iron nomal
Ferritin primary iron storage protein of body
Transferrin transports iron in blood
Porphyriasconditions of defective heme synthesis that lead to the accumulation of heme precursors.


Question Answer
Lead poisoning (2)1. Affects Ferrochelatase and ALA dehydratase
2. Accumulates protoporphyrin (blood)
Lead poisoning presenting symptoms (3)1. Microcytic anemia, GI and kidney disease
2. Children: mental deterioration (after exposure to lead paint)
3. Adults: headache, memory loss, demyelination
Lead poisoning acronymLEAD:
L= lead lines on gingivae and epiphyses of long bones on x-ray (burton lines)
E= encephalopathy and erythrocyte basophilic stippling
A=abdominal colic and sideroblastic anemia
D=drops (wrist and foot)
Lead poisoning tx1. EDTA first line of treatment
2. Succimer for kids
Acute intermittent porphyria1. Affects porphobilinogen deaminase (aka uroporphyrinogen-1-synthase)
2. Accumulation of Porphobilinogen, d-ALA, uroporphyrin (urine)
Acute intermittent porphyria symptoms (5)1. Painful abdomen
2. Pink urine
3. Polyneuropathy
4. Psychological disturbance
5. Precipitated by drugs
Acute intermittent porphyria treatment1. Glucose and heme
- these inhibit ALA synthase(rate-limiting step in heme synthesis)
[treatment for?]
Porphyria cutanea tarda1. Missing uroporphyrinogen decarboxylase
2. Accumulates uroporphyrin (tea-colored urine).
3. Presents with blistering cutaneous photosensitivity.
-MC porphyria.
Heme synthesis (8)1. Glycine+Succinyl CoA⇢delta-aminolevulinic acid synthase (rate limiting, B6 cofactor) ⇢ 2. Delta aminolevulinic acid (delta aminolevulinic acid dehydratase) ⇢ 3. Porphobilinogen⇢(porphobilinogen deaminase)⇢4. Hydroxymethylbilane⇢5.Uroporphyrinogen III ⇢ (Uroporphyrinogen decarboxylase)⇢ 6. Corproporphyrinogen III ⇢ 7. Protoporphyrin ⇢ (Ferrochelatase) ⇢ 8. Heme
Ferrochelatase insufficiency1. happens because of Lead poisoning
2. Accumulates protoporphyrin
Uroporphyrinogen decarboxylase insufficiency1. Called Porphyria cutanea tarda
2. Accumulates uroporphyrin (tea-colored urine).
3. Presents with blistering cutaneous photosensitivity. MC porphyria.
Porphobilinogen deaminase deficiency (4)1. Acute intermittent porphyria
2. Accumulation of Porphobilinogen, d-ALA, uroporphyrin (urine)
3. Presents with painful abdomen, Pink [FA 2011 says "Red wine-colored"] urine, Polyneuropathy, Psychological disturbances
4. Precipitated by drugs [deficiency in?]
Delta aminolevulinic acid dehydratase deficiency1. Happens because of lead poisoning
2. Accumulated D-ala (But in blood only protophyrin will be acum)
Delta-ALA Syn. deficiency (6)1. Sideroblastic anemia
2. X-linked
3. Tx w/pyridoxine (B6) therapy
4. Reversible etiologies from alcohol and lead.
5. ↑ Iron, normal TIBC, ↑Ferritin
6. smear shows ringed sideroblasts (with iron laden mitochondria) [deficiency in what?]
Platelet abnormalities⇢ microhemorrhage: mucous membrane bleeding, epistaxis, petechiae, purpura, ⇡ bleeding time, possible ⇣ platelet count (PC)
Bernard-Soulier disease(platelet disorder)
1. Defect in platelet plug formation
2. ⇣Gp1b = defect in platelet to collagen adhesion
3. ⇣PC, ⇡BT
Glanzmann’s thrombasthenia(platelet disorder)
1. Defect in platelet plug formation
2. ⇣GpIIb/IIIa = defect platelet to platelet aggregation
3. Blood smear shows no platelet clumping
4. ⇡ BT
Idiopathic thrombocytopenic purpura (ITP)(platelet disorder)
1.⇣ platelet survival
2. Defect in anti-GpIIb/IIIa antibodies = peripheral platelet destruction
3. ⇡ megakaryocytes(trying to compensate)
4. ⇣PC, ⇡BT
Thrombitic thrombocytic purpura (TTP)(platelet disorder)
1. ⇣ platelet survival
2. Deficiency in ADAMTS⇣ degradation of vWF multimer
3. ⇣ PC, ⇡BT
4. Pentadof neuro and renal sx, fever, thrombocytopenia and microangiopathic hemolytic anemia


Question Answer
PT testsfunction of factors 1,2,5,7,10(extrinsic pathway) - a defect leads to ⇡ what?
PTT testsfunction of all factors except 7 and 13 (intrinsic pathway) - defect =⇡ [in what test]
Hemophilia A or B (2)(coagulation disorder)
1. Intrinsic pathway defect, A=deficiency in 8, B = deficiency in 9
2. Macrohemorrhage in hemophilia - hemarthroses (bleeding into joints), easy bruising, ⇡ PTT
Vitamin K deficiency(coagulation disorder)
1. General defect, ⇣ synthesis of factors II, VII, IX, X, Protein C and S. 2. ⇡ PT and PTT
Von Willebrand’s disesase(mixed plat/coag disorder)
1. Intrinsic pathway defect and platelet plug formation defect (vWF protects factor 8 and helps in platelet to collagen adhesion.
2. Mild, but MC inherited bleeding disorder (autosomal dominant)
3. ⇡BT and norm or⇡PTT
DIC(mixed plat/coag disorder)
1. Widespread activation of clotting leads to deficiency in clotting factors. 2. Labs show schistocytes, ⇡ fibrin split products (d-dimers), ⇣ fibrinogen and factors 5 and 8
DIC causes (7)1. Sepsis (gram -)
2. Trauma
3. Obstetric complications
4. Acute Pancreatitis
5. Malignancy
6. Nephrotic syndrome
7. Transfusion
(STOP Making New Thrombi)
Factor V Leiden diseaseProduction of mutant factor V that cannot be degraded by protein C. -MC cause of inherited hypercoagulability
Prothrombin gene mutationMutation in 3' untranslated region associated w/ venous clots
ATIII deficiencyInherited deficiency; reduced ⇡ in PTT after administration of heparin
Protein C or S deficiency⇣ ability to inactivate factors 5 and 8. ⇡ risk of thrombotic skin necrosis following administration of warfarin


Question Answer
Leukemia vs LymphomaLeukemia =lymphoid neoplasms with widespread involvement of bone marrow, tumor cells are usually found in peripheral blood.

Lymphoma= discrete tumor masses arising form the lymph nodes
Hodgkin’s Lymphoma (6)1. RS cells
2. Single group of nodes, extranodal rare, contiguous spread
3. Constitutional symptoms (fever, night sweats, weight loss)
4. Nontender mediastinal lymphadenopathy
5. 50% cases assoc w/ EBV (bimodal distribution).
6. Good progonosis with ⇡lymphocytes and ⇣RS
Hodgkins symptoms1. "B" symptoms=Constitutional symptoms ( mild fever, night sweats, weight loss)
2. Nontender mediastinal lymphadenopathy
Non-Hodgkins lymphoma1. Multiple, peripheral nodes: extranodal involvement common -noncontiguous spread.
2. May be associated w/ HIV
3. Majority involve B-cells
4. Fewer constitutional signs/symptoms
5. Peak incidence for certain subtypes at 20-40 yrs
Reed-Sternberg cells1. Binucleate/bilobed w/2 halves as mirror images (owl’s eyes).
2. Assoc w/ Hodgkin’s
3. Cd30+, CD15+B cell origin.
Nodular sclerosing hodgkins1. Most common: collagen banding; lacunar cells; FEMALES - primarily young adults
2. RS +
3. Lymphocyte +++
4. Excellent prognosis
Mixed cellularity hodgkins (4)1. Second most common
2. Numerous RS cells++++
3. Lymphocyte +++
4. Intermediate prognosis
Lymphocyte predominant Hodgkins (4)1. 3rd most common
2. Very high lymphocyte to RS cell ratio
3. Excellent prognosis
4. Happens in <35 yr old males
Burkitt’s Lymphoma(Neoplasm of mature B-cells)
1. Starry sky appearance (sheets of lymphocytes w/ interspersed macrophages)
2. T(8:14) c-myc gene moves next to heavy chain Iggene
3. Assoc w/EBV.
4. Jaw lesion= in endemic form in africa
pelvis or abdomen= in sporadic form.
5. Adolescents or young adults
Diffuse large B-cell lymphoma (3)(Neoplasm of mature B-cells)
1. Most common adult NHL
2. May be mature T-cell in origin(20%).
3. Usually older adults, but 20% in children
Mantle cell lymphoma(Neoplasm of mature B-cells)
1. T (11:14)
2. Poor prognosis
3. Cd5+
4. Happens in older males
Follicular lymphoma (3)(Neoplasm of mature B-cells)
1. T (14:18) bcl2 expression (inhibits apoptosis)
2. Difficult to cure with indolent course.
3. Occurs in adults
Adult T-cell lymphoma (4)(neoplastm of mature T-cells)
1. Caused by HTLV-1
2. Presents with cutaneous lesions
3. Occurs in adults, especially in Japan, West Africa and Caribbean.
4. Aggressive
Mycosis fungoides/Sezary syndrome(neoplasm of mature T-cells)
1. Presents with cutaneous patches/nodules
2. Indolent CD4+
Multiple myeloma (8)1. Monoclonal plasma cell neoplasm - large amounts of IgA, IgG*.
2. CRAB - hyperCalcemia (from destructive bone lesions), Renal insuff, Anemia, Bone Pain/Back Pain
3. Arises in marrow
4. MC primary tumor of bone in elderly
5. ⇡ susceptibly to infection and anemia
6. Assoc w/primary amyloidosis
7. Punched out lytic lesions on x-ray 8. If asx = monocloncal gammopathy of undetermined significance (MGUS)
Multiple myeloma characteristics1. M protein spike on serum protein electrophoresis
2. Lytic bone lseions
3. Bence jones proteins in urine (Ig light chains)
4. Hypercalcemia
5. Bone/back pain
6. Anemia
Multiple myeloma blood smearRBCs stacked like poker chips (rouleaux formation)


Question Answer
LeukemiasUnregulated growth of leukocytes in bone marrow changes circulating leukocyte number and ⇢ marrow failure ⇢ anemia, infections and hemorrhage.
-Leukemic cell infiltrates in liver, spleen and LN are possible
ALL (7)1. Occurs in children
2. Present w/BM involvement or mediastinal mass in adolescent males
3. BM replaced by ⇡ ⇡ ⇡ lymphoblasts
4. TdT+ (preT/B) CALLA+
5. Most responsive to therapy
6. May spread to CNS and testes
7. T(12;21) = better prognosis
SLL/CLL (5)1. Occurs in older adults (>60y)
2. Asx
3. Smudge cells in smear
4. Warm antibody hemolytic anemia
5. CLL has ⇡ peripheral blood lymphocytes compared to SLL
Hairy cell leukemia (4)1. Occurs in elderly
2. Mature B-cell tumor
3. Cells have filamentous hairlike projections.
4. Stains TRAP + (tartrate-resistant acid phosphatase)
AML (3)1. In adults
2. Auer rods
3. ⇡ ⇡ ⇡ circulating myeloblasts on peripheral smear
4. M3 subtype response to all-trans retinoic acid treament (vit A) ,induces differentiation of myeloblasts
CML (5)1. Bcr-abl t(9;22) = philadelphia chromosome)
2. ⇡ nphils, metamyelocytes, basophils. Splenomegaly
3. May accelerate and become AML or ALL.
4. Very low leukocyte alkaline phosphatase.
5. Responds to imatinib (small molecule inhibitor against bcr-abl tyrosine kinase)
ALL approx age<15y
AML approx agemedian 60y
CML approx age30-60 y
CLL approx age>60y
Acute leukemias1. Blasts predominate
2. In children or elderly
3. Short and drastic course
Chronic leukemia1. More mature cells
2.Midlife age range
3. Longer, less devistating course
Leukemoid rxn⇡ WBC count w/left shift and ⇡ leukocyte alkaline phosphatase. Normal physiologic response to stress or infection
Auer bodiesPeroxidase+ cytoplasmic inclusion in granulocytes and myeloblasts. Seen in M3 AML
- treatment of M3 AML can release these and lead to DIC


Question Answer
T(9:22)CML - philadelphia chromosome - bcr-abl hybrid
T(8:14)Burkitt’s lymphoma (c-myc activation)
T (14:18)Folliclular lymphomas (bcl-2 activation)
T(15:17)M3 type of AML= responsive to all-trans retinoic acid(Vit A)
[chromosomal translocation]
T(11:22)Ewings sarcoma [translocation]
T(11:14)Mantle cell lymphoma [translocation]
Langerhans cell hisiocytosis (histiocytosis X) (4)1. Prolif disorder of dendritic cells from monocytic lineage.
2. S-100 and CD1a+
3. Birbeck granules on EM (Tennis rackets)
Polychythemia veraChronic myeloproliferative disorder.
1. ⇡RBCs, ⇡WBCs,⇡Plats
2. Has Jak2 mutations
3. Abnormal clone of hematopoietic stem cells that are increasingly sensitive to growth factors
Essential thrombocytosisChronic myeloproliferative disorder
1. ⇡ Plats
2. 30-50% Jak2 mutations
3. Only megakaryocytes are increasingly sensitive to growth factors
MyelofibrosisChronic myeloproliferative disorder
1.⇣ RBCs, variable effects on WBCs and plats
2. 30-50% Jak2 mutation - Fibrotic obliteration of bone marrow
3.Tear drop cells