Heme Diagnosis

Question 1

immune thrombocytoenic purpura

Answer 1

CBC and smear- normal

Bone marrow aspiration - megakaryocytes

Question 2

heparin induced thrombocytopenia

Answer 2

Thrombocytopenia, thrombosis, and timing of platelet drop.

HIT antibody testing.

Question 3

disseminated intravascular coagulation (DIC)

Answer 3

Increased thrombin formation –> decreased fibrinogen.
Bleeding –> increased pt, ptt, inr; thrombocytopenia.
Increased fibrinolysis –> increased d-dimer.
Peripheral smear –> fragment rbcs, schistocytes.

Question 4

hemophilia a and b

Answer 4

PTT prolonged.
Normal PT.
Platelets normal.

Question 5

von willebrand disease

Answer 5

aPTT (to check factor VIII activity) - usually prolonged
vWF antigen test - decreased vWF antigen or activity
vWF activity (Ristocetin cofactor assay) - in VWD, no platelet aggregation will occur
Factor VIII activity - may be decreased

Question 6

factor v leiden mutation

Answer 6

activated protein c resistance assay and if + confirm with dna testing.
Nml pt and ptt.

Question 7

protein c or s deficiency

Answer 7

functional assay of protein c and s

plasma protein and c and s antigen levels

Question 8

hemolytic anemias

Answer 8

peripheral smear: spherocytes, schistocytes, increased reticulocytes

Question 9

sickle cell trait

Answer 9

electrophoresis: Presence of hemogloblin A and Hemoglobin S

blood counts and peripheral smear: normal

Question 10

sickle cell disease

Answer 10

Counts -> decreased hemoglobin and/or hematocrit when in crisis.
Peripheral smear -> sickled cells, target cells, Howell-Jolly bodies (indicates functional asplenia)
Electrophoresis -> HbS present, little to no HbA, increased HbF
DNA analysis is the definitive test for diagnosis

Question 11

alpha thalassemia- aka hemoglobin h disease

Answer 11

RBC count = increased
RBC shape = microcytic
RBC color = hypochromic
MCHC = low
RBC shape = Heinz bodies, schistocytes, target cells, tear drop cells
Reticulocytes = increased
Electrophoresis = presence of beta chain tetramer (HbH)
Iron = normal or increased serum iron due to iron overload

Question 12

beta thalassemia major (Cooley’s Anemia)

Answer 12

Skull x-rays
Frontal bossing
“Hair on end” appearance of the skull

Blood
RBC count = normal or increased
RBC shape = microcytic
RBC color = hypochromic
MCHC = low
RBC shape = target cells, tear drop cells
Reticulocytes = decreased
Electrophoresis = Increased HgbF and HgbA2, little to NO HgbA
Iron = normal or increased serum iron due to iron overload

Question 13

G6PD deficiency

Answer 13

Normocytic hemolytic anemia during crises.
Peripheral smear = during episodes, schistocytes (or bite cells), Heinz bodies is hallmark
Increased reticulocytes, increased bilirubin, decreased haptoglobin.
Enzyme assay for G6PD
DNA testing

Question 14

Hereditary spherocytosis (HS)

Answer 14

Blood counts = microcytic, hyperchromic (increased MCHC)
Smear = spherocytes, possible schistocytes, increased reticulocytes
EMA Binding = preferred test (most accurate)-Flow cytometric analysis of eosin-5’-maleimide-labeled intact red blood cells & acidified glycerol lysis test
Osmotic fragility test - RBCs placed in a relatively hypotonic solution rupture easily due to the increased permeability of the RBC membrane
Negative Coombs testing

Question 15

autoimmune hemolytic anemia

Answer 15

Decreased Hgb
Increased reticulocytes
Increased MCHC
Peripheral smear = polychromasia, microspherocytes
POSITIVE DIRECT COOMB test

Question 16

thrombotic thrombocytopenia purpura (TTP)

Answer 16

Thrombocytopenia with normal coagulation studies
Peripheral smear = hemolysis -> schistocytes, bite or fragmented cells, reticulocytes
Increased LDH & bilirubin
Decreased haptoglobin (protein that the body uses to clear free hemoglobin from circulation)
Decreased ADAMTS13 levels
Coombs negative

Question 17

Hemolytic uremic syndrome (HUS)

Answer 17

Labs the same as in TTP
Thrombocytopenia with normal coagulation studies
Peripheral smear = hemolysis -> schistocytes, bite or fragmented cells, reticulocytes
Increased LDH & bilirubin
Decreased haptoglobin
Increased BUN & creatinine
Coombs negative

Question 18

Paroxysmal Nocturnal Hemoglobinuria

Answer 18

Hemoglobinuria
Increased reticulocytes
Increased bilirubin
Flow cytometry to look for CD55-CD59-deficient RBCs
Coombs negative

Question 19

iron deficiency anemia physical exam

Answer 19

Koilonychia (nail spooning)
Angular cheilitis
Tachycardia
Glossitis
Pallor

Question 20

iron deficiency anemia

Answer 20

Counts = microcytic (low MCV), hypochromic (low heme)
Smear = decreased reticulocytes

Iron Studies: 
Ferritin = decreased (pathognomonic)
TIBC = increased
Transferrin saturation = < 20-15%
Serum Iron = decreased

Question 21

lead poisoning

Answer 21

Serum lead levels: > 10 mcg/dL (venous sampling more accurate than finger stick)
Peripheral smear: microcytic, hypochromic anemia with basophilic stippling
Bone marrow: ringed sideroblasts

Iron Studies:
Serum iron: normal or increased
TIBC: decreased

Question 22

anemia of chronic disease

Answer 22

Counts = Hgb around 9-10 mg/dL; RDW = normal to increased
Smear = normocytic, normochromic, decreased reticulocytes -> will eventually become microcytic

Iron Studies:  
Ferritin normal to increased
TIBC decreased
Serum iron decreased 
Hepcidin increased

Question 23

aplastic anemia

Answer 23

CBC = at least two cytopenias
Smear = few or absent reticulocytes
Bone marrow biopsy = most accurate test -> hypocellular, fatty bone marrow

Question 24

b12 deficiency

Answer 24

Counts = MCV increased (macrocytic)
Smear =
Megaloblastic anemia = hypersegmented neutrophils, macro-ovalocytes, mild leukopenia and/or thrombocytopenia
Reticulocytes decreased

Serum B12 decreased
Homocysteine increased
LDH increased
Methylmalonic acid increased (differentiates it from folate deficiency)

Question 25

folate deficiency

Answer 25

``` Counts = MCV increased (macrocytic) Smear = megaloblastic anemia Reticulocytes = decreased Serum folate = decreased Homocysteine = increased Methylmalonic acid = normal (B12 deficiency -> increased) ```

Question 26

hereditary hemochromatosis

Answer 26

Iron studies: Serum iron, ferritin & transferrin saturation = increased TIBC normal or decreased Genetic testing for HFE gene Liver biopsy = most accurate test -> increased hemosiderin

Question 27

polycythemia vera (primary erythrocytosis) PE

Answer 27

Hepatosplenomegaly Facial plethora (flushed face) Engorged retinal veins

Question 28

polycythemia vera (primary erythrocytosis)

Answer 28

All three major indicators OR two major and 1 minor: Major Increased RBC mass (increased Hgb & Hct [54% men; 51% women]). Bone marrow biopsy with hypercellularity (extra erythroid, granulocytic & megakaryocyte cells). JAK2 mutation. Minor Decreased serum erythropoietin levels. Increased leukocyte alkaline phosphatase. Increased granulocytic WBCs, platelets or B12. Iron deficiency.

Question 29

myelodysplastic syndrome

Answer 29

CBC with peripheral smear = decrease in one or more myeloid cell lines (platelets, neutrophils or RBCs); hypo-segmented neutrophils, normocytic or macrocytic anemia Bone marrow biopsy = Normal or hypocellular (20% associated with hypocellularity) Dysplastic bone marrow is the HALLMARK - increased myeloblasts but < 20%, ringed sideroblasts, pseudo Pelger-Huet cells (hypo-segmented and hypo-granulated neutrophils)

Question 30

acute myeloid leukemia (aml)

Answer 30

GOLD STANDARD = bone marrow biopsy -> AUER rods and >20% myeloblasts BEST INITIAL TEST = CBC with peripheral smear -> normocytic, normochromic anemia with normal or decreased reticulocyte count, thrombocytopenia and possible circulating myeloblasts. Immunophenotyping/FISH analysis = most accurate test -> myeloperoxidase positive

Question 31

chronic myelogenous leukemia

Answer 31

CBC with peripheral smear = leukocytosis with granulocytic cells (neutrophilia, basophilia, eosinophilia). Leukocyte alkaline phosphatase score = decreased Bone marrow biopsy = granulocytic hyperplasia: Chronic -> < 5% blasts Accelerated = 5-30% blasts Acute blast crisis = > 20% blasts Immunophenotyping/FISH analysis = Philadelphia chromosome

Question 32

acute lymphocytic leukemia (all) PE

Answer 32

Hepatomegaly or splenomegaly most common finding, which can manifest as anorexia, weight loss, abdominal distention or abdominal pain. Lymphadenopathy

Question 33

acute lymphocytic leukemia (all)

Answer 33

CBC and peripheral smear = WBCs 5000-100,000, anemia, thrombocytopenia Bone marrow aspiration = hypercellular with >20% blasts (definitive diagnosis)

Question 34

chronic lymphocytic leukemia (cll) PE

Answer 34

``` Lymphadenopathy = Most common finding (cervical, supraclavicular axillary); LN are usually firm, round, nontender and freely mobile. Splenomegaly = painless and nontender Hepatomegaly Skin lesions (leukemia cutis) ```

Question 35

chronic lymphocytic leukemia (cll)

Answer 35

CBC with peripheral smear = absolute lymphocytes > 5,000/microL; small, well-differentiated normal-appearing lymphocytes with scattered smudge cells (lab artifact when the fragile B cells become crushed by the cover slip during slide prep); neutropenia Hypogammaglobulinemia -> increased incidence of autoimmune hemolytic anemia; may have evidence of ITP. Immunophenotypic analysis = expression of B-cell associated antigens (CD19, CD 20, CD 23) and B-cell maturity (CD5). Bone marrow aspiration not needed

Question 36

multiple myeloma

Answer 36

Serum protein electrophoresis = monoclonal protein spike = IgG most common (60%) Urine protein electrophoresis = Bence-Jones proteins CBC and peripheral smear = ROULEAUX formations; increased ESR Skull radiographs = “punched out” lytic lesions Bone marrow aspiration= plasmacytosis > 10% = definitive diagnosis

Question 37

hodgkin lymphoma

Answer 37

Excisional whole lymph node biopsy = Reed Sternberg cell pathognomonic (cells with “owl eye appearance”). Imaging (PET/CT scan) for staging.

Question 38

non hodgkin lymphoma

Answer 38

Lymph node and/or tissue biopsy | Staging via PET/CT scan

Question 39

labs for tumor lysis syndrome

Answer 39

Hyperphosphatemia, hypocalcemia, hyperuricemia, hyperkalemia and acute kidney injury