Hematology

Front 1

What's the lifespan of a platelet?

Back 1

8-10 days

Front 2

What are in platelet dense granules? and alpha granules?

Back 2

Dense granules: ADP, calcium, 5-HT
Alpha granules: vWF, fibrinogen, factors V and VIII, plasminogen, plasminogen activator inhibitor

Front 3

What are some causes of eosinophilia?

Back 3

NAACP:
Neoplastic
Asthma
Allergic processes
Collagen vascular diseases
Parasites (invasive)

Front 4

What disease are hypersegmented PMNs typical of?

Back 4

Megaloblastic anemia (vit B12 or folate deficiency)

Front 5

What are in neutrophil granules?

Back 5

Hydrolytic enzymes
Lysozyme
Myeloperoxidase (responsible for green color in pus/mucus)
Lactoferrin (antimicrobial activity)

Front 6

CD3, CD4, CD8, CD19, CD20... what cells are they in?

Back 6

CD3- all T cells
CD4- Th cells
CD8- Tc cells
CD19- B cells & follicular dendritic cells
CD20- all B cells (but not on pro-B cells and plasma cells)

Front 7

What drugs block the ADP receptor on platelets, and what does this do?

Back 7

Clopidogrel and ticlopidine (more side effects)
- ADP binding to platelets causes expression of Gp-IIb/IIIa on platelet surface, which can then bind fibrinogen --> block of ADP binding inhibits platelet aggregation

Front 8

What is Bernard-Soulier syndrome?

Back 8

Deficiency of Gp-Ib (mediates binding of platelets to vWF at high shear stress) --> bleeding

Front 9

What is Glanzmann's thrombasthenia?

Back 9

Deficiency of Gp-IIb/IIIa (on platelets; binds fibrinogen) --> bleeding

Front 10

How does warfarin work?

Back 10

Inhibits epoxide reductase, which is needed to reduce (activate) vitamin K to serve as a cofactor for factor synthesis (II, VII, IX, X, proteins C & S)

Front 11

What does protein C do?

Back 11

It's activated by protein S + thrombomodulin --> activated protein C cleaves and inactivates factors Va and VIIIa

Front 12

When might you see acanthocytes?

Back 12

Liver disease, abetalipoproteinemia
- Acanthocytes = spur cells

Front 13

When might you see basophilic stippling of RBC?

Back 13

TAIL: Thalassemias, Anemia of chronic disease, Iron deficiency, and Lead poisoning
"Baste" (Basophilic Stippling) the ox TAIL

Front 14

When do you see bite cells?

Back 14

G6PD deficiency

Front 15

When do you see macro-ovalocytes?

Back 15

Megaloblastic anemia (also would see hypersegmented PMNs), marrow failure

Front 16

When do you see ringed sideroblasts?

Back 16

Sideroblastic anemia (seen in myelodysplastic syndrome)
- Ringed sideroblasts have accumulated granules of iron in mitochondria in ring around nucleus of developing RBC; due to impaired heme synthesis

Front 17

When do you see schistocytes or helmet cells?

Back 17

DIC, TTP/HUS, traumatic hemolysis (microangiopathic hemolytic anemias)

Front 18

When do you see spherocytes, aside from hereditary spherocytosis?

Back 18

Autoimmune hemolysis

Front 19

When do you see teardrop cells?

Back 19

Myelofibrosis (bone marrow infiltration)

Front 20

When do you see target cells?

Back 20

HALT: HbC disease (incl. HbSC disease), Asplenia, Liver disease, Thalassemia
"HALT," said the hunter to his TARGET

Front 21

What are Heinz bodies, and when do you see them?

Back 21

Oxidized iron (ferrous --> ferric) leads to denatured Hb --> precipitation in cell --> damage to RBC membrane
- Leads to bite cells
- Seen in G6PD deficiency and alpha-thalassemia

Front 22

What are Howell-Jolly bodies, and when do you see them?

Back 22

Basophilic nuclear remnants found in RBCs
- Seen in pts w/ functional hyposplenia or asplenia, since they would normally be removed by the spleen

Front 23

What pts do you see alpha-thalassemia in? And beta-thalassemia?

Back 23

Alpha- Asians, Africans
Beta- Mediterranean populations

Front 24

What is Hb Barts?

Back 24

Hb made of 4 γ chains (γ4)
- Results from alpha-thalassemia with deletion of all 4 alpha genes--pts can't make alpha chains, so make Hb Barts --> hydrops fetalis

Front 25

What is Hb H?

Back 25

Hb made of 4 β chains (β4)
- Seen in alpha-thalassemia with deletion of 3/4 alpha genes
- Deletion of 1/4 or 2/4 alpha genes is not associated with anemia

Front 26

Pt with increased levels of HbA2 (>3.5%)... what is it?

Back 26

Beta-thalassemia minor (heterozygote)

Front 27

What happens to HbF in pts with beta-thalassemia major and minor?

Back 27

Both have increased HbF (α2γ2)

Front 28

What does lead poisoning do?

Back 28

Inhibits ferrochelatase and ALA dehydratase --> decreased heme synthesis
- Also inhibits RNA degradation --> basophilic stippling

Front 29

What causes hereditary sideroblastic anemia?

Back 29

X-linked defect in ALA synthase gene --> impaired heme synthesis --> ringed sideroblasts (iron-laden mitochondria)
- ALA synthase is the rate limiting enzyme in heme synthesis

Front 30

What causes non-hereditary sideroblastic anemia?

Back 30

Alcohol, lead poisoning (things that inhibit heme synthesis)

Front 31

How do you treat sideroblastic anemia?

Back 31

Pyridoxine (B6) therapy (B6 is a cofactor in heme synthesis)

Front 32

What is megaloblastic anemia and what causes it?

Back 32

Big cells due to nuclear:cytoplasmic asynchrony in erythropoiesis (slowed/impaired DNA synthesis means that nuclear maturation is retarded as cytoplasmic production of Hb continues)
- Caused by folate or B12 deficiency, certain drugs (5-FU, nucleoside analogues, hydroxyurea), liver disease, metabolic disorders, etc.

Front 33

What causes anemia of chronic disease?

Back 33

Inflammation --> ↑ IL-1 and TNF-α --> ↑ hepcidin and ferritin --> limits the Fe that can be freed to transferrin, which is required to get Fe to bone marrow for erythropoiesis

Front 34

Anemia with decreased serum Fe, decreased TIBC, increased ferritin... what is it?

Back 34

Anemia of chronic disease

Front 35

Anemia with decreased serum Fe, increased TIBC, decreased ferritin... what is it?

Back 35

Iron deficiency anemia

Front 36

Peripheral blood smear with normal cell morphology, bone marrow with fatty infiltration and few cells... what is it and what causes it?

Back 36

Aplastic anemia
- Caused by XRT, drugs (chemo), viral agents (parvovirus B19, EBV, HIV), Fanconi's anemia (defect in DNA repair), idiopathic

Front 37

What mutation causes sickle cell anemia?

Back 37

Single amino acid replacement in beta chain gene (glu --> val: substitution of normal glutamic acid with valine)

Front 38

What happens to serum transferrin and transferrin saturation in pregnancy/OCP use?

Back 38

Serum transferrin goes up
Transferrin saturation goes down
Ferritin and serum iron don't change

Front 39

Blistering cutaneous photosensitivity, tea-colored urine that contains uroporphyrin... what is it and what's deficient?

Back 39

Porphyria cutanea tarda
- Deficiency of uroporphyrinogen decarboxylase --> uroporphyrinogen accumulates
- Most common porphyria

Front 40

Severe abdominal pain, muscle weakness, mental disturbances, uroporphyrin in urine... what is it and what's deficient?

Back 40

Acute intermittent porphyria
- Deficiency of porphobilinogen deaminase (= uroporphyrinogen-I-synthase) --> porphobilinogen and δ-ALA accumulate (uroporphyrin shows up in urine)
- Can be asymptomatic

Front 41

What are the symptoms of acute intermittent porphyria?

Back 41

5 P's:
Painful abdomen
Pink urine (contains uroporphyrin)
Polyneuropathy (muscle weakness)
Psychological disturbances
Precipitated by drugs

Front 42

How do you treat acute intermittent porphyria?

Back 42

Glucose and heme, which inhibit ALA synthase

Front 43

Headache, memory loss, inability to concentrate, wrist and foot drop, basophilic stippling in peripheral RBC... what is it?

Back 43

Lead poisoning
- Inhibits ferrochelatase (adds Fe to protoporphyrin to make heme) and ALA dehydratase --> impaired heme synthesis, protoporphyrin accumulation

Front 44

How do you treat lead poisoning?

Back 44

Adults- dimercaprol, EDTA
Kids- succimer

Front 45

What causes idiopathic thrombocytopenic purpura?

Back 45

Anti-Gp-IIb/IIIa antibodies --> peripheral platelet destruction
- Increased megakaryocytes, but decreased platelet survival --> thrombocytopenia --> purpura

Front 46

What causes thrombotic thrombocytopenic purpura?

Back 46

Deficiency of ADAMTS 13 (vWF metalloprotease) --> decreased degradation of vWF multimers --> increased thrombosis
- Labs: schistocytes, elevated LDH

Front 47

What is ADAMTS 13?

Back 47

vWF metalloprotease (degrades vWF multimers)
- Deficiency --> TTP (increased thrombosis)

Front 48

Neurologic and renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia, schistocytes, elevated LDH... what is it?

Back 48

Thrombotic thrombocytopenic purpura (TTP)

Front 49

What is prothrombin time (PT) a test of?

Back 49

Extrinsic pathway function (factors I, II, V, VII, X)
- Defects in above factors --> increased PT
- PT used to derive INR

Front 50

What is partial thromboplastin time (PTT) a test of?

Back 50

Intrinsic pathway function (all factors except VII and XIII)
- Defects --> increased PTT

Front 51

What happens to the PT and PTT in pts with hemophilia?

Back 51

PT doesn't change, PTT increases
- Due to intrinsic pathway coagulation defect

Front 52

What happens to the PT and PTT in pts with von Willebrand's disease?

Back 52

PT doesn't change, PTT increases (this is because vWF binds and stabilizes factor VIII; so deficient vWF --> functional factor VIII deficiency)
- Other platelet disorders have normal PT and PTT

Front 53

What things can cause DIC?

Back 53

"STOP Making New Thrombi":
Sepsis (gram negative)
Trauma
Obstetric complications
Pancreatitis (acute)
Malignancy
Nephrotic syndrome
Transfusions

Front 54

Pts with hereditary thrombosis syndrome due to mutated prothrombin gene--what is the causative mutation?

Back 54

Mutation in 3' untranslated region of the prothrombin gene
- Assoc. with increased risk of DVT

Front 55

What causes the hemorrhagic skin necrosis seen with warfarin admin?

Back 55

Deficiency of protein C or S (decreased inability to inactivate factors V and VIII)
- Proteins C and S have shorter half-lives than the vitamin K-dependent coagulation factors --> initial prothrombotic effect seen with warfarin admin

Front 56

When might you see an increased leukocyte alkaline phosphatase (LAP)? What about a decreased LAP?

Back 56

- Increased LAP in benign myeloproliferative disorders, like leukemoid reaction
- Decreased LAP in CML

Front 57

Erythrocytosis, leukocytosis, thrombocytosis, decreased erythropoietin, JAK2 mutation... what is it?

Back 57

Polycythemia vera
- JAK2 = signaling protein that's mutated in many benign myeloproliferative disorders

Front 58

Platelet counts >1,000,000... what is it?

Back 58

Essential thrombocytosis
- Like polycythemia vera, but for platelets

Front 59

Teardrop-shaped erythrocytes, thrombocytosis... what is it?

Back 59

Myelofibrosis

Front 60

Bcr/abl transformation... what is it?

Back 60

CML
- Negative for JAK2 mutations, which are seen in benign myeloproliferative disorders

Front 61

How do you monitor pts on heparin tx?

Back 61

Follow PTT (measure of intrinsic pathway)

Front 62

How do you monitor pts on warfarin tx?

Back 62

Follow PT/INR (measure of extrinsic pathway)

Front 63

How do you treat heparin overdose?

Back 63

Protamine sulfate (doesn't work as well on LMWH/enoxaparin)

Front 64

How do you treat warfarin overdose?

Back 64

IV vitamin K and fresh frozen plasma

Front 65

How do you treat tPA overdose?

Back 65

Aminocaproic acid (inhibitor of fibrinolysis)

Front 66

When might you see a decreased ESR?

Back 66

Sickle cell anemia (due to altered shape), polycythemia vera, and CHF (unknown why)