Heme Path: Rbc

Front 1

MCV

Back 1

hct / RBC

Front 2

MCH

Back 2

hgb/RBC

Front 3

MCHC

Back 3

hgb/hct

Front 4

HbA

Back 4

α2β2

Front 5

HbA2

common situation this is increased?

Back 5

α2δ2 (delta)

beta-thal

Front 6

HbF

Back 6

α2γ2 (gamma)

Front 7

HbS

Back 7

α2βs2

Front 8

What is this called?

What RBC parameters are affected?

Causes?

Back 8

Spherocyte
Loss of membrane without volume loss

MCHC is increased
Osmotic fragility is increased

HS, warm aiha, old blood, burn, venom, oxidant damage

Front 9

How is HS inherited & what is the defect?

Back 9

AD

Defect in spectrin / ankyrin RBC membrane protein

(ankyrin is MOST COMMON, chrom 8)

Front 10

Name?

Causes?

Back 10

Echinocyte (Burr cell)

ACUTE RENAL FAILURE
Acidic environment; sitting in EDTA too long

"Prickle cells" of pyruvate kinase deficiency

Front 11

Name?
How is this different than burr cell?

Seen in what 3 classic pictures?

Back 11

Acanthocyte (Spur cell)
Irregular, fewer, blunted projections

LIVER DISEASE
Kx deficiency (McLEOD PHENOTYPE)
aB-lipoproteinemia
-also in hypothyroid, MDS

Front 12

Name?
Seen in?

Back 12

Codocyte (target cell)
too much membrane = decreased osm fragility

Seen in:
Asplenia
IDA
Liver disease
Hemoglobinopathies

Front 13

Name?

Classically seen in?

Back 13

Bite cell

Seen in cases of oxidative damage (G6PD!!!!!!)

(spleen bites out Heinz bodies)

Front 14

How to tell normal from pathologic?

Classically seen in?

Back 14

Basophilic stippling
- Reticulocytes have small fine blue dots; pathologic states tend to be coarser

LEAD POISONING
Pyrimidine 5' nucleotidase deficiency
MDS
Infection
Sideroblastic anemia
Porphyria

Front 15

Seen in?

Back 15

Howell Jolly bodies
-DNA / nuclear remnant; 3D; peripheral
-Spleen normally bites these out

Indicate asplenia (functional or real)
-SCD, neuroblastoma, IBD, GVHD, ai)

Front 16

What are these made of?

Back 16

pappenheimer bodies

multiple. See with Howell-Jolly.
IRON

See with asplenia; iron overload

Front 17

What are these and what stain is this?

Back 17

Heinz bodies
See with reticulin stain - don't see with Wright Giemsa

Represent oxidized hemoglobin: G6PD, unstable hgb, 3deletion alpha thal

Bite cells have them bitten out

Front 18

Back 18

Rouleaux

secondary to large proteins: fibrinogen, immunoglobulin

Front 19

How is this different than rouleaux?

causes?
How to correct?
What indices will be changed?

Back 19

Autoagglutination
RBC clumping

COLD AGGLUTININS
(IgM autoantibody: EBV, mycoplasma)
Correct by warming

increased MCV, decreased RBC

Front 20

Back 20

Babesia

Babesia parasites resemble Plasmodium falciparum, however Babesia has several distinguishing features: the parasites are pleomorphic (vary in shape and size), can be vacuolated, and do not produce pigment.

Can be extracellular

Front 21

Vector for babesia?

Back 21

IXODES DAMMINI (same as Lyme)

Front 22

Fast migrating Hb?

Back 22

J N I H Barts

Front 23

Alkaline hgb electrophoresis

What are the bands?

Back 23

AFSC

A Fat Santa Claus

Front 24

What classically migrates with S in alkaline?

Back 24

S D G Lepore

Front 25

What classically migrates with C on alkaline?

Back 25

C E O A2

Also C-Harlem

Front 26

What does the star represent?

Back 26

Fast migrating hemoglobins (JNIHBarts)

Front 27

What is a classic slow-migrating hemoglobin on alkaline?

Back 27

Constant Spring

Front 28

Acid hb electrophoresis. What are the bands?

Back 28

F A S C


Lots migrate with A...

Front 29

The patient is in lane 1. There was an abnormal hemoglobin on alkaline gel in the C lane. What is it?

Back 29

Hemoblobin E.

The abnormal hemoglobin migrates as Hb C on cellulose acetate and as Hb A in acid agar.

Diagnosis : Hb E trait (heterozygote for Hb E)

Comment : Hb E is very common among southeast Asians.

Front 30

African American with jaundice after fava beans

disease?
Inheritance?
Triggers?

Back 30

G6PD
10% Af Amer
(wildtype is type B***)
Susceptible to oxidative damage; Heinz bodies, hemolysis

RETICULOCYTES ARE NORMAL

XR (boys)
Triggers: fava beans, sulfa drugs, antimalarials, infxn (hepatitis, pna, thyroid)

COOMBS TEST IS NEGATIVE
G6PD protects against malaria!

Front 31

Thal minor

Inheritance?

Clues?

Back 31

One damaged Beta chain

AR chrom 11

Microcytic anemia with increased RBC (MCV/RBC<13)

HbA2 > 3.5% (vs IDA!!)

Front 32

Thal major, a.k.a...?

Population?
Inheritance?

Clues?
Clues?

Back 32

Cooley's anemia
2 damaged B chains

AR, Chrom 11, Mediterranean

Marked anisopoikilocytosis
Splenomegaly, death < 20y

Front 33

Inheritance of alpha thal?

Back 33

AR chrom 16

Front 34

Why is beta-thal picked up in the first year of life while alpha-thal is diagnosed in utero?

Back 34

Because B thal can make HbF, which is normal at birth. Beta chain production (and hence hgb A) is not predominant right away.

vs. Alpha thal: alpha chain is required for all types of hgb

Front 35

Hgb types in B thal minor


Major?

Back 35

HbF < 5%
HbA2 4-10%

Major: HbF 90%

Front 36

1-deletion alpha thal

Back 36

silent carrier

slight decreased MCV, MCH

Front 37

2 deletion alpha thal

Does it matter if it is -/- a/a or -/a -/a?

Back 37

"alpha thal trait"
Mild microcytic anemia

-/- a/a seen in Chinese
-/a -/a in African Americans
matters for inheritance

Front 38

3-deletion alpha thal

Back 38

get tetramers. microcytic anemia. Heinz bodies. Splenomegaly.

HbH (4 beta chains) (GOLF BALLS)

and

HbBarts (gamma x 4)(normally in HbF)

-both have HIGH affinity for O2

Front 39

4-deletion alpha thal

Back 39

No alpha chains.
HbBarts (tetrameric gamma)
Fatal
Hydrops fetalis

Front 40

Hemoglobin that is made of 2 alpha chains and 2 delta-beta fusion chains?

What does it mimic?

Back 40

Hemoglobin Lepore

Mimics thal trait (B thal minor)

Front 41

delta-beta thalassemia

Back 41

deletion of both delta and beta chains on chrom 11

heterozygous (~thal minor) or homozygous (~thal intermedia)

also known as "F thalassemia" since there are no A or A2 hemoglobins produced (since no delta or beta), they have only F

Front 42

How to tell hereditary persistance of fetal hemoglobin vs. delta-beta thal?

Back 42

Both have increased HbF!!!!!!

BUT
delta-beta thal will have decreased total hemoglobin resulting in a low MCV, low MCHC, high normal to elevated erythrocyte counts and often low or low normal HbA2. In contrast, in HPFH the total amount of hemoglobin produced is sufficient to prevent these abnormalities

Front 43

Back 43

Heterozygous beta thal

Front 44

Back 44

nice graphic

Front 45

name the lanes

Back 45

Lanes 1 and 5 are hemoglobin standards.
Lane 2 is a normal adult.
Lane 3 is a normal neonate.
Lane 4 is a homozygous HbS individual.
Lanes 6 and 8 are heterozygous sickle individuals.
Lane 7 is a SC disease individual.

Front 46

Ratio of HbA to HbS in heterozygous SA? Homozygous SS?

Back 46

60%A, 40% S

>80%S

Front 47

Classic cause of aplastic crisis in SCD?

Back 47

Parvovirus

Front 48

HbS is made of what hemoglobin chains?

What would happen in S/alpha-thal?
S/beta thal?

Back 48

alpha x 2
abnormal beta x 2

S/alpha thal: Decreased S (because need alpha chain)
S/beta thal: Increased S (because you can't make HbA, and you can make SOME S)

Front 49

For what 2 purposes would you do iron studies in thalassemias?

Back 49

1. To differentiate btwn Fe defic. anemia and Beta thal minor
2. To evaluate iron overload in Thal major.

Front 50

What symptoms do you see in HbE?

population?

Back 50

None.
HbE is one of the most rare variants of normal hemoglobin.

COMMON IN SE ASIA

Front 51

HbC

Back 51

reduces the normal plasticity of host erythrocytes causing a hemoglobinopathy.

In those who are heterozygous for the mutation, about 28–44% of total hemoglobin (Hb) is HbC, and no anemia develops.

In homozygotes, nearly all Hb is in the HbC form, resulting in mild hemolytic anemia.

= MILD DISEASE
TARGET CELLS, CLAM CELLS, CRYSTALS

Front 52

What is the paradox in this disease?

Back 52

hemoglobin SC disease
Targets, sickles, and crystals

Paradox: usually have LESS sickled cells, but higher incidence of complications

Front 53

RBC lifespan in HbS?

Back 53

30 days

Front 54

Things that increase hemoglobin affinity for O2?
LEFT SHIFT

Back 54

HbF
Cape Town, Chesapeake, Bethesda
Alkalosis
Hypothermia

Front 55

Things that decrease hemoglobin affinity for O2?
RIGHT SHIFT

Back 55

Acidosis
Hyperthermia
2,3-DPG
Kansas, Providence, Seattle, Beth Israel

Front 56

Unstable hemoglobins (prone to precipitate)

Back 56

Kolu, Hasharon, Zurich
(Heinz body --> hemolysis)

Dx with heat instability test, isopropanol, n-butanol test

Front 57

CO-hb

Back 57

Increased O2 binding x 200
Cherry pink blood and skin
NO CYANOSIS

Front 58

HbM mechanism

Back 58

= methemoblobinemia
higher than normal level of methemoglobin (metHb, i.e., ferric [Fe3+] rather than ferrous [Fe2+] haemoglobin)

DECREASED OXYGEN BINDING
CYANOSIS

Front 59

HbM types

Back 59

1: congenital. deficiency methemoglobin reductase (may also see with pyruvate kinase def)

2: Ingestion of oxidizing agents: MOTH BALLS, ANTIFREEZE

3: Inherited: Hg Boston, Saskatoon, Milwaukee

Front 60

Drugs that cause HbM

Back 60

Nitrates
Benzocaine
Dapsone
antibiotics (trimethoprim, sulfonamides and dapsone), local anesthetics (especially articaine and prilocaine), and others such as aniline dyes, metoclopramide, chlorates and bromates.

infants under 6 months of age are particularly susceptible to methemoglobinemia caused by nitrates ingested in drinking water (called blue-baby syndrome)

Front 61

HbM treatment

Back 61

Reducing agents
methylene blue
ascorbic acid

Front 62

what is this test and what is it used to dx?

Back 62

Ham test

PNH

Urine passed 7am is dark containing a large amount of free haemoglobin which leaks out of PNH red-cells as they burst. The urine generally clears during the day.

Front 63

Genetics of PNH and pathophys?

Back 63

Acquired stem cell disorder
Mutant PIG-A gene on chrom 22
Lose GPI anchor and therefore lose expression of membrane proteins

loss of CD55/DAF --> complement mediated lysis

Intravascular hemolysis, thrombocytosis, bone marrow failure
IRON DEFICIENCY

Front 64

Anti-i seen in?
Anti-I?

clinical pic?

Back 64

anti-i : EBV

anti-I: Mycoplasma pna

Cold autoimmune hemolytic anemia. IgM!!!!!

Front 65

What is Donath-Landsteiner hemolytic anemia?

Classic triggers?

Back 65

PCH (paroxysmal COLD hemoglobinuria)

a polyclonal IgG anti-P autoantibody binds to red blood cell surface antigens in the cold.

anti-P seen in Mumps, Measles, Mono, syphilis

usually self limited

Front 66

What is anti-P seen in?

Back 66

PCH

Front 67

Renal abnormalities
cafe au lait spots
Mental retardation
Short stature
NO THUMB

increased risk AML & solid tumors

Back 67

Fanconi anemia

AR
Pancytopenia (****) at 5-10y

Front 68

Pica, glossitis, esophageal webs

Back 68

Iron deficiency anemia

Can cause THROMBOCYTOSIS and HYPERSEGMENTED NEUTROPHILS

Front 69

Back 69

Hookworm
Ancylostoma duodenale (one of 2 that infect humans)
Cause IDA by attaching to intestintal wall and sucking blood

A. duod has 2 pairs of teeth, which ID it from Necator

Front 70

Back 70

Necator americanus, the other hookworm that infects humans.

Cutting plates on mouth

Front 71

Elevated adenosine deaminase
Short stature, <1y.o.
Malfunctioning ribosomal proteins
RPS19 gene

Back 71

Diamond Blackfan anemia

RBC aplasia

Front 72

Acquired causes of RBC aplasia?

Back 72

Thymoma
Parvovirus

autoimmune
drug
malignancy
infection

Front 73

Schilling test

Back 73

used for patients with vitamin B12 deficiency. The purpose of the test is to determine whether the patient has pernicious anemia. many parts to it!

Front 74

Megaloblastic anemia
Achlorhydria

Sensitive test?
Specific test?

Back 74

Pernicious anemia
(chronic atrophic gastritis)
attack parietal cells; get low acid; get hypergastrinemia leading to achlorhydria

anti-parietal cell (sens)
anti-IF (specific)

Front 75

Which is better to measure folate deficiency: Serum folate or RBC folate?

Back 75

RBC FOLATE!

sources of folate: leafy greens, EtOH, short bowel syndrome

Front 76

B12 deficiency

Back 76

elevated homocysteine
elevated MMA

can be caused by diphyllabothrium latum
can cause infertility

Front 77

Anemia of chronic disease

Back 77

Low iron
low transferrin
HIGH FERRITIN

Front 78

Sideroblastic anemia treatment?

causes?

Back 78

B6

Tb drugs
Pb poisoning
EtOH
Zinc

Front 79

Mechanism of Pb poisoning

Back 79

Blocks ALA synthetase, ALA dehydrase, heme synthetase

increased protorphyrin

Front 80

What migrates with A on hemoglobin electrophoresis in acid?

Where does O go?

What migrates with S?

Back 80

A, A2, D, E, G, M

(M also migrates with A on alkaline)

O stays at the origin in acid

C-Harlem migrates with S on acid (migrates with C on alk)

Front 81

Where is the origin on hemoglobin electrophoresis?

Back 81

Alk: at the cathode (-). all flow to the (+)

Acid: in the middle. C & S flow to (+), F & A to (-)

Front 82

What is another way to identify hemoglobinopathies?

Back 82

HPLC

Also: PCR (useful in fetal cases - don't need fetal blood can use any tissue)

Front 83

Name the rows

Back 83

Front 84

Name the rows

Back 84

Front 85

True or false: Therapeutic splenectomy is generally avoided in Hereditary stomatocytosis.

Back 85

True - there is a marked tendency towards thrombosis following splenectomy

Front 86

What Rh phenotype is associated with hereditary stomatocytosis?

Back 86

Rhnull

Front 87

The cytoskeletal disorders of RBCs are inherited in what manner?

Back 87

AD

Front 88

Splenomegaly is common in all chronic hemolytic disorders except?

Back 88

Sickle cell disease

Front 89

EPO-secreting neoplasms?

Back 89

RCC
Hemangioblastoma
Leiomyomas of the uterus
HCC

Front 90

Causes of reactive erythrocytosis

Back 90

Hypoxia
High affinity hemoglobins (Chesapeake; Denver)
EPO producing tumors