Essential Hematology I Keep Forgetting

Front 1

Hodgkins Lymphoma

Back 1

t(8,14)
c-myc gene from Chr 8 to the region of
chromosome 14 (bcl-2) that contains a promoter for an immunoglobulin gene.

predictable spread

non tender, movable >1cm

reed sternberg / lacunar cells

Pel-Ebstein fever

pain in LN on drinking alcohol

Front 2

Sideroblastic anemia

Back 2

Fe in the PBS cause basophilic stippling (pappenheimer bodies), in the BM cause siderophoric rings

can take up the iron, but can't use it.
Congenital or Acquired: alcohol, lead poisoning, chloramphenicol

overall macrocytic, but there are populations of large and small cells

Front 3

poikilocytosis vs anisocytosis

Back 3

poikilo = shape differences - Thalassemia major or Fe deficiency

anisocytosis - different sizes = Fe deficinecy

Front 4

EBV causing cancer?

Back 4

giant cell in the periphery - look like huge abnormal plasma cell

predisposition to Hodgkins Lymphoma

4 cancers:
Burkitt’s lymphoma,
Hodgkin’s lymphoma,
B lymphoproliferative disease
Nasopharyngeal carcinoma

Front 5

HTLV causes what cancer?

Back 5

Adult T-cell leukemia

Front 6

most common kind of Hodgkins

Back 6

Nodular Sclerosis Hodgkin’s Disease

Front 7

NHL: B cell vs T/NK in order of aggressiveness

Back 7

90% B-cell
Indolent:
SLL (small lymphocytic L)
Follicular
HCL (hairy cell L)
Mantle cell


Intermediate:
DLBL (diffuse large B cell lymphoma)
Mediastial L

High grade:
Burkitts,
Lymphoblastic Lymphoma


T/NK:
indolent:
Mycosis Fungoides
Sezary

intermediate:
anaplastic large cell Lymphoma
peripheral T cell L

high grade:
Lymphoblastic T -LL
Adult T cell Lymphoma (HTLV)

Front 8

leukemia age brackets

Back 8

0-14 ALL
15-39 AML
40-59 CML/AML
>60 CLL

Front 9

predisposition to lymphoma

Back 9

Autoimmune
EBV – Burkitt
CMV
HTLV – adult T-cell
H/ pylori (gastic Malt Lymphoma)
STLV
HIV – Burkitt
From past Tx: Radiation; Immunotherapy – after transplant

Front 10

retuximab

Back 10

anti CD-20
This antibody helps destroy the tumor – via the Immune system – it tags the tumor for destruction

Front 11

what's more sensitive to radiation?
HL/NHL

Back 11

HL

Front 12

follicular NHL - what's the translocation?

Back 12

t(14,18)

Front 13

who gets most H&N tumors?

Back 13

china (nasopharyngeal - viral

smokers

Front 14

target cells

Back 14

H - Hbc
A - Asplenia
L - Liver disease
T - thalassemia

Front 15

findings with asplenia

Back 15

Asplenia
1. Howell-Jolly bodies
2. Target cells
3. Acanthocytes
4. Aniso-, poikilocytosis and fragments

Front 16

stomatocytes

Back 16

alcohol
congential

Front 17

differential of microcytic anemia

Back 17

Iron Deficiency
Thalassemia minor
Anemia of Chronic disease
Sideroblastic anemia

Front 18

Fe deficiency clinical

Back 18

Need to ask about pica—ice eating etc
Need to look at the nails for spooning or koilonychia. Blue Sclerae, angular stomatitis.
Patients can also have dysphagia.

Front 19

spherocytosis diff

Back 19

Hereditary Spherocytosis
Autoimmune - warm - IgG -
oxidant hemolysis or exposure to chemical agents, copper or hypophosphatemia are rare cause



if the Coombs is negative ==> HS

Front 20

what are some WBC congenital changes (whierd looking PML)
2 AR
2 AD

Back 20

Pelger-Huёt anomaly
• AD 1:5000
• Heterozygotes: “prince-nez” 2 lobes in 50-75% of PMN

May-Hegglin Anomaly
• AD rare
• Giant platelets
• Large inclusions “Döhle like”

Chediak-Higashi Syndrome
• AR rare
• Giant, red/green/blue granules
• Partial occulocutaneous albinism
• Recurrent Infx

Alder-Reilly Anomaly
• AR; Mucopolysaccharidoses

Front 21

Non-megaloblastic macrocytic anemia

Back 21

Liver disease, Alcohol, Reticulocytosis,
hypothyroid, Sideroblastic

Front 22

Howell - Jolly bodies

Back 22

H - hemolytic anemia
A - asplenia
M - MDS
M - Megaloblastic anemia
S - spherocytosis (HS)

Front 23

G6PD def

Back 23

can't handle oxidative stress --> oxidation of Hg =Heinz bodies
destruction of these via Macrophages causes BITE CELLS

Fava beans (divicine), primaquine, Bactrim, Nitrofurantoin (UTI),

Front 24

TTP

Back 24

• TTP
o Adults, CNS sx, fever, thrombocytopenia 50K
o Congenital: ADAMTS13-vWF cleaving metalloprotease deficiency  huge vWF -clots
o Acquired: antibody to ADAMTS13;  huge vWF –clots
 Tx: plasma exchange!!!
o Tx: Platelet transfusion is COUNTERINDICATED
o

Front 25

HUS

Back 25

• HUS
o Children, renal compromise, fever, thrombocytopenia 21K
o Shiga-toxin producing bacteria: O157:H7 E.coli
o Usually self-limited,

Front 26

PNH

Back 26

• PIG-A gene on X-chromo; GP1-anchor is not working = loss of the GPI bridge, so during the night, when conditions are perfect, the complement proteins attach more  dark urine in the morning
• Complications: Budd-Chiari (abdominal pain, ascites, Hepatomegaly = occlusion ofhepatic vein), VTE, strokes…
• Related to Aplastic Anemia (10%) and AML (5%)
• Tx: CS, BMT, Eculizumab = monoclonal Ig binds to C5

Front 27

Differential Diagnosis of ALL

Back 27

• Juvenile rheumatoid arthritis
• Infectious Mononucleosis (sore throat, lymphadenopathy..)
• ITP (platelet 2000, nl WBC, nl Hg)
• Pertussis and Parapertussis (profound lymphocytosis, but cell morphology doesn’t fit)
• Aplastic Anemia
• Other virus HHV6, HTLV
• Malignancies (small blue cell tumors)
o Neuroblastoma
o Retinoblastoma
o Rhabdomyosarcoma
o NHL
o Other small round blue cell tumors
o Hyper-eosinophilia, aplastic presentation

Front 28

Clinical Sx of ALL

Back 28

• Combination of 2 or more unexplained adenopathy or HSM, bone pain, bleeding/pallor – do CBC

Front 29

ALL cytogenetics

Back 29

• Pre-B-ALL:
• Good:
o t(12;21) TEL + AML1
o Trisomy 4 and 10
o Hyperdiploidy(MTX metabolized favorably)
• Poor:
o t(4;11)
o t(1;19)
o t(9;22) Bcr/ABL Philidelphia Chrom.
o Euploidy, Hypoploidy, extreme hyperploidy
• Burkitt B-ALL: t(8;14), t(2;8),t(8;22)
• T-ALL: t(1;14), t(8;14), t(11;14), t(7;9)
• 11q23 with MLL in infants

Front 30

what AML is good and what is bad
cytogenetics

Back 30

• Most common is M2 with 50% with t(8;21)
• Good: t(8;21),inv(16), t(5;17)
• Poor: del 5/5q or 7/7q-

Front 31

CLL good/bad?

Back 31

Chromosome 13 good

11, 17 bad

Front 32

ET suspicion...

Back 32

how's the ferritin lvl?

o Young women
o Hard to diagnose;
 Many are Asx
 No cytogenetics
 Only 50% have Jak2 mut
 Splenomegaly <50%
 Clonal or polyclonal?
o Morbidity: thrombotic/bleeding
o Diagnosis:
 Platelet count >600 000/µL (now 450 000/µL)
 Megakaryocytic hyperplasia
 Platelet clumps
 No Philadelphia chromosome (that would be CML)
 No myelofibrosis (that would be IM)
o Ddx: “HOW IS THE FERRITIN?”
 Malignancy (Hodgkins, renal)
 Infections
 Hemolytic anemia
 Collagen-vascular and other chronic inflammations
 Fe deficiency anemia & bleeding
 Rebound Thrombocytosis
 Other myeloproliferative disorders
 Post-splenectomy
o Treatment:
 Not necessarily, but for sure in older age, higher platelet count, previous thrombosis (young woman without clotting risks – I’m just going to watch u)
 32P (risk of blast transformation)
 Alkylating agents (risk of blast transformation)
 Hydroxyurea
 IFN (useful for pregnancy)
 Anagrelide

Front 33

Myleoproliferative diseases
• Common features

Back 33

a. Acquired mutation in a hematopoietic stem cell
b. Clonal Hematopoiesis (proof: X-inactivation studies- women with G6PD isozymes –if there is a clone they express only one version of G6PD [xcept T-cells]– the swab should normally show two spots) , Ph-chromosome (CML), transferable, evolution to AML, JAK2 mutation especially PV)
c. Proliferation of granulocytes, red cells +/ platelets
d. Splenomegaly
e. BM fibrosis
f. Possibility of transforming to acute leukemia:

Front 34

MDS: 3 situations

Back 34

• Refractory anemia
o
o Dimorphic population (tear cell, large and small)
o <5% blasts in marrow
o AML in 10% at 2yrs
o Median survival 3-6yrs



• Refractory Anemia with Ring Sideroblasts
o
o >15% ringed sideroblasts
o <5% blasts in marrow
o AML in 0% in 2yrs
o Median survival 3-6yrs



• MDS associated with isolated del(5q)
o In middle aged women
o Characterized by microcytic anemia and normal or increased platelet count
o Megakaryocytes with hypolobulated nuclei
o Favourable clinical course with absence of leukemic transformation

Front 35

myeloid CD?

Back 35

CD 13,33

Front 36

Plasma cell dyscrasies:

Back 36

Plasma cell dyscrasies:

• Multiple Myeloma (malignant)
• Smoldering Multiple Myeloma (slowly progressing, to smolder = to burn sluggishly, without flame, and often with much smoke)
• Solitary Plasmacytoma
• Waldenström macroglobulinemia (IgM)
• MGUS (monoclonal gammopathy of undetermined significance)
• Amyloidosis
• Plasma cell leukemia

Front 37

Amyloidosis

Back 37

Amyloidosis
 Low molecular weight proteins – related to the other plasma dyscrasies
 Deposit in organs (when not all into urine)
 CONGO RED STAIN: apple-green birefringence


clinical:
o Cardiomyopathy, conduction abnormalities
o hepatomegaly,
o nephrotic syndrome,
o neuropathy, carpal tunnel syndrome, enlarged muscles,
o periorbital purpura, factor X deficiency, waxy skin, bruising
o fatigue


2 types:
 AL – primary – deposition of fibrils derived from Ig light chain fragments
o Often λ-restricted
o BM often <20%
o Usually no lytic bone lesions
o Mild B-J protein
o Don’t miss this when you’re diagnosing MGUS – must check if they have any neurological problems…
 AA – secondary – deposition of other types of protein that polymerize to fibrils
o Dialysis-associated amyloidosis
o In brain: Alzheimers beta-amyloid

Front 38

 Dense granules

Back 38

 Dense granules (10x LESS, ADP, ATP) – aggregation, smaller

Front 39

 Alpha granules

Back 39

 Alpha granules (vWF, PF-4, fibrinogen, Factor V) - Adhesion

Front 40

 GP Ib-IX-V =

Back 40

 Dense granules (10x LESS, ADP, ATP) – aggregation, smaller
 Alpha granules (vWF, PF-4, fibrinogen, Factor V) - Adhesion
 GP Ib-IX-V = vWF receptor
o Subendothelial collagen – vWF – GP-Ib-IX-V – platelet
o Also binds thrombin, P-selectin
o Congenital defect: Bernard-Soulier
 Macrothrombocythemia
 bleeding

Front 41

 GP IIb-IIIa =

Back 41

 GP IIb-IIIa = fibrinogen receptor;
o Conformational change with platelet activation
o Target of CAD: abciximab, tirofiban, eptafibatide
o Congenital defects: Glanzmann thrombasthenia

Front 42

 Acquired platelet dysfunction (MUCH more common!)

Back 42

o ASPIRIN!!(irreversible)!! NSAIDS (reversible)
o Other drugs (antibiotic, anti-seizure, anti-depressants)
o Renal failure
o Liver diseases
o Cardiopulmonary bypass

Front 43

2 common thrombocytopenic conditions in which platelet transfusion is contraindicated

Back 43

2 common thrombocytopenic conditions in which platelet transfusion is contraindicated
 NOT with TTP
 NOT with HIT
 NOT with pseudo-thrombocytopenia
o All because it would fuel thrombosis

Front 44

Platelet defect:

Back 44

Platelet defect: either thrombocytopenia or function defect
• Petechiae are characteristic
• Hemarthroses or deep hematomas are rare
• Sometimes there is a family Hx
• Superficial bruising is Characteristic: small multiple

Front 45

Coagulopathy

Back 45

Coagulopathy
• Petechiae are rare
• Hemarthrosis and deep hematomas are characteristic
• Positive family Hx is common
• Superficial bleeding is common: large, solitary

Front 46

DIC

Back 46

 Activation of coagulation leading to fibrin formation and consumption coagulopathy
 Fibrin formation induces thrombosis
 Consuption coagulopathy increases bleeding
 ALWAYS secondary to clinical condition: Infection, Malignancy, Obstetrics
• Gram negative infection (endotoxin), acute promyelocytic leukemia M3 (there is TF in the promyelocytes), Abruptio placenta, missed abortion, ecclampsia, amniotic fluid embolism
• Other: massive trauma, heat stroke, burns, extensive surgery
 Pathophysiology:
• Trigger: endo disturbance  TF enters circulation; Fibrinolysis always present to a variable degree – fibrin and fibrinogen are degraded by plasmin; Fibrin degradation or split products accumulate; these inhibit stable clot formation and platelet function; As the FDP or FSP increases, stable clot formation is inhibited
 Diagnosis:
• Diffuse bleeding; with predisposing condition
• LAB:
o D-dimer should be positive
o PT long
o PTT can be long, short or normal “paradoxical shortening of PTT”
o Platelet count may be decreased but can be normal or increased as acute phase reactant
o Fibrinogen can be decreased but can be normal or increased as APR
o Schistocytes may be present on peripheral blood smear
o Watch out because the baseline (pre-DIC) can be abnormally elevated:
 pregnancy or APR can increase fibrinogen + VIII
 PTT may not be prolonged if factor VIII is high
 Platelet count is increased in some malignancies, IBS or APR
 So DIC cannot be ruled out by normal values for these measurements
o PT↑, PTT↑, Fibrinogen↓, Thrombin time↑, D-Dimer↑, Platelets↓ = Death Is Coming
o Usually it’s enough if PT↑(consumption coagulopathy) and D-Dimers↑ (hypercoagulable)
• Ddx:
o Liver failure (especially this, because bleeding, prolonged PT, PTT, increased D-Dimer, Thrombocytopenia as all common to both DIC and Liver failure; the schistocytes and decreased VIII are not always present in DIC)
o Dilutional coagulopathy
o TTP (thrombotic thrombocytopenic pupura)
o HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets in pregnancy)
o Extensive thrombosis
o Can co-exist
• Treatment:
o Treat underlying cause
o Supportive
o Replace (FFP, cryo, platelet transfusion)
o Heparin (if thrombosis dominates)
o Antifibrinolytic agent

Front 47

starry sky

Back 47

lymphoma


burkitts

Front 48

flower cell

Back 48

Adult T cell Luekemia/Lymphoma. This is associated with skin lesions*
and hypercalcemia* (From Dr. Ramalingam) and especially the HTLV-1 (Human
T Cell Lymphoma Virus-1). The prognosis for this disease would be poor, since this
is a very aggressive form of leukemia/lymphoma.
Median survival rate is only 8 months!