Heme/Onc

Myelophthisic Anemia

Replacement of BM, most often by malignancy
Severe anemia; small #s of nucleated RBCs and immature granulocytes in the blood
-Tumor cells in BM

What type of anemia is associated with phenytoin use?

Megaloblastic
-Phenytoin interferes with absorption of folate

Causes of aplastic anemia

-most often d/t toxic exposure
-Radiation, benzene
-Drugs: chloramphenicol, sulfonamides, some antimalarial drugs, alkylating agents used to tx cancer
-Parvo in those with sickle cell D

What are the general characteristics of hemolytic anemia?

(increased red cell destruction)
-Increased unconjugated bili, acholuric jaundice
-Increased urine urobilinogen
-Hg in blood and urine
-Disappearance of haptoglobins
-Hemosiderosis
-Retiulocytosis
-Polychromatophilia

Warm antibody hemolytic anemia
What type of Abs?
General features?
Coombs test?

IgG Abs react with red cell surface antigens
-Usually second. to underlying disease states such as SLE or lymphomas
-Spherocytosis
-Positive direct Boombs test

Paroxysmal Nocturnal hemoglobinuria

-Increased sensitivity to complement-induced red cell lysis
-intravascular hemolytic anemia, pancytop, increased inc of thrombosis
-defect in gene PIG-A which causes impaired synthesis of GP I anchor in RBC membrane

Hereditary spherocytosis

AD
Extravascular hemolysis d/t spectrin or ankyrin defect
Small round RBCs with no central pallor
Inc. MCHC, Inc RDW
Howell-Jolly bodies present after splenectomy

G6PD deficiency

X-linked; more often in AAs
Acute, self-lim. intravascular hemolytic anemia
Caused by oxidative stress: primaquine, sulfonamides, fava beans
-Bite cells on blood smear.

What are the myeloproliferative disorders? (4)

CML
Polycythemia vera
Chronic idiopathic myelofibrosis
Essential thrombocythemia

Bernard-Soulier Disease

AR
Unusually large platelets and lack of surface glycoprotein GPIb-IX-V needed for platelet adhesion

Glanzmann thrombasthenia

Inaggregability of platelets d/t hereditary deficiency of platelet-surface GPIIb/IIa, required for formation of fibrinogen bridges.

Classic pentad of TTP

fever
Microangiopathic hemolytic anemia
thrombocytopenia
renal insufficency
Neurologic abnormalities

When do you see macro-ovalocytes? What other blood cell abnormality is associated with it?

Megaloblastic
Hypersegmented PMNs

When do you see helmet cells or schistocytes?

DIC, traumatic hemolysis

When do you see "bite cells"

G6PD deficiency

When do you see "teardrop cells"

Myeloid metaplasia with myelofibrosis

When do you see target cells?

HbC disease, Asplenia, Liver disease, Thalassemia
HALT

When do you see poikilocytes?

Nonuniform shapes in TTP/HUS, microvascular damage, DIC

When do you see Burr cells?

TTP/HUS, traumatic hemolysis

When do you see basophilic stippling?

Thalassemias, Anemia of chronic disease, Iron deficiency, lead poisoning (TAIL)

What does dec. serum haptoglobin and inc. serum LDH indicate?

RBC hemolysis

What are the microcytic, hypochromic anemias?

MCV < 80
Thalassemias
Iron Deficiency
Lead poisoning
Sideroblastic anemias

What causes macrocytic anemia?

Folate or B12 deficiency
Drugs that block DNA synthesis: sulfa, phenytoin, AZT

What causes normochromic, normocytic anemia?

Acute hemorrhage
G6PD or Pyruvate kin. deficiency
RBC membrane defects
Bone marrow disorders
Hemoglobinopathies
Autoimmune hemolytic anemia
Anemia of chronic disease

Treatment of aplastic anemia

-Withdrawal of offending agent, duh
-Allogeneic BM transplant, RBC and platelet transfusion, G-CSF or GM-CSF

CLL markers

CD5+, CD10-
Has CD19,20
Smudge cells
Generalized lymphad., hsmegaly

Hairy cell leukemia markers

TRAP +
B-cell disease
splenomegaly, pancytopenia

CML markers

t19;22 - philly chromosome
Low leukocyte alk phos
Bcr-Abl

MM markers

IgG or IgA M protein spike
Lytic bone lesions -> hypercalc.
Bence-Jones light chains in pee
Rouleux RBC formation
primary amyloidosis

Waldenstrom's markers

IgM M protein spike
Hyperviscosity

Follicular lymphoma markers

CD 19,20 +; CD5-
t(14;18)
bcl-2 (inhibits apoptosis)

Burkitt's markers

EBV
Starry sky on histo
t(8;14) c-myc
Immunocompromised more susceptible

Small lymphocytic lymphoma markers

CD5+, CD10-
like CLL

Mantle cell markers

t(11;14)
Activation of Cyclin D1 gene (bcl-2)

AML markers

M3 type has t(15;17)
Auer rods

ALL marker

most common form is CD10+

What are the 2 primary opsonins in bacterial defense

C3b and IgG

What two factors help prevent complement activation on self-cells?

DAF (decay-accelerating factor) and C1 esterase

Deficiency of C1 esterase leads to:

Hereditary angioedema

Deficiency of C3 leads to:

Severe, recurrent pyogenic sinus and URIs

Deficiency of C6-C8 lead to:

Neisseria bacteremia

C1-4 used in?

Viral neutralization

C3a and C5a used for?

Anaphylaxis

C5a is specifically linked to?

PMN chemotaxis

C5b, C6-9 are associated with?

Membrane attack complex

What does deficiency of DAF lead to?

complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria.