Hem/Onc Path Flashcards
Heinz bodies and bite cells
G6PD deficiency
oxidation of Fe from ferrous (2+) to ferric (Fe3+)
Howel Jolly Bodies
Hyposplenia Mothball ingestion (napthalene)
basophilic nuclear remnants found in RBC
Fe defficiency anemia findings
low Fe
high TIBC
low ferratin
Microcytosis and hypochromatic
Alpha Thallessemia
Defect in production of alpha Hb
high ß
Hb Barts
4 gene deletion of alpha thalassemia
4 gamma Hb
No Alpha
Hydrops fetalis
HbH
3 gene deletion alpha thalassemia
very little alpha
ß4 Hb
Alpha thallessemia carrier mutation
1 gene mutation of alpha
2 gene mutation alpha thalassemia
low Sx
ß thalassemia
point mutatio in splce sites and promoter
decreased ß synthesis
ß thalassemia Major
Homozygote
ß chain absent –> severe anemia
Marrow expansion–crew cut skull
ß thalassemia minor
heterozygote
ß chain underproduced
Dx–HbA2 > 3.5% on electrophoresis
HbF
ß thalassemia major
alpha2 gamma 2 Hb
Burton's lines on gingiva encephalopathy erythrocyte basophilic stippling abd. colic sideroblastic anemia wrist drop
Lead poisoning
Tx Pb poisoning
Dimercaprol and EDTA–adults
Succimer–kids
Hereditary Sideroblastic anemia
X linke defect of ALA synthase gene
ringed sideroblasts with iron laden mitochondria
Defect in heme synthesis
labs–increased Fe and Ferratin, normal TIBC
Sideroblastic Anemia Tx
Pyridoxine (B6)
Increased homocystein
Normal MMA
Megaloblastic Anemia
Folate Deficiency
Increased Homocystein
Increased MMA
megaloblastic anemia
Vit B12 def.
Orotic Aciduria
Genetic mutation of enzyme that synth uridine from orotic acid
kid with megaloblastic anemia that can’t be cured with B12
Orotic Aciduria Tx
uridine monophosphate
non-megaloblastic macrocytic anemia
Liver disease
ETOH
reticulocytosis –> inc. MCV
Rx
Anemia of chronic disease
incresed hepcidin
dec. Fe and TIBC
Increased Ferratin
normocytic anemia
Fanconi’s Anemia
DNA repair defect
Aplastic anemia
Viruses that cause aplastic anemia
Parvovirus B19
EBV
HIV
HCV
Positive osmotic fragility test
Defect in membrane proteins
Hereditary spherocytosis
Back pain
Hemoglobinuria a few days later
bite cells
heinz bodies
G6PD Def.
Decreased glutathione
RBCs more susceptible to oxitative stress
X linked
Pyruvate Kinase Deficiency
Hemolytic Anemia in Newborn
defect in pyruvate kinase –> decreased ATP –> rigid RBCs
HbC defect
Glutamic acid to LYSINE mutation at residue 6 in ß-globin
Hemolytic Anemia
pancytipenia
venous thrombosis
increased compliment mediated RBC lysis
Paroxysmal Nocturnal Hemoglobinuria
acquired mutation of hematopoeitic stem cells
Paroxysmal Nocturnal Hemoglobinuria Labs
CD55/59 negative RBCs
Paroxysmal Nocturnal Hemoglobinuria Tx
Eculizumab
Sickle Cell Anemia mutation
substitution of Glutaminc Acid with Valine at position 6 on ß chain
Sickle Cell trait
Heterozygote
Malaria resistance
Virus that cuases aplastic crisis in sickle cell
Parvovirus B19
Osteomyelitis in sickle cell
Salmonella
Sickle Cell Tx
Hydroxyurea (increased HbF)
Bone marrow transplant
Warm and Cold autoimmune hemolytic anemia Ig’s
Warm–IgG
Cold–IgM (pentamer)
Coomb’s Positive for both
Warm hemolytic anemia associated with
SLE
CLL
Rx (alpha methyldopa)
Cold hemolytic anemia associated with
CLL
Mycoplasma pneumoniae
EBV (mono)
Direct Coomb’s test
Anti-Ig added to pts serum
Indirect coomb’s test
normal RBC’s added to pt’s serum
Porphyria cutanea tarda
Defect in uroporphyrinogen decarboxylase
Uroporphyrin accumulates–tea colored urine
Acute intermitent porphyria
Porphobilinogen deaminase defect
Porphobilinogen, ALA, uroprphyrine accumulate
Lead poisoning effect on heme synthesis
Ferrochelatase and ALA dehydratase affected
protoporphyrin and ALA accumulate
Hemophilia A and B defect
A VIII
B IX
X linked
Hemophilia Sx
bleeding
Hemarthroses
easy bruising
Inc. PTT
Defect in plug formation
Blood clots but won’t stick to wall
Decreased Plt count
Increased bleeding Time
Bernard-Soulier Syndrome
Decreased GpIb –> blood will clot but not adhere to vWF on endothelium
Defect in platelet plug formation
no plt clumps on blood smear
incresed bleeding time
normal plts
Glanzmann’s Thrombocytopenia
Dec. GpIIb/IIIa–defect in plt-plt aggregation
Defect in anti-GpIIb/IIIa Ab’s
decreased Plts
increased bleeding time
increased megakaryocytes
Idiopathic Thrombocytopenic purpura
increased megakaryocytes
Pentad of renal and neurologic Sx fever thromobocytopenia microangiopathic hemolytic anemia Increased BT Increased LDH Schistocytes
Thrombotic Thrombocytopenia purpura
Thrombotic Thrombocytopenia purpura Deficiency
ADAMTS 13 –> vWF not degraded
DDx HUS with Thrombotic Thrombocytopenia purpura
No neuro Sx with HUS
von Willibrand’s Disease
Plts can’t adhere to endothelium due to decreased vWF (like Bernard Soulier)
Intrinsic Pathway defect (normal or inc PTT)
Autosomal Dominant
von Willibrand’s Disease Dx
Ristocetin cofactor assay
von Willibrand’s Disease Tx
Desmopressin (DDAVP)
releases vWF from endothelium
DIC
Widespread activation of clotting cascade –> depletes factors
increased bleeding time, PT, PTT
Decreased plts
DIC Causes
Sepsis Trauma OB complications acute pancreatitis malignancy nephrotic syndromes Transfusion
(STOP Making New Thrombi)
DIC Labs
Schistocytes
incresed DDQ
decreased fibrinogen, factors V and VIII
Most common inherited hypercoag in whites
Factor V Leiden
Factor V resistant to protein C degradation
PT gene mutation
increased PT production –> increased venous clots
PTT stops increasing after heparin administration
Inherited antithrombin Deficiency
Inability to inactivate factor V and VIII
Protein C and S deficiency
Warfarin skin necrosis risk
Protein C and S deficiency
Clincal use of FFP
DIC
Cirrhosis
Warfarin overdose (immediate)
Clinical use of Packed RBCs
Acute blood loss
severe anemia
Clinical use of Plts.
Stop sig. bleeding
Cryoprecipitate use
Coagulation factor deficiencies involving fibrinogen and factor VIII
Lymphoid and myeloid neoplasms with wide spread involvement of bone marrow
Leukemia
Discrete tumor masses arising from lymph nodes
Lymphoma
DDx leukemoid reaction with CML
Both have increased WBC, neutrophils, band cells (left shift)
Leukemoid rxn–increased Leukocyte Alkaline Phosphatase
CML–decreased LAP
Hodgkin’s lymphoma associated with what virus
EBV
Reed Sternberg cell
CD30 and CD15
binucleate cell associated with hodgkin’s lymphoma (owl’s eye)
Burkitt’s Lymphoma
NHL young pts Starry Sky pattern t(8:14), c-myc and heavy chain EBV associated
Diffuse B cell lymphoma
#1 adult NHL Old
Mantle Cell Lymphoma
old men NHL
t(11:14)
translocation of cyclin D1 and heavy chain Ig
poor prognosis CD5+
Follicular Lymphoma
Adults NHL
t(14:18)
bcl-2 and heavy chain Ig
bcl-2 inh. apoptosis
HTLV-1 (virus) cancer
Adult T cell lymphoma
monoclonal plasma cell with fried egg appearance Clock Face chromatin high IgG Elderly pt Rouleaux formation
1 elderly cancer of bone
Multiple Myeloma
Multiple Myeloma associated with
Infection increase 1º amyloidosis (AL) Punched out lytic bone lesions M spike on protein electrophoresis Ig light chain in urine (Bence Jone's Protien) Rouleaux formation
Bence Jone’s Protein in urine
Multiple Myeloma
Ig light chain
DDx multiple myeloma from Waldenstrom’s Macroglobulinemia
No lytic bone lesions–WM
Both have M spike (IgM) causing hyperviscosity Sx
Asymptomatic precurser to multiple myeloma
M spike
monoclonal expansion of plasma cells
MGUS (monoclonal gammoglobinopathy of undetermined significance)
< 15 years old Mediatinal Mass Increasd lymphoblasts in blood and bone marrow TdT+ CALLA+ Responds well to Tx
ALL
ALL associated with
Down’s Syndrome
ALL transposition
t(12:21)–better prognosis
t(9:22)–philly chromosome bcr-abl
> 60 yrs.
Smudge cel in peripheral blood smear
increased peripheral lymphocytosis
bone marrow involvement
CLL
TRAP+
Mature B cell tumor
Elderly pt
Cells with projections
Hairy Cell Leukemia
Hairy Cell leukemia Tx
Cladribine (Adenosine Analogue)
Auer Rods
> 65 years old
increased circulating myeloblasts
DIC
AML
DIC in M3
AML transposition (M3) and Tx
t(15:17)
Vitamin A (retinoic acid)
Auer rods
Peroxidase positive cytoplasmic inclusion in granulocytes and myeloblasts
AML
Philidelphia Chromosome
t(9:22)
bcr-abl
t(8:14)
Burkitt’s Lymphoma
c-myc
t(11:14)
Mantle Cell Lymphoma
cyclin D1 activation
t(14:18)
Follicular Lymphoma
bcl-2 activation
t(15:17)
M3 AML
Responsice to All trans retinoic acid (Vit. A)
Child with lytic bone lesions and skin rash
Birbeck Granules
proliferative disorder of dendritic cells
T cells not stimulated
S-100 (neural crest) and CD1a + cells
Langerhans Cell Histiocytosis
Birbeck Granules
Tennis racket looking cells in Langerhans Cell Histiocytosis
Polycythemia Vera
JAK2 mutation
proliferation of stem cells without EPO stimulation
Increase of all blood cell types
Pt. often itches with hot shower
Increased Megakaryocytes and plts.
JAK2 mutation
Essential Thrombocytosis
Fibrotic obliteration of bone marrow
Tear drop cells (Dacrocytes)
Decreased RBCs
JAK2 mutation
Myelofibrosis
bcr-abl transposition
increased cell division without apoptosis
Decreased RBC
Increased WBC and Plts
CML
Philly +
Relative Polycythemia
decrease in plasma volume only
concentrates cells–increased Hct
Appropriate Absolute polycythemia
Increased RBC mass, decreased O2 sat
lung disease, heart disease, high altitude
Inappropriate Absolute polycythemia
Increase RBC mass
No ∆ plasma V or O2 sat
Causes of Inappropriate absolute polycythemia
RCC Wilm's Tumor Cyst HCC Hydronephrosis Ectopic EPO
Polycythemia Vera findings
increased plasma V
greatly increased RBC mass