Hematology, oncology Flashcards
Treatment for refractory ITP?
splenectomy
What binds GPIIB/IIIA?
*Fibrinogen
Weibel-palade
Granules that contain VW factor and P-selectin in endothelial cells.
erythrocyte structure
enucleate + lacks organelles
RBC life span
120 days
anisocytosis
RBCs of varying sizes
poikilocytosis
RBCs of varying shapes
What does bluish color on Wright-Giemsa stain of reticulocytes represent?
Residual ribosomal RNA
thrombocyte life span
8-10 days
What do platelets interact with to form platelet plugs?
fibrinogen
What are alpha granules?
Granules within platelets that contain vWF + fibrinogen + fibronectin.
What are dense granules?
Granules within platelets that contain ADP + calcium.
storage site for platelets?
1/3 of platelet pool is stored in the spleen.
Etiology of petechiae
thrombocytopenia OR decreased platelet function
What is the receptor for vWF?
GpIb
What is the fibrinogen receptor?
GpIIb/IIa
granulocytes?
1) neutrophils
2) eosinophils
3) basophils
Mononuclear cells?
1) monocytes
2) lymphocytes
normal neutrophil range
54-62%
normal lymphocyte range
25-33%
normal monocyte range
3-7%
normal eosinophil range
1-3%
normal basophil range
0-0.75%
What are contained in neutrophil granules?
1) leukocyte alkaline phosphatase (LAP)
2) collagenase
3) lysozyme
4) lactoferrin
What are azurophilic granules?
Lysosomes in neutrophils that contain proteinases, acid phosphatase, myeloperoxidase, and beta-glucuronidase.
Why do hypersegmented neutrophils indicate?
B12/folate deficiency
What do increased bands indicate?
States of myeloid proliferation (bacterial infections, CML)
Neutrophil chemotactic agents
1) C5a
2) IL-8
3) LTB4
4) kvllikrein
5) platelet-activating factor
What is a monocyte?
precursor to macrophage. Monocytes exist in the blood, and when they reach tissue, differentiate into macrophages.
Monocyte description
1) Large, kidney-shaped nucleus.
2) extensive “frosted glass” cytoplasm.
describe macrophage involvement in septic shock pathogenesis
Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock.
eosinophil functions
1) defense against helminths
2) highly phagocytic for antigen-antibody complexes
eosinophil description
1) bilobate nucleus
2) large eosinophilic granules of uniform size
What do eosinophils produce?
1) MBP
2) *histaminase (inactivates histamine)
Causes of eosinophilia
NAACP Neoplasia Asthma Allergic processes Chronic adrenal insufficiency Parasites (invasive)
Basophil functions
1) Mediate allergic reactions
2) Synthesize and release leukotrienes on demand.
What do basophilic granules contain?
1) heparin
2) histamine
Basophilia think…
CML
Mast cell function?
Mediate allergic reactions in local tissues (type 1)
mast cell in allergic reactions mechanism
Bind the Fc portion of IgE to membrane. IgE cross-links upon antigen binding leading to degranulation and release of histamine, heparin, tryptase, and eosinophil chemotactic factors.
Cromolyn sodium clinical use + mechanism
1) asthma prophylaxis
2) prevents mast cell degranulation
What is the link between the innate and adaptive immune systems?
Dendritic cell
What do dendritic cells express on their surface?
MHC class II + Fc
Lymphocyte?
B cell, T cell, or NK cell
Lymphocyte description
Round, densely staining nucleus with small amount of pale cytoplasm.
What is the costimulatory signal necessary for T-cell activation?
CD28
Plasma cell characteristics
1) “clock-face” chromatin distribution and eccentric nucleus
2) abundant RER
3) well-developed Golgi apparatus
Where are plasma cells usually found?
Bone marrow. Normally do not circulate in peripheral blood.
Fetal erythropoiesis timeframe
Young Liver Synthesizes Blood
1) Yolk sac (3-8 weeks)
2) Liver (6 weeks–birth)
3) Spleen (10-28 weeks)
4) Bone marrow (18 weeks to adult)
So in neonatal period, there’s RBC production in the liver + spleen + bone marrow.
What are the embryonic globins
zeta and epsilon
fetal hemoglobin structure
2 alphas, 2 gammas
Clinical relevance of AB blood type
1) Universal recipient of RBCs
2) universal donor of plasma (no antibodies produced)
What immunoglobulin type is anti-B or anti-A?
IgM
Clinical relevance of O blood type
1) If they receive any non-O blood they’ll get a hemolytic reaction.
2) Universal donor of RBCs (no antigens expressed on surface)
3) **universal recipient of plasma
Clinical relevance of Rh positive blood?
Universal recipient of RBCs
What immunoglobulin isotope is against Rh proteins?
IgG
Rhogam mechanism
Anti-D Ig immunoglobulins, which attack and hemolyze fetal RBCs in the maternal blood stream in order to prevent her from developing an immune response to Rh proteins and attacking the fetus.
How do you prevent anti-D IgG production?
Give RhoGAM in third trimester.
more common hemolytic disease of the newborn?
ABO hemolytic disease
Usual scenario of ABO hemolytic disease?
Type O mother with a type A,B, or AB fetus.
Difference between Rh hemolytic disease and ABO hemolytic disease?
1) ABO can occur in a first pregnancy because maternal anti-A or anti-B are formed early in life.
2) ABO doesn’t worsen with future pregnancies.
ABO hemolytic disease presentation
Mild jaundice in the neonate within 24 hours of birth.
ABO hemolytic disease treatment
Phototherapy or exchange transfusion.
missense mutation in HbS?
glutamic acid –> valine
missense mutation in HbC?
glutamic acid –> lysine
hemoglobin electrophoresis mnemonic?
A Fat Santa Claus
A migrates the farthest, followed by fetal hemoglobin, HbS, and HbC. See FA 383
bradykinin affects
1) vasodilation
2) increased permeability
3) increased pain
direct thrombin inhibitors
argatrobran
bivalirudin
dabigatran
thrombolytics
alteplase
reteplase
*streptokinase
tenecteplase
kallikrein mechanism
HMWK –> bradykinin
Tissue factor function
VII –> VIIa
What steps in the coagulation cascade require Ca, phospholipid?
1) VII –> VIIa
2) VIIa –> X
3) VIIa
4) Va
Epoxide reductase?
Enzyme that reduces vitamin K, allowing it to act as a cofactor
Gamma-glutamyl transferase function?
Uses vitamin K to activate vitamin-k dependent components of coagulation cascade.
Vitamin K dependent components?
II,VII,IX,X,C and S
Warfarin mechanism
Inhibits epoxide reductase
vWF function?
Carries and protects factor VIII
Protein C and S mechanism
Thrombin-thrombomodulin complex on endothelial cells activates protein C. Activated protein C and protein S cleave and inactivate Va, VIIIa.
tPA mechanism
Activates plasminogen to plasmin
Plasmin function?
fibrinolysis:
- cleavage of fibrin mesh
- destruction of coagulation factors
Antithrombin mechanism
Inhibits activated forms of factors II, VII, IX, X, XI, and XII.
heparin mechanism
Enhances activity of antithrombin.
Principal targets of antithrombin
Thrombin + factor Xa
Factor V leiden mechanism
Produces a factor V resistant to inhibition by activated protein C
Weibel-palade bodies?
Granules in endothelial cells that contain vWF
Primary hemostasis
platelet plug formation
platelet plug formation mechanism
1) injury
2) exposure
3) adhesion
4) activation
5) aggregation
describe injury step of primary hemostasis
Endothelial damage –> transient vasoconstriction via neural stimulation reflex and endothelin (released from damaged cell)
describe exposure step of primary hemostasis
vWF binds to exposed collagen
describe adhesion step of primary hemostasis
Platelets bind vWF via GpIb receptor at the site of injury –> platelets undergo conformation change –> platelets release ADP and Ca2+ (necessary for coagulation cascade) and thromboxane –> ADP helps platelets adhere to endothelium.
ADP function in primary hemostasis?
1) Helps platelets adhere to endothelium.
2) binding to receptor induces GpIIb/IIIa expression at platelet surface
describe activation step of primary hemostasis
ADP binding to receptor induces GpIIb/IIIa expression at platelet surface.
describe aggregation step of primary hemostasis
Fibrinogen binds GpIIb/IIIa receptors and links platelets. Balance between pro-aggregation and anti-aggregation factors. Temporary plug stops bleeding but it’s unstable and easily dislodged. Secondary hemostasis occurs afterward with the coagulation cascade.
Anti platelet aggregation factors?
1) PGI2 and NO (released by endothelial cells)
2) Increased blood flow
pro aggregation factors
1) TXA2
2) *decreased blood flow
3) increased platelet aggregation
source of thromboxane?
Platelets
what is thrombogenesis?
Formation of insoluble fibrin mesh.
GpIIB/IIIa inhibitors?
Abciximab
Eptifibatide
Tirofiban
Ristocetin mechanism?
Activates vWF to bind GpIb.
Failure of agglutination assay with ristocetin indicates..
1) vWF disease
OR
2) Bernard-Soulier syndrome
Thromboplastin
Plasma protein that aids in blood coagulation through catalyzing conversion of prothrombin to thrombin.
What are acanthocytes associated with?
1) liver disease
2) abetaliproteinemia (states of cholesterol dysregulation)
Abetalipoproteinemia
♣ Code: baby looking like kevo on the ground with a distended abdomen + shitting really nasty-smelling poop/manifests during first year of life with symptoms of malabsorption (abdominal distention + foul-smelling stool). /inherited inability to synthesize apolipoprotein B, an important component of chylomicrons and VLDLs. Fern like structures sticking out of the walls everywhere clear fatty deposits in them/lipids absorbed by the small intestine cannot be transported into the blood and accumulate in the intestinal epithelium, resulting in enterocytes with clear or foamy cytoplasm. Tyrion in the bunk bed + /autosomal recessive loss-of-function mutation in the MTP gene. Baby is swing a medieval ball and chain/acanthocytes. Bunk to right is a yellow taxi + eye on the window looking like below/other presentation = progressive ataxia + retinitis pigmentosa (progressive degeneration of rod photoreceptors.
♣ Location: Bunkroom
What is associated with basophilic stippling?
1) lead poisoning
2) sideroblastic anemias
3) myelodysplastic syndromes
dacrocyte?
teardrop cell
degmacye?
bite cell
Burr cell?
echinocyte
Where are echinocytes found?
1) ESRD
2) liver disease
3) pyruvate kinase deficiency
Differentiating echinocytes from acanthocytes?
Echinocyte projections are more uniform and smaller.
Hereditary elliptocytosis
1) blood smear
2) presentation
3) genetics
1) elliptocytes
2) usually asymptomatic
3) mutation in genes encoding RBC membrane proteins (eg spectrin)
Macro-ovalocytes seen in..
1) megaloblastic anemia
2) marrow failure
Schistocytes seen in…
1) DIC
2) TTP/HUS
3) HELLP syndrome
4) mechanical hemolysis (heart valve prosthesis)
helmet cell
type of schistocyte
When does sickling occur?
1) dehydration
2) deoxygenation
3) high altitude
When are spherocytes seen?
1) hereditary spherocytosis
2) drug and infection-induced hemolytic anemia.
When are target cells seen?
HALT said the hunter to his target. HbC disease Asplenia Liver disease Thalassemia
Etiology of Heinz bodies
Oxidation of Hb -SH groups to -S–S- –> Hb precipitation
When are Howell-Jolly bodies seen?
1) functional hyposplenia
2) asplenia
What are Howell-Jolly bodies?
Basophilic nuclear remnants. Remnants of the nucleus. They are normally removed from RBCs by splenic macrophages.
Other anemia that can by microcytic…
Late stage of ACD
Distinguishing an H pylori duodenal ulcer from ZES ulcer?
H pylori is in first part of duodenum. ZES ulcers generally more distal.
approach to anemia problems?
1) look at MCV
2) look at reticulocyte count
What does reticulocyte count tell you?
If it’s normal or decreased it’s a non hemolytic anemia. If increased, it’s a hemolytic anemia.
Normocytic anemias with decreased reticulocyte count…
1) *early IDA
2) early ACD
3) aplastic anemia
4) CKD
anemia related to copper deficiency…
Microcytic sideroblastic anemia
Megaloblastic macrocytic anemias
1) folate deficiency
2) B12 deficiency
3) *orotic aciduria
non-megaloblastic macrocytic anemia
1) liver disease
2) alcoholism
3) Diamond-Blackfan anemia
Approach to macrocytic anemias…
Determine if megaloblastic or non-megaloblastic
How to determine MCV on blood smear
Lymphocyte nucleus is roughly the same size as a normocytic RBC. If RBC is larger than lymphocyte nucleus, consider macrocytosis. If smaller –> microcytosis.
When do you get iron deficient
1) chronic bleeding
2) malnutrition
3) absorption disorders
4) pregnancy (increases demand in final step in heme synthesis)
labs in IDA
Decreased iron
Increased TIBC
Decreased ferritin
When do RBCs look like in IDA?
small and area of central pallor (hypochromasia)
What does pica indicate?
Iron deficiency anemia
krukenberg related to..
diffuse GI cancer
Sister mary joseph related to..
intestinal GI cancer
spoon nails medical term..
koilonychia
other RF for intestinal GI cancer
type A blood
What is Hb Barts?
Excess gamma-globing formation (all subunits gamma) from 4 allele deletion.
What is HbH disease?
3 alelle deletion: inheritance of chromosome with cis deletion + a chromosome with 1 allele deletion.
Components of HbH
Very little alpha-globin. Excess Beta-lgobin forms (4 betas)
What happens with 2 alpha alleles deleted?
Less clinically severe anemia.
What happens with 1 alpha allele deleted?
No anemia (clinically silent)
Genetics of beta-thalassemia?
Point mutations in splice sites and promoter sequences.
beta-thalassemia minor presentation?
Usually asymptomatic.
B-thalassemia diagnosis?
HbA2 greater than 3.5 on electrophoresis.
B-thalassemia major presentation
severe anemia. These people need blood transfusion.
Major cause of secondary hemochromatosis?
Beta-thalassemia major
Beta-thalassemia features
1) “crew cut” on skull x-ray
2) skeletal deformities
3) “chipmunk” facies
4) hepatosplenomegaly (due to extramedullary hematopoiesis
What are beta thalassemia major patients at increased risk for?
parvovirus B19-induced aplastic crisis.
Hemoglobin in beta-thalassemia major components?
Increased fetal hemoglobin. (a2gamma2)
Presentation of HbS/beta-thalassemia heterozygote?
Mild to moderate sickle cell disease depending on amount of beta-globin production.
Lead poisoning etiology and effect
lead inhibits ferrochelatase and ALA dehydratase, leading to decreased heme synthesis and increased RBC protoporphyrin.
What else does lead inhibit?
rRNA degradation. This is why you get rRNA aggregates (basophilic stippling)
Lead poisoning Presentation
LEAD
Lead lines on gingival and on metaphases of logan bones.
Encephalopathy and Erythrocyte basophilic stippling.
Abdominal colic and sideroblastic Anemia
Drops– wrist and foot drop
sideroblastic anemia inheritance
X-linked defect
sideroblastic anemia etiology
defect in delta-ALA synthase gene
Causes of sideroblastic anemia…
1) genetic
2) myelodysplastic syndromes
3) alcohol
4) lead
5) B6 deficiency
6) copper deficiency
7) isoniazid
treatment for sideroblastic anemia
pyridoxine (B6, which is a cofactor for delta-ALA synthase)
Labs in sideroblastic anemia
1) Increased iron
2) normal to decreased TIBC
3) increased ferritin
blood smear finding in sideroblastic anemia
basophilic stippling of RBCs
what causes megaloblastic anemia?
Impaired DNA synthesis, so nucleus maturation is delayed relative to cytoplasm.
physical exam finding in megaloblastic anemia…
Glossitis (inflammation, soreness of the tongue)
What else can cause folate deficiency?
1) hemolytic anemia
2) pregnancy
How do you differentiate folate from b12 deficiency.
*no neurologic symptoms with folate deficiency.
labs in B12 deficiency
Increased homocysteine + increased methylmalonic acid
Why do you subacute combined degeneration in b12 deficiency?
B12 is involved in fatty acid pathways and myelin synthesis.
What is subacute combined degeneration?
spinocerebellar tract + lateral corticospinal tract + dorsal column dysfunction.
Orotic acuduria etiology
Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect in UMP synthase.
orotic acuduria inheritance
autosomal recessive.
Megaloblastic anemia refractory to folate and B12 think…
orotic aciduria
treatment for orotic acuduria?
uridine monophosphate to bypass mutated enzyme.
How do you differentiate orotic aciduria from ornithine transcarbamylase deficiency?
No hyperammonemia in orotic aciduria.
Physical exam finding in orotic aciduria?
Orotic acid in urine
Diamond-Blackfan anemia
Rapid-onset anemia within 1st year of life due to intrinsic defect in erythroid progenitor cells.
Diamond-Blackfan anemia
Increased HbF but decreased total Hb.
Diamond-Blackfan anemia presentation?
Short stature + craniofacial abnormalities + upper extremity malformations (triphalangeal thumbs).
Nonmegaloblastic anemia
Microcytic anemia in which DNA synthesis is unimpaired.
Nonmegaloblastic anemia on smear
RBC macrocytosis without hypersegmented neutrophils
If there are no hypersegmented neutrophils and macrocytic?
1) alcoholism
2) liver disease
Where would you block the brachial plexus?
Between anterior and middle scalenes.
Findings in intravascular hemolysis
1) decreased haptoglobin
2) Increased LDH
3) schistocytes and increased reticulocytes on blood smear
urine findings with intravascular hemolysis
1) hemoglobinuria
2) hemosiderinuria
3) urobilinogen
4) possibly increased unconjugated bilirubin
What is extravascular hemolysis?
Macrophages in spleen clearing RBCs
Findings in extravascular hemolysis
1) spherocytes in peripheral smear
2) Increased LDH.
3) ***no hemoglobinuria/hemosiderinuria
4) increased unconjugated bilirubin.
urine findings with extravascular hemolysis
1) urobilinogen
ACD associations
1) RA
2) SLE
3) neoplasia
4) CKD
ACD findings
1) decreased iron
2) decreased TIBC
3) increased ferritin
treatment for ACD related to CKD?
EPO
ACD classification
Normocytic, but can become microcytic
Underlying etiology of aplastic anemia
destruction of myeloid stem cells
Drugs that can cause aplastic anemia?
1) benzene
2) chloramphenicol
3) alkylating agents
4) antimetabolites
viruses that can cause aplastic anemia?
1) parvovirus B19
2) EBV
3) HIV
4) hepatitis
falcon anemia
short stature + increased incidence of tumors/leukemia + cafe-au-lait spots + thumb/radial defects.
Other common cause of aplastic anemia
Following acute hepatitis
Labs in aplastic anemia?
1) decreased reticulocyte count
2) increased EPO
dry bone marrow tap…
aplastic anemia
symptoms of aplastic anemia..
Fatigue + malaise + pallor + purpura + mucosal bleeding + petechiae + infection.
Aplastic anemia treatment
1) stop the drug.
2) immunosuppression with antitymocyte globulin Or cyclosporine
3) bone marrow allograft
4) RBC/platelet transfusion
5) bone marrow stimulation (eg, GM-CSF)
defective proteins in hereditary spherocytosis
1) nnkyrin
2) band 3
3) protein 4.2
4) spectrin
hemolysis type in hereditary spherocytosis?
extravascular. Spleen is removing RBCs
What accumulates with lead poisoning?
protoporphyrin
