HemeOnc First Aid Flashcards
What do RBC membranes contain?
Cl-/HCO3- antiporter; allows export of HCO3 and transport CO2 from periphery to lungs
What granules do thromboyctes have and what do they contain?
- dense granules
- ADP
- Ca2+
- alpha granules
- vWF
- fibrinogen
- fibronectin
vWF receptor is:
Fibrinogen receptor is:
GpIb
GpIIb/IIIa
What do specific granules of neutrophils contain?
leukocyte alkaline phosphatase (LAP), collagenase, lysozyme, and lactoferrin
what do azurophilic granules (lysosomes) of neutrophils contain?
proteinases, acid phosphatase, myeloperoxidase, and B-glucuronidase
Hypersegmented neutrophils are seen in
Vit B12/folate deficiency
increased number of band cells reflect states of
increased myeloid proliferation (bacterial infections, CML)
found in the blood, this cell has a large, kidney shaped nucleus and extensive “frosted glass” cytoplasm
monocyte
What role do macrophages have in precipitating septic shock?
Lipid A from bacterial LPS binds CD14 on macrophages to initiate septic shock
causes of eosinophilia include
NAACP
- Neoplasia
- Asthma
- Allergic process
- Chronic adrenal insufficiency
- Parasites (invasive)
What do basophils contain?
heparin and histamine
basophilia is uncommon but can be a sign of
myeloproliferative disease, esp CML
What do mast cells release once they bind the Fc portion of IgE and IgE crosslinks?
histamine, heparin, tryptase, and eosinophil chemotactic factors
What do dendritic cells express on their surface? What are these cells called in the skin?
MHC class II and Fc receptors
Langerhans cells in the skin
Once mature, B cells migrate to peripheral tissues including
follicles of lymph nodes, white pulp of spleen, and unencapsulated lymphoid tissue
All T cells have what CD marker?
CD28 (costimulatory signal) necessary for T cell activation
What cells have “clock-face” chromatin distribution and eccentric nucleus, abundant RER, and well-developed Golgi?
plasma cell
vWF is from where?
Weibel-Palade bodies of endothelial cells and alpha-granules of platelets
What drugs inhibit GpIIb/IIIa directly?
abciximab, eptifibatide, and tirofiban
What activates vWF to bind GpIb?
failure of aggregation of this is seen in…
ristocetin
von Willebrand disease and Bernard-Soulier syndrome
what does an acanthocyte look like and what pathology is associated with it?
spur cell
Liver disease, abetalipoproteinemia (states of cholesterol dysregulation)
What is a dacrocyte and when would I see it?
teardrop cell
bone marrow infiltration (eg myelofibrosis); mechanically squeezed out of its home in the bone marrow
What is the official name of a bite cell?
Degmacyte
When would I see echinocytes?
burr cells
ESRD, liver disease, pyruvate kinase deficiency
projections more uniform than acanthocyte
When do you see target cells?
HbC disease, Asplenia, Liver disease, and thalassemia
4 alpha globin allele deletions
Hb Barts - gamma4
hydrops fetalis
3 alpha-globin allele deletions
HbH (beta 4)
secondary hemochromatosis, “crew cut” on skull XR, “chipmunk facies”, increased risk of Parvovirus B19
Beta-thalassemia major
lead inhibits ferrochelatase and ALA dehydratase leading to
decreased heme synthesis and increased RBC protoporphyrin
Ssx of lead poisoning?
- Lead lines on gingivae (Burton lines) and on metaphyses of long bones on XR
- Encephalopathy and erythrocyte basophilic stippling
- Abdominal colic and sideroblastic anemia
- Drops - foot and wrist
What is used for lead chelation in kids?
succimer
genetic cause of sideroblastic anemia is
Xlinked defect in ALA synthase gene
How do you differentiate orotic aciduria from ornithine transcarbamylase deficiency?
both will have increase orotic acid, but ornithine transcarbamylase deficiency will also have hyperammonemia
in orotic aciduria, what is the defect in?
defect in UMP synthase with inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway)
Historically, how was vit B12 deficiency diagnosed?
diagnosed with Schilling test, a 4 stage test that determines if the cause is dietary insufficiency v malabsorption
Nonmegaloblastic macrocytic anemia is likely caused by…
RBCs still have macrocytosis but without
alcoholism, liver disease
hypersegmented neutrophils
rapid onset of anemia within first year of life due to intrinsic defect in erythroid progenitor cells
dx?
what is a major physcial feature of this person?
Diamond Blackfan anemia
triphalangeal thumbs
notable causes of intravascular hemolysis
mechanical hemolysis
paroxysmal nocturnal hemoglobinuria
microangiopathic hemolytic anemias
hemolytic anemia in a newborn
pyruvate dehydrogenase deficiency
AR, decrease ATP, rigid RBCs, extravascular hemolysis
increase 2,3BPG leads to decreased hemoglobin affinity for O2
coombs negative hemolytic anemia, pancytopenia, and venous thrombosis
paroxysmal nocturnal hemoglobinuria
What labs will you see with PNH?
CD55/59 negative RBCs on flow cytometry
Porphyria cutanea tarda condition affects what enzyme?
uroporphyrinogen decarboxylase (AD mutation)
Prophobilinogen deaminase, previously known as uroprophyrinogen I synthase has an autosomal dominant mutation in what condition?
acute intermittent porphyria
acute intermittent porphyria has what symptoms?
How is this treated?
- painful abdomen
- Port-wine colored urine
- Polyneuropathy
- Psychological disturbances
- Precipitated by drugs (P450 inducers, alcohol, starvation)
tx with glucose and heme, which inhibit ALA synthase
PT tests function of what factors?
common and extrinsic pathway (I, II, V, VII, X)
PTT tests function of what factors?
common and intrinsic pathway (all factors except VII and XIII)
In a mixing study, where normal plasma is added to a pt’s plasma, how do you know if you have a clotting factor deficiency v factor inhibitor?
clotting factor deficiencies should correct (PT or PTT returns to normal) whereas factor inhibitors will not correct
hemophilia A, B, and C are deficiencies of what factors?
What are their inheritence patterns?
A - factor VIII (X linked recessive)
B - factor IX (X linked recessive)
C - factor XI (autosomal recessive)
What will vitamin K deficiency do to PT, PTT and bleeding time?
increase both PT and PTT
bleeding time is normal
inhibition or deficiency of ADAMTS 13 causes
Thrombotic thrombocytopenic purpura
decreased degradation of vWF multimers; increased platelet adhesion, increased platelet aggregation and thrombosis
Anti-GpIIb/IIIa antibodies are seen in
immune thrombocytopenia
defect in platelet integrin alpha IIB beta3 (GpIIb/IIIa) leading to defect in platelet-to-platelet aggregation, and therefore platelet plug formation
normal platelet count
Glanzmann thrombasthenia
Defect in platelet plug formation causing large platelets, decreased GpIb (Defect of platelet to vWF adhesion)
Bernard-Soulier Syndrome
tx for von Willebrand disease?
desmopressin, which releases vWF stored in endothelium
What are complications of Factor V Leiden?
DVT, cerebral vein thromboses, recurrent pregnancy loss
thrombotic skin necrosis with hemorrhage after administration with warfarin, I am thinking…
pt has protein C deficiency
What does cryoprecipitate have in it?
fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
Why is there a risk of hyperkalemia with blood transfusions?
RBCs may lyse in old blood units and then get transfused with their contents everywhere
What are the four types of Hodgkin lymphoma?
- nodular sclerosis
- lymphocyte rich
- mixed cellularity
- lymphocyte depleted
Genetics of Burkitt lymphoma
t(8:14)
c-myc (8) and heavy chain Ig(14)
genetics of diffuse large B cell lymphoma
alterations in Bcl-2, Bcl-6
(MC type NHL in adults)
genetics of follicular lymphoma
t(14:18)
heavy chain Ig (14) and BCL-2 (18)
presents with painless “waxing and waning” lymphadenopathy
follicular lymphoma
genetics of mantle cell lymphoma
t(11:14)
adult males - cyclin D1 (11) and heavy chain Ig (14), CD5+
marginal zone lymphoma genetics and association with
t(11;18)
cyclin D1 (11) and BCL-2 (18)
a/w chronic inflammation (eg Sjogren syndrome, chronic gastritis/MALT lymphoma)
In this AIDS-defining illness, with variable presentation, mass lesions on MRI need to be distinguished from toxoplasmosis via CSF analysis or other lab tests
Primary Central Nervous System Lymphoma
atypical CD4+ cells with “cerebriform” nuclei and intraepidermal neoplastic cell aggregates (Pautrier microabscesses)
mycosis fungoides/Sezary syndrome (T cell leukemia)
ssx of multiple myeloma
CRAB
- hyperCalcemia
- Renal involvement
- Anemia
- Bone lytic lesions/Back pain
Multiple myeloma: Monoclonal M protein spike
What disease other than multiple myeloma has an M protein spike =IgM?
How can it be differentiated?
Waldenstrom macroglobulinemia
hyperviscosity syndrome (eg blurred vision, Raynaud phenomenon, no CRAB ssx)
monoclonal expansion of plasma cells but bone marrow shows <10%
Monoclonal gammopathy of undetermined significance (MUGS)
no CRAB ssx, can become multiple myeloma
Pseudo Pelger Huet anomaly is
a myelodysplastic syndrome
neutrophils with bilobed nuclei typically seen after chemo
Kids with ALL and this mutation have a better prognosis
t(12:21)
smudge cells are seen in
CLL
What is Richter transformation?
CLL/SLL transformation into an aggressive lymphoma, most commonly DLBCL
dry tap on aspiration
hairy cell leukemia
hairy cell leukemia will stain positive for
TRAP - tartrate-resistant acid phosphatase
has been replaced by flow cytometry for the most part
tx for hairy cell leukemia
cladribine, pentostatin
Aeur rods are found in
AML
myeloperoxidase positive cytoplasmic inclusions seen mostly in
APL (formerly M3 AML)
APL: t(15;17) responds to
all-trans retinoic acid (vit A), inducing differentiation of promyelocytes
Philadelphia chromosome t(9:22), BCR-ABL is in
CML
CML can accelerate and transform into
AML or ALL (blast crisis)
tx CML with
bcr-abl tyrosine kinase inhibitors like imatinib
what disorders are associated with V617F JAK2 mutation?
Chronic myeloproliferative disorders
- polycythemia vera
- essential thrombocytopenia
- myelofibrosis
What is erythromelalgia and what does it occur in?
severe burning pain and red-blue coloration due to episodic blood clots in vessels of extremities
polycythemia vera and essential thrombocythemia
Presents in a child as lytic bone lesions and skin rash or as recurrent otitis media with a mass involving the mastoid bone
langerhans cell histiocytosis
What are characteristics of cells in langerhans cell histiocytosis?
cells are functionally immature and do not effectively stimulate primary T cells via antigen presentation.
Cells express S-100 (mesodermal origin) and CD1a
Birbeck granules (tennis raquets or rod shaped on EM)
reverse dapigatran with what drug?
idarucizumab
What class of drugs do abciximab, eptifibatide, and tirofiban go into?
Gp IIb/IIIa inhibitors
