Heme/Onc pt 2 (FA) Flashcards
t(8,14)
Burkitt’s Lymphoma
t (9, 22)
Chronic Myelogenous Leukemia
t (11; 14)
Mantle Cell Lymphoma
t ( 14;18)
follicular cell lymphoma
t( 15;17)
APL (acute myeologenous leukema type M3)
Langerhans Cell histiocytosis
overproduction of dendritic cells
+S100, CD1a, beribeck granules
symptoms: bone lesions, otitis media with mass on mastoid, skin rash
affects children
Polycethmia:
relative vs absolute (2ndary)
relative: decrease in blood vol such as dehydration or burn
absolute: actual increase in RBC can be “appropriate” or “physiologic” like when you are at high altitudes, have OSA/heart failure/OSA
can be absolute “innapropriate” usually due to ectopic EPO production due to RCC, HCC,hydronephrosis
polycythemia vera (primary/essential)
due to mutation causing consititutively active JAK2, which causes increased RBC production (note EPO will be low unlike in 2ndary)
Essential Thrombocythemia
increase in platelets and megakaryocytes (may be big or malformed) (JAK2)
Myelofibrosis
fibrosis obliterates bone marrow, teardrop cells (JAK2)
Acute Lymphoblastic Leukemia
CHILDREN ; TDT+
t-cell: mediastinal mass/ SVC syndrome
B-cell: CD10+
DOWN’S SYNDROME
what indicates better prognosis of ALL
t (12; 21)
Chronic Lymphoblastic Leukemia
B cell neoplasm
Smudge cells “crushed little lymphocytes”
CD20+, CD35+, CD5+
Richter Transformation: becomes DLBCL
Hairy Cell Leukemia
EBV related, TRAP+,
Bcell with hairy filamentous projections
bone marrow fibrosis
affects adult males
Acute Myelogenous Leukemia
Auer rods, MPO+, APL= t(15;17), DIC,
Down’s association
exposure to alk chemo, radiation, myeloprolif disorders
Chronic Myelogenous Leukemia
t (9; 22) Philadelphia chromosome; BCR-ABL
low LAP
can become AML or ALL in “blast crisis”
CML t(x)
tyr kinase inhibitor imatinib
Hairy Cell Leukemia t(x)
cladribine, pentostatin
Multiple Myeloma
plasma cell neoplasia
"CRAB" hyperCalcemia Renal involvement/ Rouleaux formation of RBC Anemia/ can lead to amyloidosis (AL) Bone lytic lesions/Back pain
MM has increase in what proteins
M spike
increase in IgG or IgM
this poor variability of Ig’s causes decreased immunity
MGUS
just an isolated M spike without CRAB symptoms
asymptomatic with 1% chance of becoming MM
Waldenstrom Macroglobulinemia
M spike with hyperviscosity of blood (blurry vision+ Raynaud’s)
no CRAB symptoms
Myelodysplastic Syndromes
stem cell disorder w/ ineffective hematopoiesis
can be sporadic or related to exposure to radiation/benzene/chemo
can become AML
Pseudo-Pelger-Huet Anomaly
seen post-chemo
neutrophils w bilobed nuclei
Burkitt Lymphoma (BCELL)
t(8;14) c-myc(8)
starry night, sheets of lymphocytes, tingeable body (macrophage)
children
EBV
DLBCL (BCELL)
BCL2, BCL6
most common non-hodgekin lymphoma
older adults
Follicular Lymphoma (B CELL)
t ( 14; 18) "fo-llicular.. fo--rteen" BCL2( 18) middle age adults "waxing waning lymphadenopathy" small cleaved cells= grade 1, large cells= 3
Mantle Cell Lymphoma (B CELL)
t (11;14) CYCLIND1 (11); CD5+
adult males
very aggressive
Marginal Zone Lymphoma (BCELL)
t (11;18) CYCLIND1 (11)
association with inflamm d(x) like SLE, Sjogren, MALT
Primary CNS(BCELL)
AIDS defining illness
confusion/mem loss/seizures
MRI looks like Toxo
Adult T cell Lymphoma
HTLV
IVDU
cutaneous T cell lesion
lytic bone lesions, hypercalcemia
Mycosis fungoides
adult T cell Lymphoma
skin patches/plaques of CD4+ T cells with “cerebriform nuclei” and “pautrier microabcess”
Sezary Syndrome
if Mycosis Fungoides progresses to Tcell leukemia
Hodgekin’s vs NonHodgekins
Hodgekins has Reed-Steernberg cells (owl)
bimodal age distribution (young adults and over 55)
single lymphnodes or contiguous
better prognosis
EBV assn
most common Hodgekin’s lymphoma
nodular sclerosis
best prognosis Hodgekin’s lymphoma
lymphocyte rich
Hodgekin’s lymphomas seen in immunocompromised
Lymphocyte depleted
mixed cellularity
Antithrombin def
no change in PT, PTT, Thrombin time
but Heparin is less effective, evidenced by less lengthening of PTT
inherited or acquired (renal failure causes antithrombin lost in urine)
Factor V Leiden
resistant to inactivation by protein C leads to hypercoag state (DVT, miscarraige, cerebral v thromboses)
POINT mutation near cleavage site
Protein C or S deficiency
cant inactivate Factor Va and Factor VIIIa
increased risk of thrmbotic skin necrosis upon warfarin
prothrombin gene mutation
prothrombin made too much bc of mutation in 3’ UTR
hypercoag state
DIC
activation of widespread clotting– clotting factor def– widespread bleeding
note that platelets will be decreased, BT/PT/PTT increased
increased Ddimer, decreased fibrinogen
causes of DIC
STOP Making New Thrombi Sepsis (gram neg) Trauma Obstetrics Pancreatitis Malignancy Nephrotic Syndrome Transfusion
what changed in VWF disease
both bleeding time and PTT increased b/c decreased VWF but also decreased Factor VIII
Thrombotic thrombocytopenic purpura
ADAMSTS13 defect
can’t cleave VWF, so platelet aggregation and thrombosis
s(x)- neuro, renal, fever, thrombocytopenia, and microangiopathic hemolysis
Immune Thrombocytopenia
antibodies against G2b3a
platelets/antibody complex is removed by spleen so low platelet count
Hemolytic Uremic Syndrome
EHEC 0157:H7 causes injury to endothelial wall causing platelet consumption and microangiopathic hemolysis
usually preceeded by bloody diarrhea and seen in kiddos
Glanzmann
defect in G2b3a
platelets cant aggregate
no platelet “clumping”
(note, platelet count is normal!)
Bernard Soulier
GP1b defect
Sideroblastic Anemia? deficiency
ALA synthase def
Lead Poisoning? deficiency
ALA dehydratase and/or ferrochetalase def
AIP? deficiency
PBG deaminase def
PCT? deficiency
Urophrinogen decarboxylase def
s(x)- bilstering photosensitive rash+ hyperpigmentation+ “tea colored urine”
PCT
PCT and AIP inheritance
AD
AIP symptoms?
5P's painful abdomen port wine urine polyneuropathy psych disturbances precipitated by CYP450 inducers, starvation, alc
AIHA (+ Direct Coombs)
warm- IgG- chronic anemia- SLE/CLL/alpha methyl dopa
cold- IgM- acute anemia- Mononucleosis and M.Pneumo
triggered by cold– Raynaud’s
Microangiopathic Hemolytic Anemias
HUS, TTP, DIC, SLE, HELLP, malignant htt
SCHISTIOCYTES
macroangiopathic hemolytic anemia
mechanical valves, AS
schistiocytes
HbC disease
Glutamic Acid is replaced with lyCine
note that this travels the shortest distance on electrophoresis bc it is +, but the + also leads to milder disease bc no neutral pockets to sickle
RBC will show target cells and crystal shaped RBC (not sickle!)
Paroxysmal Nocturnal Hemoglobinuria
defect in PIGA gene so can’t attach GPI anchors to RBC, these GPI anchors would normally display CD55 and CD59. Without CD55 and CD59 displayed RBC are vulnerable to attack by complements.
presentation will include pancytopenia, hemolytic anemia, and thrombuses in weird places
what does PNH increase incidency of
leukemias (like AML)
what is PNH treatment
Eculizumab (complement inhibitor)
Pyruvate Kinase def
AR deficiency of Pyruvate Kinase
no glycolysis so no ATP.
RBC stiff and prone to hemolysis w/ decreased O2 affinity and increased levels of 2,3BPG
can cause hemolytic anemia of newborn
G6PD type of inheritance
XR
G6PD
XR mut in G6PD, inhibits HMPshunt, so decreased NADPH levels
without NADPH glutathione can’t be repleted and there is increased oxidative stress
situations of added oxidative stress will cause hemolysis- antimalarials, Fava beans, sulfa drugs, infections
RBC findings in G6PD
Heinz Bodies (want some Heinz ketchup with those FAVA beans?) Bite cells
Hereditary Spherocytosis inheritance?
AD
RBC of Spherocytosis
smaller/same size with no central pallor and increased MCHC
Aplastic Anemia
Fatty infiltration of bone marrow resulting in pancytopenia
Retic count will be LOW (bc low production capability) EPO will be high (assuming kidney intact)
causes of Aplastic Anemia
radiation :benzene, chlorompenicol, and alkylating agents
Viral: parvo, EBV, HIV, and Heps
Fanconi- renal involvement too w short stature and thumb/radial defects
idiopathic
pathophysiology of Anemia of Chronic Disease
inflammation -> increase in Hepcidin -> blocks Ferroprotin-> Fe stuck in (1) macrophages and (2)can’t be absorbed from SI
Low Iron, High Ferritin, Low TIBC
causes of inflammation are SLE, RA, CKD, neoplasia
Diamond Blackfan Anemia
Macrocytic anemia without issues in DNA synthesis
seen before 1yo
issue with erythroid progenitor (note %HbF increased)
short, craniofacial abnormal, UE malformed, triphalangeal joints
Orotic Aciduria
one cause of megaloblastic anemia: AR defective UMP synthase
UMP synthase makes orotic acid into dUMP which is used to then make dTMP, without which DNA synth will be halted
labs: increased orotic acid without hyperammonemia
treatment of orotic aciduria
uridine triacetate to bypase UMP synthase
how to tell folate def and B12 def apart
folate def: can occur sooner, alcoholics, increased demand of folate, pregnancy, drugs like MTX and phenytoin, absorption happens in prox jeju
Folate def: increase in homocysteine but not in methyl malonic acid
B12 def: increase in both homocysteine and methylmalonic A. Also subacute combined degeration of spinal cord
causes:years of veganism, pernicious anemia, gastrectomy, diphillobotrom,
megaloblastic anemia rbc?
hypersegmented neutrophils
RBC macrocytosis
what are the Microcytic Anemias?
SALTI sideroblastic anemia of chronic disease lead poisoning thalassemia iron deficiency
sideroblastic anemia
XR or reversible/acquired ALA synthase deficiency
alcohol, cu def, and decreased B6/ Isoniazid use
labs will show: increased iron and ferritin (not even being used in RBC right?) and decreased TIBC
sideroblastic anemia rbc?
siderblasts in bone marrow
basophilic stippling in blood stream
t(X) of sideroblastic anemia
pyridoxine
Lead Poisoning symptoms?
LEAD
Lead lines on gingiva (Burton lines) and on long bones
Encephalopathy and erythrocyte basophilic stippling
Abdominal colic and sideroblastic anemia
Drops- foot/wrist drop (also t(x)- Dimercaprol, eDta)
Lead Poisoning t(x)
Dimercaprol, EDTA, succimer for the kiddos
what is wrong in lead poisoning?
lead inhibits ALA dehydratase and Ferrochetalase, so RBC not made
rRNA degradation also inhibited so basophilic stippling seen
Beta Thalassemia caused by?
point mut at splice sites and promoter sequences (not a problem with DNA but a problem in mRNA!) which causes decreased Bglobin SYNTHESIS
what is alpha thalassemia caused by
alpha globin GENE deletion.
4 genes deleted- HbBarts which is 4gamma, incompatible with life– hydrops fetalis
3 genes deleted- HbH disease, bc so little alpha is produced, beta globin forms tetramers- B4
2 genes deleted- less clinically severe (cis= Asian, trans= Africans)
1 allele deleted- no anemia
Iron Def Anemia
due to: bleeding, malabsorption, malnutrition, increased demand(pregnancy)
needed for ferrochetalase enzyme
labs: decreased iron, decreased ferritin, increased TIBC
symptoms of Iron Deficiency Anemia
PICA, koilonychia (spoon nails)
maybe glossitis, cheilosis, Plummer-Vinson (esophageal webs + dysphagia)
Bortezomib, Carfilzomb (in FA not in sketchy!)
proteasome inhibitor, stops cell cycle at G2/M
used for MM and mantle cell lymphoma
AE: peripheral neuropathy and Herpes Zoster reactivation
