Heme Onc Flashcards Preview

Step 1 Flash Cards > Heme Onc > Flashcards

Flashcards in Heme Onc Deck (68):

platelet granules

- dense granules contain ADP and Ca
- alpha granules contain vWF, fibrinogen



- differentiates into macrophages in the tissues
- large, kidney shaped nucleus
- extensive "frosted glass" cytplasm



- differentiate from circulating blood monocytes
- activated by gamma-interferon
- CD 14 cell surface marker



- defends against helminths
- produces histaminidase and arylsulfatase (limits reaction following mast cell degranulation)



- mediates allergic reaction
- granules contain heparin, histamine and leukotrienes


mast cell

- IgE cross-links upon antigen binding, causing degranulation which releases histamine, heparin and eosinophil chemotactic factor
- involved in Type I HS reactions
- systemic mastocytosis: mast cell proliferation in the BM and other organs (increased gastric acid 2/2 histamine)


dendritic/Langerhans cells

- MHC Class II and Fc receptor on surface
- APCs
- Langerhans cells in the skin have "racket shaped" intracytoplasmic granules- Birbeck granules


platelet plug formation cascade

- injury causes subendothelial collagen to expose vWF
- adhesion of platelets to vWF via GpIb receptor
- platelet degranulation releases ADP and Ca, which causes platelets to expose GPIIb/IIIa receptors
- fibrinogen binds GpIIb/IIIa receptors --> platelet aggregation


increased ESR seen in

- infections, AI disease, malignant neoplasms, GI disease like UC, pregnancy


decreased ESR seen in

- polycythemia, sickle cell, CHF, microcytosis, hypofibrinogenemia


acanthocytes indicative of

- liver disease, abetalipoproteinemia


basophilic stippling indicative of

- anemia of chronic disease, Etoh abuse, Lead poisoning, Thalassemias
- Basically, ACiD alcohol is LeThal


schistocyte/helmet cells indicative of

- DIC, TTP/HUS, traumatic hemolysis (mechanical heart valve)


tear drop cell indicative of

- bone marrow infiltration (myelofibrosis)


target cell indicative of

- HbC disease, Asplenia, Liver disease, Thalassemia
- "HALT" said the hunter to his target


iron deficiency anemia labs

decrease iron, inc TIBC, low ferritin, inc RDW
- can have pitted nails
- increased free protoporphyrin because heme = iron + protoporphyrin and you are not making enough iron


Plummer-Vinson syndrome

- a manifestation of iron deficiency anemia
- triad: Fe def anemia, esophageal webs (dysphagia) and atrophic glossitis (beefy red tongue)


alpha thalassemia

- cis deletion in Asians, trans deletion in Africans
- 4 allele deletion - hydrops fetalis
- 3 allele deletion - HbH disease
- 2 allele deletion - no clinically significant anemia


beta thalassemia minor

- point mutations at splice sites and promoter sequences lead to decreasedB globin synthesis
- prevalent in mediterranean populations
- B chain is underproduced
- usually asymptomatic
- diagnose with increased HbA2 (< 3.5%) on electrophoresis
- carrier status carries protection from plasmodium falciparum malaria


beta thalassemia major

- homozygote mutation, B chain is absent --> severe anemia requiring blood transfusion
- marrow expansion leads to skeletal deformities ("chipmunk" facies)
- increased risk of parvo B19 aplastic anemia
- HbF is protective, so symptoms show up at 6 months


HbS/B thalassemia heterozygote

- mild to moderate sickle cell disease depending on the amount of B globin production


lead poisoning

- inhibits ferrochelatase and ALA dehydratase --> decreased heme synthesis and inc RBC protoporphyrin
- LLEEAADD: Lead Lines, Encephalopathy and Erythrocyte basophilic stippling, Abdominal colic and sideroblastic Anemia, Drops (foot and wrist drop) and Dimercaprol/EDTA for treatment
- give succimer to kids cause it "sucks" to be a kid with lead poisoning


sideroblastic anemia

- defect in protoporphyrin synthesis (heme = Fe + protoporphyrin, so defect in heme synthesis)
- can be hereditary defect in ALA synthase or aquired myelodysplastic syndromes or reversible (alcohol, lead, B6 def, copper def, isoniazid)
- Fe enters the mitochondria to form heme, but there is no protoporphyrin to combine with --> Fe laden macrophages around the nucleus
- increased iron, normal TIBC, inc ferritin
- treat with pyroxidine


Schilling Test

- enteric B12 + IM B12 - if increased in urine, diagnoses deficiency
- enteric B12 + IF - if increased in urine now, then its a IF deficiency
- if it never increases in the urine, its malabsorption (pancreatic insufficiency, ileal disease, or SIBO)


orotic aciduria

- cannot convert orotic acid to UMP (defect in UMP synthase)
- AR
- megaloblastic anemia non-responsive to folate or B12
- no hyperammonemia
- treat with uridne monophosphate to bypass mutated gene


intravascular hemolysis

- decreased haptoglobin, increased LDH, schistocytes and reticulocytes, urobilinogen in urine


extravascular hemolysis

- spherocytes, increased LDH + increased unconjugated bili


anemia of chronic disease

- inflammation causes the liver to release hepcidin, which binds ferritin and suppresses EPO
- low iron, low TIBC and high ferritin, increased free erythrocyte protoporphyrin
- treat the primary disease and some people get EPO (esp cancer pts)



- most common enzymatic disorder of RBCs
- X linked recessive
- defect in G6PD leads to decreased glutathione, increased RBC susceptibility to oxidative stress and hemolysis
- back pain (Hgb is nephrotoxic), hemoglobinuria
- Heinz bodies and bite cells


pyruvate kinase deficiency

- AR defect in pyruvate kinase
- decreased ATP and rigid RBCs
- hemolytic anemia of the newborn


Hgb C defect

- glutamic acid to lysine mutation at residue 6 in B globin
- Hgb C crystals seen in smear
- will no travel as far on electrophoresis because there is decreased total negative charge
- Pts with HbCS have milder disease than Hb SS



- inreased complement mediated lysis of RBCs due to lack of GPI anchor for factors that prevent from complement destruction
- resp acidosis at night causes complement mediated RBC lysis -->coombs negative hemolytic anemia, pancytopenia, and venous thrombosis
- CD55/59 negative cells - acquired mutation in the precursor cell
- treat with eculizumab
- increased incidence of AML


Warm agglutinin hemolytic anemia

- IgG mediated, can be seen with SLE, CLL and certain drugs (penicillin, methyldopa)
- coombs +ve


cold agglutinin hemolytic anemia

- IgM mediated, acute anemia triggered by cold, seen in CLL, mycoplasma pneumonia, and infectious mono
- coombs +ve


lead poisoning
- enzymes affected, accumulated substrate and presenting symptoms

-ALA synthase and ferrochelatase
- protoporphyrin, d-ALA
- microcytic anemia, GI and kidney disease


acute intermittent porphyria
- enzyme affected, accumulated substrate and presenting symptoms

- porphobilinogen deaminase
- porphobilinogen, d-ALA, coporphobilinogen (urine)
- symptoms (5 P's): painful abdomen, port-wind colored urine (gets darker when exposed to air), polyneuropathy, psychological disturbances, precipitated by drugs, alcohol and starvation
- treat with glucose and heme, which inihibit ALAS


porphyria cutanea tarda
- enzyme affected, accumulated substrate and presenting symptoms

- uroporphyrinogen decarboxylase
- uroporphyrin (tea colored urine)
- blistering cutaneous photosensitivity
- most common porphyria


Bernard-Soulier syndrome

- dec platelet count, increased bleeding time
- defect in platelet plug formation due to decreased Gp1b --> defect in platelet-vWF adhesion


Glanzmann thrombasthenia

- increased bleeding time
- defect in platelet plug formaiton due to decreased GpIIb/IIIa --> defective platelet aggregation
- blood smear shows no platelet clumping


immune thrombocytopenia

- dec platelet count, increased bleeding time
- anti-GpIIb/IIIa Abs --> splenic macrophage consumption of platelet/Ab complex
- may be triggered by viral illness, decreased platelet survival
- increased megakaryocytes on BMB



- inhibition or deficiency of ADAMTS 13 (vWF metalloproteinase) --> decreased degradation of vWF multimers
- large multimers increase platelet adhesion and increase platelet aggregation and thrombosis
- decreased platelet survival
- labs show schistocytes and increased LDH
- sympt (pentad): neurologic and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia
- treat with exchange transfusion and streroids


vWF disease

- increased bleeding time with normal or increased PTT
- vWF protects factor 8
- mild inherited bleeding disorder , AD
- diagnosed with ristocetin cofactor assay (decreased agglutination is diagnostic)
- treat with DDAVP


Factor V Leiden

- factor V resistant to inhibition by activated protein C, so adding protein C will not change the normal PTT
- most common cause of hypercoaguability in whites


prothrombin gene mutation

- mutation in the 3' untranslated region --> increased production of prothrombin --> increased plasma levels and venous clots


antithrombin deficiency

- antithrombin deficiency - doesnt have any direct effect on PT/PTT, but PTT will not increase as much with heparin administration


protein C or S deficiency

- decreased ability to inactivate factors V and VIII
- increased risk of thrombotic skin necrosis with hemorrhage following coumadin


leukemoid reaction vs. CLL

- leukemoid reaction will have increased ALP
- CLL will have decreased ALP


Reed-Sternberg cells

- seen in Hodgkin lymphoma
- "owl eye" nuclei, CD15 and CD30+ (2 owl eyes x 15 = 30)
- nodular sclerosing type most common
- lymphocyte-rich forms have better prognosis


Burkitt Lymphoma

- occurs in adolescents and young adults
- t(8;14) - translocation of c-myc and heavy chain IgG
- starry sky appearance, sheets of lymphocytes with interspersed macrophages
- med sized lymphocytes with high proliferation ( high KI-67 fraction)
- associated with EBV
- jaw lesion in endemic form in Africa, pelvis and abdomen in sporadic form


diffuse large B cell lymphoma

- usually older adults, 20% kids
- t (14;18)
- most common type of non-Hodgkin lymphoma in adults


mantle cell lymphoma

- older males
- t (11;14) translocation of cyclin D1 and heavy chain IgG
- CD5+


follicular cell lymphoma

- adults
- t(14;18) traslocation of heavy-chain Ig and Bcl-2
- indolent course
- bcl2 inhibits apoptosis
- present with painless "waxing and waning" lymphadenopathy


adult T cell lymphoma

- occurs in adults
- caused by HTLV-1 (associated with IV drug abuse)
- adults present with cutaneous lesions, esp affects populations in Japan, West Africa, and the Carribean
- Lytic bone lesions, hypercalcemia


mycosis fungoides/Sezary syndrome

- common in adults
- adults present with cutaneous patches/plaques/tumors with potential to spread to lymph nodes and viscera
- circulating malignant cells seen in Sezary syndrome
- indolent, CD4+



- age < 15 years
- T cell ALL can present with mediastinal mass (dysphagia, dyspnea)
- associated with Downs "we ALL fall down"
- TdT +
- B cell form is CD10+
- most responsive to therapy
- may spread to the CNS and testes
- t( 12;21) has better prognosis


Small lymphocytic lymphoma/Chronic lymphocytic leukemia

- age > 60 years
- CD 20+, CD5+ B cell neoplasm
- often asymptomatic, progresses slowly, smudge cells in peripheral blood smear, autoimmune hemolytic anemia
- SLL is the same as CLL except CLL has increased peripheral blood lymphocytosis or BM involvement


hairy cell leukemia

- age: adults, mature B cell tumor of the elderly
- cells have filamentous, hair-like projections
- TRAP +ve
- causes marrow fibrosis (dry tap)
- treat wtih cladribine (2CDA), an adenosine analog (inhibits adenosine deaminase)



- median onset 65 years
- Auer rods, peroxidase +, cytoplasmic inclusions seen in M3
- risk factors: prior exposure to alkylating chemo, radiation, myeloproliferative disorders, downs
- t(15;17) --> M3 responds to all-trans retinoic acid
- M3 due to PML/RARa fusion gene which prevents differentation
- can present with DIC if Aurer rods are released into plasma



- peak incidence 45-85 years
- defined by philadelphia chromosome t(9;22)
- very low leukocyte alk phos
- responds to imatinib (tyrosine kinase inhibitor)


9;22 translocation

- philadelphia chromosome - CML


8;14 translocation

Burkitt lymphoma (c-myc activation)


11;14 translocation

mantle cell lymphoma (cyclin D1 activation)



follicular lymphoma (bcl2 activation)



M3 type AML


Langerhans cell histiocytosis

- lytic bone lesions and skin rash or recurrent OM with mastoid mass
- immature APCs
- express S-100 and CD1a
- have Birbeck "tennis racket" granules


Polycythemia Vera

- a chronic myeloproliferative disorder where hct > 55%
- somatic (non-hereditary) mutation of Jak2 gene -- receptor associated tyrosine kinase
- often presents as intense itching after the shower
- rare but classic symptom is erythromelalgia (severe, burning pain and reddish or bluish discoloration) due to episodic blood clots in extremity vessels


essential thrombocytosis

- similar to polycythemia vera, but specific overproduction of abnormal platelets --> bleeding, thrombosis
- bone marrow contains enlarged megakaryocytes



- fibrotic obliteration of the BM
- teardrop RBCs and immature forms of the myeloid line