Hematology and Oncology Flashcards
What component of the erythrocyte membrane allows transport of CO2 from the periphery to the lungs?
Chloride HCO3- antiporter - exports HCO3- and imports CO2
What are the dense granules in platelets? Alpha granules?
Dense: ADP, calcium
Alpha granules: vWF, fibrinogen
What is contained in the specific granules of neutrophils?Azurophilic granules?
Specific granules: ALP, collagenase, lysozyme, and lactoferrin
Azurophilic granules: Proteinases, acid phosphatase, myeloperoxidase, and Beta glucuronidase
Cell marker for macrophage?
CD14
What is the difference between a mast cell and a basophil?
Both release histamine and heparin and mediate allergic reaction
Mast cell: Binds Fc portion of IgE and releases eosinophil chemotactic factors
Basophil: Releases leukotrienes
What is the difference between a mast cell and a basophil?
Both release histamine and heparin and mediate allergic reaction
Mast cell: Binds Fc portion of IgE causing degranulation; releases eosinophil chemotactic factors
Basophil: Releases leukotrienes
What two factors are necessary to turn fibrin monomers into a fibrin mesh (one is activated by thrombin)?
Factor XIIIa (activated by thrombin) and calcium
What activates Protein C?
Thrombomodulin (and vitamin K allows precursor Protein C to become mature form beforehand)
Protein S allows protein C to cleave and inactivate Va and VIIIa
What is ESR?
Erythrocyte sedimentaiton rate - acute phase reactants (fibrinogen) can cause RBC aggregation
What increases ESR?
What decreases ESR?
Increase: Infections, autoimmune diseases (SLE, RA, temporal arteritis), malignant neoplasms, ulcerative colitis, pregnancy
Decrease: Polycythemia, sickle cell anemia, CHF, microcytosis, hypofibrinogenemia
What is an acanthocyte and when is it seen?
AKA a spur cell
Associated with liver disease; Abetalipoproteinemia (cholesterol dysregulation)
When do you see basophilic stippling?
Anemia of chronic disease, alcohol abuse, lead poisoning, thalassemia
What is it called when there is excess iron in mitochondria? What is the defining feature?
Sideroblastic anemia; Ringed sideroblasts (due to decreased protoporphyrin)
When do you see target cells?
HbC disease, Asplenia, Liver disease, Thalassemia
What are Howell Jolly bodies?
Basophilic nuclear remnants found in RBCs
What is the triad of Plummer Vinson syndrome?
Iron deficiency anemia
Esophageal webs
Atrophic glossitis
How do different numbers of deletions affect alpha thalassemia?
4 allele deletion:
3 allele deletion:
1-2 allele deletion:
4 allele deletion: Excess gamma globulin forms (gamma-4 = Hb Barts) - incompatible with life (hydrops fetalis)
3 allele deletion: HbH disease - very little alpha globin (excess beta globin forms Beta-4 (HbH)
1-2 allele deletion: asymptomatic
What is seen on electrophoresis in beta thalassemia minor (heterozygote)?
HbA2
What is the major type of hemoglobin found in beta thalassemia major?
HbF (protective in the infant)
What musculoskeletal abnormality is associated with lead poisoning?
What CNS effect?
What biochemical effect?
Wrist and foot drop
Encephalopathy
Inhibits rRNA degradation
What is used to treat lead poisoning?
Dimercaprol and EDTA (1st line)
Succimer used for chelation for kids
What deficiency is associated with sideroblastic anemia? What is the deficiency in the hereditary form?
Defect in heme synthesis
Hereditary: X-linked defect in ALA synthase gene
What labs are used to detect Hereditary spherocytosis?
Osmotic fragility test (+); Eosin-5-maleimide binding test
What mutation leads to HbC hemoglobin?
Glutamic acid to lysine mutation at residue 6 in beta globin
What is the membrane defect in paroxysmal nocturnal hemoglobinuria?
Impaired synthesis of GPI anchor for decay accelerating factor that protects RBC membrane from complement
What is the treatment for PNH?
Eculizumab
What immunoglobulin is associated with Warm agglutinin (autoimmune hemolytic anemia)? Cold agglutinin?
Bonus: What diseases are associated with each?
Warm agglutinin: IgG - triggered by warm weather (Chronic anemia associated with SLE, CLL or certain drugs)
Cold agglutinin: IgM - triggered by cold (Acute anemia seen in CLL, Mycoplasma pneumonia or infectious mononucleosis)
What causes Eosinopenia? What is the mechanism?
Cushing syndrome, corticosteroids
Corticosteroids sequester eosinophils in lymph nodes and cause apoptosis of lymphocytes
What is the mechanism of corticosteroid induced neutrophilia?
Corticosteroids decrease activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation (so neutrophils accumulate in the blood)
Which enzyme is associated with acute intermittent porphyria? Porphyria cutanea tarda?
AIP: Porphobillinogen deaminase
PCT: Uroporphyrinogen decarboxylase (UROD)
*Don’t “cutanea” UR ROD
What are the 5 Ps of acute intermittent porphyria?
Painful abdomen Port wine-colored urine Polyneuropathy Psychological disturbances Precipitated by drugs, alcohol, and starvation
What are the causes of DIC?
STOP Making New Thrombi Sepsis (gram negative) Trauma Obstetric complications Acute Pancreatitis Malignancy Nephrotic syndrome Transfusion
What are the hereditary thrombosis syndromes that lead to hypercoagulability?
Factor V Leiden (resistant to degradation by protein C)
Prothrombin gene mutation (increased production)
Antithrombin deficiency (Diminishes the increase in PTT following heparin administration - only symptom)
Protein C or S deficiency (decreased ability to activate factors V and VIII)
When do you give cryoprecipitate therapy and what does it contain?
Contains fibrinogen, factor VIII, factor XIII, vWF and fibronectin
Use: Treat coagulation factor deficiencies involving fibrinogen and factor VIII
How is CML differentiated from a leukemoid reaction?
Both have increased WBC count but CML has a decreased leukocyte ALP whereas a leukemoid reaction has an increased leukocyte ALP
What is the difference between Hodgkin and Non-Hodgkin lymphoma in terms of nodes, cell type, and peak incidence?
Hodgkin: Localized single group of nodes (extranodal rare); Reed Sternberg cells; Bimodal age distribution (young adulthood and >55)
Non-Hodgkin: Multiple peripheral nodes (extranodal involvement); Majority involve B cells; Peak incidence at 20-40 years old
What predicts a better prognosis in ALL? What are the serum markers?
t(12:21) - better prognosis
TdT+ (marker of pre-T and pre-B cells)- it is a DNA polymerase
CD10+ (pre-B cells only)
What is the difference between CLL and SLL?
CLL has increased peripheral blood lymphocytosis or bone marrow involvement (Smudge cells in both)
What part of the spleen undergoes splenomegaly with hairy cell leukemia?
How is hairy cell leukemia distinguished from other B-cell lymphomas?
What is the treatment for hairy cell leukemia? (TRAP+)
Splenomegaly of the red pulp
Lyphoadenopathy is usually absent
Cladribine (an adenosine analog that inhibits adenosine deaminase)
What is the significance of t(15;17) in acute myelogenous leukemia (AML)?
How does AML cause DIC?
t(15;17) is seen in the M3 type of AML - Responds to all-trans retinoic acid (vitamin A) inducing differentiation of myeloblasts
Auer rods (composed of myeloperoxidase) can induce coagulation cascade leading to DIC
Name the disease and gene associated with the following... t(9:22): t(8:14): t(11:14): t(14:18): t(15:17):
t(9:22): CML (and some B-ALL) - bcr-abl hybrid (tyrosine kinase)
t(8:14): Burkitt lymphoma - c-myc activation
t(11:14): Mantle cell lymphoma - cyclin-D1 activation
t(14:18): Follicular lymphoma (or diffuse large B-cell lymphoma) - bcl2 activation (inhibits apoptosis)
t(15:17): M3 type of AML - responsive to all-trans retinoic acid
Why is there low leukocyte alkaline phosphatase in CML?
How do you treat CML?
Result of low activity in mature granulocytes
Treat with Imatinib (inhibitor of bcr-abl tyrosine kinase)
What is the presentation of langerhans cell histiocytosis?
Presents in a child as lytic bone lesions and skin rash or recurrent otitis media with a mass involving the mastoid bone
What are the characteristic findings in Langerhans cell histiocytosis?
Cells express S-100 (mesodermal); and CD1a. Birbeck granules are characterisitic
_____ is involved in hematopoietic growth factor signaling
JAK2
What happens to EPO levels in polycythemia vera?
What is the main presentation?
Decreased due to negative feedback
Intense itching after a hot shower
What three things are needed for activation of coagulation factors?
- Exposure to activating substance (Subendothelial collagen for intrinsic pathway and tissue thromboplastin for extrinsic)
- Phospholipid surface of platelets
- Calcium (derived from platelet dense granules)
Heparin induced thrombocytopenia is due to heparin forming complexes with…
How does this result in thrombocytopenia?
Platelet factor 4 on the surface of platelets
IgG antibodies are formed against these complexes - results in consumption of these platelets by the spleen
What inactivates plasmin?
How does this relate to a DIC-like condition?
What is the treatment?
Alpha-2 antiplasmin
Cirrhosis of liver causes decreased production of alpha2 antiplasmin leading to increased bleeding that resembles DIC
Treated with aminocaproic acid
Explain warfarin skin necrosis and Protein C or S deficiency
Normally warfarin is initially given with heparin because blockade of K epoxide reductase affects C and S cells before it activates 2,7,9 and 10 leading to increased risk of thrombosis; If the patient has C or S deficiency they are more likely to have thrombosis which is called warfarin skin necrosis
In paroxysmal nocturnal hemoglobinuria, what is the main cause of death? Why is AML a complication of this disease?
The main cause of death is thrombosis of the hepatic, portal, or cerebral veins (platelets also lack DAF and their destruction leads to the release of cytoplasmic contents which can induce thrombosis)
PNH is due to a mutation in the myeloid stem cell (no GPI) and so another mutation in the myeloid stem cell is not uncommon which could produce AML
What is acute monocytic leukemia (what proliferates? what is lacking? what is the presentation?)
What is acute megaloblastic leukemia? (same as above)
Acute monocytic leukemia = proliferation of monoblasts; usually lack MPO; infiltration of gums
Acute megaloblastic leukemia = proliferation of megakaryoblasts; lack MPO; Associated with down syndrome
In orotic aciduria, what enzyme is deficient? What type of anemia does this cause?
Defect in UMP synthase Megaloblastic anemia (no hyperammonemia)
How do you differentiate between intravascular hemolysis and extravascular hemolysis?
Intravascular: Decreased haptoglobin, increased reticulocytes, urobilinogen in urine
Extravascular: Increased unconjugated bilirubin which causes jaundice
What is deficient in Thrombotic thrombocytopenic purpura (TTP)?
What is the defect in ITP?
TTP: ADAMTS13 (vWF metalloprotease)
ITP: Anti-GpIIb/IIIa antibodies
What are the CD markers on Reed Sternberg cells?
Lymphocyte (rich/poor) form has the best prognosis?
CD15+ and CD30+
Lymphocyte rich form has the best prognosis
How is mantle cell lymphoma distinguished (aside from t(11:14)) from other non-hodgkin lymphomas
only CD5+
Which T-cell neoplasm presents with cutaneous patches/plaques/tumors
Mycosis fungoides/sezary syndrome
How does CRAB related to multiple myeloma?
What interleukin is elevated?
Hypercalcemia Renal insufficiency Anemia Bone lytic lesions/back pain *elevated IL-6
How is Waldenstrom macroglobulinemia different than multiple myeloma?
M spike in IgM instead of IgG/IgA
Describe a pseudo-pelger-huet anomaly
What syndrome is this associated with?
PPH anomaly: neutrophils with bilobed nuclei (connected with a thin filament of chromatin) typically seen after chemotherapy
Associated with myelodysplastic syndromes
