Heme/Onc Random Facts Flashcards
What is the life span of a thrombocytes.
8-10 days
What are the granules in platelets?
Dense granules-contain ADP and Ca, alpha-granules contain vWF and fibrinogen
Where is 1/3 of the platelet pool stored
In the spleen
What are the granules in neutrophils?
Specific granules contain ALP, collagenase, lysozyme, and lactoferrin. Azurophilic granules (lysosomes) contain proteases, acid phosphatase, myeloperoxidase, and beta-glucuronidase
How are macrophages involved in septic shock?
Lipid A from bacterial LPS binds CD 14 on macrophages to initiate septic shock
What activates macrophages?
Gamma-interferon
What does eosinophilic mean?
Pink
What does basophilic mean?
Blue/purple
What are the causes of eosinophilia?
Neoplasia, asthma, allergy, chronic adrenal insufficiency, parasites
What die the granules in basophils contain?
Heparin and histamine. Leukotrienes synthesized and released on demand
What can basophilia be a sign of?
Myeloproliferative disease, particularly CML
What’s the universal donor and universal recipient of plasma?
AB is the universal plasma donor (because no antibodies in their plasma), O is the universal recipient of plasma (because antibodies have nothing to react with)
How does warfarin work?
It inhibits vitamin K episode reductase, which is needed to activate the vitamin K dependent clotting factors
MOA of antithrombin
Inhibits activated forms of factors 2, 7, 9, 10, 11, and 12. Principle targets of antithrombin: thrombin and factor Xa
What does tPA do?
Converts plasminogen to plasmin
MOA of protein C and S
Protein C is converted to activated protein C by thrombin-thrombin insulin complex on endothelial cells, APC is activated by protein S to cleave and inactivate factor Va and VIIIa
MOA of clopidogrel, prasugrel, and ticlipidine
Inhibit ADP-induced expression of GpIIb/IIIa
MOA of abciximab, eptifibatide, and tirifiban
Inhibit GpIIb/IIIa directly
What is Bernard Soulier syndrome
A deficiency of GpIb
What is Glazmann thrombasthenia
Deficiency of GpIIb/IIIa
When might you see a failure of agglutination with ristocetun assay?
Von Willebrand disease and Bernard-Soulier syndrome
When might you see acanthocytes (“spur cells”)
Liver disease, abetalipoproteinemia
When might you see target cells
HbC disease, Asplenia, liver disease, thalassemia
What are Heinz bodies?
Oxidation do Hb-SH groups to -S–S- causing hemoglobin precipitation with subsequent damage to RBC membrane causing bite cells
What might you see in a reticulocyte in Wright-Giemsa stain
Blue staining, represents the residual ribosomal RNA
Where does iron absorption occur?
In the duodenum and proximal jejunum so bypassing this in a gastrojejunostomy results in iron deficiency anemia
What is associated with koilonychia?
(Spoon nails) iron deficiency anemia
What happens with a four allele deletion in the alpha-globin gene?
Hemoglobin Barts (4 Gamma chains) forms. Is incompatible with life
What is hemoglobin H?
Four beta chains
What ethnicities are associated with alpha and beta thalassemia?
Alpha- Asian and African, beta-Mediterranean
How is beta thalassemia minor diagnosed?
Increased HbA2 on electrophoresis
MOA of lead poisoning
Inhibits ferrochatase and ALA dehydratase causing decreased heme synthesis and increased RBC protoporphyrin
Signs and symptoms of lead poisoning
Lead lines on gingivae and metaphysics of long bones on xray, encephalopathy and erythrocytes basophilic stippling, abdominal colic and sideroblastic anemia, drops-wrist and foot
What causes hereditary sideroblastic anemia?
X-linked defect in delta-ALA synthase gene
Causes of sideroblastic anemia
Genetic, acquired (myelodysplastic syndromes) and reversible (alcohol, lead, vitamin B6 deficiency, copper deficiency, isoniazid)
What is orotic aciduria?
AR defect in UMP synthase, presents as FTT, developmental delay, and megaloblastic anemia refractory to folate and B12. NO hyperammonemia (vs ornithine transcarbamylase deficiency)
Tx of orotic aciduria
Uridine monophosphate to bypass mutated enzyme
What might have an abnormal eosin-5-maleimide binding test
Hereditary spherocytosis
Pyruvate kinase deficiency
AR, causes decreased ATP causing rigid RBCs and extra vascular hemolytic anemia. Hyperplasia of the red pulp of the spleen
Mutation in HbC disease
Glutamic acid to lysine in beta-globin, causes extravascular hemolysis
Triad, labs, and tx in PNH
Triad: Coombs - hemolytic anemia, pancytopenia, and venous thrombosis, labs: CD55/59 neg RBCs on flow cytometry, tx: eculizumab
Warm agglutinin
Chronic anemia seen in SLE and CLL and with certain drugs (alpha-methyldopa), IgG
Cold agglutinin
IgM, acute anemia triggered by cold, seen in CLL, mycoplasma and infectious mononucleosis
What is the direct Coombs test
Anti-Ig antibody added to patient’s blood. RBCs agglutinate if RBCs are coated with Ig
Indirect Coombs
Normal RBCs added to patients serum. If serum has anti-RBC surface Ig, RBCs agglutinate when Coombs reagent is added
Effect of corticosteroids on neutrophils, eosinophils, and lymphocytes
Neutrophilia from demargination, eosinopenia from sequestration in lymph nodes, lymphopenia from apoptosis
Enzyme inhibited in acute intermittent porphyria
Porphibiligen deaminase
Enzyme deficient in porphyria Cutanea tarda
Uropirphyrinogen decarboxylase
Pathogenesis of ttp
Inhibition or deficiency of ADAMTS13 (vWF metalloprotease) causes large vWF multimers which causes increased platelet adhesion, which causes platelet aggregation and thrombosis
Pentad of ttp
Neurologic and renal sx, fever, thrombocytopenia, and MAHA
When might you give cryoprecipitate
For coagulation factor deficiencies involving fibrinogen and factor VIII
High leukocyte alkaline phosphatase means what?
Leukemoid reaction
What are Dohle bodies?
Light blue (basophilic) peripheral granules in neutrophils seen in a leukemoid reaction
What is Hodgkin lymphoma associated with?
EBV
Cell markers in reed Sternberg cells
CD15 and CD30
Genetics of Burkitt lymphoma
T(8;14) translocation of c-myc and heavy-chain Ig
What is commonly involved in diffuse large B cell lymphoma
Waldeyer’s ring (oropharyngeal lymphoid tissue) and GI tract
Genetics of follicular lymphoma
T(14;18)-translocation of heavy-chain Ig and Bcl-2. Cleaved nuclei on histo
Genetics of mantle cell lymphoma
t(11;14)-translocation of cyclin D1 and heavy chain Ig
Cerebriform nuclei
Mycoses fungoides/Sezary syndrome
Rouloux formation
Multiple myeloma
Neutrophils with bilobed nuclei seen after Chen
Pseudo-Pelger-Huet anomaly
Child with lytic bone lesions and skin rash or as recurrent otitis media with a mass involving mastoid bone
Langerhans cell histiocytosis. Calls express S100 (mesodermal origin) and CD1a. Bit beck granules (tennis rackets on EM)
T(12;21)
Better prognosis ALL
Smudge cells
Small lymphocytic lymphoma/CLL
Tx for CML
Imatinib (a small molecule inhibitor of the bcr-abl tyrosine kinase)
Mechanism of HIT
Development of IgG Ab against heparin bound platelet factor 4. The antibody-heparin-PF4 complex activates platelets causing thrombosis and thrombocytopenia
Direct thrombin inhibitors
Argatroban, bivalirudin, dabigatran
MOA of cilostazol, dipyridamole
Phosphodiesterase III inhibitor. Increases cAMP in platelets, resulting in inhibition of platelet aggregation; vasodilators
MOA of hydroxyurea for cancer
Inhibits ribonucleotide reductase
Clinical use for cytarabine
Leukemias (AML), lymphoma
Use and toxicity of Busulfan
CML. Also used to ablate patient’s bone marrow before bone marrow transplantation. Toxicity: severe myelosuppression
