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193 Cards in this Set
- Front
- Back
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What is the lifespan of RBC?
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120 days
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What are spherocytes indicative of?
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Autoimmune hemolytic anemia (AIHA) or hereditary spherocytosis
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What are target cells seen in?
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Significant liver disease, thalassemias, and hemoglobinopathies
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What are teardrop cells seen in? Hypersegmented PMN's?
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Myelofibrosis; Hypersegmented PMN's seen in megaloblastic anemia (B12 def, pernicious anemia, folic def)
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What are Burr cells seen in? Spur cells?
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Burr cells - uremic patients; Spur cells - liver disease
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What are Howell-Jolly bodies?
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Nuclear fragmentation that occurs normally but not able to be cleared and thus visualized in splenectomy/ functioining asplenia.
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Besides ferritin (ie if CRP was elevated and making it less helpful) what else can help ddx anemia of chronic disease from iron-deficiency?
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TIBC (how much transferrin is actually working to mobilize iron), soluble transferrin receptor (normal in anemia of chronic disease but high in Fe deficiency). Transferrin saturation is low in both.
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What do spherocytes look like on bood smear?
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They have lack of central pallor.
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What are other causes of iron deficiency besides blood loss?
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Pregnancy, malabsorption (celiac disease esp in young pt with voluminous stools; gastric bypass surgery), low-grade hemolysis are other causes of iron-deficiency anemia.
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What is a normal Hb electropheresis pattern?
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HbA (alpha2beta2) greater than 97.5%, and HbA2 (alpha2delta2) less than 2.5% is normal.
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What populations are alpha-thalassemias seen in? What about beta-thalassemias?
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Alpha-thalassemia is seen in African, Mediterannean, and SE Asian populations. Beta-thalassemia is seen in Middle Eastern,Mediterranean, and Asian populations.
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What are the types of alpha-thalassemia?
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Alpha-thalassemia trait is 1 alpha-locus affected- normal phenotype.
Alpha-thalassemia minor is 2 alpha loci- asymptomatic, mild if any anemia Hb H is 3 alpha loci affected- (Hb H = Beta4 tetrameres), severe hemolytic anemia. Hb Bart's- 4 loci afected, so gamma4 tetramers form Hb Bart's -- do not deliver any oxygen to the tissues causing hydrops fetalis (death in utero) |
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What is beta-thalassemia caused by and what are the types?
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Beta-thalassemia is caused by range of mutations within one Beta locus.
1)minor- heterozybotes, with mild or no anemia, a lotof microcytes. High HbA2 and mildly elevated HbF. 2)Beta-thal major (homozygous)- Cooley anemia. no Beta-globin production, so alpha-tetramers. Severe anemia, high Epo 3)Beta-thal intermedia (homozygous)- less hemolysis. increased HbF, variable presentation. |
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What is the role of iron therapy in thalassemia?
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None! Often thalassemia gets misdiagnosed as iron deficiency. Puts them at risk for iatrogenic secondary hemochromatosis.
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What does hb electrophoresis show for alpha and beta thalassemias? Other labs that clue in (but not definitive)?
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In alpha-thalassemia it is normal. In beta-thalassemia it will have an increased A2 component. Will see microcytosis and normal iron studies.
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What are symptoms of b12 deficiency? If you check B12 level and it is borderline low, what can you do to further evaluate?
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Symptoms- neuro (paresthesias to psychosis), GI (smooth sore tongue, diarrhea). If suspicious with borderline levels, check MMA and homocysteine (both are elevated in B12 deficiency. also only homocysteine is elevated in folate deficiency.)
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What do Burr cells look like?
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Regular short spiney projections seen in uremia. (as opposed to spur cells in liver failure that are irregular spines)
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What test can help ddx intravascular vs extravascular hemolysis?
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Urine hemosiderin is high in intravascular hemomlysis (iron more frequently lost in urine w/intravascular loss).
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What is the mode of transmission of G6PD deficiency? What does G6PD help do or protect against?
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X-linked recessive. You lose ability to protect against oxidative stress (from infection, meds including sulfa, dapsone, antimalarials, fava beans, DKA).
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When is the best time to test for G6PD deficiency?
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2-3 months after hemolytic event to avoid false-negative result (bc during acute event can see normal level due to brisk reticulocytosis). See Heinz bodies and bite cells.
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What is a positive direct Coombs test? Indirect coombs test?
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Direct- if patient's RBC's agglutinate in response to external ab's against IgG or C3.
Indirect- if patient's ab's cause agglutination with someone else's blood. (Coombs looks for the antigen). |
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What does pyruvate kinase deficiency present with?
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Usually presents with symptomatic hemolytic anemia without clear triggers and more severe than G6PD.
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What is the genetic abnormality in sickle cell?
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Mutation in Beta-globulin (glutamine --> valine).
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What do recurrent microinfarcts of the kidney cause? Spleen? Lung?
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Isothenuria (inability to concentrate the urine). Spleen- functional asplenia, increased risk of encapsulated organisms and Salmonella. Lung- acute chest syndrome.
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What is the presentation of sickle cell trait?
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Asymptomatic or renal papillary necrosis, painless hematuria, and isothenuria.
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What is Hemoglobin SC disease?
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One Beta gene goes to valine and the other goes to lysine. RBC's are rigid but not sickled. It can occur in children AND adults (unlike in Hgb SS) bc spleen can survive childhood sometimes.
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What are indications for exchange transfusion in sickle cell disease?
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Priapism, cerebral sickling, aplastic crisis, and acute chest syndrome.
(penis, brain, bone marrow, and lungs) |
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What population gets hereditary spherocytosis? What is the way to diagnose it? What are complications? How can you treat it?
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Northern Europeans get it. Diagnose it with a negative Coombs test, + osmotic fragility test (membrane can't bend much), molecular membrane studies.
Complications are cholelithiasis 2/2 bilirubin stones, splenomegaly, hemolysis. Can do splenectomy to help RBC survival. |
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What is paroxysmal nocturnal hemoglobinuria? How do you get it? What are complications? How do you diagnose it and treat it?
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Acquired, 2/2 defective PIG-A gene. PIG-A anchors other proteins that protect the cell membrane from complement-mediated lysis.
Complications are intravascular hemolysis, and arterial + venous thrombosis. Can also sometimes turn into leukemia or other blood d/o. You diagnose it with absence of CD55 and CD59 (need anchor protein to be present). Treat hemolysis with steroids and thromboses with anticoagulation. Also eculizumab can help hemolysis. |
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How do you diagnose and treat AIHA?
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If warm ab's (IgG): Coombs positive. Steroids and splenectomy if refractory.
If cold ab (IgM)- Coombs negative. See RBC clumping on smear and anti-C3 ab's. Treat by maintaining a warm environment and finding cause (steroids do not help here). |
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What is AIHA associated with?
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CLL, lymphoma, lupus, and mono.
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What is methemoglobin? What clues can lead to the diagnosis and how does it present?
How is it caused and how do you treat it? |
Hemoglobin with oxidized heme iron (Fe2+ --> Fe3+) that has impaired ability to bind oxygen. Patient appears cyanotic despite a normal PaO2 (bc the methemoglobin make the blood very dark).
Symptoms are h/a, dizziness, dyspnea, altered MS. It is caused by hereditary or drugs (nitrates but not NO), tylenol, 'caines, sula, dapsone. Treat with methylene blue. |
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What is the presentation of porphyrias?
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Neurologic system/psych/abdominal pain and skin affectation.
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What is the cause of hereditary hemochromatosis, mode of transmission?
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HFE gene mutated at C282Y and H63D. Autosomal recessive.
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How does hereditary hemochromatosis present commonly? How do heterozygotes present?
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Most common with fatigue, myalgias, arthralgias, abdominal pain, transaminitis and elevated transferrin saturation. Classically bronze diabetic cirrhosis but this is later in the course.
Heterozygotes do not have problems. |
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What is the most sensitive test to diagnose hereditary hemochromatosis? What is the gold standard?
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Check transferrin saturation, if >45% in women and >50% in men. Also ferritin > 1000. Then do genetic testing.
Gold standard is liver biopsy -- but now used as prognostic indicator or if genetic testing is equivocal. |
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What is the difference between NSAIDs and ASA? What does plavix do?
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ASA binds irreversibly to COX, NSAID binding is reversible.
Plavix inhibits ADP receptor on platelet (decreased platelet aggregation). |
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What is primary hemostasis and how long does it last?
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Platelet plug formation, lasts 12-24 hours (which is why hemophiliacs often have injury later after trauma).
vWF increases stickiness. Platelets meet collagen, release ADP and arachidonic acid which uses COX to make thromboxane A2 which exposes gpIIb/IIIa, which is used by fibrinogen to cross connect IIb/IIIa on platets. |
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What is secondary hemostasis? What is the key intermediary and what does it do?
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Secondary hemostasis = clotting cascade.
Tissue factor interacts with factor 7 [extrinsic]. Intrinsic pathway (8, 9, 11) works only after a small amount of thrombin has been formed by the extrinsic pathway. Thrombin (Factor 2a) is the key. (1,13 for making clot; 12, 8 for amplifying thrombin) Thrombin helps make the clot: 1) converts fibrinogen (factor 1) to fibrin 2) activates factor 13 (which causes fibrin to cross link) Also amplify to make more thrombin: 3) activates factor 12 --> which then amplifies the Intrinsic pathway by activating factor 11 --> factor 9 --> factor 10a via factor 8. 4) activates factor 8. |
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What does tPA do? What do proteins C and S do?
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tPA converts plasminogen to plasmin which breaks down fibrinogen and fibrin.
Protein c and s inactivate factors 5a (which activates 10) and 8a. Protien c also inactivates tPA's inhibitor. |
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How can you differentiate between a primary and secondary heomstatic problem at the bedside?
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Primary problem (platelet dysfunction or low platelets)- resulting in petechiae, purpura, mucocutaneous bleeding.
Secondary hemostatic d/o (eg hemophilia)- hematomas, hemarthroses |
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How do you measure the different pathways in the clotting cascade?
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PT measures the extrinsic (factor 7) and the common pathways. PTT measures the intrinsic pathway (factors 12, 11, 9, 8).
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If PTT is elevated with normal PT and everything else, what next?
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Do a mixing study to see if there is factor deficiency vs factor inhibitor (if bleeding, factor 8 inhibitor; if clotting, APLA)
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What are common causes of factor 8 inhibitor?
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Postpartum vs idiopathic
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What are common drug offenders causing ITP (immune TCP)? What are common underlying diseases that cause ITP?
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Common drug offenders are quinidine, rifampin, sulfa, digoxin, and tylenol. Note this is different from drug-inducd TCP)
Common diseases are CLL, lupus, lymphoma, HIV, Hep C. (same as AIHA). |
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Are there any lab tests useful for ITP?
How to manage it if dx'ed? |
No- antiplatelet ab is very non-specific so don't order it.
Manage it first line with steroids. IVIG for prompt (albeit transient) response. If Rh+, can do RhoGam. Splenectomy if refractory, frequent relapses, or long term steroid needed. Also vaccinate for pneumococcus, H. flu, Neisseria meningitides 2 wks before splenectomy. |
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What is TTP caused by?
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Deficiency in the activity of vWF cleaving protease ADAMTS13 (not necessarily always low levels). This causes vWF multimers to accumulate activating platelets.
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What are PT and PTT in TTP?
How do you manage TTP? |
They are normal.
Manage with FFP or steroids until you can do plasma exchange. |
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How does HUS differ from TTP?
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It has more renal involvement, rarely with neuro involvement.
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What are treatment options for HIT, short term and long term?
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Stop all heparin exposure and start direct thrombin inhibitors (lepirudin or argatroban). Lepirudin is renally cleared and argatroban is hepatically cleared.
Argatroban also artificially elevates INR (goal INR in coumadin bridging is > 4). Coumadin should be started once plts normal and continue for at least 3 months. |
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What is the main risk factor, diagnosis and management of a woman who presents with extreme thrombocytopenia presenting with petechiae or purpura approx 1 week after transfusion?
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Post-transfusion purpura. It occurs primarily in women presensitized by pregnancy.
It is treated with IVIG. |
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What is quinine used for and what are important side effects?
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Quinine is an OTC drug for nocturnal leg cramps. It can cause thrombocytopenia among other drugs.
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What is the most common inherited bleeding disorder? What is the pathophys? What is the mode of transmission?
How is it usually first picked up in the labs? |
von Willebrand disease. vWF binds plts to collagen and to other plts. It also carries factor 8.
vWD is in 1% of population, it is auotosomal dominant. You will see increased PTT (because of decreased levels of factor 8) and prolonged bleeding time. |
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How can you diagnose the most common type of von Willebrand disease?
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1) Abnormal plt function tests
2) decreased vWF ag w/proportional decrease in factor 8 activity 3) decrease in biologic activity as measured by the ristocetin cofactor assay. |
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How do you treat vWD? What is a side effect of the treatment?
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Desmopressin aka ADH/vasopressin which boosts factor 8 and vWF (except type 2B where there are vWF multimers).
Side effect of desmopressin is hyponatremia. |
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What is Bernard-Soulier syndrome? Mode of inheritence?
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Deficiency of glycoprotein Ib where platelets cannot bind vWF. Autosomal recessive inheritance.
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What is Glanzmann thrombasthenia? Mode of inheritance?
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It results from deficient glycoprotein IIb/IIIa complex (which is needed for fibrinogen to cross-link). Autosomal recessive inheritance.
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What is the effect of paraproteinemia on platelets? HOw do you treat uremia-induced platelet dysfunction?
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Paraproteinemia (as in MM) can cause plt dysfunction by coating platelets.
Treat uremia-induced platelet dysfunction with transfusion, estrogens, or DDAVP. |
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How do you treat hemophilia A?
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Factor 8 deficiency-- treat with DDAVP; if severe, give factor 8 concentrate. (Hemophilia B = factor 9 def)
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What are factor XI, XII, XIII deficiencies (presentation, labs and management)?
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Presentation- think about it in pt who has late post-surgical healing and poor wound healing.
Factor 11 deficiency- AR seen in Ashkenazi Jews. Factor 12 deficiency- no bleeding d/o, asymptomatic despite having prolonged PTT. Factor 13 deficiency- AR. cannot cross-link fibrin. All studies are normal (PT, PTT). Dx with clot lysis assay (seeing if urea can break up a clot). Treat with FFP every month. |
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What bleeding d/o may present with normal platelets, PT, PTT, and bleeding time?
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mild vWD, mild hemophilia, and factor 13 deficiency
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What should you suspect a patient to have if htey present with chronic DIC?
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Solid tumor as underlying malignancy
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How do you treat bleeding in DIC?
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Give platelets and FFP. You can give cryo if the fibrinogen level is very low. (there is a massive depletion of coagulation factors)
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What are common causes of vit K deficiency?
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Malnutrition, liver dz, broad spectrum abx and cephalosporins
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What is primary fibrinolysis associated with?
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It is a bleeding d/o associated with prostate ca.
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What are the antiphosopholipid ab's?
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Lupus anticoagulant, anticardiolipin, and anti-b2 glycoprotein1 ab's
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How do you dx APLA by labs? What are other manifestations
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You should have APLA (either lupus a/c, anticardiolipin, or anti-B2 GP-1) on at least 2 occassions at least 3 months apart.
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What are clinical manifestations of antiphospholipid syndrome in addition to clot-related problems?
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You can see livedo reticularis and heart murmurs (marantic endocarditis).
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What are the most common inherited causes of VTE? What is their pathophys and mode of inheritance?
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Factor V Leiden mutation and prothrombin gene (G20210A) mutation.
Factor V Leiden causes protein C resistance, incomplete transmission (can have medium effects w/heterozygosity) Prothrombin gene mutation is a gain of function mutation (elevated prothrombin). |
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What is the role of antithrombin and what is the presentation of antithrombin deficiency?
What is the mode of transmission of Protein C and S deficiency? |
Antithrombin deficiency inactivates thrombin, both with and without heparin (with heparin it is 4,000x potentiated).
Protein C and S deficiency is autosomal dominant. Clots occur at a young age, risk at approx 1%/year. |
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What is the prevalence vs severity relationship in the thrombotic disorders: factor V leiden, prothrombin G20210A, protein c def, protein s def, antithrombin def, APS
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APS, protein C, S and antithrombin deficiencies are less common and more severe than Factor V Leiden and prothrombin G20210A mutations.
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What determines the focus of screening for inherited vs acquired etiology of clot?
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Age of first clot (< or > 50 yo). APS should be looked for in both though.
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What drug can yield a false positive test for lupus anticoagulant?
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Coumadin
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How long do you treat a first clot with transient risk factor (eg OCP use, surgery)?
Unprovoked first clot? |
3 months
6 months |
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What are transfusion reactions?
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Acute hemolytic, delayed hemolytic, febrile transfusion, post-transfusion purpura, TRALI
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What is acute hemolytic transfusion rxn due to? How to manage it?
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It is a medical emergency caused by ABO incompatibility, intravascular hemolysis.
Treat by stopping blood and giving normal saline. |
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What is delayed hemolytic reaction due to and how to manage it?
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Extravascular hemolysis (as opposed to intravascular hemolysis in AHTR). Rh incompatibility or minor antigen mismatches.
Present with anemia, mild fever approx 1 week after transfusion. |
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What is febrile transfusion rxn?
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Rxn to leukocytes in blood product. Stop transfusion and r/o hemolysis. Treat with antipyretics and meperidine (if rigoring). In the future can use leukocyte depletion.
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What are sxs of iron overload? How to manage it?
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Glucose intolerance, cirrhosis, cardiomyopathy and hypogonadism.
Treat with iron chelation (deferoxamine) and consider it after 20-25 units of PRBC's if transfusions are ongoing. |
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What is TRALI due to? Treatment?
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Ab's present in transfused FFP.
Treatment is supportive. |
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What type of transfusions are most associated with transfusion-related bacterial infections?
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Platelets bc they are stored at room temperature.
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What does irradiated blood transfusion prevent especially in immunocompromised patients?
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Graft vs host reaction -- gets rid of donor lymphocytes
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What are medications that cause aplastic anemia? What diseases are associated with it?
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Benzene, radiation, sulfa, gold, chloramphenicol, insecticides.
Viral infections, thymoma, SLE, PNH (20% of patients with PNH get it) |
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What are prognosticators in aplastic anemia?
Treatment? What are patients with aplastic anemia at risk for? |
ANC (<500 is severe), platelets, reticulocytes
Treatment is BM transplantation. They are at risk for devleoping acute leukemia. |
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What is the difference between acute vs chronic leukemias?
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Acute leukemias is overproduction of blast cells; chronic leukemias have overproduction of one of more developing cell lines (not blasts)
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What is diagnostic of acute leukemia? What is diagnostic of AML on peripheral smear?
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BM Bx (at least 20% blasts).
Auer rods are seen in AML not ALL. |
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What is the classification system for AML?
What are favorable karyotypes in AML? What are unfavorable karyotypes? |
F-A-B (French American British).
t(8;21) in M2 AML, t(15;17) in APML aka M3 AML, and inv16 M4 AML are favorable >2 aberrations, inv(3), del(5q) are unfavorable. |
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Which AML subtype is associated with DIC?
What does FLT3 mutation mean in AML? NPM1? |
M3 AML (APML) -- procoagulants released from cytoplasmic granules
FLT3 means poor prognosis. It is a receptor tyrosine kinase. NPM1 is seen in de novo AML and favorable. |
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What is treatment for APML? What to watch out for with this treatment, and how to manage this complication?
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ATRA and daunorubicin.
ATRA syndrome presents as fever, vol overload, hypotension. Treat with high-dose decadron and withhold ATRA if necessary. |
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What is treatment for non-APML AML?
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"7+3" -- 7 days of ara-c and 3 days of daunorubicin.
Stem cell transplant is an option too. |
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What are unfavorable prognosticators in AML?
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Age>60, WBC>100,000, FLT3 mutation, poor performance status, secondary leukemia (vs de novo)
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What are unfavorable prognosticators in ALL?
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Age>30, WBC>30,000, Mature B cells or early T cells, persistent minimal residual disease, t(9;22) Philadelphia chromosome (unlike in CML where it is favorable)
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In addition to cytopenias, what else is involved in ALL presentation? How does this change treatment from AML?
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CNS involvement, retinal involvement. Therefore intrathecal chemo also needed.
Also have splenomegaly, LAD |
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What is treatment for ALL?
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Again, induction/consolidation/maintenance.
Treat with prednisone, vincristine, and daunorubicin + cyclophosphamide, L-asparaginase. Consider BMT if unfavorable prognosticators. |
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Tumor lysis sndrome is an important complication seen more in which leukemia's treatment?
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ALL -- see hyperuricemia, hyperphosphatemia, and hypocalcemia
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What are unfavorable prognosticators for MDS?
Favorable? Which of these is the most important prognosticator? |
Unfavorable prognosticators are high blasts, # of cytopenias, chromosome 7 abnormalities, age.
Favorable is deletion of 5q or 20q. (5q- syndrome is refractory anemia and thrombycytosis, responds well to lenalidomide therapy) Most important: % of blasts |
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What is treatment for MDS?
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If 5q- syndrome, give lenalidomide.
Otherwise can use azacitidine and decitabine, consider BMT. |
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What is CMML? What workup do these patients need?
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Chronic myelomonocytic leukemia. It is an overlap between leukemia and MDS (BM is hypercellular and dysplastic like MDS).
Check them for t(5;12) for PDGFRB-TEL gene -- may respond to imatinib therapy (TK inhibitor) |
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What are the myeloproliferative disorders?
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Maturation arrest (granulocytes, platelets, erythrocytes, and in BM)
CML, essential thrombocythemia, polycythemia vera, myelofibrosis |
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What mutation is found in many of the myeloproliferative disorders (and which ones)?
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JAK-2 kinase GOF mutation found in PV, ET, and myelofibrosis
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What translocation and consequent fusion protein are assoc with CML?
What are treatment options in CML? Side effects? |
9,22 producing BCR-ABL fusion protein, which is a tyrosine kinase.
BMT can cures CML. Imatinib is a TK inhibitor and can exacerbate CHF, hepatotoxicity, bleeding |
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What is the natural course of essential thrombocythemia?
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They have a normal life expectency but are at risk for thrombosis (venous and arterial) and hemorrhage.
Sxs are related to microthrombi (h/a's, vision, miscarriages) and bleeding. Also erythromelalgia (pain and redness in hands and feet). |
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What is treatment for ET?
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ASA for sx management and VTE prophylaxis. If high-risk (age>60, hx of VTE) then give hydroxyurea.
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How do you diagnose polycythemia vera?
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Increased red cell mass in the absence of EPO stimulation (can happen with hypoxemia, OSA, COPD, shunt, etc, tumor (RCCa and HCCa). So measure EPO, should be low-normal.
LAP is elevated (unlike in CML). |
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What are sxs of PV?
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Symptoms from hyperviscosity and pruritis after hot bath. Gout from rapid cell turnover. Splenomegaly.
Also, thromboses. |
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How do you treat PV?
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Phlebotomy reduces mortality. Also give ASA for thrombosis risk.
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What is the ddx for teardrop cells?
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Myelofibrosis, and other disorders that infiltrate marrow (metastatic ca, TB, fungal infections)
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What is SLL?
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SLL is small lymphocytic leukemia and it is the solid component of CLL.
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How do you initally diagnose lymphoma?
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You need an excisional biopsy of a LN.
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What categories is NHL divided into? What is treatment strategy for each category?
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Indolent lymphomas are seldom cured with chemo and so 'watch and wait'.
Aggressive lymphomas need aggressive treatment and can be cured. |
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What are the indolent lymphomas?
What are the aggressive lymphomas? |
Indolent- CLL, follicular, marginal zone, mycosis fungoides (MyMargCF)
Aggressive- DLBC, Burkitt, pre T cell, B-cell, mantle cell (MantDBTB) |
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What does NHL prognosis depend primarily on?
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subtype, Ann Arbor stage (same as staging for Hodgkin's), and LDH
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What is the most common indolent NHL? What is the hallmark genetically? What can it turn into?
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Follicular lymphoma. Hallmark is overexpression of BCL-2 caused by t(14;18).
Follicular lymphoma can transform into DLBCL. |
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In general for NHL, what is a class of drugs that works pretty well?
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Monoclonal ab's (e.g. Rituxan (CD20) and Alemtuzumab (CD52 in CLL)
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What is the staging system for CLL? Life expectancy at first stage?
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Rai system. First stage is only a high WBC (no other sxs like LAD, cytopenias, HSM) -- normal life expectancy.
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Why can CLL lead to frequent infections? How manage this?
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They can develop hypogammaglobulinemia -- give symptomatic patients IVIG.
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What can CLL transform to? What is this called?
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CLL (like follicular lymphoma) can transform to DLBCL, this is called Richter transformation.
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What will you see on peripheral smear for CLL?
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Smudge cells
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What is the treatment of CLL without symptoms?
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Watch and wait.
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How do you treat DLBCL?
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Treat with R-CHOP (rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone) and radiation.
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What is the most aggressive of the NHL's? What is the genetics and where can it spread?
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Burkitt's lymphoma. Hallmark is over-expression of C-MYC protein due to t(8;14). Spreads to CNS commonly.
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What are characteristics of mantle cell lymphoma? Genetic characteristics?
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It is an aggressive lymphoma, but like indolent lymphomas it is also incurable.
BCL-1 gene overexpressed causing increased cyclin D1 2/2 t(11;14) |
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How do you treat mycosis fungoides? Goal of rx?
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Treat with photochemotherapy, Control rather than cure.
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What is the average age in Hodgin disease? What is the common presentation?
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The average age is 30 yo. Patients often present with enlarged, painless LN.
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How do you diagnose Hodgkin disease?
Prognosis and treatment? |
Diagnose by excisional biopsy (not FNA). Look for Reed-Sternberg cell.
Prognosis is good, very high cure rate. Treat with ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) + radiation |
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What are states that put patients at risk for developing lymphoma?
Are there any treatment differences in patients with these states? |
HIV (especially aggressive NHL's) and iatrogenic immunosuppresion after solid organ tx.
In HIV, primary CNS lyphoma is almost always associated with EBV. Also post-transplant, most lymphomas are EBV-positive. Treat patients the same way except in AIDS rituxan may not benefit (increased infection risk); in post-transplant lower the degree of immunosuppression and can try chemo. |
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What diseases are seen after XRT to the chest during Rx of Hodgkin dz?
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solid tumors (lung and breast), hypothyroidism
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What diseas are associated with lymphoma?
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Hashimoto's, Sjogren's, Celiac disease, chronic H. pylori, HIV/AIDS
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What is used in staging multiple myeloma?
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High serum Beta2-microglobulin predicts poor survival (B2M found on surface of nucleated cells)
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How do you diagnose multiple myeloma?
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BM plasma cells > 10% AND presence of monoclonal protein (M spike in SPEP or UPEP) AND evidence of end-organ damage (if just one of these then it is called smoldering myeloma, Rx same way as MGUS)
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How do you diagnose MGUS? Any worry for patients w/ MGUS? How to manage these patients?
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Mild amounts of all three things used to dx MM (serum monoclonal protein, BM plasma cells, and no end-organ damage).
Some will progress to MM. Monitor with biannual SPEP's. |
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How do you treat MM to induce remission? To prolong remission? For older patients?
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Thalidomide, decadron, lenalidomide (thalidomide-like agent), Velcade induce remission.
SCT for remission prolongation. Older patients can take cyclophosphamide or melphalan + prednisone. |
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Which cancers are associated with PTHrP paraneoplastic syndrome?
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Squamous cell ca from lung or head/neck, MM, breast, T-cell
(local bony mets can also cause it) |
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What are side effects of pamidronate?
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Nephrotic syndrome, renal failure, ostenecrosis of jaw (last 2 are for all bisphosphonates)
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What cancers are most commonly associated with bone mets?
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Lung, breast, prostate, kidney. Also MM and NHL.
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When is stereotactic radiosurgery an option for brain mets?
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If less or equal to 3 brain mets that are all < 3 cm in size.
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What malignancies are associated with brain mets?
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Lung, Breast, Kidney, Malignant Melanoma, Gastric.
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What malignancy are chylous effusions commonly associated with?
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NHL is associated with chylous effusion.
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What malignancies are most often associated with pericardial effusions?
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Lung, breast, and NHL are most commonly associated with pericardial effusion.
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What is a danger with using allopurionol to treat TLS?
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TLS (phos, ca, K+, uric acid) treated with allopurinol -- can cause xanthine ppt and cause obstructive uropathy.
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What is the most common malignancy in women? What is the leading cause of death in women? 2nd leading cause of death?
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Breast cancer is most common in women. Lung ca > Breast ca in terms of mortality.
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How to differentiate allergic eczema vs Paget disease of the nipple?
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Symmetric in allergic eczema, asymmetric in Paget disease.
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What do you do for a non-lactating woman who presents with mastitis?
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Initiate workup for inflammatory breast cancer with mammogram.
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What is the most important risk factor for breast cancer?
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Increased age.
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What malignancies is BRCA1 assocaited with? What about BRCA2?
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BRCA1- Breast, ovarian, prostate, and colorectal
BRCA2- breast, ovarian, prostate, pancreatic, and melanoma. |
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What prognosis does atypical ductal hyperplasia portend? DCIS and LCIS?
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4x increased risk for malignancy
DCIS/LCIS- 10x. LCIS with increased risk of cancer in either breast (de novo) vs DCIS (which evolves) |
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BRCA1 and BRCA2 account for how much of inherited breast cancer?
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Approximately 50%
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Besides genetics what are RF's for breast ca?
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More periods (i.e., early menarche, late menopause, late first pregnancy). Also obesity, heavy EtOH, radiation therapy, 5 years of conjugated estrogen
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What cancers does estrogen therapy put you at risk for? Anything else?
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Breast ca (with or without progestin), Endometrial ca (without progestins).
Also combined Estrogen/progestin therapy is associated with: 1)increased risk of CV events after 1 year of Rx 2)VTE 3)biliary tract surgery. 4)breast ca recurrence in survivors |
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What are screening guidelines for breast ca screening?
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Screen every 1-2 years from ages 50-74.
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Who is appropriate for breast MRI screening?
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High-risk women: BRCA1 or BRCA2, FH of BRCA1 or BRCA2 and pt untested, hx of XRT to chest, carrier of FH of TP53 (Li Fraumeni sx) or PTEN mutation (Cowden syndrome)
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What is the next step of evaluating a breast mass after mammogram?
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Ultrasound -- if cystic then FNA. If solid then biopsy
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What does DCIS look like on mammogram? What is the high-risk type called?
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It is associated with microcalicifications confined to lobule and are rod-shaped or angulated. High risk type is called comedo carcinoma.
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How do you manage LCIS?
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LCIS is managed with observation although some people will opt for b/l mastectomy.
Tamoxifen is an option (although with it you have higher risk of VTE, endometrial ca). |
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How do you manage DCIS?
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Breast-conserving therapy (local excision w/ adequate margins) + XRT if possible -- if multifocal dz then probably simple mastectomy.
Adjunctive chemo - tamoxifen reduces risk of ipsilateral breast event. |
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What is the most important prognostic factor in localized invasive breast ca? Second most important prognosticator?
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Presence or absence of LN mets. Next most important is size of the primary tumor.
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What is trastuzumab?
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Herceptin
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How do you treat invasive breast ca?
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Surgery: BCT+XRT if less than 1cm. Modified radical mastectomy OR BCT+XRT if between 1cm to <4cm. Modified radical mastectomy if at least 4cm.
Adjuvant chemo: none if < 1cm. otherwise yes if >1cm and: premenopausal or HR neg. also yes if node positive. If HR+ positive than ADD tamoxifien x 5 years. |
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What is a common regimen of chemo for node negative breast ca? For node positive?
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AC (adriamycin and cyclophosphamide) for node negative.
AC+T (adriamycin and cyclophosphamide, taxol) for node positive. |
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What is tamoxifen's mechanism?
What can lead to decreased efficacy of tamoxifen? What can you use to to avoid this? What are side effects of tamoxifen? |
SERM.
specific CYP inhibitors- SSRI's, also genetic variation. If needed use venlafaxine bc it does not inhibit the specific CYP. Side effects include hot flashes, weight gain, VTE, slightly increased risk of endometrial ca. |
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What is anastrazole? What population it good for? When do you give it?
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Aromatase inhibtor, suppressing estrogen in postmenopausal women by blocking T --> E. (not good in premenopausal bc it doesn't block ovarian estrogen production).
Add it after a few years of tamoxifen to improve survival. Or can use it alone if contraindication to tamoxifen (hx of DVT or endometrial ca). Side effects are osteoperosis, bone and joint pains. |
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What are contraindications to XRT after lumpectomy?
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Pregnancy and prior XRT to the same breast for prior breast ca.
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What is the role of medications in breast ca prophylaxis?
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Tamoxifen prophylaxis for 5 years is considered for women at high-risk for invasive breast ca (although there is an increased risk for endometrial ca, VTE).
Raloxifene can be used instead in POSTmenopausal women for breast ca prevention with decreased side effects. |
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How do you treat metastatic breast ca?
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Aromatase inhibitors (anastrozole) are more effective than tamoxifen in postmenopausal women.
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What types of HPV are associated with cervical cancer?
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HPV types 16 and 18.
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What are guidelines for cervical ca screening? What if you received the vaccine?
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Starting at age 21, q2 years in 20's, q3 years after 30 (if 3 consecutive neg screens and no other RF's)
If vaccinated, still have to go through same screening. |
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Management of LGSIL? HGSIL from pap smear? What about all visible cervical lesions with pap smear that is normal?
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Both require colposcopy w/ biopsy for dx of CIN or cancer. Same for all visible lesions.
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What is the breakdown and corresponding prognosis of ovarian cancer types?
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Most (85%) is epithelial cell -- esp in postmenopausal women.
However 5% of ovarian ca is germ call (and benign) in young women. (remember germ cell ca is 95% of testicular ca) |
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What increases risk for ovarian ca?
Decreases? |
Increases: Nulliparity, +FH, BRCA, Lynch sx.
Decreases: OCP, tubal ligation, breastfeeding, early age of 1st preg, multiparity |
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What are BRCA1 and BRCA2 associated with?
What is Lynch syndrome? |
Breast and ovarian ca.
HNPCC - mismatch repair gene. colon ca and risk of ovarian ca. |
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What to do if CA-125 relapse?
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Not much- treatment does not impact survival.
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What is treatment of ovarian ca?
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Debulking and if stage 2 or 3 then chemotherapy (systemic +/-intraperitoneal)
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What are RF's for testicular ca?
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cryptorchidism, FH, infertility, and HIV infection.
Klinfelter sx is a RF for primary mediastinal germ cell tumors. |
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Management of testicular ca?
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Seminoma- less aggressive, very radiosensitive. Rx with orchiecetomy with radiation to RP LN's (if <5cm in size), chemo, or surveillance.
Nonseminoma- more aggressive. Rx with orchiectomy, can do surveillance w/salvage chemo afterwards (high relapse rate). or can do RP LN dissection. |
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What are seminoma biologic markers?
Nonseminoma? |
In Seminoma: AFP negative (Always!) and maybe hCG positive.
AFP is seen in- yolk sac tumor. also seen in liver dz, HCCa. hCG is usually in non-seminoma but can be in seminoma. |
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When should a man be considered for PSA screening?
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Age 50 (or 45 if RF's). Not if you are >75yo.
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What does staging of prostate ca involve?
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Bone scan and CT scan of pelvis (bc bone and LN's are most likely sites of mets)
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What does hormonal therapy consist of in prostate ca? Well-tolerated?
What population should this and radical prostatectomy be considered for? |
Androgen deprivation LHRH agonist (eg leuprolide) + androgen receptor antagonist (flutamide)/orchiectomy.
Significant side effects. For pts with mets, PSA-only recurrence, or undergoing radiation therapy as adjuvant therapy. Radical prostatectomy AND radiation therapy -- only if no LN's or mets. |
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What to expect in someone with metastatic prostate ca undergoing hormonal therapy as the disease progresses?
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Eventually they will become refractory to hormonal therapy (ie, aindrogen-independent prostate ca).
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What is the data on prostate ca prevention with medication?
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Finasteride (aka propecia) which is a 5-alpha-reductase inhibitor x 7 years has been shown to decrease risk, but people who do get it afterwards get high-grade ca.
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Where does carcinoid tumor usually occur? How do they present?
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Appendix (50%), small bowel, rectu - usually asymptomatic until mets to liver or lung.
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What syndrome is carcinoid seen with?
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MEN I (pituitary, PTH adenoma, pancreatic islet cell tumor).
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What is the syndrome of carcinoid syndrome?
How to diagnose it? Treat? Prognosis? |
Flushing, valvular heart disease, diarrhea
Dx with urinary 5-HIAA. Rx localized with surgery and spread with sx relief including octreotide. Even if metastatic, usually fairly benign disease. |
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What cancers is tobacco associated with? alcohol? both? asbestos?
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head and neck, lung, esophagus, bladder.
alcohol- liver, head and neck, esophagus both- synergistic effect asbestos- lung, mesothelioma of pleura and abd peritoneum esp if with tobacco |
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What ca's are assoc with estrogen? nitrites? animal fat? ionizing radiation? UV radiation? radon gas? viruses?
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Estrogen- uterine, vaginal, breast
Nitrites- stomach Animal fat- colon, breast, prostate Ionizing XRT- leukemia and thyroid UV XRT- all skin Radon gas- lung Viruses- HHV-8, Hep B and C, HPV (cervical and oropharyngeal), EBV, HIV (Kaposi and NHL), HTLV-1 |
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Mechanism and use of each of these, and major side effect:
Rituximab Imatinib- (Gleevec) Trastuzumab ATRA Paclitaxel Lenalidomide Tamoxifen |
Rituxan- antiCD20 for low grade lymphomas
Imatinib- TK inhibitor ofr CML Trastuzumab (herceptin)- can cause reversible CHF ATRA- tretinoin. APML. Rx retinoic acid sx with holding ATRA and giving steroids. Paclitxel (taxol)- for ovarian, breast, and lung ca. can cause anaphylactic infusion rxn. Lenalidomide- for MM and 5q- MDS. can cause birth defects Tamoxifen- SERM. inc endometrial ca. |
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Associations to know:
cyclophosphamide 5-fu hydroxyurea rituxan alpha-interferon |
cytoxan- hemorrhagic cystitis
5-fu- sun sensitivity hydroxyurea- leg ulcers rituxan- infusion reactions including bronchospasms alpha-interferon- flu-like illness (used in CML and Kaposi sarcoma if CD4>200) |
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Major side effects:
alkylating agents (eg cycolophosphamide, platins) and procarbazine (MOPP) |
very toxic to germinal cells of testes, often causes permanent sterility.
alkylating agents are also leukemogenic |
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vinblastine's dose limiting toxicity?
vincristine's? |
vinblastine- myelosuppression
vincristine- neurotoxicity- especially DTR's, quadriceps weakness |
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cisplatin's adverse effects?
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magnesium-wasting, neurotoxicity, nephrotoxicity, emetogenic
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anthracyclines.
taxanes and carboplatin and monoclonal ab's? |
dose-dependent cardiomyopathy, vesicants w/ extravation (skin and tissue damage).
significant infusion related hyperensitivity reactions |
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biologic agents like bevacizumab, sorafenib, sunitinib?
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vascular events and hypertension
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risks with Epo? when should you give it ever?
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1)Give it for chemo-induced anemia w/Hgb < 10. (but not cancer-related bc it can worsen survival).
2)also give it for anemia in HIV pts taking AZT 2)if anemia is 2/2 chronic renal failure. risk of thrombosis esp if Hgb>12. |
