Term
What is the condition with the following clinical findings?
- pallor
- lethargy
- microcytic hypochromic anemia, normal WBC
- decreased serum iron, increased TIBC, decreased sat
- decreased bone marrow iron
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Definition
Iron deficiency anemia. What type of morphology occurs first, microcytosis or hypochromasia?
microcytic |
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Term
what disease is likely with the following lab findings?
- decreased plasma iron
- normochromic, normocytic rbcs
- decreased TIBC
- decreased % saturation
- iron stores in bone marrow
- normal serum transferrin receptor
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Definition
| Anemia of chronic disease. Cells are hypochromic before becoming microcytic. |
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Term
| What are the common causes of anemia of chronic diseases? How does this cause anemia? |
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Definition
Caused by chronic infections, chronic inflammations, malignancy. This impairs RES release of iron derived from senescent RBC.
There is also cytokine inhibition of EPO production and an inappropriate response to EPO. |
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Term
| What is the treatment for iron deficiency disorder? |
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Definition
| Find the etiology and treat the underlying disorder. administer iron and observe reticulocyte response. continue therapy for six month after normal HgB achieved. |
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Term
| What kind of defect in metabolism causes sideroblastic anemia and what histological findings will this result in? What 3 classes/causes are there? |
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Definition
Recall that iron is incorporated into heme in the mitochondria. Defects in heme synthesis result in non ferritin iron accumulating in a mitochondria ring around the nucleus.
1. hereditary x-linked disorders and autosomal recessive
2. acquired primary; genotypic alterations in bone marrow stem cell clones
3. acquired secondary: reversible and associated with drugs, alcohol and cancer |
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Term
Basophilic stippling of red blood cells indicate what kind of environmental exposure?
How would you treat? |
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Definition
| lead poisoning, treat by lead free environment and chelators. |
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Term
What are some symptoms of hereditary hemochromatosis? What kind of tissue would you expect to see an accumulation of iron?
how would you treat? |
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Definition
1. hyperpigmentation
2. enlarged liver
3. diabetes
4. hypogonadism
5. cardiac failure
parenchymal tissue
phlebotomy |
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Term
| What isotype of immunoglobulin mediates intravascular hemolytic anemia? extravascular? |
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Definition
intravascular-IgM
extravascular- IgG |
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Term
| What are the two ways to measure RBC survival? |
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Definition
1. random labeling: RBCs are tagged with 51Cr and reinfused, samples collected at regular intervals and 51Cr activity is measured
2. cohort labeling: IV injection of 59Fe bound to transferrin. labeled Fe is incorporated into new RBC precursors and produces a cohort of RBCs of defined age. |
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Term
| How does hemolysis result in pulmonary hypertension? |
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Definition
| Hb is released into the circulation and binds NO. This results in vasoconstriction. |
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Term
A patient has increased reticulocyte number and nucleated RBCs in the peripheral blood. There are also increased levels of LDH. What broad class of pathology could these lab findings result form?
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Definition
hemolytic anemia
Analysis of urine also shows hemoglobinuria. does this make you suspect a intravascular or extravascular process?
intravascular as hemoglobin is released directly into the plasma. May occur during extensive extravascular hemolysis and RBCs are not phagocytosed by macrophages |
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Term
Which of the following lab findings increase in hemolysis and which decrease?
1. reticulocyte count
2. Haptoglobin
3. Hemopexin
4. LDH |
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Definition
1. increased reticulocyte count
2. decreased or absent haptoglobin
3. decreased hemopexin
4. increased LDH |
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Term
A peripheral blood smear shows Heinz bodies in the red blood cells. What enzyme deficiency does this result from?
How would you diagnose this condition? |
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Definition
| G6PD. assessed by rapid fluorescent screening test or quantitative spectrophotometric analysis. |
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Term
A peripheral blood smear shows RBCs with no central pallor. What is the suspected diagnosis and what is the molecular basis?
What would you expect to find on physical exam? |
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Definition
hereditary spherocytosis. abnormality in structural membrane proteins. spectrin, ankyrin, Band 3
splenomegaly due to work hypertrophy. |
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Term
| A patient with end stage renal disease has just had an AV fistula placed into their left bicep. What changes would you expect in their peripheral blood smear? |
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Definition
| Trauma from abnormal blood vessels and heart valves. intravascular RBC destruction occurs. You may see schistocytes. |
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Term
| A patient comes in complaining of lethargy and lack of energy. In addition they are worried about how brown their urine has been lately. What is this condition likely to be caused by? |
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Definition
Hemosiderinuria caused by intravascular hemolytic anemia. How does the hemosiderin get into the blood? highlight below:
When lysing RBCs release hemoglobin into the blood, the hemoglobin is usually bound by haptoglobin. When the haptoglobin is depleted, excess hemoglobin in excreted in the urine. However some hemoglobin is reabsorbed in the proximal tubule where the iron portion is removed and stored as ferritin or hemosiderin. The brown color comes form when the tubule cells are sloughed off. |
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Term
| What does hemopexin bind to and where does it transport it to? |
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Definition
| Hemopexin binds to ferrihemes and transports them to hepatic parenchymal cells. |
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Term
| A patient has been referred to the heme/onc clinic because a routine cbc has shown that they have leukopenia and thrombocytopenia. A peripheral blood smear shows hypersegmented neutrophils. The budding clinician in you knows that this reduces your differential diagnosis to folate or B12 deficiency. However, lab results for both are equivocal. What other lab tests could you perform to distinguish the two? |
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Definition
Methylmalonic acid and homocysteine levels. What would you expect to see in folate deficiency? In B12 defiency?
folate: pure folate deficiency will only elevate homocysteine levels
B12: will increase MMA and homocysteine |
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Term
| In a third year clinical rotation you are being pimped by a really old semi retired doctor about the Schilling test. He doesn't realize nobody uses it anymore, but luckily you learned about this test in Med 1. How does the Schilling test work and what is it measuring? Furthermore you suggest a newer, less time consuming test, what might that be? |
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Definition
1. give radioactive B12 into stomach
2. give intramuscular B12
3. measure urine excretion. If >10% of urine is radioactive then B12 absorption is normal. Pernicious anemia is when <5% of the urine B12 is radioactive.
In other words the small intestine is not absorbing B12 properly.
4. next step give IF with radioactive B12
5. give antibiotics in case of gastritis
Antibodies. |
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Term
| What is the therapy for B12 deficiency? |
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Definition
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Term
| HbA is the major component of adult hemoglobins. What are the subunits for HbA2? |
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Definition
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Term
| What is the functional abnormality associated with Hb G-Philadelphia? |
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Definition
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Term
| HbM represents what kind of hemoglobinopathy? |
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Definition
| methemoglobinemia; causes iron to remain in the Fe3+ from which cannot bind oxygen. this causes cyanosis |
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Term
| An African american woman and her partner come in for genetic counseling. The woman has lived with incredibly painful sickle cell anemia her whole life and does not want children if they are at risk for getting the disease. She is worried that her partner might have sickle cell trait so he was tested. Instead they found that he had alpha thalassemia. What are the chances of developing Sickle cell disease? |
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Definition
None, S-α-thalassemia is clinically insignificant and is more like sickle cell trait. If the father was instead heterozygous for ß-thalassemia gene, what are the chances of sickle cell in their children?
50%. S-ß-thalassemia is similar to SS disease as there is no "good" copy of the beta globin gene. |
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Term
| hydroxyurea has multiple utilities. what two conditions have we learned that can be treated with this drug? |
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Definition
1. treat sickle cell anemia by increasing HbF levels
2. treat myeloproliferative disorders especially polycythemia vera and essential thrombocytosis by inhibiting DNA synthesis |
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Term
| Someone is homozygous HbC. what symptoms would you expect and what would their peripheral blood smear look like? |
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Definition
| mild anemia. blood smear would show target cells. |
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Term
| What is HbH disease? how severe is it? In contrast what is Hb Barts and how severe is it? |
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Definition
α-thalassemia with only 1/4 copies of the alpha globin genes. β4 tetramers precipitate. life long mild to moderate anemia but there is a normal life expectancy.
Hb Barts is when there are no copies of alpha globin gene resulting in stillbirth or death with hours of birth |
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Term
| A 12 year old patient comes in with mild anemia, decreased MCV, increased RBC count. blood smear shows target cells and basophilic stippling. Serum iron, TIBC and transferrin receptor levels are normal. You initially suspect lead poisoning but serum lead levels are normal. Strangely HbF levels are elevated. This leads you suspect what genetic condition? |
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Definition
| β-thalassemia minor. (see kraut slide 59) |
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Term
| What is the main treatment for β-thalassemia major and what complications can arise from this? |
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Definition
| blood transfusions; can result in secondary hemochromotosis requiring iron chelation therapy. |
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Term
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Definition
| fusion δβ globin gene resulting from erroneous meiotic recombination. homozygotes and heterozygotes have similarites to β-thalassemia |
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Term
| CD19, C20 and CD23= what type of pathology? |
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Definition
| CLL. also displays pan T-cell marker CD5 and IgG |
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Term
| What is the cause of death in most CLL patients? |
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Definition
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Term
| Which of the following cytogenetic abnormalities would you most like to see in a CLL patient? del11q, +12, del 13q, del17p or normal? Which one would you least what to see? |
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Definition
| del13q have the longest time of survival. del17p have the lowest. look at slide 26 for andristos |
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Term
| What is CLL? What would you look for in blood smear? |
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Definition
| Chronic lymphocytic leukemia is a clonal lymphoproliferative disorder leading to an accumulation of mature appearing but biologically immature lymphocytes. You would see smudge cells and lymphocytes with condensed chromatin and inconspicuous nucleoli |
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Term
| You give a CLL patient the shingles vaccine. why do you get sued later? |
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Definition
| CLL patients should not receive live vaccine because of humoral immune defects. |
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Term
| What type of anemia are CLL patients associated with? |
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Definition
| (warm antibody) autoimmune hemolytic anemia |
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Term
| You can distinguish Waldenstrom's macroglobinemia from multiple myeloma by the monoclonal antibody isotype produced. What is produced in waldenstroms and what symptom's does it lead to? |
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Definition
| IgM: circulates as a pentamer causing hyperviscosity and also attacks myelin sheaths of neurons causing neuropathy. |
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Term
| A patient is found to have elevated levels of IgG in their blood serum. Bone biopsy reveals less than 10% clonal plasma cells in marrow but no CRAB signs and symptoms. This is? |
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Definition
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Term
| How do you distinguish smoldering myeloma from multiple myeloma? |
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Definition
| smoldering myeloma can be thought of as durie salmon stage 1 MM. there are >10% plasma cells in bone marrow, monoclonal protein in serum and urine BUT no crab signs or symptoms. |
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Term
| For multiple myeloma, what is the ISS stage 1 blood levels? stage 3? |
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Definition
stage 1: beta-2microglobulin <3.5, albumin >3.5
stage 3 beta-2 microglobulin >5.5, albumin can be anything |
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Term
| for multiple myeloma, what cytogenetics can indicate high risk? |
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Definition
| 17p deletion, 13q deletion, complex karyotype, hypodiploid karyotype |
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Term
| What are the treatment options for MM? |
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Definition
1. BMT
2. or if ineligble for BMT, 3 drug combo |
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Term
| What gene is dysregulated in MM? |
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Definition
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Term
| In multiple myeloma, what is the cause of kidney failure? |
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Definition
| excess immunoglobulin can plug up kidney tubules/filters. poor kidney reserve can also make patients sensitive to medication toxicity |
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Term
| Anemia in multiple myeloma is caused by? |
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Definition
| renal failure(no more EPO), B12 deficiency and crowding out of normal hematopoietic cells in bone marrow |
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Term
| hypercalcemia in MM results from? |
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Definition
| lytic lesions in bone leading to bone destruction and release of calcium. cytokines also play a role |
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Term
A 24 y/o woman with a history of periodic, unexplained fevers presents with abnormal liver function studies and progressive renal failure. 24h urine shows 12g proteinuria. These have been shown to be lamda light chain immunoglobulins. What pathology do you suspect...be specific!
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Definition
| primary AL amyloidosis. malignant plasma cells in marrow are elaborating a monoclonal protein. |
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Term
| What are the common mutant proteins in familial amyloidosis? |
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Definition
transthyretin and apolipoprotein
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Term
| what is the etiology for secondary AA amyloidosis |
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Definition
chronic inflammation, such as rheumatoid arthritis, lupus, crohn's, TB etc.
hereditary fever syndrome can also be a cause |
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Term
| Primary amyoidosis and multiple myeloma are both plasma cell malignancies. A good proportion of the time they can overlap in their diagnostic criteria. However what symptoms and lab findings can distinguish the 2? |
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Definition
primary amyloidosis: BM PC<10%, 3:1 lambda, renal, cardiac, liver, gut, nerve and skin symptoms, coagulopathy
MM: BM PC>10%, 2:3 kappa, CRAB and hyperviscosity |
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Term
| What does familial amyloidosis therapy consist of? |
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Definition
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Term
| amyloidosis results in what hematologic deficiency? what is the treatment? |
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Definition
| factor X deficiency resulting in increased risk of bleeding, only therapeutic option is recombinant factor VII |
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Term
| How do you detect cardiac involvement in amyloidosis? |
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Definition
| thickened interventricular septum on surface echocardiogram |
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Term
| What is the goal of therapy for primary amyloidosis and what is the current therapy? |
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Definition
| eradicate clonal plasma cells which are the source of excess immunoglobulin. Current therapy involves melphalan with dexamethasone. or autologous stem cell transplant in a select few patients |
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Term
| what is the amyloid protein in AA? |
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Definition
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Term
| t(14:18) is associated with what pathology and genes? |
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Definition
| follicular lymphoma; bcl-2 IgH |
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Term
| chromosome 3 abnormalities/translocations are associated with what gene and pathology? |
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Definition
| bcl-6 and diffuse large b-cell lymphoma |
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Term
| A patient has diffuse large B-cell lymphoma. what is the standard treatment? |
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Definition
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Term
| A patients peripheral blood smear show's Reed-Sternberg cells. This is indicative of what type of lymphoma? What markers would you expect them to stain for? what common T and B cell markers would you find lacking? |
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Definition
| Hodgkin lymphoma: positive for CD15 and CD30, negative for T-cell CD3, CD5 and B-cell CD19, CD20 |
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Term
| In one rare form of Hodgkin's lymphoma you would not see Reed-Sternberg cells in the blood smear. instead you would see what type of cell? what is the name of this form of hodgkin's lymphoma? Immunohistochemically how else is it distinguished from other types of HL? |
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Definition
popcorn cells: indicative of nodular lymphocyte predominant HL.
Cells are C20 and CD45 positive
Absent eosinophil and neutrophils |
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Term
| What are the 2 most common types of classical HL? |
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Definition
nodular sclerosing(young peeps, stage I/II) and mixed cellullarity(older peeps and HIV. stage III/IV with B symptoms)
other two types are lymphocyte rich and lymphocyte depleted. |
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Term
| A HL patient has enlarged hard enlarged lymph nodes in both the cervical region and supraclavicular region. According to the Ann Arbor staging what stage is their disease? |
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Definition
| Stage II because still on same side of diaphragm. |
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Term
ABVD chemotherapy is the front-line treatment for Hodgkin's lymphoma. what are the symptoms related to each drug?
what advantages does ABVD have over MOPP (especially for younger patients?) |
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Definition
A-adriamycin: congestive heart failure
B- Bleomycin- interstitial pneumonitis
V- vinblastine: peripheral neuropathy
D- dacarbazine- chemical phlebitis
ABVD does not cause infertility, no risk for secondary leukemia and less myelosupression |
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Term
what is the difference between stage IIA and stage IIB hodgkin's lymphoma?
how will this change treatment? |
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Definition
stage IIB are patients displaying B symptoms (night sweats, fever, weight loss)
the number of ABVD cycles is increased |
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Term
| Why are PFTs and MUGAs part of HL clinical assessments? |
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Definition
| ABVD therapy for HL can produce cardiac and pulmonary complications |
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Term
| You see auer rods in a peripheral blood smear of a patient complaining of lethargy that has been getting worse and worse. What pathology is this indicative of? |
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Definition
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Term
| Meingeal infiltration is more common in what type of leukemia? |
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Definition
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Term
| The presence of Auer rods in a patient has helped you diagnose them with AML. You want to see if they have M3 or acute promyelocytic leukemia to help you decide is ATRA treatment is appropriate. What other tests can you perform? |
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Definition
flow cytometry: APL does not express HLA-DR
cytogenetics: APL has a t(15:17) translocation |
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Term
For AML cytogenetic risk plays a big part in risk stratification. Which of the following are favorable and which are unfavorable (some are neither but related to other patholgies):
t(8;21), -5, t(14;18), complex, del(5q), t(9;22), t(8:14), t(11;22), t(15;17), inv(16), -7, t(3;multiple), abnormal 3q |
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Definition
favorable: t(8:21), t(15:17), inv(16)
adverse: -5, -7, del(5q), abnormal 3q, complex
t(14:18): follicular lymphoma (bcl-2)
t(8:14): burkitt's lymphoma (c-myc)
t(11;22): ewing's sarcoma (don't need to know)
t(9;22): CML
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Term
| What are the cytogenetics of patients that do better with high doses of Ara-C with their chemotherapy? |
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Definition
|
|
Term
| what is the histologically marker indicative of ALL? |
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Definition
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Term
| t(9;22) is associated with? |
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Definition
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Term
| What do t(9;22) and t(v11q23) have in common? |
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Definition
| bad prognostic factors for ALL |
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