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Pathophysiology - Hematology > First Pass Miss > Flashcards

First Pass Miss Flashcards

1
Q

What is the lifespan of an average neutrophil, platelet, or RBC? How long does it take to make an RBC in the bone marrow?

A

Neutrophil - 6-8 hours
Platelet - 7-10 days
RBC - 120 days, produced in about 7 days

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2
Q

Where does hematopoesis first begin and where does it ultimately move to / when?

A

Starts in yolk sac, then liver / spleen, before finally moving to bone marrow

Moves to primarily bone marrow / some lymph nodes by birth

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3
Q

What causes basophilic stippling in RBCs?

A

Aggregation of residual ribosomes and RNA, seen in sideroblastic anemia, lead poisoning, etc

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4
Q

What are myeloid precursors called, where should they be found, and what CD markers are they positive for?

A

Myeloblasts, present in small amounts in bone marrow (should NOT be in blood)

Positive for CD34 and CD117
-> note, CD34 will be negative in APML because it is past the stem cell stage

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5
Q

What are some causes of neutrophil defects in chemotaxis?

A

Congenital - LAD1

Acquired - corticosteroid therapy (downregulates P-selectin), myelodysplastic syndromes

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6
Q

What is Hand-Schuller-Christian disease and what is it associated with?

A

Langerhan’s cell histocytosis seen in age >2 (greater than 2 names)
-> scalp rash, skull defects, exophthalmos, and diabetes insipidus (due to posterior pituitary involvement)

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7
Q

What is hemophagocytic syndrome? Symptoms?

A

Usually an acquired disease where histiocytes in bone marrow ingest RBCs, white cells, and/or platelets

Due to infection or cancer

Symptoms: pancytopenia, hepatosplenomegaly, fever, multi-organ dysfunction

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8
Q

What is Rosai-Dorfman disease?

A

Sinus Histiocytosis with Massive Lymphadenopathy

  • > Marked expansion of lymph node sinuses causng a lymphadenopathy
  • > chronic, cervical lymphadenopathy of unknown cause
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9
Q

What are the three forms of Gaucher’s disease? What disease is it associated with?

A
  1. Chronic, adult-type with no CNS involvement (most common)
  2. Acute, infantile type - CNS involvement but not bone involvement
  3. Subacute with CNS and bone, adolescent onset, better prognosis

Associated with multiple myeloma

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10
Q

In what states will you see target cells and why?

A

Target cells caused by too much cytoskeleton which is normally removed by spleen and liver to not be removed.

Can be seen in asplenia or liver disease
Also seen in iron deficiency -> overproduction of hypochromic, microcytic RBCs which do not have time to be properly filtered by spleen

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11
Q

When is G-CSF used?

A

To produce a rise in circulating neutrophils:

  1. Post-chemotherapy, radiotherapy, or stem-cell transplant to shorten neutropenia
  2. Severe neutropenia (congenital or acquired)
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12
Q

What problems can cause deficiencies in neutrophil chemotaxis?

A
  1. LAD-1 - integrin problem (CD18)
  2. Corticosteroid use - downregulates P-selection
  3. Myelodysplastic syndromes
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13
Q

What is the definition of anemia for men / women?

A

Decrease in hemoglobin in the blood

Men: Hgb < 13 g/dL or <40% hematocrit

Women: HgB <12 g/dL or <36% hematocrit

Hct is typically 3x the Hgb

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14
Q

What is the DDx of normocytic anemias?

A 
Anemia of chronic disease - most common, can also be microcytic
Chronic kidney disease - loss of EPO 
Blood loss 
Hemolysis 
Mixed etiologies, i.e. genetic 
Bone marrow disease
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15
Q

What is polychromasia and in what causes of anemia does it happen? What count is indicative of increased RBC turnover?

A

Increased reticulocytes (100,000 = absolute count showing increased turnover) on blood smear (stain blue due to residual DNA in cytoplasm, and are larger than normal RBC)

Happens in anemia due to acute blood loss or hemolysis -> more erythropoesis

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16
Q

What are some other important studies in the workup of anemia?

A
  1. Hemoglobin trend
  2. Creatinine - chronic kidney disease can cause anemia
  3. Iron studies - microcytic
  4. Hemolytic workup - reticulocyte count, LDH, bilirubin, haptoglobin
  5. Liver function tests - if macrocytic
  6. TSH - if macrocytic
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17
Q

What are the major storage and carrier proteins for iron?

A

Storage - ferritin, within reticuloendothelial cystem

Carrier - Transferrin - delivers iron to macrophages in RES and developing erythrocytes in bone marrow via transferrin receptor

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18
Q

What are the congenital and acquired causes of sideroblastic anemia?

A

Congenital - ALA synthase mutation
Acquired:
1. Alcohol - mitochondrial poison
2. Lead - inhibits ALA dehydratase and ferrochelatase
3. B6 deficiency - usually due to isoniazid therapy
4. myelodysplastic syndromes

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19
Q

What are more specific signs and symptoms for iron deficiency anemia (IDA)?

A

Pica - wanting to eat ice, baking power, clay, chalk

Restless legs - remember, iron is used to make dopamine and low levels (Ferritin <50) can cause RLS

Koilonychia - spooning of the nails - very severe cases, most specific

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20
Q

Why might a patient be refractory to ferrous sulfate / how long should they take to improve?

A

RBCs start increased in 4-7 days, resolution of anemia within 4-6 weeks depending on deficiency

Refractory reasons: 
Noncompliance 
Wrong diagnosis (more than one) 
Not enough iron - excessive bleeding 
Malabsorption
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21
Q

What is the cause of Classic hereditary hemochromatosis? What chromosome? Is it common?

A

Autosomal recessive HFE gene mutation on chromosome 6
-> increased intestinal absorption of iron, decreased hepcidin production, increased ferroportin transport

Most common inherited single-gene disease in US

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22
Q

Where does iron tend to accumulate in hereditary hemochromatosis?

A

Liver, pancreas, skin, heart, pituitary, and joints

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23
Q

What are the hepatic manifestions of HH?

A

Hepatomegaly, fibrosis and cirrhosis, with common progression to hepatocellular carcinoma (most common cause of death)

Causes restrictive -> dilated cardiomyopathy in heart

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24
Q

What is the classic triad of HH?

A

BCD

Bronzing of the skin - hyperpigmentation
Cirrhosis
Diabetes (due to pancreatic insufficiency)

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25
Q

What are the joint and pituitary manifestations of HH?

A

Joint - arthropathy of MCP and PIP joints

Pituitary - hypogonadism

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26
Q

How is HH treated if ferritin is >500 or there is end-organ damage? What is the goal? What if patient has sickle cell?

A

Serial phlebotomies - keep ferritin to <50-100

If intolerant to phlebotomy - i.e. patient has sickle cell disease
-> Desferoxamine IV or Deferasirox PO

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27
Q

What are the symptoms of acute intermittent porphyria?

A

NEUROVISCERAL SYMPTOMS

5 P’s of porphyria

Painful abdomen
Port-wine urine
Polyneuropathy - tingling nof limbs, respiratory failure
Psychological disturbances
Precipitated by drugs, alcohol and starvation

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28
Q

How is diagnosis of the porphyrias typically made?

A

Urine porphyrins, making sure to minimize light exposure which would break them down

  • > best collected in acute exacerbation
  • > test urine, blood, stool, then do genetic testing to confirm
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29
Q

How is PCT treated?

A

Avoid ETOH consumption (hepatic toxin), avoid sun exposure (werewolf), phlebotomy to reduce iron levels

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30
Q

What things precipitate AIP? Treatment?

A

Remember the last P of porphyrias:
Precipitated

Dehydration, starvation, CYP inducers induce ALA synthase (anticonvulsants), alcohol (also induces)

Treatment:
IV dextrose and heme to inhibit ALA synthase

Fluids and narcotics for pain

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31
Q

There are three alleles for the HFE gene, two of which cause some form of hereditary hemochromatosis. What combination is most likely to cause symptomatic overload.

Alleles include:

  1. Wild type
  2. C282Y
  3. H63D
A

Homozygous C282Y (C282Y/C282Y)

heterozygotes may have mild disease: C282Y / H63D

All others very unlikely to produce significant disease

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32
Q

What is a positive hemolytic workup?

A

increased reticulocyte count, increased LDH, increased bilirubin, decreased haptoglobin

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33
Q

What are the symptoms of Porphyria cutanea tarda (PCT)?

A

Cutaneous symptoms and iron overload (chronic)

  • > blistering photosensitivity, hypertrichosis, iron overload, and chronic liver disease (associated with alcohol consumption)
  • > makes you look like a werewolf
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34
Q

What is the DDx for macrocytic anemias?

A 
Megaloblastic anemias (b9/b12) 
chronic liver disease / alcoholism 
hypothyroidism 
drugs 
bone marrow disorders 
red cell agglutination (warm or cold) 
very brisk reticulocytosis
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35
Q

Describe the pathway by which B12 is ingested and absorbed.

A

Ingested in animal products. Stomach enzymes detach B12 from protein and attach it to R-binder which was released by salivary glands.

In the duodenum, proteases detach R-binder from B12

B12 binds intrinsic factor released from parietal cells in the duodenum

IF-B12 complex attaches to receptor in terminal ileum for absorption

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36
Q

What can be seen on blood smear due to B9/B12 deficiencies?

A

Macro-ovalocytes (not round as in liver or hypothyroidism)

Hypersegmented neutrophils 5% with >5 lobes or any with >6

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37
Q

What are the usual causes of folate deficiency?

A

Alcoholism - inhibits absorption and poor diet
Intestinal malabsorptive disorders
High demand states: Hemolytic anemias, pregnancy
Drugs - phenytoin, pyrimethamine, trimethoprim, methotrexate

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38
Q

What are the neurological features of B12 deficiency and do the symptoms appear before or after anemia?

A

Subacute combined degeneration

Symmetrical polyneuropathy affecting legs more than arms

  • > paresthesias happen more than motor
  • > loss of proprioception and vibratory sense due to DC-ML loss
  • > spastic paresis due to loss of lateral corticospinal tract

Can also affect memory / personality

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39
Q

What things do we typically screen our blood donations for nowadays?

A

Bacterial contamination, Hep B/C, HIV, HTLV, T. cruzi, syphilis, and Zika

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40
Q

What is fresh frozen plasma and cryoprecipitate?

A

Fresh frozen plasma is made from heavily spinning platelet-rich plasma, and removing platelets

Cryoprecipitate is composed of specific components of FFP
-> vWF, fibrinogen, Factor 8, Factor 13

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41
Q

What is the process of pre-transfusion compatibility testing?

A
  1. Forward ABO typing - test patient’s RBCs
  2. Reverse ABO typing - test patient’s blood type based on what antibodies they have in their serum
  3. Rh Typing - positive or negative
  4. Identification of allo-antibodies in patient’s plasma (if present)
  5. Selecting appropriate blood components
  6. Cross-match
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42
Q

What plasma can you transfuse to patients with the following blood types

  1. Group A
  2. Group B
  3. Group AB
  4. Group O
A
  1. Group A - A or AB
  2. Group B - B or AB
  3. Group AB - AB only (A, B, or O would have antibodies to A or B)
  4. Group O - universal receiver
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43
Q

Who are the universal RBC donors and universal plasma donors?

A

RBC - Type O
-> no antigens to react with anti A or anti B antibodies in plasma
O-neg given in emergencies

Plasma - Type AB
-> no antibodies to react with any blood type surface antigens

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44
Q

What are the symptoms of delayed hemolytic transfusion reaction? Treatment?

A

Worsening anemia after transfusion, bilirubin / jaundice, hemolysis evidence

renal failure / death are rare in this cause (extravascular, not as severe)

Treatment: supportive care

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45
Q

What is tranfusion associated acute lung injury (TRALI)? Treatment?

A

Siimilar to TACO, but noncardiogenic pulmonary edema and no cardiomegaly

  • > due to donor antibodies against recipient neutrophils resulting in capillary leak
  • > give supportive therapy and mechanical ventilation if needed

TACO (Transfusion associated circulatory overload) presents with CHF like symptoms and will have generalized edema

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46
Q

What process is done to prevent transfusion reactions in immunocompetent hosts? What type of tranfusion reaction is this normally?

A

Leukoreduction
-> filter out WBCs

Usually a febrile, non-hemolytic reaction due to Abs against donor leukocytes/platelets or cytokines present in donor plasma

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47
Q

Who is likely to have homozygous alpha+ trait vs alpha0 trait?

A

Homozygous alpha+ trait = two alpha genes knocked out, but on opposite chromosomes
-> trans, more common in Africans

alpha0 trait = two alpha genes knocked out on same chromosome, other chromosome is homozygous functional
-> cis, more common in Asians

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48
Q

What is thalassemia minor vs thalassemia major?

A

Bn / B+ or Bn / B0 = thalassemia minor

Any thalassemia without at least one Bn = thalassemia intermedia. Worst is B0/B0 = thalassemia major

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49
Q

What are the features of beta thalassemia anemia? What is seen on electrophoresis in minor / major?

A

Hypochromic, microcytic anemia with target cell formation

Minor: decreased HbA and mildly increased HbA2 (>4%) / HbF (>2%)

Major: little to no HbA (20%), almost all HbA2 (4+%) / HbF (70+%)

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50
Q

What happens when alpha chains accumulate in thalassemia major?

A
  1. Alpha chains are toxic to cell division and arrest hematopoiesis
  2. Alpha chains make RBC deformed for splenic removal
  3. RBC damage causes K+ flux

These factors all lead to intramedullary death and short RBC survival -> hemolytic anemia

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51
Q

What happens if beta thalassemia is left chronically untreated?

A

Splenomegaly due to work hypertrophy, bone changes (especially skull and facial bones) due to expanded hematopoesis (extramedullary), increased iron absorption from elevated EPO levels, growth failure, and cardiac dysfunction

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52
Q

What is the primary treatment of beta thalassemia major and what is the target?

A

Hypertransfusions of blood - target is 9 to 10 gm/dL

Improves growth, less organomegaly, fewer fractures, less facial deformity

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53
Q

What needs to be added to treatment regimens on patients with chronic blood transfusions as in beta thalassemia major? Name / describe them and their limitations

A

Iron chelators

Desferrioxamine - safest but cumbersome and painful - infused daily for 8-12 hours

Desferasirox and deferiprone - taken orally, have hepatic, renal and bone marrow side effects, but much easier

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54
Q

What is the difference between an intrinsic and an extrinsic hemolytic anemia?

A

Intrinsic - changes to RBC cause anemia, i.e. membrane changes, hemoglobin changes, enzyme changes

Extrinsic - Autoimmune, microangiopathic, and macroangiopathic (i.e. mechanical)

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55
Q

What are the clinical characteristics of Sickle cell trait? Is it common in the US?

A

Benign because HbA is made slightly more efficiently than HbS, and need >50% HbS for disease

  • > hematuria, loss of urine concentration because hypertonicity of medulla causes sickling, causing microinfarctions & loss of ability to concentrate urine
  • > problems with high altitude (hypoxia)

->10% carrier rate in US blacks

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56
Q

How does a vaso-occlusive crisis occur?

A

Whenever the sickled RBCs are stuck to the endothelial wall, they can rip off the endothelium as they are pulled away, exposing collagen and starting a clotting cascade
-> leads to thrombosis and further narrowing of vessel lumen

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57
Q

What symptom of sickle cell disease is often mistaken for osteomyelitis?

A

Dactylitis - swollen hands and feet due to vasoocclusive infarcts in bones

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58
Q

What is an inexpensive test to tell you if a patient may have sickle cell trait or disease?

A

Solubility test, uses a reagent to lyse RBCs and something to deoxygenate hemoglobin.

If a sample contains HbS, the solution will be turbid.

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59
Q

What is characteristic of the blood smear with hemoglobin C and what symptoms does it cause?

A

Hemoglobin C “c”rystals in RBCs, with target cells

Symptoms: mild extravascular hemolytic anemia with associated splenomegaly

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60
Q

Where is Hemoglobin E found and when is it a problem?

A

Found in patients in far east (Asia)

Trait - like beta thalassemia minor
Homozygous recessive - will cause mild hypochromia and microcytosis
E/B0 - transfusion dependent, like beta thalassemia major -> this heterozygous phenotype is bone bad.

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61
Q

What is the confirmatory test used to diagnose spherocytosis?

A

Eosin-maleimide (EMA) binding by flow. Spherocytosis will bind less EMA.

-> spherocytes have lower surface area to bind

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62
Q

What things precipitate hemolysis in G6PD deficiency? is this intravascular or extravascular?

A

Predominantly intravascular hemolysis, so will cause kidney damage (no splenomegaly)

Antimalarials (i.e. primaquine), slufa drugs, nitrofurantoin, Fava beans, naphthelene (mothballs, think mothball / basket cells), overwhelming infections

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63
Q

What causes Paroxysmal Nocturnal Hemoglobinuria?

A

Acquired defect in glycosylphosphatidylinositol (GPI) gene within myeloid stem cells
-> lack of GPI anchor prevents expression of decay-accelerating factor (CD55) and CD59, which are needed to inhibit C3 convertase and thus fixation of complement

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64
Q

What causes cold reactive AIHA? What type of antibodies are they?

A

IgM antibodies usually active at 2 to 4 degrees C in the lab, works more in cold temperatures of extremities

Antibodies (cold agglutinins) made in lymphoma, infectious mononucleosis, and Mycoplasma pneumoniae

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65
Q

What is Evan’s syndrome?

A

When autoimmune hemolytic anemia also associated with attacking platelets
-> causes mild thrombocytopenia not associated with bleeding

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66
Q

What is drug induced antibody hemolysis?

A

Very similar to warm agglutinin IgG-mediated disease, happens in one of two ways.

  1. Antibody is formed to drug-RBC membrane complex (i.e. penicillin)
  2. Antibody is formed to RBC membrane due to presence of drug, hemolytic anemia persists in absence of drug (i.e. a-methyldopa)
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67
Q

What are common causes of macroangiopathic anemia? What will be seen on blood smear?

A

Prosthetic heart valves, aortic stenosis, or arterial grafts
-> mechanical destruction of RBCs with Schistocytes on peripheral smear.

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68
Q

How is AIHA managed?

A

Keep hemoglobin at safe levels (>4 g/dL) with transfusions

High dose steroids - prevent Ab production

Alkalize urine to protect kidneys

Plasmapheresis - strain out Abs

Splenectomy

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69
Q

What mutations are associated with each of the four main Myeloproliferative neoplasms?

A
  1. Polycythemia Vera (PV) - JAK2 always
  2. Essential Thrombocytopenia (ET) - JAK2 50%
  3. Primary Myelofibrosis (MF) - JAK2 50%
  4. Chronic Myelogenous Leukemia (CML) - philadelphia chromosome
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70
Q

What are the rarer but classic symptoms of polycythemia vera?

A
  1. Intense pruritis (itching) following a shower due to increased mast cells (WBCs can also go up in this condition)
  2. Erythromelalgia - pain and red-blue discoloration in hands and feet
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71
Q

Including polycythemia vera, what, in general, can myeloproliferative disorders ultimately progress to?

A

Marrow fibrosis w/cytopenias, or acute leukemia

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72
Q

What are some causes of secondary polycythemia? One of these is a pseudopolycythemia.

A
  1. High EPO levels - i.e. malignancy
  2. Chronic hypoxemia in smokers
  3. Lung disease
  4. High altitudes
  5. Severe dehydration - reduced plasma volume makes a relatively increased hemoglobin
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73
Q

What are the treatments for ET? What can it progress to? What will peripheral smear show?

A

Aspirin (platelets) and hydroxyurea

Can progress to myelofibrosis and AML, much like all other myeloproliferative syndromes

Peripheral smear shows >10 platelets per hpf

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74
Q

What systemic symptoms are likely to develop in primary myelofibrosis and why?

A
  1. Massive hepatosplenomegaly due to extramedullary hematopoesis in liver and spleen since there’s no room in bone marrow to do this anymore
  2. Hypermetabolic state due to cytokines secreted by platelets, leading to fever, bone pain, and night sweats
  3. Anemia is also common
75
Q

What does the peripheral blood smear show for PMF? Why?

A

Leukoerythroblastic smear - spleen is not built to hold all these hematopoesis so immature cells leak out

Includes “tear drop RBCs”, nucleated RBCs, and immature neutrophils

76
Q

What are the phases of CML infection and when are most patients diagnosed?

A

Chronic phase - most patients diagnosed here by CBC when asymptomatic
Accelerated phase - increased output of mature myeloid cells, marked by enlargement of the spleen
Terminal blast crisis - right before it becomes an acute leukemia

77
Q

What other malignancy displays the philadelphia chromosome and how can it be distinguished from CML?

A

De novo ALL (acute lymphoblastic leukemia not preceded by CML)

ALL has a 190kD fusion protein, whereas CML has a 210kD fusion protein

78
Q

What are three ways that CML can be told from a normal leukemoid reaction (reactive neutrophilic leukocytosis)?

A

CML:

  1. Leukocyte alkaline phosphatase (LAP) negative. LAP+ = neutrophils made to fight infection, more well developed than CML
  2. Increased basophil count (absent in leukemoid)
  3. Philadelphia chromosome
79
Q

What are myelodysplastic syndromes (MDS)? What can it progress to?

A

Heterogeneous disorders of myeloid stem cells with ineffective hematopoiesis (RBC production)

Can progress to AML

80
Q

What is seen on peripheral blood smear of MDS in general?

A

Cytopenias - with variable reduction RBCs, platelets, and granulocytes, some with functional defects.

RBCs = normocytic or **macrocytic** 
WBCs = abnormal nuclear lobation and granules with impaired killing activity
81
Q

How do patients with MDS diagnosis present?

A

Usually older adults with nonspecific symptoms due to cytopenias.

Anemia symptoms most common - macrocytic

Neutropenia causes infections

Thrombocytopenia causes bleeding

82
Q

How do the RBCs appear in MDS?

A

Macrocytic and dysplastic

  • multinucleated
  • dyssynchrony between cytoplasm and nucleus
  • ring sideroblasts could be present (failure to make RBCs properly)
83
Q

How can you track how quickly MDS is progressing to AML? What are the two most common cytogenetic abnormalities of MDS?

A

WHO classifications of refractory anemia with excess blasts

RAEB-1 - 5-10% blasts - not very close
RAEB-2 - 10-20% blasts - getting very close
-> less blasts than this and you have some other type of MDS, i.e. Refractory anemia with ring sideroblasts, but must be less than 5%

5q deletion MDS which can be treated with lenalidomide, and 7q deletion

84
Q

How are low, medium, and high risk patients with MDS treated?

A

Based on degree of cytopenias, %blasts in marrow, and cytogenetic abnormalities

Low - tranfusions and iron chelation

Medium - hypomethylating agents to stop methylation of tumor suppressors (slows progression)

High - bone marrow transplant

85
Q

What is Fanconi anemia caused by? Symptoms?

A

Autosomal recessive mutation in DNA repair enzymes causing chromosomal breakages and bone marrow failure

Short stature, increased cancer incidence, cafe au lait spots, thumb /radial defects

86
Q

What genetic abnormalities and benign hematologic disease can predispose to MDS?

A

Genetic - Down syndrome (also predisposes to AML), Fanconi anemia, Bloom syndrome, Ataxia-Telangectasia

Hematologic - Paroxysmal nocturnal hemoglobinuria, congenital neutropenia

Usually, however, this arises post-chemotherapy (alkylating agents, radiation), or benzene / tobacco carcinogens

87
Q

What are the treatments for aplastic anemia, especially when autoimmune? How does it arise?

A

Immunosuppressive regimens: cyclosporine (blocks T cells), antithymocyte globulin

Bone marrow transplant

Transfusions and bone marrow stimulation via GM-CSF can also be tried

Usually arises idiopathically post-hepatitis, but can be post-viral, post-drug, or associated with Fanconi anemia / dyskeratosis congenita
-> overaction of lymphocytes following an adjuvating factor suppresses the bone marrow

88
Q

How does inhibition of normal hematopoiesis explain the classic signs of acute leukemias?

A

Anemia -> fatigue, pallor
Thrombocytopenia -> bleeding (ecchymosis, epistaxis, menorrhagia, petechiae)
Neutropenia -> infections

Fever / bone pain from crowding out of bone marrow by blast cells

89
Q

What leukemias are associated with Down syndrome and at what ages?

A

Before age 5: Acute megakaryoblastic anemia (type of AML)

After age 5: Acute lymphoblastic leukemia (ALL)

90
Q

What are the monocyte markers for flow cytometry? What are the myeloid markers?

A

CD11 (integrin receptors for ICAM binding)
CD14 (TLR4)
-> note, these cells will also stain nonspecific esterase positive

Myeloid markers include: CD13 and CD33

91
Q

What are the flow cytometry markers for B-cell ALL?

A

CD10
CD19
CD20
CD22

92
Q

What genetic analysis is done on leukemic cells and why? Which AML has the worst prognosis? Best?

A

Whole genome molecular marker analysis

Worst: FLT-3+ (FMS-related tyrosine kinase)
Best: NPM1+, CEBPA+

NPM: Nucleophosphomin

93
Q

What are the three AML’s which do NOT require >20% blasts in bone marrow to diagnose them as AML (this is unique)? What is wrong in the first two of them?

A

First two are related to dysfunction in core binding factors (CBF) which are essential for normal hematopoesis

  1. t(8;21) - RUNX1 - remember one less than 9;22
  2. inversion (16)
  3. t(15;17) - RAR dysfunction promyelocytic leukemia

(any number of blasts = AML)

94
Q

How do you recognize APL and why is it important to recognize it early? What do RBCs look like in it?

A

Cells are distinctive because of many cytoplasmic granules and stacks of Auer rods (MPO+)

Recognize early because when cells are lysed, MPO activates coagulation cascade, causing a procoagulant state

DIC is a common presentation in these patients

RBCs - schistocytes due to microangiopathic cleavage

95
Q

How do we treat fit patients with good risk in AML?

A

Good risk - any MDS exception, and FLT-3 negative

Induction - standard chemotherapy regimen of 7 days Ara-C + 3 days anthracycline

Consolidation with 3-4 cycles of high dose Ara-C

Fit patients with medium/high risk = might do some chemotherapy, but probably go right to bone marrow transplant

Non-fit (older) - supportive care, hypomethylating agents to slow progression of disease

96
Q

What will PAS stain show for ALL? How does the nucleus of the lymphoblasts generally appear in ALL?

A

PAS - dot-like positive staining encircling nucleus

Nucleus has folds or grooves in them

97
Q

What ALL is most commonly seen in children and has a good prognosis?

A

t(12;21) - B cell leukemia

98
Q

How does treatment of ALL differ from AML?

A

Although the response to chemotherapy is excellent, ALL generally requires prophylaxis to the scrotum and CSF
-> cannot pass these blood barriers without direct injection of chemo (i.e. intrathecal)

99
Q

In general, what patients have good prognosis vs high risk in AML?

A

Good risk:
t(8;21), inv16, t(15;17), (<20% leukemias) or normal cytogenetics with FLT-3 wild type

High risk: del(5) MDS progression, FTL-3 positive, multiple cytogenetic abnormalities

100
Q

What disease are frequently treated by allogeneic transplantation?

A
  1. AML
  2. ALL
  3. MPD / MPN
  4. MDS
  5. Aplastic anemia
  6. Hemoglobinopathies

(only autologous would be multiple myeloma + HL / NHL)

101
Q

What chromosome are the HLA antigens located on and what antigens do we need to match?

A

Chromosome 6

Need to match HLA-A,B,C, and HLA-DR

8/8 match is best

102
Q

What is done in the conditioning phase of both allogeneic and autologous stem cell transplant?

A

Both - chemotherapy and radiation to reduce tumor burden

Allogeneic only - immunosuppress patient to allow engraftment

103
Q

What is done in the recovery phase of stem cell transplant? What does recover coincide with?

A

Intense supportive care with platelets and transfusions

Reversible damage occurs to skin, liver, GI tract, and lung due to high dose chemotherapy. Infections are common due to disrupted mucosal barriers and immunosuppression

Recovery coincides with recovery of WBC count (~2 weeks after conditioning down to 0)

104
Q

What are the common manifestations of GVHD in terms of which tissues are affected?

A
  1. Skin -> often maculopapular rash acutely, with dermal fibrosis chronically
  2. Liver -> often jaundice due to injured bile ducts
  3. GI Tract -> Mucosal surfaces like GI tract, eyes, and mouth can be damaged leading to N/V, eye dryness

Later - lymphoid organs -> destruction of thymus and LN

105
Q

How is leukocytosis vs leukopenia defined?

A

Leukopenia - <5k / ul
Leukocytosis - >10k / ul

Lymphopenia - <1.5k / ul
Lymphocytosis - >4k / ul, 9k in children

106
Q

A patient has lymphadenopathy AND lymphocytosis. What findings suggest the cause is more likely malignant than benign?

A

> 5 cm lymph node. (very large, anything over 1 cm is abnormal)

SEVERE anemia or thrombocytopenia (viral may be mild)

Older patient or constitutional symptoms

107
Q

What are the general causes of generalized lymphadenopathy?

A

Infections

Non-infectious inflammatory processes (sarcoidosis, SLE, RA)

Malignant processes which have spread more

Miscellanous (drug reactions, hyperthyroidism, sinus histiocytosis with massive lymphadenopathy)

108
Q

What are the benign chronic causes of lymphocytosis / lymphadenopathy (L/L)?

A

Brucellosis
Tuberculosis
Toxoplasmosis
Secondary and congenital syphilis

109
Q

What are the four types of lymph node hyperplasia which can be detected by biopsy?

A

Follicular - stimulation of B cells

Paracortical - T cell hyperplasia

Sinus - expansion of sinus histiocytes (Rosai-Dorfman)

Angiofollicular hyperplasia - “onion skinning appearance”
-Castleman’s disease

110
Q

What are the two types of Castleman’s disease? What is usually associated with second type, and their overall clinical course?

A
  1. Unicentric - localized angiofollicular hyperplasia - indolent, benign course
    - > hyaline vascular type, onion peel mantle zone with lollipop appearance from penetrating sclerotis vessels
  2. Multicentric - multicenter angiofollicular hyperplasia -HHV-8-associated, aggressive, lymphoma-like course
    - > looks like sheets of plasma cells, treated like myeloma
    - >IL-6 driven
111
Q

What are the criteria for hypersplenism and its underlying pathophysiology?

A
  1. Splenomegaly
  2. Reduction of at least one cell line in the blood
  3. Normal bone marrow function
  • > spleen is enlarging due to sequestering more WBCs/RBCs
  • > may be an indication for splenectomy
112
Q

What are the benign acute causes of lymphocytosis / lymphadenopathy (L/L)?

A

Bordetella Pertussis (think of the popcorn spilling in sketchy)

Infectious mononucleosis (reactive lymphocytosis in infectious process)

Infectious Hepatitis

113
Q

Is MPN or MDS more likely to have splenomegaly and why?

A

Myeloproliferative neoplasms / disorders-> because you have an excess of elements in the blood due to too much proliferation, and they tend to accumulate in the spleen

Both conditions will have hypercellular marrow, but difference is in peripheral blood (Cytopenias in MDS, cytoses in MPNs)

114
Q

What hemoglobin levels are P. vera diagnostic in men vs women?

A

Men: >18.5 g/dL
Women: >16.5 g/dL

115
Q

What is refractory anemia with multilineage dysplasia?

A

A type of myelodysplastic syndrome causing more than just anemia (2+ cytopenias) but <5% blasts in bone marrow still
-> otherwise would be RAEB1 or RAEB2

116
Q

What is the most common leukemia? Who gets it? What are the flow cytometry markers?

A

CLL - always older adults

Phenotype by flow cytometry:
CD19+,CD20+ (B-cell), CD5+ (T cell marker)
-> these are naive B cells which co-express B and T cell markers

Must be differentiated from mantle cell lymphoma
CLL: CD23+, FMC7-
MCL: CD23-, FMC7+

117
Q

What are good and poor prognostic factors to have by FISH for CLL? By flow cytometry?

A

FISH:
Good: del13 - miRNA
Bad: del17 - p53

Flow cytometry, bad prognosticators:
High ZAP70
Positive CD38

118
Q

What is the sister disease of CLL? How exactly are they related?

A

SLL = small lymphocytic lymphoma - involvement of lymph nodes leading to generalized lymphadenopathy. Absolute leukocyte count <5k

CLL = bone marrow and blood presentation, absolute lymphocyte count >5k

Both features present = phenotypically the same = treat the same

119
Q

How is CLL staged?

A

Via the Rai Staging
0 - monoclonal lymphocytosis >5k
I - >5k + any lymphadenopathy
II - >5k +/- lymphadenopathy + hepatomegaly or splenomegaly
III - >5k + Anemia (<11 gm/dL) +/- lymphadenopathy or organomegaly
(progressed to AIHA)
IV - >5k + Thrombocytopenia (platelets <100K/ul) +/- lymphadenopathy or organomegaly
(progressed to Evan’s syndrome)

120
Q

What are the distinctive clinical features of PLL?

A

Massive splenomegaly WITHOUT lymphadenopathy (except for T-cell PLL)

High lymphocyte count

More aggressive than CLL with poorer prognosis -> treat more aggressively

121
Q

What will physical exam and CBC show with HCL? Why do these things happen?

A

Massive splenomegaly due to accumulation of hairy cells in red pulp

NO lymphadenopathy (similar to PLL)

Pancytopenia will be the rule
-> due to massive fibrosis of bone marrow

similar to myelofibrosis

122
Q

What are the lab staining features of hairy cell leukemia? How do they look on peripheral smear? What is the mnemonic?

A

Mature B cells with hairy cytoplasmic processes (appear fuzzy on LM with indistinct borders)

Lab features - TRAP + (tartrate resistant acid phosphatase)

Remember these hairy cells are TRAPPED in the bone marrow (causing fibrosis) and TRAPPED in the red pulp causing splenomegaly

123
Q

What will the CBC show for Large Granular Lymphocytic Leukemia (LGLL) and what does the peripheral smear show?

A

CBC shows cytopenias (neutropenia, anemia) with lymphocytosis

Peripheral smear shows GRANULES in lymphocytes (vs CLL) -> shows they are NK (CD56,CD57) or CD8 T cells

  • > associated with rheumatoid arthritis
  • > give no treatment, or G-CSF for neutropenia / steroids / MTX
124
Q

How is PLL told apart from CLL?

A

PLL will be associated with massive splenomegaly while CLL is less so (still some). Also PLL usually has no lymphadenopathy while CLL usually does.

PLL is CD23- and FMC7+, CD5- (vs MCL)
CLL is CD23+ and FMC7-, and CD5+ (T cell marker)

125
Q

How does the lymph node spread pattern differ between NHL and HL? Extranodal involvement?

A

Both are painless, non-tender lymphadenopathy

HL - usually contiguous lymph nodes and localized

NHL - usually skips lymph nodes (noncontiguous) with more extranodal involvement common

126
Q

What are stages I-IV of the Ann Arbor staging system for lymphomas?

A

I - involvement of one group of LN
II - involvement of 2 or more groups of LN on same side of diaphragm (above or below)
III - 2 or more groups of LN on BOTH above and below diaphragm
IV - involvement of any organs or tissues outside of lymphatic system (extranodal sites), including bone marrow

127
Q

What is the presentation of Adult T-cell leukemia/lymphoma?

A

Most common in Caribbean and Japan (endemic areas)

A diffuse erythematous rash due to skin infiltration, generalized lymphadenopathy with hepatosplenomegaly.
Lytic bone lesions, hypercalcemia

-> Easily confused with multiple myeloma, but note the presence of the rash

Bizarre clover-leaf nuclei of T-cells with CD4+ phenotype

128
Q

What are the four types of classic HL? Which is most common?

A
  1. Nodular sclerosis - most common, especially females
  2. Lymphocyte-rich - best prognosis
  3. Mixed cellularity - high eosinophils due to RS cells producing IL-5
  4. Lymphocyte depleted - seen in immunocompromised, worst prognosis (elderly and HIV positive)
129
Q

What is the treatment for HL?

A

Aggressive radiation in early stages, with ABVD regimen in all four stages

130
Q

What are the CBC findings in HL?

A

Normocytic anemia
Leukocytosis
Lymphopenia (in advanced stage)
Platelets (increased early, decreased reactive)

Leukocytosis early because we have a reactive proliferation of plasma cells, lymphocytes, macrophages, and eosinophils

Elevated ESR due to cytokine production

131
Q

What are the indolent (low grade) lymphomas?

A

Follicular lymphoma
Small lymphocytic lymphoma (sister of CLL)
Marginal zone lymphoma (MZL)
Waldenstrom’s macroglobulinemia

132
Q

What are the three stages of follicular lymphoma?

A

Grade 1 - small cleaved cells
Grade 2 - mixture
Grade 3 - Large cells (getting closer to diffuse B cell lymphoma)

14;18 translocation

133
Q

What is marginal zone lymphoma? What is the most common type?

A

Neoplastic proliferation of small B cells that expands the marginal zone (post-germinal center B cells)

Most common type is MALT (mucosal associated lymphoid tissue) lymphoma

-> primary splenic MZL exists, can cause massive splenomegaly without lymphadenopathy, despite being indolent

134
Q

What are examples of intermediate aggressiveness lymphomas?

A

Diffuse large B cell lymphoma (DLBCL)

Mantle cell lymphoma - t(11;14)

135
Q

What are the germinal center markers expressed by follicular lymphoma?

A

CD10 and Bcl-6

136
Q

What is the most common NHL overall? What does it usually arise from?

A

Diffuse large B cell lymphoma - with poorly differentiated cells

Arises from follicular lymphoma progression, or Richter transformation of CLL

137
Q

What causes mantle cell lymphoma? What chromosomal abnormality is associated?

A

Proliferation of small B cells that expands the mantle zone

Associated with t(11;14) - cyclin D1 from chromosome 11 is put at heavy chain locus

-> aggressive movement through growth cycle

138
Q

What are the two forms of Burkitt lymphoma?

A
  1. Endemic form - Africa = jaw presentation in children

2. Sporadic - more loosely associated with EBV, lesion in pelvis (especially kidneys) or abdomen

139
Q

What is the name of the disease causing Pautrier microabscesses, and what do the cells inside look like?

What is Sezary syndrome? Prognosis?

A

Mycosis fungoides

  • > cells are called Sezary cells
  • > CD4+ T cells with folded, cerebriform nucleoli

Sezary syndrome: Progression of mycosis fungoides to T cell leukemia -> sezary cells in blood.

Prognosis = indolent but incurable course

140
Q

What T-cell lymphoma is not caused by HTLV-1 and causes a nodular rash rather than psoriasis-like? How do the cells look?

A

Anaplastic Large Cell Lymphoma (ALCL)

-> cells look anaplastic and bizarre, but prognosis is actually good

Cells have t(2;5), express CD30 but not CD15

141
Q

What are the classic symptoms of symptomatic myeloma? Give why all these symptoms happen

A

CRAB
Calcemia - hypercalcemia due to plasma cells activating RANK on osteoclasts, increasing bone resorption

Renal impairment - Free light chain excreted in urine damages kidney tubules, renal failure

Anemia - normo-cytic or macrocytic - Rouleaux formation

Bone disease - lytic lesions due to increased bone resportion

142
Q

What is smouldering myeloma vs symptomatic myeloma?

A

Symptomatic:

  • Monoclonal protein in serum or urine
  • > 10% plasma cells in bone marrow
  • CRAB symptoms

Smouldering:
Asymptomatic - still >10% plasma cells and monoclonal protein, but no CRAB

<10% plasma cells = MGUS

143
Q

How do plasma cells appear in MM? What markers do they express?

A

Deep blue cytoplasm with perinuclear halo where the Golgi is

Plasma cells nuclei are eccentric with clock-face chromatin

Express CD38 and CD138

144
Q

What causes renal injury in MM?

A
  1. Bence Jones protein - kappa or lamda light chains deposit in renal tubules
  2. Amyloid deposition - in glomeruli and blood vessels
  3. Calcium deposition - nephrocalcinosis due to hypercalcemia
  4. Pyelonephritis - from inflammatory cells
  5. Uric acid crystal deposition (hyperuricemia from cell turnover)
145
Q

What protein is produced by plasma cells and has prognostic value in MM? Give the staging scheme.

A

B2-microglobulin - a part of MHC1

<3.5 mg/L is favorable (Stage I), along with albumin >3.5 g/dL
Middle: Stage II
>5.5 mg/L is poor (Stage III)

146
Q

What is the best new treatment for multiple myeloma, and what is the most common symptomatic treatment? What can you do if MM is located only at one site?

A

Only at one site - radiation may be effective

Common symptomatic treatment - bisphosphonates (for hypercalcemia and bone disease, stops osteoclasts)

Best new - Anti-CD38 (plasma cell marker) called Daratumumab

147
Q

What condition sometimes follows multiple myeloma but is rarely a primary condition? What is the clinical definition?

A

Plasma Cell Leukemia (PCL)
>20% plasma cells in blood, with absolute plasma cell count >2k

Clinical features of pancytopenia with CRAB

148
Q

What are the symptoms of Waldenstrom macroglobulinemia?

A

-> hepatosplenomegaly (absent in MM)
-> cytopenias
-> generalized lymphadenopathy
Hyperviscosity syndrome w/polyneuropathy

149
Q

What are the clinical features of hyperviscosity syndrome?

A

All due to engorgement of small vessels with impaired platelet aggregation

Visual disturbances and retinal changes due to retinal hemorrhages / occlusion

Lethargy, confusion, weakness - stroke symptoms due to poor blood flow

Epistaxis - bleeding due to small vessels in nose and poor platelet function

CHF due to increased afterload

150
Q

What are the two types of granules in platelets and what do they release?

A

Delta = Dense = Dark -> release 4 things: ATP, ADP, serotonin, Ca+2

Alpha granules - light colored, release all the rest

151
Q

What type of bleeding occurs in disorders of primary hemostasis and why?

A

Primary hemostasis - blood vessel / platelet problem - bleeding from skin or mucous membranes (no initial plugs are formed), i.e. petechiae, ecchymoses and easy bruising

152
Q

What is the platelet aggregation assay / how does it work?

A

Take platelet-rich plasma, measure the optical density with spectrophotometer

  • > add an agonist
  • > as platelets begin to clot, the optical density of the solution falls (reduced turbidity)
  • > release of ADP by activated platelets also contributes
153
Q

What agonists are used to detect defects in GPIIb/IIIa and fibrinogen via the platelet aggregation assay? What disease may see a defect in this?

A

ADP, epinephrine, collagen, and thromboxane A2

Glanzmann thrombasthenia may be detected (GPIIb/IIIa deficiency) -> glassman saying 2 be or not 2b

154
Q

What machine has now supplanted the bleeding test, and what drugs extend the coagulation time with Epinephrine and with ADP as an agonist?

A

Platelet function analyzer-100

Collagen + epi: Prolonged by aspirin

Collagen + ADP: prolonged by clopidogrel

155
Q

What are some common causes of prolonged aPTT?

A
  1. Heparin - inhibits Xa and IIa
  2. Fibrin or fibrinogen degradation products / increased consumption - DIC
  3. Antiphospholipid / anticardiolipin antibodies - Lupus anticoagulant
  4. Liver disease

causes of prolonged PT are the same except 1 = vitamin K deficiency (warfarin, fat malabsorption, newborn) and 3 is not present.

156
Q

What is the TT and what does it measure? What are some causes of prolongation?

A

Thrombin Time
Thrombin-induced conversion of fibrinogen to fibrin, while bypassing all other factors
-> qualitative or quantitative defects in fibrin
-> thrombolytic therapy or heparin / thrombin inhibitor use

157
Q

What vascular disease is also known as Osler-Weber-Rendu syndrome and what are its symptoms? Inheritance pattern?

A

Hereditary hemorrhagic telangiectasia - autosomal dominant

Dilated microvascular swellings (telangiectasias) which start in chidhood and increase in adulthood

  • > recurrent bleeding of nose, skin, GI tract, and kidney
  • > can lead to iron deficiency anemia and GI hemorrhage
158
Q

What is Henoch-Schonlein syndrome and how is it acquired? Triad?

A

Most common childhood systemic vasculitis - follows acute URI

Triad: skin + GI + IgA nephropathy

Skin: palpable purpura on buttocks and lower legs
GI: abdominal pain
IgA nephropathy: hematuria and renal failure

Can also cause arthralgias

159
Q

What is the TT and what does it measure? What are some causes of prolongation?

A

Thrombin Time
Thrombin-induced conversion of fibrinogen to fibrin, while bypassing all other factors
-> qualitative or quantitative defects in fibrin
-> thrombolytic therapy or heparin / thrombin inhibitor use

160
Q

What vascular disease is also known as Osler-Weber-Rendu syndrome and what are its symptoms? Inheritance pattern?

A

Hereditary hemorrhagic telangiectasia - autosomal dominant

Dilated microvascular swellings (telangiectasias) which start in chidhood and increase in adulthood

  • > recurrent bleeding of nose, skin, GI tract, and kidney
  • > can lead to iron deficiency anemia and GI hemorrhage
161
Q

What is Henoch-Schonlein syndrome and how is it acquired? Triad?

A

Most common childhood systemic vasculitis - follows acute URI

Triad: skin + GI + IgA nephropathy

Skin: palpable purpura on buttocks and lower legs
GI: abdominal pain
IgA nephropathy: hematuria and renal failure

Can also cause arthralgias

162
Q

What are the pentad of symptoms seen in TTP?

A
  1. Fever
  2. Thrombocytopenia
  3. Microangiopathic hemolytic anemia (with schistocytes)
  4. Renal symptoms (worse in HUS)
  5. NEUROLOGIC symptoms - i.e. involving CNS vessels

treat with plasmapheresis + replacement of ADAMTS13 w/ donor plasma, but platelet replacement is contraindicated

163
Q

What is the pathogenesis and treatment for ITP?

A

IgG antibodies are made to platelet receptors, and platelets are rapidly eaten by splenic macrophages

Treatment: Steroids, IVIG to distract macrophages, Rituximab to slow AB production, and splenectomy if refractory (removes site of removal)

164
Q

How do you tell Bernard Soulier syndrome from von Willebrand disease?

A

Bernard-Soulier - bleeding tendency + thrombocytopenia + LARGE platelet size + no response to ristocetin

vWD - bleeding tendency + NO thrombocytopenia + NORMAL platelet size + no response to ristocetin

165
Q

What are the pentad of symptoms seen in TTP?

A
  1. Fever
  2. Thrombocytopenia
  3. Microangiopathic hemolytic anemia (with schistocytes)
  4. Renal symptoms (worse in HUS)
  5. NEUROLOGIC symptoms - i.e. involving CNS vessels

treat with plasmapheresis + replacement of ADAMTS13 w/ donor plasma, but platelet replacement is contraindicated

166
Q

What are the three broad types of von Willebrand disease?

A

Type 1 - All vWF multimer sizes present, but at low levels
Type 3 - All multimers absent
Type 2 - decrease in one particular multimer size

Autosomal dominant

167
Q

How do you tell Bernard Soulier syndrome from von Willebrand disease?

A

BS: Mild thrombocytopenia + platelets appear large

168
Q

What anomaly is associated with thrombocytopenia in Alport syndrome?

A

May-Hegglan anomaly
-> Autosomal dominant mutation in myosin heavy chain gene

Giant platelets, Dohle bodies in WBC, thrombocytopenia

Basically looks like BS + Dohle bodies

169
Q

What are the three broad types of von Willebrand disease?

A

Type 1 - All vWF multimer sizes present, but at low levels
Type 3 - All multimers absent
Type 2 - decrease in one particular multimer size

Autosomal dominant

170
Q

What is the definition of antiphospholipid syndrome and what is it commonly seen in? What two antibodies are normally seen?

A

Arterial or venous thrombosis or recurrent miscarriage in association with evidence of persistent antiphospholipid antibodies

  • > commonly seen as lupus anticoagulant syndrome (anticardiolipin antibodies)
  • > Two antibody types: anticardiolipin and anti-Beta2 glycoprotein
171
Q

What is the classic presentation for an acute hypercoagulable state? How should you test them in the acute phase and why?

A

Classic presentation is recurrent DVTs or DVTs at a young age

Test them with DNA-based tests since the acute-phase response and anticoagulant therapy can affect test results
-> use schematic testing for inherited thrombophilia based on most common disorders

172
Q

What is the second most common inherited hypercoagulability disorder in Caucasians and what causes it?

A

Prothrombin G->A Mutation

  • > point mutation in 3’-UTR what causes overexpression of prothombin
  • > increased prothrombin levels leads to hypercoagulability

Most common is Factor V Leiden, arginine to glutamate

173
Q

What is the definition of antiphospholipid syndrome and what is it commonly seen in? What two antibodies are normally seen?

A

Arterial or venous thrombosis or recurrent miscarriage in association with evidence of persistent antiphospholipid antibodies

  • > commonly seen as lupus anticoagulant syndrome (anticardiolipin antibodies)
  • > Two antibody types: anticardiolipin and anti-Beta2 glycoprotein
174
Q

How long should clopidogrel be held before surgery, and what are the adverse effects of concern?

A

At least 5 days as well (like aspirin)

GI distress and bleeding may occur (especially if history of NSAID-induced ulcers)

Thrombotic thrombocytopenic purpura may be associated

175
Q

What are the advantages of Dabigatran over warfarin? Include standard time window for stopping dabigatran before surgery.

A
  1. No INR monitoring is required (aPTT values often not elevated)
  2. Significantly shorter onset / offset action (can stop 1-2 days before surgery)
  3. Reduced risk for intracranial bleeding (tissue factor - 7 complex needed to control intracranial bleeds)
176
Q

What are the disadvantages of dabigatran vs warfarin?

A
  1. Renally cleared -> may need more time to clear from system in chronic renal failure (up to 5 days)
  2. No antidote except a monoclonal antibody
  3. More GI bleeding and dyspepsia (acidic)
  4. No reliable way to measure anticoagulation state in the ACUTE setting (i.e. MI, stroke, PE)
177
Q

What are the contraindications of prasugrel?

A

Prior TIA or stroke
>75 years of age (elderly)
Underweight patients <60kg

178
Q

What are two hypomethylating agents and what is their mechanism? Why does it take a while for them to work?

A

Azacitidine, Decitabine

Inhibit DNA methyltransferase by incorporating into the DNA and inhibiting enzymatic function. Takes a couple cycles of semiconservative replication before an entire strand becomes demethylated and the effect is seen.

Improves survival in myelodysplastic syndromes
-> when no other treatment is available, it slows progression of cancer

179
Q

What side effects does bolus dose 5-FU cause vs continuous infusion dose?

A

Bolus dose - RNA effects more -> myelosuppression

Slow drip - DNA incorporation more -> hand-and-foot syndrome
-> pain, redness, numbness, and desquamation of palms bilaterally

“Schedule dependent toxicity”

180
Q

What are the contraindications of prasugrel?

A

Prior TIA or stroke
>75 years of age (elderly)
Underweight patients <60kg

181
Q

What is the most common side effect of anti-fibrinolytic agents and why?

A

Dyspepsia -> acidic nature of the drugs (aminocaproic acid and tranexamic acid) makes for local irritation of the GI tract

-> much like dabigatran

182
Q

Patients with which deficiencies will present with prolonged aPTT but no history of bleeding?

A

Factor 12
Prekallikrein
HMWK

183
Q

What are the prognostic factors for diffuse large B cell lymphoma?

A

Age, stage, performance status, LDH, number of extranodal sites

Pathophysiology - Hematology (14 decks)

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