Heme/Onc Flashcards
(551 cards)
1
Q
What is anisocytosis?
A
RBCs of varying size
2
Q
What is poikilocytosis?
A
RBCs of varying shapes
3
Q
<p>What is contained in alpha/delta/lambda granules of platelets?</p>
A
<p>alpha granules - clotting factors vWF, factor V; delta granules - ADP/ATP, serotonin, histamine; lambda granules - hydrolytic enzymes (anti-coagulant)</p>
4
Q
<p>vWF binds to what platelet receptor?</p>
A
<p>GpIb (deficiency = Bernard-Soulier syndrome)</p>
5
Q
Fibrinogen binds to what platelet receptor?
A
GpIIb/IIIa (Deficiency = Glanzmann’s thrommasthenia)
6
Q
CD14 is a cell surface marker for..
A
Macrophages
7
Q
Eosinophils fight helminths using what protein?
A
Major basic protein
8
Q
CD19 and CD20 are cell surface markers for…
A
B cells
9
Q
What role does ADP play in the clotting cascade?
A
ADP induces GpIIb/IIIa receptor expression at platelet surface, allowing platelet aggregation.
10
Q
What is primary hemostasis?
A
Formation of a platelet plug - mediated by interaction of the platelet and a vessel wall.
11
Q
What is secondary hemostasis?
A
Stabilization of the platelet plug by products of the coagulation cascade.
12
Q
What is the first step in primary hemostasis?
A
Transient vasoconstriction of blood vessels. Mediated by endothelin and neural input.
13
Q
Where does vWF come from (2)?
A
- The platelet itself 2. Endothelial cells (Weibel-Palade body)
14
Q
What two important things are contained in the Weibel-Palade body?
A
- P-selectin 2. vWF
15
Q
What are the 4 steps of primary hemostasis?
A
- Transient vasoconstriction 2. Adhesion of platelets (vWF/GpIb) 3. Release of platelet contents (ADP and TXA2) 4. Platelet aggregation (fibrinogen/ GpIIb/IIIa)
16
Q
What molecule do platelets use to cross-link?
A
Fibrinogen
17
Q
TXA2 is a derivative of…
A
Platelet cyclooxygenase
18
Q
What is the size of petechiae, purpura, and ecchymoses?
A
Petechiae - pinpoint bleeding Purpura - 3 mm or greater Ecchymoses - greater than 1 cm
19
Q
<p>Anti-Gp IIb/IIIa antibodies</p>
A
<p>ITP</p>
20
Q
<p>What is the cause of ITP?</p>
A
<p>IgG autoantibodies against GpIIb/IIIa receptors. Antibody bound platelets are consumed by splenic macrophages, resulting in thrombocytopenia. Decreased platelet survival </p>
21
Q
What are the Platelet count, PT/PTT, Bone marrow biopsy in ITP?
A
Platelet count is low; PT/PTT is normal; Bone marrow biopsy shows increased megakaryocytes (trying to make more platelets)
22
Q
What 2 effects does splenectomy have on patients with ITP?
A
Eliminates the primary source of antibody and site of platelet destruction.
23
Q
What two disorders can produce a microangiopathic hemolytic anemia and what is the classic cell seen on peripheral smear in these disorders?
A
TTP/HUS. Will see schistocytes (helmet cells).
24
Q
How do schistocytes form in TTP?
A
Uncleaved vWF multimers (normally cleaved by ADAMTS13) lead to abnormal platelet adhesion, resulting in microthrombi that shear RBCs.
25
What enzyme is deficient in TTP and what is its normal function?
ADAMTS13 - normally degrades multimers of vWF.
26
ADAMTS-13 function and associated pathology.
Function - degrade vWF multimers. Pathology - ADAMTS13 is defective in TTP.
27
What is the pentad of symptoms seen in TTP?
FATRN : fever, anemia (microangiopathic), thrombocytopenia, renal failure, neurologic symptoms.
28
How do schistocytes form in HUS?
Infection with E. coli O157:H7 results in production of toxin that damages endothelial cells, resulting in platelet microthrombi, which deposit and cause shearing of RBCs.
29
What is the Platelet count, PT/PTT, Peripheral smear, bleeding time and bone marrow biopsy in HUS/TTP?
Thrombocytopenia, increased bleeding time, NORMAL PT/PTT, peripheral smear shows anemia with Schistocytes and bone marrow biopsy shows increased megakaryocytes
30
What is the defect in Bernard-Soulier syndrome?
Genetic GpIb deficiency - platelet ADHESION to vWF impaired.
31
What is seen on blood smear in Bernard-Soulier syndrome?
Thrombocytopenia with enlarged platelets (producing immature platelets from bone marrow)
32
What is the defect in Glanzmann thrombsthenia?
GpIIb/IIIa deficiency - platelet AGGREGATION is impaired
33
What pathways does PT measure? aPTT?
PT: Extrinsic/common; aPTT: Intrinsic/common
34
List the factors unique to the intrinsic and extrinsic pathways.
Intrinsic: XII, XI, IX, VIII; Extrinsic: VII
35
What is used to measure heparin effect?
PTT
36
What is used to measure warfarin effect?
PT (INR)
37
What is deficient in hemophilia A?
Factor VIII
38
What is deficient in hemophilia B?
Factor IX
39
What happens to the bleeding time, PTT and PT in hemophilia A?
Increased PTT, normal PT, normal bleeding time
40
What happens to the bleeding time, PTT and PT in hemophilia B?
Increased PTT, normal PT, normal bleeding time
41
How is hemophilia A distinguished from a patient with autoantibodies for factor VIII?
PTT corrects in hemophilia A when patient's plasma is mixed with normal plasma (replace factor VIII). PTT does NOT correct in patients with VIII autoantibodies (the antibodies take out factor VIII).
42
What is the most common inherited coagulation disorder?
von Willenbrand disease (autosomal dominant).
43
What are the two functions of vWF?
1. Bind GpIb receptors on platelets to start primary hemostasis. 2. Stabilize factor VIII in the circulation
44
What happens to the bleeding time, PTT and PT in von Willenbrand disease?
Increased bleeding time, Increased PTT (vWF stabilizes factor VIII, normal PT, Abnormal ristocetin test
45
What is the ristocetin test?
Introduction of ristocetin to normal platelets causes platets to aggregate. In patients with von Willenbrand disease, platelets won't aggregate with ristocetin.
46
What is the treatment for von Willebrand disease, how does it work, and how is it given?
Intranasal desmopressin - increases vWF release from Weibel-Palade bodies of endothelium.
47
What factors require vitamin K as a cofactor?
II, VII, IX, X, Protein C, Protein S
48
What antibodies does the patient develop in heparin-induced thrombocytopenia?
IgG antibody towards heparin-platelet factor 4 complex, which activates platelets.
49
What happens to the platelet count, PT, PTT in DIC?
Decreased platelet count, Increased PT/PTT
50
What is the best screening test for DIC?
Fibrin split products (D-dimer). D-dimer is elevated in DIC.
51
A patient has symptoms of DIC but no elevated D-dimer. What should you consider?
A disorder of fibrinolysis (elevated urokinase after a prostatectomy, decreased alpha-2 antiplasmin in liver failure).
52
What is the antidote for t-PA and other thrombolytics?
Aminocaproic acid.
53
What class of drugs is used to anticoagulate patients with HIT?
Direct thrombin inhibitors (bivalrudin, lepirudin, argatroban, dabigatran).
54
What is given for rapid reversal of heparin toxicity?
Protamine sulfate (positively charged molecule binds negatively charged heparin).
55
What are lines of Zahn?
RBC/fibrin lines seen in thrombi formed pre-mortem.
56
What is Virchow's triad and what does it describe?
Disruption in blood flow, Endothelial damage and hypercoagulable state. Virchow's triad describes the risk for thrombosis
57
How does B12 or folate deficiency increase risk for thrombosis?
Increased homocysteine levels in B12 and folate deficiency increase risk for thrombosis secondary to endothelial damage.
58
What is the function of proteins C and S?
Protein S serves as a cofactor for protein C, which inactivates factors V and VIII.
59
What will happen if you give warfarin to a patient with protein C or S deficiency and why?
Skin necrosis because protein C and protein S have lowest half life of the vitamin K-dependent proteins, so they decrease the fastest, resulting in a transient hypercoagulable state (unopposed factors II, VII, IX, X). Need to have heparin on board when starting warfarin.
60
Describe the pathophysiology of factor V Leiden.
Mutated factor V is resistant to degradation of protein C and S, leading to a hypercoagulable state.
61
Patient given heparin shows no increase in PTT. What are you thinking?
Anti-thrombin III deficiency, higher risk for thrombus.
62
Why does estrogen use increase risk of thrombosis?
Estrogen increases production of coagulation factors.
63
What is the histological hallmark of a cholesterol embolus?
Cholesterol clefts in the clot (white cholesterol crystals).
64
What are the signs and symptoms of a fat embolus?
Dyspnea (lung involvement) and petechiae on the skin overlying the chest following a broken bone.
65
Why do patients with amniotic fluid emboli get DIC?
Amniotic fluid has tissue thromboplastin, which activates the coagulation cascade
66
What is seen on histological examination of an amniotic fluid embolus?
Squamous cells and keratin debris from fetal skin.
67
What is the MCV in a microcytic anemia?
< 80
68
What are the 4 general causes of microcytic anemia?
Iron deficiency, anemia of chronic disease, sideroblastic anemia, thalassemia.
69
Where in the gut is iron absorbed?
Duodenum enterocytes
70
What is the function of transferrin?
Transportation of blood iron, delivering it to liver and bone marrow macrophages for storage.
71
What is the function of ferritin?
Storage of intracellular iron
72
What is the function of ferroportin?
Transporting iron into the blood from duodenal enterocytes
73
TIBC is a measurement of...
How many transferrin molecules are in the blood
74
Serum ferritin is a measurement of...
How much iron is present in storage in bone marrow macrophages and liver
75
Early iron deficiency anemia presents as...
Normocytic anemia (progresses to a microcytic, hypochromic anemia).
76
What is seen in RDW, Ferritin, TIBC, serum iron, percent saturation, and free erythrocyte protoporphyrin (FEP) in iron deficiency anemia?
RDW increased (varying size RBC because iron deficiency anemia is a normocytic anemia that progresses to microcytic); Decreased ferritin (decreased iron in storage); Increased TIBC (trying to use as much iron in the blood as possible). Decreased serum iron; Decreased % saturation; Increased FEP (Since heme = iron + protoporphyrin, if iron is low, protoporphyrin is still produced at normal levels, so it is high because it is not being incorporated into hemoglobin).
77
Why is free erythrocyte protoporphyrin increased in iron deficiency anemia?
Since heme = iron + protoporphyrin, if iron is low, protoporphyrin is still produced at normal levels, so it is high because it is not being incorporated into hemoglobin.
78
What is the triad seen in Plummer-Vinson syndrome?
Esophageal webs, iron deficiency anemia, glossitis. Seen in pregnant women.
79
What are the two functions of hepcidin?
Sequestration of iron in storage sites ("hides" iron from bacteria in anemia of chronic disease), suppression of EPO production.
80
Describe the changes seen in ferritin, TIBC, serum iron, % saturation, FEP in anemia of chronic disease.
Increased ferritin (hepcidin leads to increased stored iron), Decreased TIBC (want to keep iron away from bugs), decreaesd serum iron, decreased % saturation, and increased FEP
81
What causes sideroblastic anemia?
Defective protoporphyrin synthesis
82
What is the RLS in production of protoporphyrin?
Production of aminolevulinic acid by aminolevulinic acid synthase
83
What is a ringed sideroblast?
Iron accumulating in mitochondria in a ring around nuclei. Seen in sideroblastic anemia (iron can't be incorporated into heme).
84
Where is iron located in ringed sideroblasts?
Mitochondria
85
What is the most common cause of hereditary sideroblastic anemia?
ALAS (aminolevulinic acid synthase) mutations - X linked.
86
ALAS (aminolevulinic acid synthase) deficiency
Congenital sideroblastic anemia (#1 cause).
87
What are 3 causes of acquired sideroblastic anemia?
Alcoholism (mitochondrial toxin); Lead poisoning (denatures ALAD and ferrochetalase); B6 deficiency (cofactor for ALAS)
88
What is the treatment for sideroblastic anemia?
B6 supplementation (cofactor for ALAS)
89
A patient with TB develops sideroblastic anemia. What caused this?
INH causes B6 deficiency, which is necessary as a cofactor for ALAS (the RLS in protoporphyrin snythesis). B6 deficiency leads to sideroblastic anemia.
90
Describe what will be seen in ferritin, TIBC, serum iron, % saturation in a patient with sideroblastic anemia.
Increased ferritin (bone marrow macrophages ingest excess blood iron); decreased TIBC, Increased serum iron (defective production of protoporphyrin = increased iron), Increased % saturation
91
What is the underlying pathology in thalassemia?
Decreased production of globin chains
92
What is the underlying cause of all forms of alpha thalassemia?
Alpha globin chain deletion (there are 4 copies on chromosome 16).
93
What is the consequence of deletion of 1 alpha globin gene?
Asymptomatic
94
What is a "cis" deletion in alpha thalassemia?
Deletion of two alpha globin chain genes on the same chromosome (normally have 4 copies). Increases the risk for severe thalassemia in offspring. Seen in Asian individuals.
95
What is the consequence of deletion of 3 alpha globin genes?
Severe anemia. Beta chains form tetramers (HbH) that damage RBCs.
96
What is hemoglobin H?
Beta globin tetramers seen in 3 alpha globin chain deletions.
97
What is the consequence of deletion of 4 alpha globin gene?
Lethal in utero. Gamma chains form tetramers (Hb Barts) that damage RBCs. Leads to hydrops fetalis
98
What is hemoglobin Barts?
Gamma chain tetramers seen with 4 alpha globin chain deletions (hydrops fetalis).
99
What is the underlying pathophysiology of beta thalassemia?
Gene mutations in beta chain
100
What is the cause of beta thalassemia minor?
Beta chain mutations causing underproduction of the beta chain. Usually asymptomatic, may have microcytic, hypochromic RBCs and target cells on smear.
101
Isolated increase in hemoglobin A2 on electrophoresis...
Beta thalassemia minor
102
What are some signs and symptoms of beta thalassemia major?
Expansion of hematopoiesis into marrow of skull and facial bones (causing frontal bossing and "crew cut" appearance on x-ray), hepatosplenomegaly (spleen undergoes RBC production).
103
Crew cut appearance on x-ray...
Beta thalassemia minor or SCA (due to marrow expansion and hematopoiesis in the skull) .
104
What is seen on electrophoresis in a patient with beta thalassemia major?
No HbA; Increased HbA2 (alpha 2, delta 2); Increased HbF (alpha 2, gamma 2)
105
What is HbA2 composed of?
Alpha 2, delta 2
106
What is HbF composed of?
Alpha 2, gamma 2
107
What is HbA composed of?
Alpha 2, beta 2
108
What is the MCV in a macrocytic anemia?
> 100
109
Why are the cells big in a macrocytic anemia?
RBCs undergo one less division because of disruption of DNA precursors.
110
Where in the gut is folate absorbed?
Jejunum
111
What happens to the levels of serum homocysteine and methylmalonic acid in B12 and folate deficiency?
B12 deficiency: both homocysteine and MMA are elevated; Folate deficiency: only homocysteine is elevated, MMA is normal.
112
Normal MMA, high homocysteine
Folate deficiency
113
High MMA, high homocysteine
B12 deficiency.
114
Why does pancreatic insufficiency cause B12 deficiency?
Because the pancreas produces R binder which binds and protects B12.
115
Why does Crohn disease cause B12 deficiency?
Because B12 is absorbed in the ileum
116
What is an infectious cause of B12 deficiency?
Diphyllobothrium latum tapeworm infection
117
Why is dietary deficiency of B12 rare?
Because the liver has lots of stores of B12.
118
What is subacute combined degeneration and what causes it?
Degeneration of multiple tracts of the spinal cord (DCML, LCST) due to B12 deficiency causing defective myelin synthesis.
119
What is the MCV in normocytic anemia?
80-100
120
What are the two general causes of normocytic anemia and how are the two distinguished?
Increased peripheral destruction or underproduction of RBCs. Distinguish between the two by looking at reticulocyte count. Reticulocytes will be increased with RBC destruction.
121
Why are reticulocytes blue?
Because of RNA in the cytoplasm
122
Why are reticulocytes falsely elevated in anemia?
Because they are measured as a percentage of RBCs. If RBC mass is decreased and reticulocyte count stays constant, the percentage is increased.
123
How is reticulocyte count corrected for in normocytic anemia?
Multiplying reticulocyte count by Hct/45.
124
Normocytic anemia with corrected reticulocyte count > 3%
Autoimmune anemia
125
Normocytic anemia with corrected reticulocyte count < 3%
Problem with bone marrow production of RBCs
126
Macrophage consumption of RBCs produces which byproducts?
Globin --> amino acids; Heme --> iron + protoporphyrin; Protoporphyrin --> unconjugated bilirubin (bound to albumin, goes into bile).
127
What is the function of haptoglobin?
Binds iron in the blood from metabolized RBCs, takes it to the spleen to be re-processed
128
What happens to haptoglobin levels in intravascular hemolysis?
Decreases (it binds iron to return it to make new RBC). This is the initial change with intravascular hemolysis.
129
What causes hemosiderinuria in hemolytic anemia?
Iron being taken up be tubular cells, which slough off after a few days.
130
What are the 3 most common mutations in hereditary spherocytosis and what is the normal function of these proteins?
Ankyrin, spectrin, band 3.1 proteins - normally serve as cytoskeleton membrane tethering proteins.
131
Why is RDW increased in hereditary spherocytosis?
Red cells differ in size because they form membrane blebs which are constantly removed by the spleen over time. Older cells have had more blebs removed and are smaller.
132
Why does the spleen enlarge in hereditary spherocytosis?
Work hypertrophy - the macrophages hypertropy because they consume the blebs on the spherocytic RBCs.
133
Parvovirus B19 infects...
Erythroid precursor cells (aplastic crisis in SCA, HS).
134
Positive osmotic fragility test...
Hereditary spherocytosis
135
Test used to diagnose hereditary spherocytosis
Osmotic fragility test
136
Tretment for hereditary spherocytosis
Splenectomy
137
What are Howell-Jolly bodies and why do they form?
Basophilic nuclear remnants found in RBCs following splenectomy. They form because the spleen functions to remove abnormal RBCs from the circulation.
138
What is the mutation in sickle cell anemia?
Glutamic acid --> valine at position 6 on beta chain of hemoglobin. Result is hemoglobin S.
139
Why do patients with sickle cell disease not present until a few months old?
Because HbF is protective for the first few months of life.
140
MOA/use of hydroxyurea
Prevent sickling crises in SCA by causing production of HbF (alpha 2 gamma 2)
141
What is the common presenting sign of SCA in infants?
Dactylitis
142
What happens to the spleen over a long period of time in SCA?
Shrinks and becomes fibrotic
143
What is the most common cause of death in kids with SCA?
Infection with encapsulated organisms
144
What is the most common cause of death in adults with SCA?
Acute chest syndrome - vaso-occlusion in pulmonary microcirculation. Precipitated by pneumonia (hypoxia).
145
Gross hematuria and proteinuria in a patient with SCA
Renal papillary necrosis
146
What is the most common site of infarction in a patient with sickle cell trait and how does it present?
Renal medulla - microinfarctions lead to microscopic hematuria and decreased ability to concentrate urine.
147
What is the metabisulfite test?
Test for sickle cell anemia or trait- causes sickling of cells in either disorder.
148
What is hemoglobin C?
Autosomal recessive mutation in beta chain of hemoglobin - glutamic acid replaced by lysine (Hb C - lyCine).
149
What is seen on peripheral smear in a patient with hemoglobin C?
Peripheral HbC crystals due to glutamic acid being replaced by lysine (AR).
150
What are the two primary causes of extravascular hemolytic anemia?
SCA, HS
151
Ecalizumab - use and MOA
Treats PNH; mAB against complement C5
152
Why are RBCs not destroyed by complement?
Because they contain MIRL (membrane inhibitor of reactive lysis) and DAF (decay accelerating factor) on their surface. These are connected to the RBC by GPI, which is lost in PNH.
153
What is GPI, what function does it serve, and what is some pathology associated with it?
GPI anchors MIRL and DAF to the surface of the RBC to prevent it from being destroyed from complement. GPI is lost in PNH
154
What is the mechanism of inheritance of PNH?
Acquired (not inherited)
155
Triad of hemolytic anemia, pancytopenia and venous thrombosis
PNH
156
Why do patients with PNH get hemolysis at night?
Because shallow breathing during sleep causes a slight acidosis, which activates complement, allowing for destruction of RBCs that don't have GPI anchoring MIRL and DAF to their surface.
157
What CD markers are lost in PNH?
CD55/CD59 (these use GPI as a linker molecule)
158
What is the main cause of death in PNH?
Thrombosis of hepatic, portal, or cerebral veins (platelets lack GPI).
159
What destroys cells in PNH?
Complement
160
Treatment for PNH and its MOA
Ecalizumab - C5 complement inhibitor
161
What is the function of G6PD in the RBC?
To produce NADPH for regeneration of reduced glutathione to prevent oxidative damage of RBCs.
162
How is G6PD deficiency inherited?
X-linked recessive
163
What is a Heinz body?
Precipitation of hemoglobin sulfhydryl groups in RBCs seen in G6PD deficiency.
164
What causes bite cells?
Removal of Heinz bodies by splenic macrophages in G6PD deficiency.
165
What are the two cell morphologies seen in G6PD deficiency?
Heinz bodies (precipitated hemoglobin) Bite cells (removal of Heinz bodies by splenic macrophages).
166
Where are RBCs primarily destroyed in G6PD deficiency?
Extravascularly
167
Warm agglutinin AIHA antibody
IgG
168
Cold agglutinin AIHA antibody
IgM
169
List 3 causes of warm agglutinin AIHA
SLE, CLL, methyldopa
170
What RBC morphology will be seen on warm agglutinin AIHA?
Spherocytes
171
List 2 infectious causes of cold agglutinin AIHA
Mycoplasma pneumoniae, mono
172
How do you do a direct Coombs test?
Add anti-Ig antibody to the patient's serum. RBCs agglutinate if they are coated with Ig. (Do I have RBCs coated with Ig?)
173
How do you do an indirect Coombs test?
Add normal RBCs to a patient's serum. Agglutination = serum has surface Ig. (Does the patient have antibodies in their serum?)
174
What cells are the hallmark of microangiopathic hemolytic anemia?
Schistocytes
175
What causes macroangiopathic hemolytic anemia and what cells are hallmark for it?
Typically, caused by RBCs shearing against cardiac valve prostheses and in aortic stenosis. Schistocytes
176
Hypocellular bone marrow on biopsy
Aplastic anemia
177
What cells are deficient in aplastic anemia?
RBCs, leukocytes, platelets
178
What cells are seen in a myelophthisic process?
Dakryocytes (teardrop cells)
179
Name the cells produced in the myeloid lineage
RBCs, neutrophils, basophils, eosinophils, monocytes, megakaryocytes
180
Name the cells produced in the lymphoid lineage
CD8/CD4 T cells, B cells, NK cells
181
What two drugs can be used to increase neutrophil count?
GM-CSF, G-CSF
182
Which cells in the blood are most sensitive to radiation?
Lymphocytes (check lymphocytes if you suspect radiation toxicity).
183
Decreased Fc receptor expression on neutrophils is suggestive of..
A left shift (decreased CD 16)
184
Immature neutrophils will have decreased numbers of what CD marker?
CD 16 - due to decreased Fc receptor expression
185
What causes eosinophilia seen in Hodgkin disease?
Increased IL-5 production
186
Basophilia is associated with...
CML
187
What bacteria causes a lymphocytic leukocytosis?
B. pertussis (produces a protein that prevents lymphocytes from leaving blood into the nodes)
188
What part of the lymph node is inflamed in mononucleosis?
Paracortex (where the CD8 T cells are)
189
What part of the spleen is inflamed/enlarged in mononucleosis?
Periarterial lymphatic sheath (PALS- where the T cells are)
190
What are heterophile antibodies?
IgM produced in mono that attacks RBCs from other species (sheep, horse). Tested in Monospot test.
191
What is screened for as a confirmatory test for EBV?
EBV viral capsid antigen
192
What defines an acute leukemia?
> 20% blasts in the bone marrow
193
What is the key marker to identify a lymphoblast?
TdT
194
What is TdT and what does it signify?
TdT is DNA polymerase. Its presence means that the cell is a lymphoblast.
195
What is an Auer rod composed of?
Crystallized myeloperoxidase - specific for a myeloblast, AML.
196
Crystallized myeloperoxidase seen in a cell
Auer rod - seen in myeloblasts of AML
197
Name the marker seen on each cell that would differentiate a myeloblast from a lymphoblast.
Myeloblast - myeloperoxidase (Auer rod) Lymphoblast - TdT (DNA polymerase)
198
What 2 leukemias are associated with Down syndrome?
Acute megakaryoblastic leukemia (before age of 5); ALL (after age of 5)
199
Name the 3 CD markers classically expressed by B cells in ALL
CD 10, CD 19, CD 20
200
CD 10, CD 19, CD 20 positive blasts
B cell ALL
201
What are two areas that must be closely watched or prophylaxed in patients with ALL?
Testes/CNS
202
What leukemia spreads to CNS?
ALL
203
t(12;21)
Good prognosis in ALL
204
Translocation associated with good prognosis in ALL
t(12;21)
205
Translocation associated with bad prognosis in ALL
t(9;22)
206
t(9;22) ALL
Bad prognosis
207
Name the CD markers seen in T cell ALL
CD2-CD8 (NOT CD10)
208
What are the "T's" of T cell ALL?
Thymic mass in Teenager (actually a lymphoma because it is a mass)
209
In what leukemia do you prophylax the CNS and testes with chemo in kids?
ALL
210
t(15;17)
M3 AML (APL) - treat with ATRA
211
How does APL commonly present?
DIC
212
Smear shows cells with numerous Auer rods.. Dx?
M3 AML (APL) - treat with ATRA
213
What is the mutation seen in APL?
Disruption of the retinoic acid receptor, causing promyelocytes to accumulate.
214
What is the treatment for APL (M3 AML) and how does it work?
ATRA - works by binding retinoic acid receptor inducing differentiation in promyelocytes (causes them to mature)
215
What is the marker for a hematopoietic stem cell?
CD34
216
Acute monocytic leukemia typically infiltrates...
Gums (patients present with gum involvement)
217
Disorder associated with acute megakaryoblastic anemia.
Down syndrome (after the age of 5)
218
Abnormal myeloid maturation with increased blasts that comprise < 20% of cells
Myelodysplastic syndrome (can progress to AML if blasts > 20%).
219
What is the underlying pathophysiology of myelodysplastic syndrome?
Hypercellular bone marrow with cytopenias after radiation or chemotherapy
220
Abnormal myeloid maturation with increased blasts that comprise > 20% of cells
AML (<20% = myelodysplastic syndrome).
221
What is a pseudo-Pelger-Huet cell?
Bi-lobed PMN seen in myelodysplastic syndrome
222
Chronic leukemia is a proliferation of...
Mature circulating lymphocytes
223
Naive B cells expressing CD5 and CD 20
CLL
224
Smudge cells
CLL
225
CLL involving lymph nodes is known as...
Small lymphocytic lymphoma
226
Why is infection the #1 cause of death in CLL?
Because neoplastic B cells don't secrete Ig, resulting in hypogammaglobulinemia
227
What is the Richter transformation?
CLL transforming into DLBCL (patient with CLL with rapidly enlarging spleen and LN).
228
TRAP positive cells
Hairy cell leukemia
229
Hairy cell leukemia cells are neoplastic proliferations of...
Mature B cells
230
Treatment for hairy cell leukemia
Cladribine, also known as 2-CDA (guanosine)
231
What causes splenomegaly in hairy cell leukemia?
Expansion of the red pulp
232
What is the MOA and use of cladribine?
Adenosine deaminase inhibitor, causing adenosine to accumulate to toxic levels in neoplastic B cells. Used in hairy cell leukemia.
233
Classic presentation of hairy cell leukemia
Dry tap, pancytopenia, splenomegaly, patient in 50s/60s
234
Neoplasm associated with HTLV-1
ATLL (adult T cell leukemia/lymphoma)
235
Cause of adult T cell leukemia/lymphoma and where it is seen geographically
HTLV-1 - Japan/Caribbean
236
Patient presents with lytic bone lesions, hypercalcemia, and cutaneous rash. Dx?
Adult T cell lymphoma (don't jump on multiple myeloma! HTLV-1 ATLL will cause a rash).
237
Which malignant lymphoma shows involvement of the epidermis?
Mycosis fungoides
238
What are Pautrier microabscesses?
Aggregates of neoplastic T cells in epidermis seen in MF/Sezary syndrome
239
What is the immunophenotype of cells in mycosis fungoides?
CD3 and CD4 + (malignant neoplasm of T helper-inducer lymphocytes)
240
What are Sezary cells?
Malignant T cells with cerebriform nuclei (nucleus looks like a brain).
241
Malignant T cells with cerebriform nuclei
Sezary cells
242
What is a myeloproliferative disorder?
Accumulation of mature myeloid cells (RBCs= PV, leukocytes = CML, platelets = essential thrombocytosis). Cells of ALL myeloid lineage will be increased, but the disorder is named for the predominant cell.
243
t(9;22)
CML - Philadelphia chromosome (also bad prognosis in ALL)
244
What is BRC-ABL?
Tyrosine kinase fused in CML
245
Treatment for CML
Imatinib - blocks intrinsic tyrosine kinase activity of BCR-ABL tyrosine kinase
246
Why do patients with CML progress to either AML or ALL?
Because the hematopoietic stem cell is what is actually mutated
247
How is a leukemoid reaction differentiated from CML?
Leukemoid reaction = high leukocyte alkaline phosphatase, CML = low leukocyte alanine phosphatase; CML = increased basophils (LR not); CML = t(9;22) (LR not)
248
What is a leukemoid reaction?
Increased WBC count with increased neutrophils, and HIGH leukocyte alkaline phosphatase (will be LOW in CML).
249
What is the mutation in polycythemia vera?
JAK2 - tyrosine kinase
250
What is Polycythemia?
Neoplastic proliferation of mature myeloid cells, especially RBCs
251
Aquagenic pruritus
Polycythemia vera - itching after a shower (increased mast cells)
252
What is a common cause of death in patients with polycythemia vera?
Budd-Chiari syndrome- thrombosis in hepatic vein resulting in liver infarction
253
How is polycythemia vera differentiated from reactive polycythemia?
In reactive polycythemia, EPO would be high (due to hypoxia in lung disease or ectopic tumor production of EPO - renal cell CA). EPO will be low in PV.
254
What is essential thrombocythemia?
Neoplastic proliferation of mature myeloid cells, especially platelets. Associated with JAK 2 kinase mutation
255
What mutation causes essential thrombocythemia?
JAK 2 kinase
256
What mutation causes myelofibrosis?
JAK 2 kinase
257
Where are B cells present in the LN?
Cortex (outermost layer - expanded in bacterial infection)
258
Where are T cells present in the LN?
Paracortex (expanded in viral infection)
259
t(14;18)
Follicular lymphoma
260
Translocation in follicular lymphoma
t(14;18)
261
What is the molecular mechanism of the translocation in follicular lymphoma?
Translocation of the heavy chain Ig (14) and bcl-2 (18)
262
Ig/bcl-2 translocation
Follicular lymphoma
263
What is the normal function of bcl-2?
Stabilizes the mitochondrial membrane, preventing cytochrome C from leaking and causing apoptosis. Mutated in follicular lymphoma - lose apoptosis in B cells t(14;18).
264
Why do LN lack tingible body macrophages in follicular lymphoma?
Apoptosis is lost because bcl-2 is lost. Would normally see macrophages consuming debris of B cells that were negatively selected in LN.
265
t(11;14)
Mantle cell lymphoma
266
Neoplastic proliferation of cells expanding the region immediately adjacent to the follicle in a LN.
Mantle cell lymphoma (mantle region is the region immediately adjacent to the follicle).
267
What translocation is seen in mantle cell lymphoma?
t(11;14)
268
What is overexpressed in mantle cell lymphoma?
Cyclin D
269
Cyclin D overexpression
Mantle cell lymphoma
270
What is the function of cyclin D?
Promotion of G1/S transition in cell cycle
271
What proteins are fused due to the translocation in mantle cell lymphoma?
Cyclin D1 (11) and Ig heavy chain (14).
272
What lymphoma is associated with chronic inflammatory states?
Marginal zone lymphoma (marginal zone is formed by activation of cells in chronic infection/inflammation).
273
Sjogren syndrome is related to what lymphoma?
Marginal zone lymphoma
274
Hashimoto thyroiditis is related to what lymphoma?
Marginal zone lymphoma
275
H. pylori infection is related to what lymphoma?
MALToma (marginal zone lymphoma in mucosal sites)
276
What are the two forms of Burkitt lymphoma and where do they typically arise?
African - Jaw, Sporadic - abdomen
277
t(8;14)
Burkitt lymphoma
278
Translocation in Burkitt lymphoma
t(8;14)
279
What proteins are fused due to the translocation in Burkitt lymphoma?
c -myc oncogene (8) and Ig heavy chain (14)
280
Starry sky appearance of lymphocytes
Burkitt lymphoma
281
Infection that causes Burkitt lymphoma
EBV
282
Histology of Burkitt lymphoma
Starry sky appearance
283
What lymphoma can metastasize into the CNS?
DLBCL
284
Describe the shape of growth of cells in DLBCL.
Sheets
285
DLBCL can arise from what chronic leukemia?
CLL, via the Richter transformation
286
What is the hallmark of Hodgkin's lymphoma?
Reed-Sternberg cell
287
Large B cell with a multilobed nucleus and prominent nucleoli
Reed-Sternberg cell
288
What CD markers is a Reed-Sternberg cell positive for?
CD15 and CD30
289
CD15 and CD30 positive B cell
Reed Sterngerg cell (HL)
290
What causes B symptoms in HL?
Cytokine production by Reed-Sternberg cells
291
What is the most common form of HL?
Nodular sclerosing (lacunar Reed-Sternberg cells)
292
Lacunar cells
Reed Sternberg cell in nodular sclerosing HL (RS cell in a cleared out area - "lake).
293
What form of HL has the best prognosis?
Lymphocyte rich
294
What form of HL has the worst prognosis?
Lymphocyte depleted
295
What is seen in mixed-cellularity HL and what causes it?
Abundant eosinophils, called in by IL-5
296
RA + splenomegaly + neutropenia
Felty syndrome
297
High serum IL-6 is associated with what blood neoplasm?
Multiple myeloma
298
What type of lesions are seen on x-ray in a patient with multiple myeloma?
Punched out, lytic lesions
299
How does multiple myeloma cause hypercalcemia?
Neoplastic plasma cells activate RANK receptor on osteoclasts
300
What is the CRAB criteria?
hyperCalcemia; Renal insufficiency; Anemia; Bone lytic lesions/Bone pain - in multiple myeloma
301
What causes increased serum protein in multiple myeloma?
Plasma cells secreting immunoglobulin
302
What is seen on electrophoresis in multiple myeloma?
Spike in the gamma globulin (M-spike)
303
What does an M spike mean?
Overproduction of a monoclonal immunoglobulin (NOT necessarily IgM).
304
What is a Roleaux formation and what is it seen in?
Piled up RBCs seen in multiple myeloma
305
Piled up RBCs seen in multiple myeloma
Roleaux formation
306
What is Bence Jones protein?
Free light chain (from Ig) excreted in urine.
307
What type of amyloidosis is seen in multiple myeloma?
Primary (AL)
308
What substance is produced by the plasma cells in multiple myeloma to cause hypercalcemia?
Osteoclast-activating factor (also produces bone pain).
309
What is MGUS?
Increased serum protein with M spike on SPEP but no other features of multiple myeloma.
310
What is the rate of progression of MGUS to multiple myeloma?
1-2% per year
311
Isolated M spike with no multiple myeloma symptoms.
MGUS (monoclonal gammopathy of undetermined significance)
312
B cell lymphoma with monoclonal IgM production
Waldenstrom macroglobulinemia
313
What is Waldenstrom macroglobulinemia?
B cell lymphoma with monoclonal IgM production.
314
M spike due to IgM
Waldenstrom macroglobulinemia
315
Plasma cell dyscrasia causing hyperviscosity
Waldenstrom macroglobulinemia | note that there's NO lytic bone lesions!
316
Birbeck granules on EM
Langerhans cell histiocytosis
317
Tennis racket shaped granules on EM
Langerhans cell histiocytosis (Birbeck granules)
318
What stain is used to detect Langerhans cell histiocytosis?
S100
319
S100 positive cells
Langerhans cell histiocytosis (also melanoma, schwannoma). Also CD1a positive
320
CD1a positive cells
Langerhans cell histiocytosis (also melanoma, schwannoma). Also S100 positive
321
Presentation of Langerhans cell histiocytosis
In kids as lytic bone lesions and skin rash
322
What type of receptor is JAK-2?
Non-receptor tyrosine kinase
323
High Ki-67 fraction...
Burkit Lymphoma
324
Name 3 NNRTIs
NeVIRapine, efaVIRenz, delaVIRidine ("vir" in the middle)
325
What HIV drug causes nightmares?
EfaVIRenz (NNRTI)
326
What is the dose-limiting side effect of AZT?
Bone marrow suppression
327
Name 6 NRTI's
Tenofovir; Emtricitabine; Abacavir; Lamivudine; Didanosine; Stavudine
328
What suffix is indicative of a protease inhibitor?
ends in -navir (ritonavir, indinavir, etc.)
329
What is ralTEGRAvir?
HIV inTEGRAse inhibitor
330
Name 1 HIV integrase inhibitor
RalTEGRAvir
331
What is emtracitabine?
NRTI
332
What is abacavir?
NRTI (NOT a protease inhibitor because it ends in -avir, not -navir).
333
What is zidovudine?
NRTI
334
What is the dose-limiting side effect of abacavir?
Life threatening allergy (it is an NRTI)
335
What is ritonavir?
Protease inhibitor (-navir)
336
What is indinavir?
Protease inhibitor (-navir)
337
What is saquinavir?
Protease inhibitor (-navir)
338
What is the main side effect of protease inhibitors?
Disordered lipid and CHO metabolism with central adiposity (buffalo hump) and insulin resistance.
339
Name a fusion inhibitor.
EnFUrvatide (FUsion inhibitor)
340
What is enFUrvatide?
Fusion inhibitor
341
Name a drug that binds gp41
EnFUrvatide (FUsion inhibitor)
342
What is maraviroc?
CCR5 inhibitor
343
Name a CCR5 inhibitor
Maraviroc
344
What is a unique side effect of indinavir?
Nephrolithiasis
345
What is neVIRapine?
NNRTI (vir in the middle)
346
What is efaVIRenz?
NNRTI (vir in the middle)
347
What is delaVIRidine?
NNRTI (vir in the middle)
348
How do NNRTIs work?
They bind to reverse transcriptase at a site different from NRTIs. They don't require phosphorylation.
349
What antiretroviral is contraindicated in pregnancy?
efaVIRenz (NNRTI) - risk of NTD's.
350
What should be given to babies born to HIV positive mothers?
AZT (zidovudine)
351
What is erythrocytosis?
polycythemia = increased hematocrit
352
what is the life span of a platelet?
8-10 days
353
What is the vWF receptor and what is the fibrinogen receptor?
vWF binds GpIb
| Fibrinogen binds GpIIb/IIIa
354
what is the normal leukocyte count?
4000 - 10,000 cells/mm3
355
What is the WBC differential from highest to lowest?
```
Neutrophils Like Making Everything Better
Neutrophils (54-62%)
Lymphocytes (25-33%)
Monocytes (3-7%)
Eosinophils (1-3%)
Basophils (0.0.75%)
```
356
What are band cells?
Increased band cells (immature neutrophils) reflect states of increased myeloid proliferation like in bacterial infections or CML
357
What are contained in the small more numerous granules of neutrophils vs the larger less numerous azurophilic granules (lysosomes)?
Small more numerous specific granules: alkaline phosphatase, collagenase, lysozyme, and lactoferrin
Larger less numerous azurophilic granules (lysosomes): acid phosphatase, peroxidase, and beta glucuronidase
358
which cell type contains a large kidney shaped nucleus?
Monocyte
359
what are the cell surface markers found on macrophages?
CD14, B7, MHC1, MHC2, CD40
360
which cytokine activates macrophages?
interferon gamma
361
What is CD14?
Cell surface marker for macrophages - CD14 binds to LPS on gram negative bacteria and induces macrophages to make acute phase cytokines (IL1, IL6 and TNF alpha)
362
what do eosinophils use to defend against helminthic infections?
major basic protein
363
Which cell type is "highly phagocytic for antigen-antibody complexes"?
Eosinophils
364
What are histaminase and arylsulfatase?
Produced by eosinophils to help limit the reaction following a mast cell degranulation
365
List 5 cases of eosinophilia
```
NAACP
Neoplastic
Asthma
Allergic processes
Collagen vascular diseases
Parasites (invasive)
```
366
What is contained in granules within basophils?
heparin, histamine and leukotrines (LTD4)
367
Which cell type mediates an allergic reaction ?
Basophils or mast cells in local tissues
368
What enzyme can you follow as an activator of mast cell activation?
tryptase
369
Which cell type functions as a link between the innate and adaptive immune system?
```
Dendritic cells
Express MHC class II and Fc receptor on surface
```
note that these are called Langerhans cells in the skin
370
Can B lymphocytes function as an APC?
yes they contain MHC2
371
which cell type contains an off center nucleus with a clock face chromatin distribution?
Plasma cells
372
Which cell type mediates the cellular immune response?
T cells
373
Which cytokine is necessary for T cell activation?
CD28 (costimulatory signal)
374
What type of antibodies are anti-A and anti-B?
IgM antibodies - do not cross the placenta
375
What type of antibody is anti-Rh?
IgG antibody - can cross the placenta
376
Which blood type is the universal donor? Universal acceptor?
Universal donor of RBCs: Type O
Universal donor of plasma: AB
Universal recipient of RBCs: AB
Universal recipient of plasma: O
377
Describe Blood type A
Blood type A contains the A antigen on the RBC surface and anti-B antibodies in the plasma
378
Describe blood type AB
Has both A and B antigens on the RBC surface and no antibodies in the plasma
as compared to blood type O which has neither A nor B antigens on the RBC surface but has both antibodies in the plasma
379
What is Rhogam?
IgG anti Rh antibodies given at 28 weeks gestation and immediately post-partum to block maternal immune response to the foreign fetal RhD antigens - it prevents the maternal antibodies from recognizing the fetal RBCs
You want to prevent hemolytic disease in the NEXT Rh+ child
380
What is the hypersensitivity if you transfuse the wrong blood type?
Type II hypersensitivity
381
How does Rhogam work?
Binds to the fetal RBCs that have gotten intot he mothers body and prevents exposure of the surface Rh-D antigen to the moms immune system
382
List the coagulation factors in the extrinsic pathway
7
383
List the coagulation factors in the intrinsic pathway
12, 11, 9, 8
384
What does PT and PTT measure?
PT measures the extrinsic pathway
| PTT measures the intrinsic pathway
385
What are accelerating factors?
Factor VIIIa and Factor Va - both are inhibited by protein C and protein S
386
What carries and protects Factor VIII?
vWF
387
What is epoxide reductase?
Enzyme that catalyzes oxidized vitamin K to reduced vitamin K so it can activated 2, 7, 9, 10, C and S
388
What does antithrombin do?
antithrombin inhibits activated forms of factors 2, 7, 9, 10, 11 and 12
antithrombin is activated by heparin
389
How is it possible for Factor V to be resistant to inhibition by protein C?
Factor V Leiden mutation
390
name 4 anti-aggregation factors that stop platelet aggregation
PGI2 and NO - released by endothelial cells
Increased blood flow
decreased platelet aggregation
391
What do ticlodipine and clopidogrel inhibit?
ADP induced expression of GpIIb/IIIa expression
392
What does Aciximab inhibit?
Directly inhibits GpIIb/IIIa
393
what is clopidogrel synergistic with?
Warfarin
clopidogrel decreases the metabolism of warfarin making it stick around longer
394
Do you have an increased or decreases ESR in polycythemia vera?
decreased
also decreased in sickle cell anemia, congestive heart failure, microcytosis and hypofibrinogenemia
395
What is the effect of TXA2?
Vasoconstriction and platelet aggregation
396
What is an acanthocyte and when will you see one?
Spur cell, RBC with irregular spikes
| seen in liver disease, abetalipoproteinemia
397
When do you see basophilic stippling in a RBC?
Thalassemias, Anemia of chronic disease and lead poisoning
also alcohol abuse
Caused by inhibition of the enzyme that breaks down RNA - so you get clumps of denatured RNA in the RBC
398
What is a Bite cell and when do you see it?
Seen in G6PD deficiency
| Due to removed Heinz bodies from cells by the spleen
399
What is an elliptocyte?
pencil shaped RBC - hereditary elliptocytosis
400
What is a ringed sideroblast?
RBC with excess iron IN THE MITROCHONDRIA
due to sideroblastic anemia (lead poisoning, drugs, genetic conditions, myelodysplastic syndromes)
due to a protoporphyrin deficiency
401
what is a schistocyte?
Helmet cells
| seen in DIC, TTP/HUS, and traumatic hemolysis
402
What causes a tear drop cell?
Bone marrow infiltration (like myelofibrosis)
403
List 4 causes of target cells
```
"THAL"
Thalassemia
HbC disease
Asplenia
Liver disease
```
404
What are Heinz bodies?
Oxidation of iron from ferrous to ferric form leads to denatured hemoglobin precipitation and damage to RBC membrane
Leads to formation of bite cells
405
What is a Howell Jolly body?
Basophilic nuclear remnants found in RBCs
Seen in patients who don't have a spleen (hyposplenia, asplenia) or after mothball ingestion (naphthalene)
406
List the 5 causes of microcytic anemia?
Iron deficiency, anemia or chronic disease (may start as normocytic), thalassemias, lead poisoning, sideroblastic anemia
407
List the 3 causes of non-hemolytic normocytic anemia
Anemia of chronic disease (only starts as normocytic), Aplastic anemia and Chronic kidney disease
408
List the 5 causes of intrinsic hemolytic normocytic anemia?
RBC membrane defect (hereditary spherocytosis), RBC enzyme deficiency (G6PD, PK), HbC, Sickle cell anemia, Paroxysmal nocturnal hemoglobinuria
409
List the 4 causes of extrinsic hemolytic normocytic anemia
Autoimmune, microangiopathic, macroangiopathic, infections
410
List the 6 causes of macrocytic anemia?
Megaloblastic - Folate deficiency, B12 deficiency, orotic aciduria
Non-megaloblastic - Liver disease, alcoholism, Reticulocytosis
411
What are the findings in a patient with iron deficiency anemia?
decreased iron, increased TIBC and decreased ferritin
412
What is the trans deletion seen in alpha thalassemia?
prevalent in African populations.
| leads to one deletion on each chromosome
413
Which population commonly gets Beta thalassemia mutations?
Point mutations in splice sites and promoter sequences that lead to decreased Beta globin synthesis
Prevalent in Mediterranean populations
414
Which beta thalassemia results in absent beta chain?
beta thalassemia major leads to increased HbF
| patient will require transfusions - leads to secondary hemochromatosis
415
What is the defect that occurs in lead poisoning?
Lead inhibits ferrochelatase and ALA dehydratase leading to decreased heme synthesis
- also inhibits rRNA degradation causing RBCs to retain aggregates of rRNA (basophilic stippling)
416
What are the clinical findings in a patient with lead poisoning?
LEAD
Lead Lines on gingiva (burton's lines) and on metaphyses of long bones on Xray
Encephalopathy and Erythrocyte basophilic stippling
Abdominal colic and sideroblastic Anemia
Drops - wrist drop and foot drop.
417
What is the treatment for lead poisoning?
Dimercaprol and EDTA are first line of treatment
| SUCcimer is used for chelation for kids (it SUCks to be a kid who eats lead)
418
what are the lab findings in sideroblastic anemia?
increased iron, normal TIBC and increased ferritin
419
What is the treatment for sideroblastic anemia?
Pyridoxine (B6) which is cofactor for d-ALA synthase
420
What are the hereditary and reversible causes of sideroblastic anemia?
Hereditary - X linked defect in d-ALA synthase gene
| Reversible - alcohol, lead, and isoniazid
421
List 3 drugs that can cause folate deficiency
Methotrexate, trimethoprim, and phenytoin
422
What fluke can lead to B12 deficiency?
Diphyllobothrium latum - fish tapeworm
note that proton pump inhibitors, crohn's disease and vegans can also get this, pernicious anemia
423
Why do patients with B12 deficiency get neurologic symptoms?
Subacute combined degeneration due to involvement of B12 in fatty acid pathways and myelin synthesis
leads to peripheral neuropathy with sensorimotor dysfunction, posterior columns (loss of vibration/proprioception), lateral corticospinal tracts (spasticity) and dementia
424
children have megaloblastic anemia that hasn't been cured by folate or B12 - what's wrong with them?
Orotic aciduria - deficiency of UMP synthase which is involved in pyrimidine synthesis.
TX with uridine monophosphate to bypass mutated enzyme
note that these patients have hypersegmented neutrophils, glossitis, and orotic acid in urine
425
Describe what happens in anemia of chronic disease
Inflammation increases IL6 leading to the liver making hepcidin.
Increases hepcidin inhibits ferroportin on intestinal mucosal cells and macrophages therefore inhibiting iron transport leading to decreased release of iron from macrophages
426
what can cause aplastic anemia?
- radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
- viral agents (parvovirus B19, EBV, HIV, HCV)
- Fanconi's anemia (DNA repair defect)
- idiopathic (immune mediated, primary stem cell defect) may follow acute hepatitis
427
why does chronic kidney disease lead to nonhemolytic normocytic anemia?
Due to decreased erythropoietin leading to decreased hematopoiesis
428
what is the inheritance pattern of hereditary spherocytosis?
AD
429
What are the findings in hereditary spherocytosis?
Increased MCHC, increased red cell distribution width, positive osmotic fragility test. normal to decreased MCV with abundance of cells - masks microcytia
430
What is the inheritance pattern of G6PD deficiency?
X linked
431
A patient has back pain and then a few days later develops hemoglobinuria. what would you see on blood smear?
This is G6PD deficiency
| you'll see Heinz bodies and bite cells
432
which disease has polymerized hemoglobin and deformed cell membrane?
Sickle cell disease
433
What is pyruvate kinase deficiency?
AR deficiency leads to decreased ATP and rigid RBCs - can cause hemolytic anemia in a newborn
434
What is the triad seen in paroxysmal nocturnal hemoglobinuria?
Hemolytic anemia, pancytopenia and venous thrombosis
Positive Ham's test - red cell lysis at decreased pH due to activation of complement
Labs will show CD55(DAF)/59 - RBCs
435
What is the treatment for a patient with paroxysmal nocturnal hemoglobinuria?
Eculizumab - inhibits complement
436
What is the inheritance pattern of sickle cell disease?
Autosomal recessive, mutation is on chromosome 11
437
what is the treatment for sickle cell anemia?
Hydroxyurea (increases HbF) and bone marrow transplant
438
What would the treatment of salmonella osteomyelitis in a sickle cell patient be?
Cirpfloxacin or another fluoroquinolone
| also do coverage against Staph aureus (naficillin/oxacillin, cefazolin, vancomycin)
439
What is the warm and cold agglutinins seen in autoimmune hemolytic anemia?
Warm agglutinin - IgG
| Cold agglutinin - IgM
440
When do you see warm agglutinin Autoimmune hemolytic anemia?
chronic anemia seen in SLE, CLL or with certain drugs like alpha methyldopa
441
When do you see cold agglutinin autoimmune hemolytic anemia?
Acute anemia triggered by the cold, seen in CLL, mycoplasma pneumonia infections or infectious mononucleosis (EBV)
442
What are the lab findings in a patient with hemochromatosis?
Increases serum iron (if primary), decreased TIBC, increased ferritin, increased % saturation
443
What are the lab findings in a patient with pregnancy or on OCPs?
increased TIBS, decreased transferrin saturation
444
What are the lab findings in a patient with sideroblastic anemia?
increased serum iron, decreased TIBC, normal or increased ferritin, increased %saturation
445
What is the affected enzyme in a patient with acute intermittent porphyria?
Porphobilinogen deaminase
446
What are the symptoms in a patient with acute intermittent porphyria?
```
5 Ps
painful abdomen
port wine colored urine
polyneuropathy
psychological disturbances
Precipitated by drugs (barbiturates, seizure drugs, rifampin, metoclopramide)
```
447
What is the treatment in a patient with acute intermittent porphyria?
glucose and heme which inhibit ALA synthase
448
What is porphyria cutanea tarda?
Defected uroporphyrinogen decarboxylase leading to accumulation of uroporphyrin (tea colored urine)
patients have blistering cutaneous photosensitivity. This is the most common porphyria
449
What are the lab changes in hemophilia A and B
Increased PTT
450
What are the clinical findings in patients with hemophilia A or B?
Macrohemorrhage in hemophilia - hemarthroses (bleeding into joints), easy brusing, increased PTT
451
What are the lab changes in a patient with Vitamin K deficiency?
Increased PT and PTT
452
What is seen with platelet abnormalities?
microhemorrhage: mucous membrane bleeding, epistaxis, petechiae, purpura, increased bleeding time and POSSIBEL decreased in platelet count
453
What are the lab findings in a patient with Bernard-Soulier syndrome?
Decreased platelet count and increased bleeding time
454
What are the lab findings in a patient with Glanzmann's thrombasthenia?
Increased bleeding time. Blood smear will show no platelet clumping. note that platelet count is NORMAL
455
What are the labs seen in idiopathic thrombocytopenic purpura?
decreased platelet count and increased bleeding time. Note that there will be increased megakaryocytes
456
What are the lab findings in thrombotic thrombocytopenic purpura?
decreased platelet count, increased bleeding time and increased LDH. the patient will also have schiztocytes
457
What is the treatment for Hemophilia A? for vWF disease?
Desmopressin - promotes release of factor VIII and vWF and t-PA from endothelial cells
458
What are the symptoms in Thrombotic thrombocytopenic purpura?
FAT RN
| Fever, microangiopathic hemolytic Anemia, Thrombocytopenia, Renal symptoms, Neurological symptoms
459
What are the lab findings in a patient with vWF?
increased bleeding time and normal or increased PTT
460
What are the lab findings in a patient with DIC?
decreased platelet count, increased bleeding time, increased PT and increased PTT
The patient will also have schistocytes, increased fibrin split products (D-dimers), decreased fibrinogen, decreased factors V and VIII
461
Name 4 diseases that are hereditary thrombosis syndromes leading to hypercoagulability
Factor V leiden, Prothrombin gene mutation, Antithrombin deficiency, and Protein C or S deficiency
462
What is factor V leiden disease?
Production of mutant factor V that is resistant to degradation by activated protein C. Most common cause of inherited hypercoagulability in whites
So factor V stays activated longer leading to increased coagulation
463
What is Prothrombin gene mutation?
Mutation in 3' untranslated region leading to increased production of prothrombin and therefore increased plasma levels and venous clots
G20210A
464
What is antithrombin deficiency?
Inherited deficiency of antithrombin that has no direct effect on PT, PTT, or thrombin time but diminishes the increase in PTT following heparin administration - these patients are probably resistant to heparin in these patients
465
What is Protein C or S deficiency?
decreased ability to inactivate factors V and VIII. Increased risk of thrombotic skin necrosis with hemorrhage following administration of warfarin
466
Whats the point of fresh frozen plasma?
Increases coagulation factor levels - used for DIC< warfarin overdose or cirrhosis
467
What is the point of giving cryoprecipitate?
Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin. used to treat coagulation factor deficiencies involving fibrinogen and factor VIII
468
What is the lymphocyte predominant type of Hodgkin's lymphoma?
Least common but has the best prognosis - found in younger men
469
What is the nodular sclerosing type of Hodgkin's lymphoma?
Most common type, good prognosis, biopsy shows bands of collagen, sclerosis and fibrosis, seen in young adults more common in females
470
What is the mixed cellularity type of Hodgkin's lymphoma?
Second most common, has the worst prognosis
471
What is the lymphocyte depleted type of Hodgkin's lymphoma?
very poor prognosis
472
What is the translocation in burkitt's lymphoma?
c-myc and heavy chain t(8;14)
| 8urk14
473
What is the most common adult non Hodgkin lymphoma?
Diffuse large B cell lymphoma
474
what type of lymphoma is caused by HTLV-1?
Adult T-cell lymphoma
this is aggressive- adults present with cutaneous lesions - especially effects populations in japan, west Africa and the caribbean
475
What type of amyloidosis appears in multiple myeloma?
Primary amyloidosis (AL)
476
What is seen on a blood smear of multiple myeloma?
Clock face chromatin and whitish intracytoplasmic inclusions containing immunoglobulins
477
What is the treatment for hairy cell leukemia?
Cladribine - an adenosine analog
478
What are auer rods?
Peroxidase positive cytoplasmic inclusions in granulocytes and myeloblasts. Commonly seen in acute promyelocytic leukemia (M3). Treatment of AML M3 can release Auer rods leading to DIC
479
A child presents with lytic bone lesions and a skin rash - what might it be?
Langerhands cell histiocytosis
480
What do you follow when administering heparin?
PTT
| Heparin is a cofactor for the activation of antithrombin - leads to decreased thrombin and factor Xa
481
What do you follow for warfarin?
PT
482
why can you use heparin during pregnancy?
It doesn't cross the placenta
483
what is the antidote to heparin overdose?
Protamine sulfate (positively charged molecule that binds negatively charged heparin)
484
How does low molecular weight heparin work?
Acts more on factor Xa - has better bioavailability and 2-4 times longer hald life than heparin. Can be administered subcutaneously without lab monitoring
485
What is Heparin induced thrombocytopenia?
Development of IgG antibodies against heparin bound to platelet factor 4. The antibody-heparin-PF4 complex activates platelets leading to thrombosis and thrombocytopenia
seen in a patient that's on heparin and their platelet counts are dropping
486
What is the MOA of warfarin?
interferes with normal synthesis and gamma-carboxylation of vitamin K dependent clotting factors 2, 7, 9, 10 C and S
487
What do you give for warfarin overdose?
Vitamin K
488
What is a possible effect of warfarin?
Skin necrosis
489
What is the MOA of thrombolytics
Directly or indirectly aid conversion of plasminogen to plasmin which cleaves thromobin and fibrin clots
Increases PT and PTT but does not change the platelet count
490
how do you treat overdose of thrombolytics?
Aminocarpoic acid
491
How does aspirin work?
Irreversible inhibits cyclooxygenase enzyme by covalent acetylation.
Increases bleeding time, decreases TXA2 and prostaglandins.
NO effect on PT or PTT
492
what is the clinical use of aspirin?
antipyretic, analgesic, anti-inflammatory, antiplatelet
493
name 4 ADP receptor inhibitors
Clopidogrel, ticlopidine, prasugral, ticagrelor
494
How do ADP receptor inhibitors work?
Inhibit platelet aggregation by irreversible blocking ADP receptors.
Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
495
What do Cilostazol and dipyridamole do?
Phosphodiesterase III inhibitors, increased cAMP in platelets thus inhibiting platelet aggregation, they also cause vasodilation
used for patients with intermittent claudication
496
name 3 GPIIb/IIIa inhibitors?
Abciximab, eptifibatide, tirofiban
497
which antineoplastic drug acts by decreasing thymidine synthesis?
Methotrexate, 5-FU
498
Which antineoplastic drug acts by decreasing purine synthesis?
6-MP
499
Which antineoplastic drug acts by inhibiting topoisomerase II??
Etoposide
500
Which antineoplastic drug inhibits microtubule formation?
Vinca alkaloids
501
Which antineoplastic drug inhibits microtubule disassembly?
Paclitaxel
502
how does methotrexate work?
Folic acid analog that inhibits dihydrofolate reductase leading to decreased dTMP therefore decreased DNA and protein synthesis
503
how does 5-FU work?
Pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid. This complex inhibits thymidylate synthase leading to decreased dTMP and therefore decreased DNA and protein synthesis
504
How do you treat an overdose with 5-FU?
rescue with thymidine
505
What is Cytarabine?
arabinofuranosul cytidine
| pyrimidine analog that leads to inhibition of DNA polymerase
506
What is the MOA of doxorubicin and daunorubicin?
Generates free radicals, noncovalently intercalates in DNA leading to breaks in DNA and decreased replication
507
What can you use to prevent cardiotoxicity when taking doxorubicin?
Dexrazoxane (iron chelating agent) used to prevent cardiotoxicity
508
What is Dactinomycin?
Actinomycin D - intercalactes in DNA
used for Childhood tumors like Wilm's tumor, Ewing's sarcoma, rhabdomyocarcoma
children ACT out = dACTinomycin
509
What is the MOA of bleomycin?
Induces free radical formation which causes breaks in DNA strands
510
What is the clinical use of bleomycin?
Testicular cancer and Hodgkin's lymphoma
511
What are the side effects of using Bleomycin?
Pulmonary fibrosis, skin changes
512
What is the MOA of cyclophosphamide and ifosfamide?
Covalently X link DNA at guanine N-7
| Requires bioactivation by the liver!
513
What are the side effects of cyclophosphamide and ifosfamide?
Myelosuppression, hemorrhagic cystitis (due to toxic metabolite acrotein)
514
What is the toxic metabolite of cyclophosphamide and ifosfamide and how do you prevent it?
Toxic metabolite if acrotein - partially prevented with mesna - the thiol group in mesna binds to the toxic metabolite
515
What are the Nitrosureas?
Carmustine, lomustine, semustine and streptozocin
| mustard gas
516
what is the MOA of nitrosureas and the side effects?
Requires bioactivation and crosses the blood brain barrier into the CNS so it is used to TX brain tumors like glioblastoma multiforme
but because it crosses the BBB it has CNS toxicity like ataxia and dizziness
517
WHat is the MOA of Busulfan?
Alkylates DNA
518
What is the used for Busulfan?
CML. Also used to ablate patient's bone marrow before a bone marrow transplant
519
What are the side effects of Busulfan?
Pulmonary fibrosis and hyperpigmentation
520
what are Paclitaxel and Doetaxel used to treat?
Ovarian and breast carcinomas
521
what is the MOA of Vincristine and Vinblastine?
Alkaloids that bind to tubulin in the M phase and block polymerization of microtubules \so that mitotic spindles can't form (no cell division)
522
What is the side effects of Vincristine and Vinblastine?
Vincristine - neurotoxicity leading to areflexia, peripheral neuritis. and also paralytic ileus
Vinblastine - Blasts bone - (bone marrow suppression)
523
What is the MOA of Paclitaxel and Docetaxel?
Hyperstabilizes polymerized microtubules in the M phase so that the mitotic spindle can't break down - anaphase can't occur
524
What is the MOA and use of Cisplatin, carboplatin and oxaliplatin?
Cross link DNA
| used for testicular, bladder, ovary and lung carcinomas
525
what is the MOA of etoposide and teniposide?
Inhibits topoisomerase II leading to increased DNA degradation
remember that Topoisomerase II is used to unwind supercoils as you unwind DNA
526
WHat is the toxicity of Cisplatin and carboplatin?
Nephrotoxicity and acoustic nerve damage
527
How can you prevent nephrotoxicity when using cisplatin and carboplatin?
Amifostine (free radical scavenger) and chloride diuresis
528
What are the nephrotoxic/ototoxic drugs?
Vancomycin
Aminoglycosides
Loop diuretics
Cisplastin/carbplastin/oxaliplatin
529
How do you treat testicular cancer?
Eradicate Ball Cancer
| Etoposide, Bleomycin (or ifosfamide) and Cisplastin
530
WHat are the side effects of etoposide and teniposide?
Myelosuprression, GI irritation and ALOPECIA
531
What is the MOA of hydroxyurea?
Inhibits ribonucleotide reductase leading to decreased DNA synthesis (S-phase specific)
532
What are the uses for Hydroxyurea?
Melanoma, CML and sickle cell disease (increases HbF)
533
What are the side effects of using hydroxyurea?
bone marrow suppression and GI upset
534
What is the MOA of prenisone and prednisolone?
May trigger apoptosis. may even work on nondividing cells
This is the most commonly used glucocorticoid in cancer chemotherapy
used in CLL and non-Hodgkin's lymphomas
535
Name two SERMs
Tamoxifen and raloxifene
536
What's the MOA of tamoxifen?
ER antagonist in the breast
ER agonist in the bone
ER partial agonist in the endometrium
537
What is the MOA of Raloxifene?
ER agonist in the bone (TX osteoporosis)
| ER antagonist in the breast and endometrium
538
What are the differences in the toxicity between Tamoxifen and Raloxifene?
Tamoxifen - partial agonist in the endometrium so it can increased the risk of endometrial cancer, can cause hot flashes
Raloxifene - no increase in endometrial carcinoma because it's an endometrial antagonist
539
What is the MOA of Trastuzumab?
AKA Herceptin
Monoclonal antibody against HER-2 (c-erbB2) a tyrosine kinase,
Helps kill breast cancer cells that overexpress HER-2 possibly through antibody dependent cytoxicity
540
What is the toxicity of Trastuzumab?
Cardiotoxicity
| Herceptin hurts the heart
541
What is the MOA of imatinib?
Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
542
What is the side effect of imatinib?
fluid retention
543
WHat is the MOA of Rituximab?
Monoclonal antibody against CD20 which is found on most B cell neoplasms
544
What is the clinical used of Rituximab?
Non-Hodgkin's lymphoma, Rheumatoid arthritis (with methotrexate) and Pemphigus vulgaris, vasculitis, ITP
545
WHat is the MOA of Vemurafenib?
Small molecule inhibitor of forms of the B-Raf kinase with the V600E mutations
546
What is the clinical use of Vemurafenib?
Metastatic melanome
547
What is the MOA of Bevacizumab?
Monoclonal antibody against VEGF so it inhibits angiogenesis
used for solid tumors
548
Name two neoplastic drugs that can cause cardiotoxicity?
Doxorubicin and Trastuzumab
549
Which drug can cause hemorrhagic cystitis?
Cyclophospamide
550
List three drugs that can cause myslosuppression?
5-FU
6-MP
Methotrexate
551
List two drugs that are both nephrotoxic and can also cause acoustic nerve damage
Cisplastin, Carboplatin
