Heme Flashcards
1
Q
What does it mean to have a chemotherapeutic agent with 1st order kinetics?
A
Drug will kill a constant PROPORTION of cancer cells (regardless of HL or cell cycles)
2
Q
Pt got treated w/ high dose folic for anemia and returned w/ bilateral foot numbness and difficulty walking. What happened?
A
Her megaloblastic anemia is actually from B12 (cobalamin) deficiency and not folate deficiency. Folate deficiency doesn’t have neurologic involvement.
3
Q
Low platelet, leukocytes, RBCs; bone marrow bx show lots of fat. Dx?
A
Aplastic anemia
Key dx finding is ABSENCE of splenomeg
4
Q
Hemoglobin electropheresis shows pt’s band migrating less and so being farther away from anode (+ electrode) than normal and sickle cell disease patient. What mutation is this?
A
Missense
It’s HbC disease -> glutamate (- charge) replaced by lysine (+ charge), which makes Hb even less negative (and farther away from + electrode) than sickle cell (where negative glutamate is replaced by neutral valine)
5
Q
Young pt w/ blasts in peripheral blood smear, worsening dysphagia, dyspnea, tachypnea, stridor. What’s the dx?
A
T-ALL
b/c more likely than B-ALL to present w/ mediastinal mass (thus compression of eso and trachea), SVC syndrome
6
Q
What do you take with cisplatin to prevent ATI?
A
Amifostine (free radical scavenger) and IV normal saline (establishing chloride diuresis keeps cisplatin in unreactive state)
7
Q
What does basophilic stippling look like?
A
Abnormal aggregation of ribosomes in RBC, so shows up as bluish dots in RBC (in a background of hypochromic, microcytic anemia)
8
Q
Replaced histidine w/ serine in hemoglobin beta subunit and gets decreased binding to 2,3-BPG. The Hb is now like what kind of Hb?
A
HbF (serine replaces positively charged histidine so can’t bind w/ negatively charged 2,3-BPG as well
9
Q
What’s the AA replacement in sickle cell?
A
Glutamate (negative) replaced BY valine (neutral)
10
Q
What’s the AA replacement in HbC?
A
Glutamate (negative) replaced BY lysine (positive)
11
Q
What enzyme in the heme synthesis pathway is negatively regulated by the final pathway product (heme)?
A
ALA synthase (rate-limiting step, first step) So administering heme prep in ppl w/ AIP (deficiency of downstream enzyme makes ALA accumulate) will help them feel better
12
Q
What are the 2 enzymes that are inhibited by lead poisoning?
A
ALA dehydratase (cytoplasm) Ferrochelatase (mitochondrial)
13
Q
3 risk factors that promote sickling
A
- Low O2 level: including high 2,3-DPG and oxygen unloading state, or the organs where blood move slowly (spleen, liver, kidney)
- Increased acidity (thus decreased pH) -> does NOT mean proton release, as proton release actually is from deoxyhemoglobin in lungs where the high pO2 favors the release of CO2 and oxygen binding to Hb -> so proton release actually signifies high O2 content
- Low blood volume (dehydration)
14
Q
Bernard-Soulier syndrome vs. Glanzmann thrombasthenia
A
Bernard-Soulier: BS = “Big Sucker” -> see enlarged platelets, thrombocytopenia (even tho it’s a qualitative disorder), adhesion impaired (GPIb deficiency)
Glanzmann thrombasthenia: normal # of platelets, aggregation impaired (GPIIb/IIIa deficiency) -> aggregation w/ ristocetin will be normal, but is decreased w/ addition of ADP
15
Q
What does uremia disrupt w/ respect to platelet fx?
A
Both adhesion and aggregation
16
Q
What activates factor VII and initiates extrinsic pathway?
A
Tissue thromboplastin
17
Q
How do you tell between hemophilia A and coagulation factor inhibitor?
A
Mixing normal plasma w/ pt’s plasma -> PTT corrected in hemophilia B but not in coagulation factor inhibitor (Ab against factor 8)
18
Q
Mode of transmission in most common vWF disease? What test will show up abnormal?
A
AD w/ variable penetrance -> decreased vWF
Abnormal ristocetin test: no agglutination (ristocetin can’t induce agglutination by causing vWF to bind platelet GPIb)
19
Q
What parameter is used to follow effect of liver failure on coagulation?
A
PT (even tho liver’s role is in vitamin K gamma carboxylation of factors II, VII, IX, X, C, S)
20
Q
DIC vs. disorders of fibrinolysis
A
Both present w/ bleeding and prolonged PT/PTT, differences are
DIC: increase in both FDPs (fibrin degradation products - so from fibrin OR fibrinogen) and D-dimers (from fibrin only), low platelet counts
Disorders of fibrinolysis (release of urokinase from radical prostatectomy activates plasmin, and liver cirrhosis reduces production of a2-antiplasmin): increased FDPs w/out D-dimers (no cross-linked fibrin to start w/), normal platelet counts
21
Q
Thrombomodulin (fx and origin)
A
Redirects thrombin to activate protein C -> inactivates factor V and VIII
Secreted by endothelium
22
Q
3 causes of endothelial cell damage
A
- Atherosclerosis
- Vasculitis
- High homocysteine (why B12 and folate deficiencies + cystathionine beta synthase predispose you to thrombosis)
23
Q
Pathogenesis of prothrombin 20210A
A
Inherited point mutation -> increased gene expression -> increased prothrombin -> increased thrombin -> thrombosis risk
24
Q
PTT doesn’t rise w/ standard heparin dosing. What disease should you suspect?
A
Antithrombin III deficiency (nothing for heparin to bind)
25
4 conditions you see target cells in
"HALT" said the hunter to his target
- hemoglobin C disease
- asplenia
- liver disease
- thalassemia
26
Composition of HbF, HbA, HbA2, HbH, Hb Barts
HbF: a2g2
HbA: a2b2
HbA2: a2d2
HbH: b4 (seen in a-thalassemia w/ 3 genes deleted)
Hb Bart: g4 (seen in a-thalassemia w/ 4 genes deleted -> very high affinity to O2 -> doesn't release O2 to tissue -> tissue hypoxia)
27
Diff between a-thalassemia and b-thalassemia causes?
a: gene deletion (chr 16)
b: gene mutation (chr 11)
28
Crewcut appearance on X-ray & chipmunk facies are seen in? And what creates these appearances?
Globin defects/deficiency -> so seen in b-thalassemia major and sickle cell
It's from massive erythroid hyperplasia -> expansion of hematopoiesis into skull & facial bones -> reactive bone formation
29
1 conditions where you see macrocytic anemia + megaloblastic change? 3 conditions where you see macrocytic anemia w/out megaloblastic change?
W/ megaloblastic change in rapidly dividing epithelial cells: B12 and folate deficiency
W/out megaloblastic change: alcoholism, liver disease, 5-FU drug
30
What molecule do you look at to distinguish between B12 and folate deficiencies as a cause of megaloblastic anemia?
Methylmalonic acid -> normal level in folate deficiency, accumulation in B12 deficiency (leading to subacute combined degeneration of spinal cord -> affects pos. column and lateral corticospinal tract)
31
What is corrected reticulocyte count used for?
Distinguishing between diff causes of normocytic anemia
Reticulocyte = young RBC -> % falsely elevated in anemia b/c of decreased total RBCs
Corrected reticulocyte % calculated by RC in % x Hct/45
If > 3% -> anemia is due to peripheral destruction (good marrow response -> marrow hyperplasia)
If < 3% -> anemia is due to underproduction
32
What does serum haptoglobin screen for?
Intravascular hemolysis -> haptoglobin decreased b/c it binds Hb and gets destroyed in liver w/ Hb
33
What is osmotic fragility test used for?
Dx of hereditary spherocytosis (increased fragility in those cells in hypotonic solution b/c of loss of membrane tethering proteins), sickle cell & thalassemia
Plot a graph of % hemolysis (y) vs. NaCl conc (x) -> graph of HS will shift right from normal (higher % hemolysis for any given NaCl conc) and graph of thalassemia will shift left (have target cells w/ extra room to fill things in), SS will shift left as well (decreased osmotic fragility even tho its mechanical fragility is increased
34
What's Howeell-Jolly body and what does it mean to have this floating arond?
RBC containing fragments of nuclear material
Means you no longer have functioning spleen to remove cells that should have been removed -> so seen in splenectomy (ie as tx for hereditary spherocytosis), sickle cell anemia (autosplenectomy)
35
What 2 circumstances do you see increased MCHC?
Increased MCHC -> Hb becomes more concentrated in the cells
Hereditary spherocytosis
Autoimmune anemia (cause of acquired spherocytosis)
36
What is metabisulfite screen used for?
Positive in both sickle cell disease and trait -> causes any amount of HbS to sickle
37
What are sucrose test and acidified serum test used for?
These tests activate complement
Sucrose test: screening test for PNH
Acidified serum test: confirmatory test for PNH
38
2 complications of PNH?
Iron deficiency anemia (from chronic loss of Hb in urine)
| AML (from likelihood to develop mutations in myeloid cells)
39
What other condition do you see spherocytes in besides hereditary spherocytosis?
Immune hemolytic anemia (both warm and cold agglutinin types)
40
Wht is it called when pathologic process (like metastatic cancer) replaces bone marrow and creates pancytopenia?
Myelophthistic process
41
What is basophilia classically seen in?
CML
42
The one bacteria that promotes leukocytosis (normally a virus thing) instead of elevated neutrophils?
Bordetella pertussis -> lymphocytosis-promoting factor blocks circulating lymphocytes from leaving the blood to enter LN
43
What is Downey cell? And what is it seen in?
Atypical T lymphocyte -> reactive CD8+ T cells from EBV infection (even tho EBV actually infects and lays dormant in B cells, T cells are the ones reactive)
44
What are heterophile antibodies
IgM that cross reacts w/ horse or sheep RBC -> detects EBV (monospot test)
Infectious mononucleosis w/ negative monospot -> consider CMV
45
What 2 things are you not supposed to do after having infectious mononucleosis?
```
Contact sports (splenomegaly makes capsule prone to rupture)
Take ampicillin -> maculopapular rash
```
46
Large cell w/ punched out nucleoli & positive nuclear staining for TdT
Lymphoblasts
| TdT = DNA polymerase
47
Large cell w/ punched out nucleoli, Auer rods & positive cytoplasmic staining for MPO
Myeloblasts
| Auer rods = crystal aggregates of MPO
48
2 subsets of AML that lack MPO?
Acute monocytic leukemia (gum infiltration)
| Acute megakaryoblastic leukemia (Down kids before age 5)
49
What do you call the disease where you have cytopenias + blasts < 20%
Myelodysplastic syndrome (not high enough blasts to be called AML) -> from prior exposure to alkylating agents or radiotherapy
50
Richter transformation?
CLL -> diffuse large B-cell lymphoma
| See enlarging LN or spleen
51
Dx for proliferation of cells that co-express CD5 and CD20/CD19?
CLL (mature B cell leukemia)
| CD5 normally on T cells, CD20/CD19 normally on B cells, but these cells are naive B cells
52
Dx for B cells positive for TRAP + expansion of splenic red pulp + dry tap on bone marrow aspirate
Hairy cell leukemia
| TRAP = tartrate-resistant acid phosphatase
53
Dx for punched-out bone lesions w/ generalized LAD + rash
Adult T-cell leukemia/lymphoma (assc. w/ HTLV-1 which is a Retroviridae esp in southern Japan)
If NO rash -> think MM
54
Dx for Pautrier microabscesses + lymphocyte w. cerebriform nuclei
Mycosis fungoides -> chronic leukemia of mature CD4+ T cells
Pautrier microabscesses: aggregates of neoplastic cells in epidermis
Sezary cells: lymphocyte w. cerebriform nuclei
55
What can CML transform into?
AML (2/3) or ALL (1/3) b/c mutation is in pluripotent stem cell
56
Distinguish CML from leukemoid rxn?
In CML, see negative LAP (leukocyte alkaline phosphatase) stain or reduced LAP level & increased basophils
57
One condition where you can see tear-drop RBC (dacrocytes)?
Myelofibrosis (myeloproliferative disorder - "atypical megakaryocytic hyperplasia") -> RBC stretched out to leave bone marrow (which is fibrosed from excess PDGF produced by excess megakaryocytes)
58
3 regions of hyperplasia in LAD and their assc.
1. follicular hyperplasia (B-cell area): RF, early stage of HIV (follicular dendritic cells are CD4+)
2. paracortex hyperplasia (T-cell area): viral infection
3. sinus histiocyte hyperplasia: cancer
59
What's tingible body and what does it mean if you don't see this in LN?
Macrophage containing debris
If don't see this in LN follicles -> disruption of normal LN architecture -> probably follicular lymphoma
Normal follicular hyperplasia will have tingible bodies
60
Reed-Sternberg cells + Owl-eyed nulei
Hodgkin lymphoma
61
Dx of CD15 and CD30 (no CD20 even tho it's B cells)
Hodgkin lymphoma
62
Lytic bone lesion + M pike + hypercalcemia + AL amyloid + rouleaux formation of RBC
MM
63
M spike + retinal hemorrhage or stroke + bleeding
Waldenstrom macroglobulinemia
similar features to MM but NO lytic bone lesion
M spike composed of IgM (instead of IgG and IgA like MM)
64
Cells that are CD1a+ and S100+?
Langerhans cell
65
Lytic skull defects + DI + exophthalmos in a child
Hand-Schuller-Christian disease (one of langerhans cell histiocytosis)
Also can see scalp rash
66
How does the chance of hemolytic disease of newborn and erythroblastosis differ w/ maternal blood type?
Maternal blood type A and B: mom has IgM Ab so doesn't cross placenta -> no hemolysis
Maternal blood type O: mom has IgG Ab so does cross placenta -> see cases of hemolysis
Unlike Rh, ABO disease can occur w/ first pregnancy
67
What are smudge cells seen in?
CLL
68
AIDs-related lymphomas?
Non-hodgkins, esp those assc w/ EBV -> Burkitt's, diffuse large cell
Primary CNS lymphoma (universally assc w/ EBV)
69
What virus is assc. w/ adult T cell leukemia and lymphoma?
HTLV-1
70
Most common cause of aplastic crisis in sickle cell pts & other chronic hemolytic disease pts?
Parvovirus B19 -> infects erythrocyte precursor cells
71
Pathogenesis and 3 causes of pure red cell aplasia (PRCA)
Pathogenesis: IgG autoAb or CD8+ T cells target erythropoietic precursors
Causes: thymoma (so should do chest CT in PRCA), lymphocytic leukemia, parvovirus B19 (detects anti-B19 IgM)
72
3 tumors that can produce EPO
Renal cell carcinoma
Cerebellar hemangioma
Uterine fibroids
73
Timeline of Hb types from conception to the time you switch to HbA?
Earliest Hb in fetus (yolk sac): zeta2epsilon2 (Hb Gower) -> then Hb Portland -> then Hb Gower 2
10-12 wks of gestation (liver now): HbF
FIRST 6 MOs of life (bone marrow): HbA gradually replaces HbF
74
How to differentiate bet. absolute and relative polycythemia and what are common causes of each? How do you tell bet. primary and secondary polycythemia?
Absolute polycythemia: increase in RBC mass -> from polycythemia vera or 2ndary erythrocytosis (to increased EPO, such as in hypoxia) -> tell apart from the fact that 2ndary polycythemia will only have increased RBC and nothing else, whereas there's elevation in all cell types in primary polycythemia vera
Relative polycythemia: normal RBC mass -> from dehydration, excessive diuresis (so think of this in pt who was recently treated for HF exacerbation!)
75
How low does O2 have to go to cause secondary polycythemia?
SaO2 < 92% (PaO2 < 65 mmHg)
76
What are 4 conditions assc. w/ autoimmune hemolytic anemia?
SLE & other autoimmune diseases
Hodgkin & non-Hodgkin lymphoma
Mycoplasma infection (cold agglutinins)
Infectious mononucleosis
77
Pt w/ hx of motor vehicle accent died of Strep pneumo despite being initiated on broad spectrum antibiotics. What process is impaired?
Bacterial clearance
Probably had spleen removed after that accident -> no clearance by splenic opsonizing Ab -> overwhelming postsplenectomy infection -> susceptible to encapsulated bac like Strep pneumo, H. influenzae, N. meningitidis
78
What anticoagulant should you use in acute coronary syndrome?
```
Unfractionated heparin -> has both anti-factorXa and anti-thrombin effects -> will treat existing clot + prevent propagation
The LMWH (Enoxaparin) and Fondaparinux only inhibit factor Xa -> no effect against thrombin
```
79
What happens to bleeding time, TT, PT, and PTT in dysfibrinogenemias?
Abnormalities in fibrinogen molecules -> excessive bleeding
Bleeding time is unaffected
TT, PT, and PTT are prolonged
80
What does factor XIII do? What happens to bleeding time, PT, and PTT in the deficiency state? What's the sx?
Factor XIII is a transglutaminase that cross-links fibrin polymers -> stabilizes clots
Deficiency: does NOT prolong bleeding time, PT, or PTT (altho might see delayed bleeding)
Sx: hemophilia-like bleeding (deep tissue)
81
Infant w/ anemia, jaundice, edema, nucleated erythrocytes, extramedullary hematopoiesis. What should you suspect?
Hemolytic disease of the newborn (esp Rh-related)
Don't think about infant immune system having anything to do w/ it -> their humoral defence first 6 mos come from maternal circulating IgG (placental) and mucosal IgA (breastfeed)
82
Why do defects in early steps of heme synthesis not cause photosensitivity but late steps do?
Photosensitivity is induced by formation of porphyrin-mediated superoxide free radicals from O2 upon exposure to sunlight
So if no porphyrin -> no photosensitivity (why it's not a component of AIP)
83
What is the difference bet. FFP and cryoprecipitate?
FFP: all coagulation factors (so give in warfarin toxicity)
Cryoprecipitate: only cold-soluble proteins -> factor VIII, XIII, vWF, fibrinogen, vitronectin
84
What do you give in rodenticide poisoning before sx shows? After sx shows?
Before sx shows: give syrup of ipecac to induce vomiting
After sx shows (bleeding stuff): rodenticide contains derivative of 4-hydroxycoumarin -> so sx are from depleted vit K-dependent clotting factors -> give FFP + Vit K1
85
What is "nuclear maturation defect due to defective DNA synthesis" a pathophysiologic mechanism of?
Megaloblastic anemia
86
Menorrhagia since menarche and frequent nosebleeds as a child. Most likely dx?
vW disease -> diff from ITP b/c in ITPbleeding is episodic (not chronic and unrelenting since childhood)
87
What does protein C deficiency predisposes to?
Recurrent DVT
88
What does wVF bind to on its two ends?
One end binds to GpIb (platelet glycoprotein)
| Another end binds to exposed collagen underneath damaged endothelium
89
What areas does diffuse large cell lymphoma commonly involve?
```
Waldeyer ring (oropharyngeal lymphoid tissue)
GI tract
```
90
What should you suspect in "waxing and waning" LAD?
Follicular lymphoma - most common indolent non-Hodgkin lymphoma in adults
91
What deficiency are you thinking about when alcoholics present w/ megaloblastic anemia?
Folate more common than B12 in alcoholics
92
What is hepcidin and how does it work?
Central regulator f iron homeostasis, secreted by liver -> it binds ferroportin and induces its degradation -> so get decreased intestinal iron absorption and decreased release from macrophages
If too much iron or inflammatory condition -> increased hepcidin to sequester iron
If hypoxia, more EPO, and anything that would make you wanna make more RBCs -> decreased hepcidin to release iron
93
Iron channels on enterocytes on the gut lumen side and blood side?
```
Gut lumen (apical): DMT-1
Blood side (basolateral): ferroportin (also on macrophages)
```
94
What makes RBCs blue w/ increased bone marrow erythropoeisis (such as after administering iron in iron deficiency anemia)
Reticulocytes -> blue on Wright-Giemsa stain is from reticular precipitates of residual ribosomal RNA
95
Dx of "diffuse medium-sized lymphocytes and proliferation fraction (Ki-67 fraction) of > 99%"?
Burkitt lymphoma
| High proliferation/high mitotic index is represented by Ki-67 fraction
96
Dx of lymphoma w/ "large cells, big nuclei, and prominent nucleoli" assc w/ HHV-8?
Primary effusion lymphoma
97
What's the difference bet. anemia caused by glycolytic defects vs. by HMP shunt defects?
Glycolytic defects: chronic hemolytic anemia
| HMP shunt defects: episodic hemolytic anemia
98
What kind of abnormal RBCs do you see in abetalipoproteinemia?
Acanthocytes
99
Dx of "diffuse sheets of large lymphocyttes w/ nuclei at least 5x the size of small lymphocytes"?
Large B-cell lymphoma
100
2 other names for leucovorin? For what drug can be used for prevention of myelosuppression?
Leucovorin = folinic acid = N5-formyl-tetrahydrofolate
Reverse toxicity of methotrexate but NOT 5-FU
Leucovorin bypasses the DHF reductase step (which is a step inhibited by methotrexate) so can be used to rescue it. But 5-FU blocks a different step (thymidylate synthetase)
101
Why can you use leucovorin to potentiate toxicity off fluoropyrimidines (like fluorouracil)?
Leucovorin strengthens the assc. of the drug w/ thymidylate synthase
102
What is defective in beta thalassemia?
transcription, processing, and translation of mRNA
| NOTHING TO DO w/ DNA synthesis!
103
When to use heparin or aspirin as prophylaxis?
Heparin: prevents DVT/PE in high risk situations (post. hip surgery, etc)
Aspirin: prevents recurrent coronary thrombosis and ischemic strokes
104
What's the defect in bare lymphocyte syndrome?
Expression of HLA II Ag on surfaces of Ag-presenting cells
105
What happens to Ig production in CLL? What happens to RBC?
Depressed Ig production
| Normochromic, normocytic anemia
106
What should you be thinking w/ eosinophilic casts in renal tubules + low Hb + back pain?
MM!
Eosinophilic casts are NOT the same as eosinophil cell cast
They're Bence Jones proteins (light chains)
107
What happens to kidney in chronic lead intoxication?
Chronic tubulointerstitial nephritis
108
Electrolyte complications after blood transfusion?
Hypocalemia & hypomagnesemia (esp if receive a lot of blood): citrate added to stored blood chelates Ca2+ and Mg2+
109
What happens to PT, PTT, platelet count & bleeding time in pts who bleed around catheter sites who's also happen to have ESRD?
ESRD -> think uremic platelet dysfx! -> so everything else is normal (incl. platelet count) but bleeding time is prolonged b/c it's a qualitative platelet disorder
110
Triad characteristics of PNH?
Hemolytic anemia
Hypercoagulability (eg Budd chiari)
Pancytopenia
111
What should you assc. low CD55 and CD59 w/?
PNH!
CD55 = DAF
CD59 = MAC inhibitory protein
112
What does thrombin time evaluate? What 2 conditions prolong thrombin time?
Evaluates rate of conversion of fibrinogen to fibrin
| Prolonged by heparin and dysfibrinogenemia
113
Dx of 5-yo who had fever + abd pain + diarrhea mixed w/ small amount of blood who later develop pallor and oliguria?
Recognize this as a two out of HUS triad! = acute renal failure & microangiopathic hemolytic anemia
So should expect thrombocytopenia (last part of triad) -> prolonged bleeding time
114
What do you see on spleen histology in young vs. old sickle cell pts?
Younger pts: congestion from splenic sequestration (can be emergency - rapidly enlarging spleen and hypovolemic shock)
Early adulthood ohward: probably will see scarring, fibrosis, and atrophy of spleen (autosplenectomy completed)
115
What kind of anemia is assc. w/ sickle cell disease and other hemolytic anemias?
Folic acid deficiency from increased erythrocyte turnover -> macrocytic anemia
116
What drugs are assc. w/ microangiopathic hemolytic anemia?
Cisplatin, cyclophosphamide
117
A girl w/ Hb abnormality that shifts O2 dissociation curve to the left. What's the sequelae of this?
Erythrocytosis 2ndary to EPO release
Don't even think of HbF generated from sickle cell in this scenario -> the MAIN defect is this weird Hb that shifts the curve left; in SC the main defect is HbS which actually shifts the curve right
118
What do you find in antiphospholipid Ab syndrome besides hypercoagulability?
Paradoxical PTT prolongation + spontaneous abortions
119
What's really wrong w/ HbS?
There's altered hydrophobic part of beta chain that fits into a complementary site on alpha chain of another Hb -> allows hydrophobic interaction among Hb molecs
120
What is Hb M disease?
Mutation in heme binding pocket (either alpha or beta) -> histidine replaced w/ tyrosine -> iron phenolate complex resists reduction of iron to ferrous state -> methemoglobin
121
What 4 things should you think about w/ burr cells?
Traumatic hemolysis from mechanical damage (like prosthetic valve)
Microangiopathic hemolytic anemia -> will have thrombcytopenia too
Uremia
Pyruvate kinase deficiency
122
Who else besides Down are at an increased risk of developing acute leukemia?
```
Ataxia-telangiectasia
NF1
Patau
Bloom syndrome
Fanconi anemia
```
123
What are Pappenheimer bodies and in what condition do you see them?
Iron inclusions
| Seen in sideroblastic anemia
124
What kind of anemia does B6 deficiency cause?
```
Sideroblastic anemia (remember that it's involved in the first ALA synthase step of heme synthesis)
Hypochromic, microcytic
```
125
What does intravascular hemolysis do to serum LDH?
Increases it
126
Recurrent otitis media/sinusitis/bronchitis/pneumonia + anaphylactic rxn following blood transfusion even when it's O-. Dx?
IgA deficiency -> blood products contain small amount of IgA and ppl w/ IgA deficiency often have IgG Ab against IgA
So DON'T use gamma-globulin prep for tx of these pts!
127
Pt w/ obvious sign of hemophilia (deep tissue bleeding and such). Administer what molec would make them clot?
Things that are downstream from what they lack -> so thrombin
Don't be distracted by choices like factor XII thinking maybe that's what they lack -> if sx look like hemophilia, it's prob hemophilia, and those are either VIII or IX -> so XII would be upstream of that and won't clot
128
What 2 parasites cause microcytic anemia? How do you get them and how do you tx them?
Ancylostoma and Necator (hookworms)
Larvae penetrate skin
Tx: bendazoles or pyrantel pamoate if pregnant
129
What is a sure finding in ppl w/ sickle cell TRAITS?
They're protected from plasmodium falciparum
They do NOT have abnormal peripheral smears, elevated reticulocyte count, increased MCHC (only seen in homozygous), or painful crises -> they're generally asymptomatic besides hematuria
130
Fever and chills, hypotension, dyspnea, chest/back pain, hemoglobinuria after blood transfusion. What HSR?
Acute hemolytic transfusion -> type II HSR (Ab-mediated) -> but cell lysis is complement mediated!! (after IgM bind Ag and lead to complement activation)
Don't think of complement mediation as being exclusively type III HSR
131
Drugs that inhibit ADP in platelet aggregation? PDE? IIb/IIIa?
ADP: ticlodipine and clopidogrel
PDE: dipyridamole and cilostazol
IIb/IIIa: abciximab, eptifibatide, tirofiban
132
Dx of B cell tumor w/ predominantly small cleaved cells (centrocytes) and few large noncleaved cells (centroblasts)?
Follicular lymphoma
133
How does sickle cell disease usually present in young children?
Dactylitis (painful swelling of hands and feet) from vasoocclusion
134
Fever and sweating that occur every 48 hrs. What malaria species?
P. vivax and P. ovale -> erythrocyte lysis is what causes relapsing fever and sweating
Don't forget to use primaquine on top of chloroquine to eliminate latent hepatic infection (hypnozoites)!
135
Graph of blood level (y) vs. time (x) in pt w/ pernicious anemia who's being given IM B12. What parameter increases steadily as time passes and what parameter rises to peak then falls?
Rises steadily: Hb
| Peaks then falls: reticulocyte count
136
What is chronic lymphedema a risk factor of?
Chronic lymphedema is classically from radical mastectomy
| Risk factor of cutaneous angiosarcoma (infiltration of dermis w/ slit-like abnormal vascular spaces)
137
Diff in features of HUS and TTP? How do you treat them?
Both present w/ triad of fever + thrombocytopenia + microangiopathic hemolytic anemia
TTP: usually adults w/ predominant neurological sx
HUS: usually children w/ renal involvement
Tx both w/ emergent plasmapheresis
138
A particular phospholipid causes bronchoconstriction, vasoconstriction, platelet aggregation w/ microthrombus formation. What's the substance and what's the effector?
PAF -> acts thru Gq and PLC pathway (Ca2+)
139
What are sx of iron deficiency anemia that might not seem super obvious?
Dry mouth, atrophy of tongue papillae, alopacia, glossal pain, pagophagia
140
32-yo w/ fatigue&pallor + white patches on gingival and buccal mucosa + retinal hemorrhage. What's the dx?
Don't think of HIV
Think of acute leukemia -> sx are from pancytopenia -> fatigue and pallor from anemia, oral thrush from leukopenia, and retinal hemorrhage from low platelets
141
How do you know it's ITP when you have low platelets?
Increased # of megakaryocytes (so might say something like "anikopoikilocytosis" which means RBCs of varying shapes and sizes)
