Heme - FA Patho p396-427 Flashcards
(153 cards)
1
Q
Name heme pathologies that show an X linked inheritance pattern?
A
G6PD Deficiency, Sideroblastic Anemia, Hemophilia A & B
2
Q
Copper deficiency can lead to this heme pathology?
A
Microcytic Sideroblastic Anemia
3
Q
Clinical presentation of a pt with Iron Deficiency Anemia
A
Conjunctival Pallor, Spooned Nails (koilonychia)
4
Q
Describe the genetic defect in Alpha thalassemia? Which mutation is affiliated with which population?
A
Deletion in alpha globin gene (Ch 16). Cis deletion prevalent in Asians, Trans deletion prevalent in Africans
5
Q
Describe the genetic defect in Beta thalassemia? Which mutation is affiliated with which population?
A
Point mutation in the beta globin gene promoter and splice sites (Ch 11). Prevalent in Mediterranean populations
6
Q
What causes formation of Heinz bodies?
A
Oxidation of Hgb -SH groups to -S-S leads to Hgb precipitation = Heinz bodies
7
Q
Crew cut on skull XR, Chipmunk Facies, Extramedullary hematopoiesis
A
B thalassemia major
8
Q
Which virus can induce aplastic crisis (Clinical Presentation)? Name the heme pathologies associated with it.
A
Parvovirus B19 infection leads to slap cheek appearance in pts Patients with aplastic crisis: SCA, B Thalassemia
9
Q
What is basophilic stippling?
A
Remnants of rRNA in RBCs due decreased degradation
10
Q
Clinical Presentation of Lead Poisoning?
A
Lead lines on gums (Burton lines) and long bone metaphyses Encephalopathy Abdominal colic Dropping of wrist and foot
11
Q
Name the enzymes inhibited by Lead
A
Ferrochelatase, ALA Dehydratase
12
Q
DOC for Lead poisoning in Adults?
A
Dimercaprol, EDTA
13
Q
DOC for Lead poisoning in Children?
A
Succimer
14
Q
What is the most common cause of Sideroblastic Anemia ? Is it Irreversible?
A
Alcoholism which is reversible if given B6 as Tx
15
Q
Which three drugs are associated with folate deficiency?
A
Methotrexate, Trimethoprim, Phenytoin
16
Q
Where do you see subacute combined degeneration of the spino cerebellar tract?
A
B12 def - along with lat corticospinal tract, dorsal column dysfunction
17
Q
How do you differentiate Orotic aciduria from Ornithine transcarbamylase def?
A
There is no hyperammonemia with Orotic aciduria
18
Q
Most common causes of macrocytic anemia that is not megaloblastic?
A
Alcoholism, lIver disease, hypothyroidism,
19
Q
Defective enzyme in Orotic aciduria? Substrate?
A
Orotic Acid –> UMP, done by UMP synthase
20
Q
Short stature, thumb and radial defects?
A
Diamond Blackfan anemia and Fanconi anemia
21
Q
Two heme diseases with inc HbF?
A
B thalassemia major, Diamond blackfan anemia
22
Q
dec haptoglobin, inc LDH, target cells seen in ?
A
intravascular hemolysis
23
Q
Urine test shows Hgb, hemosiderin, and urobilinogen?
A
Intravacular hemolysis
24
Q
iron def anemia, esophageal webs, dysphagia
A
Plummer Vinson syndrome
25
Which 3 GI issue can lead to iron def anemia?
Malabsorption - celiac, etc
GI bleed - ulcers, colon cancer
26
Genetic mutation in B thalassemia?
Point mutation in splice site and promoter sequences - C replaces Guanine before AUG seq -- dec mRNA
27
Type of genetic defect in sideroblastic anemia?
X linked defect in delta- ALA synthase - req B6 as cofactor
28
Rx for Sideroblastic anemia
B6 (pyridoxine)
29
Inc risk of gallstones and BM hyperplasia with what type of hematological disordeR?
extravascular hemolysis
30
Iron, TIBC, ferritin - inc or dec in ACD (anemia of chronic disease)?
Dec FE, TIBC (indicator of transferrin) Inc Ferritin
31
What differentiates Diamond Blackfan from Fanconi Anemia?
Fanconi has cafe au lait spots
32
Is retic # inc or dec with aplastic anemia?
Dec
33
Most common congenital cause of Aplastic anemia?
Fanconi anemia
34
MCV and MCHC in heriditary spherocytosis ?
Inc MCHC (bc no central pallor) and normal to low MCV
35
Dec ATP production is a part of the pathogenesis of what heme disorder?
Pyruvate kinase deficiency - dec ATP will lead to rigid RBCs --\> extravasc hemolysis
36
What amino acid mutation in HbC disease?
glutamic acid to lysine in B globin chain
37
CD marker in Paroxysmal nocturnal hemoglobinuria?
CD 55/59
38
Tx for Paroxysmal nocturnal hemoglobinuria?
Eculizumab - complement inhibitor
39
Pathogenesis of PNH?
Impaired synthesis of GPI anchor for decay accelerating factor that protects RBC from complement
40
Why are newborns normally asymptomatic in sickle cell?
They have higher hbF and lower HbS
41
Why is there a crew cut skull in thalassemia major and Sickle cell?
Marrow expansion due to inc erythropoiesis
42
What renal issue in Sickle cell and why?
Renal papillary necrosis - due to dec pO2 in papilla
43
Why give hydroxyurea in Sickle cell?
Inc the amount of HbF
44
Sickle cell osteomyelitis is assoc with which bact?
Salmonella paratyphi
45
What Ig is seen in Warm AIHA and Cold AIHA?
IgG and IgM
46
Which 3 pathologies are associated with cold agglutination AIHA?
Mycoplasma pneumoniae, Infectious Mono, CLL
47
Drug assoc with Warm AIHA?
methyldopa (alpha)
48
Microangiopathic hemolytic anemia seen in which diseases? (6)
DIC, TTP, HUS, SLE, Malig HTN, HELLP
49
Two diseases associated wtih macroangiopathic anemia?
Prosthetic heart valves and aortic stenosis
50
What is mixed with patients blood in Direct coombs test?
anti Ig antibody
51
What in patients serum will yield a positive result in indirect coombs test?
If serum has anti RBC surface Ig, RBC will agglutinate = pos result
52
What is the difference in Labs between ACD and Hemochromatosis?
Both have low TIBC and and high ferritin, but Hemochromatosis has high Fe levels and also high %transferrin sat'n therefore.
53
Neutropenia cut off point?
\<1500 cell/mm3
54
Lymphopenia cut off point?
\<1500 cell/mm3 (\<3000 cells/mm3 in children)
55
Which drug causes neutrophilia, inspite of eosinopenia and lymphopenia?
Corticosteroids (dec activation of neutrophil adhesion molecules, dec migration out, stay in blood - However, tend to keep eosinophils in l.n and cause lymphocyte apoptosis )
56
Enzymes def in lead poisoning?
ALA DH, and Ferro chelatase - "Dont eat DAH Fucking Lead!"
57
5 Ps of Acute intermittent porphyrias?
Painful stomach, Port wine colored urine, Polyneuropathy, Psych issues, Precipitated by drugs, etc
58
Tx for AIP? (2) Why?
Glucose and Heme, they inhibit ALA synthase
59
Enzyme def in AIP?
PBG deaminase
60
Which HIV drugs are CI with Acute Intermittent Porphyria?
NNRTIs - Nevirapine, Efavirenz (p450 inducer)
61
Def enzyme in Porphyria cutanea tarda?
UPG decarboxylase
62
Which is the most common Porphyria?
PCTarda
63
Which pathology is assoc with def in ALA synthase?
Sideroblastic anemia - S = synthase and sideroblastic
64
Which porphyria is assoc with photosensitivity?
PCT
65
What causes cell death due to peroxidation of membrane lipids?
Fe poisoning
66
Symptoms of Fe poisoning?
n/v, gastric bleeding, lethargy, scarring leading to GI obstruction
67
Drugs used for Fe poisoning?
Chelation - IV deferoxamine, oral deferasirox
68
Which factors are tested in PT?
Factors I, II, V, VII, and X
69
Which factors are not tested in PTT?
All factors except VII and XIII
70
Inheritance patterns of all three hemophilias?
Hemophilia A and B - XLR, and C is AR
71
Tx for Hemophilia A?
Desmopressin + factor VIII concentrate
72
Vitamin K def will have an increase in what lab tests?
PT and PTT, Bleeding time is Normal
73
What parts of the coag pathway are affected by Vit K def?
F II, VII, IX, X, and Prot C and S
74
Which 3 hemat diseases have an issue with platelet plug formation?
Both Bernard Soulier, Glanzmann thrombasthenia, vW disease
75
Which platelet disorder has normal platelet count?
Glanzmann , vW disease
76
With which heme disorder will you potentially see enlarged platelets?
Bernard Soulier - release of relatively immature platelets to replace loss.
77
Which heme disorder is associated with inc BUN ?
TTP, DIC, Hemolytic Uremic Syndrome, PNH, Sickle Cell, porphyria, Multple Myeloma
78
What enzyme activates vit K?
vit K epoxide reductase
79
Normal bleeding time?
2-7 min
80
Normal PT time?
11-15 sec
81
Normal PTT time?
25-40 sec
82
Which two hematological disorders affect GpIIb/IIIa? How do they effect it?
Glanzmann - dec levels of GpIIb/IIIa Immune Thrombocytopenia - anti GpIIb/IIIa antibodies
83
Which hemat disorder show inc megakaryocytes on bone marrow biopsy?
ITP
84
Which hemat disorder has a def of metalloprotease?
TTP - ADAMTS 13 = vWF metalloprotease
85
Schistocytes are seen in which platelet disorder? why?
TTP - due to microthrombi formation (inc vWF multimers --\> Inc platelet adhesion --\> Inc platelet aggregation and thrombosis) DIC, HUS
86
Which (3) hemat disorders have neurological symptoms?
TTP - pentad of neuro/renal symptoms, fever, thrombocytopenia, fever, microangiopathic hemolyic anemia
Lead poisoning
B12 def
87
What is the difference between HUS in adults and children?
Children tend to have diarrhea, adults do not.
88
Most common cause of dec platelet #?
ITP
89
Which blood tests are elevated in vW disease?
BT inc, and PTT may be normal or Inc
90
Explain the Ristocetin test result of vW Disease?
No platelet aggregation, without vW.
91
Which two hemat diseases are treated with desmopressin?
Hemophilia A, vW disease (affiliated with FVIII)
92
Causes of DIC?
Sepsis, Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion, snake bite
93
Lab values of DIC?
Inc fibrin degradation, dec fibrinogen, Dec factors V and VIII
94
How does Antithrombin deficiency affect PT, PTT, and thrombin time? It can affect which of those values following an admin of which drug?
No direct effect on PT, PTT, or thrombin time. However, it can decrease the level of PTT increase following Heparin admin. (PTT is normally used to follow Heparin admin)
95
Nephrotic syndrome is associated with which two coagulation disorders?
DIC and Antithrombin deficiency
96
What type of mutation in FV Leiden?
DNA point mutation, G --\> Arg506Gln
97
The mutation is FV Leiden def stops its degradation by what protein?
Prot C
98
Most common cause of hypercoagulability in Caucasians?
F V Leiden
99
What issue specific to women must one be concerned about in terms of FV Leiden def?
1) Inc risk of PE with OCP 2) Recurrent pregnancy loss
100
Prot C and S def will lead inability to inhibit which factors?
Factor Va and VIIIa
101
Be careful with prescribing which anti-coag when it comes to Prot C or S def?
Warfarin - inc risk of skin necrosis
102
location of Gene mutation of Prothrombin?
Mutation in 3' UTR
103
Risk associated with blood transfusion?
transfusion reactions, Fe overload (could lead to 2ndary hemochromatosis) hypocalcemia, hyperkalemia
104
Viruses associated with Hodgkins and Non Hodgkins lymphoma?
Hodkins - EBV
Non Hodkins - EBV, HIV, HTLV
105
Which type of lymphoma is assoc with B symptoms? What are those symptoms?
Both hodgkin's and non hodgkin's low grade fever, night sweats, weight loss
106
CD # of Reed-Sternberg cells?
CD15, CD30
107
What are the two genes affected in Burkitts? (not the translocation itself, but the products of them)
Chr 8 - c -myc Chr 14 - Ig heavy chain
108
Tingible body macrophages associated with?
Burkitts
109
What type of lesion is seen in the sporadic form of Burkitts?
Pelvis and abdomen lesions
110
Most common type of Non Hodgkin's in adults?
Diffuse large B cell lymphoma
111
Why can blood transfusions lead to tingling sensations and paresthesias?
hypocalcemia
112
Gene products of the genes translocated in Mantle cell lymphoma?
Chr 11 - cyclin D1 (G1--\> S) Chr 14 - Ig heavy chain
113
What are the gene products of the gene translocation of Follicular lymphoma?
Chr 14 - Ig heavy chain Chr 18 - bcl2
114
Which lymphoma presents with intermittent pain of lymph nodes?
Follicular lymphoma
115
What are the cell types in grades 1-3 of Follicular lymphoma?
Grade 1 - small cleaved cells Grade 2 - Mixed Grade 3 - large cells
116
Name an AIDS defining lymphoma?
Primary Central Nervous System Lymphoma
117
Presentation of PCNSL? Assoc with which virus?
Confusion, memory loss, seizures - assoc with EBV
118
3 diseases with mass lesions in CNS?
Toxoplasmosis, PCNL, GBM
119
Which lymphoma is associated with cutaneous lesion and tremor?
ATCL (Adult T cell ), tremor due to hypercalcemia, also associated with lytic bone lesions
120
Which condition is associated with lymphocytes with cerebriform nuclei? What CD #?
Mycosis Fungoides, CD 4+
121
Ig associated with M spike in Mult myeloma and in Waldenstrom macroglobulinemia?
MM - IgG, IgA WM - IgM
122
What does the M in M spike mean?
M is not for IgM, but for Monoclonal - one clonal type of Ig
123
What type of amyloidosis seen in MM?
Primary (AL)
124
What are Bence Jones proteins?
Ig light chains
125
Name two signs of MM you'd see in a blood smear?
Stacked RBC (rouleaux) and plasma cells with "clock face" chromatin
126
The intracytoplasmic inculsions of plasma cells in MM contain what?
Ig
127
Clinical diff between MGUS and MM?
There are no Crab findings - C - HyperCalcemia R - Renal issues (due to BJ prot blocking tubules) A - Amyloid, Anemia (plasma cells taking BM) B - Bone lytic lesions, Back pain, Bence- Jones
128
What hematological issue has visual defect, bleeds, strokes, Raynauds?
Waldenstrom Macroglobulinemia - Sx from hyperviscosity
129
Neutrophils with bilobed nuclei seen after chemo?
Pseudo Pelger Huet anomaly
130
Causes of MDS?
de novo mutations, environmental (radiation, benzene, chemo)
131
MDS can lead to what type of leukemia?
AML
132
What is the Warburg effect, esp in relation to Burkitt's
Cmyc - nucl phosphated prot --\> transcription of activator that controls cell proliferation, differentiation, and apoptosis --\> leads to upreg of anaerobic gycolysis = Warburg Effect Warburg Effect - is the observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, rather than by a comparatively low rate of glycolysis followed by oxidation of pyruvate in mitochondria as in most normal cells.
133
Desmopressin also used in what neuro issue?
Enuresis
134
What disease looks very similar clinically to FV Leiden def?
Anti phospholipid syndrome
135
Deferoxamine is also used in what chemo drug tox?
Doxorubicin
136
path associated with recurrent otitis media with mass involving the mastoid bone?
Langerhans cell histiocytes
137
2 options to correct factor def?
cryoprecipitate and fresh frozen plasma
138
what is the name for leukemic cell infiltration to skin?
leukemia cutis
139
in ALL what two parts of organs are easily affected and why?
CNS and testes
140
in ALL, what CD marker is found in pre-B cell only?
CD10
141
in ALL, what is the marker for both pre-T and pre-B cell?
tDt
142
what path mimics the SVC syndrome?
ALL (mediastinal mass)
143
name 2 blood malignancies associated with splenomegaly?
CML, Hairy cell leukemia, Myelofibrosis
144
name 2 blood malignancies associated with dry tap of the bone marrow aspiration
hairy cell leukemia, myelofibrosis
145
in myelofibrosis, what is responsible for the obliteration of bone marrow?
inc fibroblast activity
146
what path is associated with intense itching after shower ?
polycythemia vera due to inc basophil
147
what leukemia is associated with CD5 marker?
small lymphocytic lymphoma/chronic lymphocytic leukemia
148
in CML, LAP is low why?
low activity in mature granulocyte (vs. leukemoid reaction when LAP is high)
149
3 paths associated with inc ectopic EPO
1. renal cell carcinoma 2. hepatocellular carcinoma 3. hydronephrosis
150
3 examples with dec O2 sat leading to high EPO
1. lung dz 2. congenital heart dz (Eisenmenger) 3. high altitude
151
in heparin induced thrombocytopenia what is the target of the IgG antibodies?
heparin bound platelet factor 4
152
what is the most common adult leukemia?
SLL/CLL
153
what gene is activated in mantle cell lymphoma?
cyclin D1
