HemePath Flashcards
1
Q
Hemophilia
CF:
Tx:
A
Hemophilia
Type: def factor
A: VIII
B: IX
C: XI
- hemarthroses, easy bruising, inc bleeding after trauma/ surgery
- Tx: Desmopressin c resp factor concentrate
2
Q
Acanthocytes/ spur cells
A
Liver disease
A betalipoprotenemia
3
Q
Echinocytes/ burr cells
A
ESRD
Pyruvate kinase def
Liver disease
4
Q
Dacrocytes/ tear drop cells
A
Bone marry infiltration, Myelofibrosis
5
Q
Schistocytes/ helmet cells
A
Dx for traumatic mech
Microangiopathic:
DIC
TTP/HUS
HELLP
Microangiopathic anemia
mechanical hemolysis: prosthetic heart valves & Aortic stenosis
6
Q
Degmacytes/ bite cells
A
G6PD def
7
Q
Spectrum mutation
A
RBC memb protein gene
Hereditary elliptocytosis
8
Q
Macro-ovalocytes
A
Megaoblastic anemia
9
Q
Target cells
A
HALT
HbC
Asplenia
Liver diseases
Thalassemia
10
Q
Ringed sideroblasts
A
Sideroblastic anemia:
Lead poisoning
Myelodysplastic syndrome
Alcoholism
MAL
11
Q
Howell-Jolly bodies
A
Hyposplenia (SCA)
Asplenia
Basophillic nuclear remnants: no iron
12
Q
Basophillic stippling
A
Sideroblastic anemia
Thalassemia
Basophillic ribosomal ppt: no iron
13
Q
Pappenheimer bodies
A
Sideroblastic anemia
Basophillic granules: IRON
14
Q
Heinz bodies
Stain?
A
G6PD def
+iron
Crystal violet stain
15
Q
Anaemia classification
A
Normocytic : MCV 80-100 fL — Hemolytic & non-hemolytic
Microcytic: MCV <80 fL — TAIL
Macrocytic: MCV >100 fL — Megaloblastic & Non-megaloblastic
16
Q
Corrected Reticulocyte count / Reticulocyte Index
A
RI = reticulocyte% x actual/ normal Hct
N Hct ~ 45%
- measure of BM response to anemia
17
Q
Microcytic anaemia
A
TAIL
Thalassemia
ACD
Iron def anemia
Lead poisoning
18
Q
Iron def anaemia labs
A
Iron: dec TIBC: inc Ferretin: dec RDW: inc RI: dec
19
Q
Normocytic non-hemolytic anaemia
A
Dec RI
Early iron def anemia
Anemia of chronic disease
Aplastic anemia
Chronic kidney disease
20
Q
Normocytic hemolytic anemia : intrinsic
A
- Membrane defects: Hereditary spherocytosis Paroxysmal nocturnal hemoglobinuria
- Enzyme deficiencies
G6PD deficiency
Pyruvate kinase deficiency - Hemoglobinopathies
Sickle cell anemia
HbC disease
21
Q
Normocytic hemolytic anemia: extrinsic
A
Autoimmune
Microangiopathic
Macroangiopathic
Infections
22
Q
Macrocytic megaloblastic anaemia
A
- Defective DNA synthesis
Folate deficiency
Vitamin B12 deficiency
Orotic aciduria - Defective DNA repair
Fanconi anemia
23
Q
Macrocytic non-megaloblastic anaemia
A
Diamond-Blackfan anemia
Liver disease
Alcoholism
24
Q
Lead poisoning
- Path
- Sx
- Tx
A
- ferochelatase & ALA synth inhib
- LEAD
Lead/ Burton lines on gingivae & long bones
Encephalopathy & Erupythrocytic basophillic stippling
Abd colic & Sideroblastic Anaemia
Drop— wrist & foot drop - I line: Dimercaprol & EDTA
Chelation in kids: Succimer
25
Sideroblastic anaemia
- Etiology
- Inheritsnce
- RF
- Labs
- Tx
- ALA synth gene defect
- XL
- Alcohol. Lead poisoning. B6 def. Cu def. Drugs ISONIAZID, LINEZOLID
- iron : inc.
TIBC: dec
Ferretin: inc
Ringed Sideroblasts
- Pyridoxine, B6
26
Alpha-Thal
| Genetics
Alpha globin gene deletion on chrom 16
27
Alpha-Thal variants
aa/a- : a-Thal minima
a-/a- : a-Thal minor, cis. (mild anaemia)
aa/- - : a-Thal minor, trans
- -/-a : HbH (beta4)
- -/ - - : Hb Barts (gamma4). (Hydrops Fetalis)
28
Beta-Thalassemia genetics
Point mutations on splice sites & promoter seq
| Chrom 11
29
Beta-Thalassemia variants
1. B-minor: dec beta chain production.
- inc HbA2
2. B-major: beta chain absent
- inc HbF, HbA2
- crew-cut app & chipmunk facies
- inc risk of Aplastic anemia (ParvoB19)
3. B-Thal heterozygous/ HbS
30
Anemia of chronic diseases
| Labs
Hepcidin: inc
Iron: dec
TIBC: dec
Ferretin: inc
31
PNH
Genetics:
CF:
Dx:
Tx:
Genetics: PIGA gene mutation > dec CD55/DAF—CD59 meadiated complement inhib > inc RBC lysis
CF: Pancytopenia, hematuria in the morning
Dx: Coombs -
Tx: Eculizumab (against C5)
32
G6PD def
Genetics:
Etiology:
CF:
Labs:
Genetics: XLR
Etiology: DSixP - Dapsone, Sulfa drugs, Primaquine, Fava beans
CF: back pain, hemoglobinuria
Labs: Heinz bodies & Bite cells
33
Macrocytic anemia causes
| SE drugs
```
PMSH
Phenytoin
Methotrexate
Sulfa drugs
Hydroxyurea
```
34
Triphalangeal thumbs w Rapid-onset Ana is within 1st year of life
Diamond-Blackfan anemia
35
RBC memb protein defects
Hereditary Spherocytosis
-ankyrin, band, spectrin,
36
Hereditary Spherocytosis
Genetics:
Etiology:
CF:
Labs:
Genetics: AD
Etiology: RBC memb defect (spectrin, ankyrin, band)
CF: spleenomeg, aplastic crisis, extravasc hemolysis
Labs: inc osmotic fragility test. Inc MCHC. N/dec MCV
37
Hemolytic anemia in newborn
Pyruvate kinase def
AR
In 2,3 BPG
38
Point mutation in beta-globin gene
SCA
39
Salmonella osteomyelitis complication of
Sickle cell crisis
40
SCA labs
Dec HbA
Inc HbS
Inc HbF
41
Glutamic acid got lysine mutation in beta-globin chain
HbC
42
Direct Coombs test
Anti-IgG (Coombs reagent) + pt RBC
+ve if RBC coated w Ig agglutinate
-ve if no agglutination
43
Indirect Coombs test
Pt serum + normal RBC
+ve if serum has anti-RBC surface Ig & agglutinates
44
AIHA
Types:
CF:
Dx:
Tx:
Coombs+
Warm: IgG mediated aRBC agglutination & alpha-Methyldopa
Cold: IgM mediated RBC agglutination. Blue fingers & toes.
Seen in CML, M.pneumonia, Mononucleosis
Tx: Rituximab
45
Malaria, Babesia
Extrinsic hemolytic anemia
46
HSR against plasma proteins in transfused blood
Type I
#MC IgA deficient pts w anti IgA ab
47
Fever, chills, dec BP, chest/back pain & hemoglobinuria following a blood transfusion
HSR type II
Acute hemolytic transfusion reaction
- complement mediated cell lysis
48
Vascular deposits of immune complex
HSR type III
SLE, RA
49
Pre-existing ab that bind antigens & activate complement, see in?
Type II HSR
ABO incompatibility
Acute hemolytic transfusion reaction
50
Head & neck cancer spread to?
Ant cervical/ Jugular LN
51
JAK2 mutation
Polycythemia Vera
- clinal prolif of erythrocytes : inc Hct
52
Glycoprotein produced by peritibular fibroblasts in renal cells
EPO
- only in response to hypoxia
53
High-volume blood transfusion (>9 units/hr) complications
Hypocalcemia (d/t Ca2+ chelation by citrate anticoagulant in stored blood. Also occurrs in low transfusion in liver diseases since citrate metabolized by liver)
Dec coagulation factors
Vol overload
54
Blood transfusion reactions & electrolyte abn
Hypercalcemia:
Hyperkalemia:
Hypercalcemia: rapid blood transfusion (d/t Ca2+ chelation by citrate anticoagulant)
Hyperkalemia: ABO incompatibility ( release of intracellular K)
55
SE of synthetic EPO
| Epoetin, Darbepoetin
Iron def anaemia d/t inc RBC production & rapid iron depletion
56
Hb switched to fetal form in?
Hydroxyurea Tx in SCA since HbF unaffected by sickling
57
What improves nuclear maturation
B9 & B12
58
Tumor lysis syndrome electrolytes
Inc K,
Inc PO4
Inc uric acid
Inc Lactate dehydrogenase
59
#MC & fatal presentation of neonatal Vit K def
Inc intracranial P d/t intracranial hemorrhage
60
Polypeptide regulator of iron hemostasis
Synth by?
Hepcidin, liver
61
Hepcidin
Release:
Inhibition:
Inc synth d/t: inc iron levels & inflamm
Dec synth d/t: hypoxia, inc erythropoesis
62
Neutropenia
Absolute neutrophil count <1500cells / mm3
63
Corticosteroid
| Inflamm response pathogenesis
Neutrophilia (d/t dec activation of neutrophil adhesion molecules, dec migration out of blood to sites on inflamm: dec inflamm response)
Eosinopena & lymphopenia (inc sequestration of eosinophils in LN & apoptosis of lymphocytes)
64
Leukoerythroblastic shift
Left shit
Inc immature cells
Seen in anemia (physiologic), fibrosis & BM tumors
65
Heme synth disorders
Enzyme: disease
ALA synth : Sideroblastic anemia
ALA dehydratase : lead poisoning
Porphobilinogen deaminase: AIP
Uroporphyrinogen decarboxylase : PCT
66
#MC porphyria
RF:
Etiology:
CF:
Tx:
PCT
- exacerbated by alcohol
- Hep C
- TEA-COLOURED URINE. blistering, photosensitivity, hyperpigmentation
- avoid sun, phlebotomy, Hydroxychloroquine
67
vWF def
- labs
- CF
- Tx
Platelet count : N
Ristocetin cofactor assay : abn
Factor VIII def
PTT inc
Menorrhagia, gingival bleeding
OCP, Desmopressin
68
VWF def vs Bernard-Soulier syndrome
Labs
N plasma + pt plasma + ristocetin
= agglutination in vWF def
= no agglutination in BSS since GpIb R deficient
69
Def of GpIb receptors
CF:
Tx:
Bernard-Soulier Syndrome
Thrombocytopenia, enlarged platelets, mucocut bleeding
70
Def of GpIIb/IIIa receptors
CF:
Tx:
Glanzmann thrombasthenia
Mucocut bleeding
71
Hageman (XII) factor def
Inc PTT
thromboemboli
72
Meds causing Sideroblastic anemia
LIC
LINEZOLID
Isoniazid (inhib pyridoxine phosphokinase: B6 to Pyridoxal 5’po4, cofactor for d-ALA synth)
Chloramphenicol
73
Heme metab
Heme -heme oxygenase- Biliverdin -biliverdin reductase- Unconj bilirubin -bilirubin glucoronyl transf- Conj bilirubin -Bact dehydrogenase- Urobilinogen — stercobilinogen
74
SCA pathogenesis
glu → val substitution : formation of a hydrophobic pocket on the beta globin surface that interacts with a complementary nonpolar residue on another hemoglobin molecule : causes polymerization of HbS molecules and subsequent erythrocyte sickling : membrane damage and permanent distortion of red blood cells.
Red cell sickling is promoted by low oxygen levels, increased acidity, and dehydration.
75
HbC pathogenesis
glu → lys
basic polar (positively charged) lysine (lys) residue. Because lys is charged (although it has opposite polarity to glu), there is no hydrophobic interaction between hemoglobin molecules and no polymerization/sickling.
76
Anti GpIIb/IIIa Ab
Etiology:
Labs:
Tx:
Immune thrombocytopenia
Seen in SLE, HIV, HCV, CLL
Inc megakaryocytes
- steroids, Rituximab, Eltrombopag, Romiplostim, IVIG
77
Inhib/ def of ADAMTS13
Pathogen:
CF:
Labs:
Tx:
- mostly females.
vWF metalloprorease
Inc platelet aggregation n thrombi formation
- Triad: thrombocytopenia, Microangiopathic HA, acute kidney injury + fever + neurological Sx
- N PT & PTT.
Platelets dec
Hb dec, LDH inc, Schistiocytes
Creatinine inc
- Rituximab. Plasmapheresis. Steroids.
78
HUS
```
Epi:
Pathogen:
CF:
Labs:
Tx:
```
Children
- shiga ~ toxin, EHEC O157:H7
- thrombocytopenia, microangiopathic HA, acute kidney injury + bloody diarrhea
- N PT & PTT.
Platelets dec
Hb dec, LDH inc, Schistiocytes
Creatinine inc
- supportive care
79
Multiple myeloma
Pathogen:
CF:
Labs:
Pathogen:
plasma cells into BM - dec hematopoesis. Dec B cell n plasma cells
CF:
inc bact infections. Bone pain. Renal insufficiency
```
Labs:
Normocytic anemia (ineffective erythropoesis). Hypercalcemia.
```
80
Hb -bound- 2,3 DPG
N
Dec O2 affinity for Hb : more O2 release in peripheral tissues
81
Beta-globing mutation causing dec 2,3BPG binding
Familial erythrocytosis
82
Hemophilia inheritance
XLR
Given phenotypically normal parents, the probability that a female sibling of a male affected by an X-linked recessive disease will give birth to an affected child is 1/8.
83
Sickling promoted by.
Dec O2
Dec blood vol
Inc blood pH
Organs w inc metabolic demand promote sickling by extracting more O2 from the blood (O2 unloading)
84
Methemoglobin induced as a Tx for
Cyanide poisoning
Amyloid nitrite induces MethHb since it binds CN & prevents CN from binding to cytochrome c in ETC
85
Cyanide poisoning antidotes
Amyl nitrite
Hydrocobalamin
NaThisulphate
86
UROD def
| Uroporphyrinogen decarboxylase
Porphyria cutanea tarda
87
RF Porphyria CT
```
Alcohol
Smoking
Halogen HC
HCV
HIV
```
88
+ve Coombs test
Autoimmune hemolytic anemia
| HDF/N
89
t(8:14)
Burkitt
Cmyc (8) oncogene
8: 2 (kappa light chain)
8: 14
8: 22 (lambda light chain)
90
t(9:22)
CML
| BCR-ABL
91
t(11:14)
Mantle cell
| Cyclin D
92
13q deletion
CLL
93
t(14:18)
Follicular lymphoma
Bcl2 (B-cell lymphoma2) 18 to 14, Ig heavy chain
Bcl2: anti-apoptotic
- over expression causes immortality
94
t(15:17)
APML
RAR-a,17 / PML, chrom 15
95
Hematogenous ca spread
Sarcoma
RCC
HCC
96
Perineural ca spread
Pancreatic ductal adenoca
| Prostate
97
Transcoelomic ca spread
Ovarian
98
Diffuse large B cell lymphoma
```
#MC NHL
rapidly enlarging mediastinal/ neck/ abd mass
#mc involves oropharyngeal lymphoid or GIT
```
- B : fever, wt loss, night sweats
99
```
#MC NHL
2#MC NHL
```
Diffuse large B cell
| Follicular
100
#MC leukemia in children
ALL
101
Spleenomeg + pancytopenia in older men
Hairy-cell leukemia
102
Hypophosphorylated Rb
(f)
Mutation
Active. Tumor suppressor gene.
13q14
regulates the G1→S checkpoint n stops it : does no let damaged DNA to proceed
```
- mutations:
Retinoblastoma
Osteosarcoma
Breast Adenoca
Small cell lung ca
Bladder ca
```
103
Molecular policeman
P53
Induced of apoptosis
104
BRCA1 n BRCA2 mutation
Breast n ovarian ca
106
#MCC anemia in elderly on antacids
Megaloblastic d/t B12 def
107
Replacement of BM w fat cells
Aplastic anemia
RF: toxic chemicals- industrial solvents/ chemicals, insecticides
108
Replacement of BM w fibrosis
Myelofibrosis
Dacrocytes / tear drop cells
109
Inc nuclear-cytoplasmic ratio
Slow nuclear division
Inc cytoplasmic maturation
Cells w inc replication rate
110
AIHA etiology
M.pneumoniae
EBV
Abx against RBC
111
Inc PTT
```
Hemophilia A (factor VIII def)
Heparin
```
112
Inc Bleeding time
Uremia/ ESRD
113
Inc aPTT n BT
```
VWF def
Platelet dys(f): inc BT
dec factor VIII: inc PTT
```
114
Inc PT, PTT , BT
DIC
115
Inc PT, PTT
Warfarin
PT >> PTT
116
Over expr/amplification of genes causing mutation
Proto-oncogenes
```
KRAS: colorectal ca
ABL
BRAF
HER1
Erb B2/ HER2/ neu
MYC
RAS
SIS
TFGA
```
117
Large irreg lymphocyte w abundant cytoplasm
EBV
118
Dry tap + spleenomeg in mid-aged men
Dx?
Hairy cell leukemia
Infiltrates BM n RES
TRAP+ve (older test)
Dx: flow cytometry
119
Loss of (f) mutation genes
Tumor-suppressor/ anti-oncogenes
```
APC/ b-catenin
BRCA1, 2 (DNA repair)
RB (G1–S checkpoint)
TP53
DCC
NF1
VHL
WT1
```
120
Hemolytic anemia, hypercoag, pancytopenia
| Dx?
PNH
121
Neck swelling w epistaxis n headaches
Nasopharyngeal ca
Pre-malignant lesion transformed to malignant d/t oncogenic viral proteins expressed by EBV
122
#MCC HNSCC in young non smokers
HPV
123
Keratin pearls
Irreg foci of keratinization
| HNSCC
124
Hemolytic anemia periph blood smear
1. Inc Reticulocytes : large, immature RBC d/t ribosomes
2. Spherocytes: reduced cell memb w dec surface area : partially phagocytized
3. Nucleated erythrocytes: immature
125
Construction worker w microcytic anemia, comstipation, neurological changes,
Lead poisoning
Basophillic stippling
126
Ringed Sideroblasts vs basophillic stippling
RS:
Bone marrow
Ppt of iron granules in dev RBC
BS:
periph blood
Ribosomal aggregation
127
Neutrophils in different stages of maturation seen in?
CML
BCR-ABL
Philadelphia chromosome
128
Pure red cell aplasia
Dec RBC production d/t inhib of precursor by IgG autoab or cytotoxic T lymphocytes
Seen in thymoma, lymphocytic leukemia, Parvovirus
129
Missense mutation in beta-globin
SCA
130
Direct polymerizarion inhib in SCA by?
Voxelotor
131
What metabolizes pro-carcinogens?
CyP450 monooxygenase
132
Child, mucocut bleeding
| + no platelet clumping
Adhesion defect d/t defective GpIIb/IIIa R on platelet surface
Glanzmann trombasthenia
Tx: Abciximab
133
New onset neurological Sx + anemia w Schistiocytes + thrombocytopenia + acute kidney injury
Dx?
TTP
134
Elderly w osteolytic lesions, inc Ca2+ , anemia, acute kidney injury
CDx?
Multiple myeloma
Dx: light chain in urine electrophoresis
135
JAK2 mutation
Cytoplasm is tyrosine kinase : clonal prolif of myeloid cells
Polycythemia Vera
136
#MC malignancy of childhood
T-ALL
Mediastinal mass
137
Stacked-coin agglutination in periph blood
Rouleaux formation
D/t inc circulating proteins which disrupt the electrostatic charge on RBC n cause aggregation
- seen in infection, RA, Multiple myeloma. Waldenstrom macroglobulinemia (inc paraproteins/ immunoglobulins)
138
Age-related changes in hematopoietic stem cells
1. Inc fat n dec mass of bone marrow
2. Dec response to stimulators cytokines : limited gen of new cells in resp to stress
3. Dec cytokine signaling n cellular BM composition : dec gen of new cells in response to blood loss or hypoxia
4. Inc medullary size d/t loss of endosteal cortica bone : inc # risk
139
Erythrocytosis
Polycythemia DDx
1. RBC mass
- Inc in Absolute erythrocytosis
- N mass in Relative
2. EPO
- Dec in 1° erythrocytosis: Polycythemia Vera
- inc in 2° d/t chronic hypoxia, smoking, COPD, abn secretion
3. SaO2 + PaO2
<92% + <65% in 2°
140
Polycythemia classification
1. Absolute (true inc in RBC mass)
i. Polycythemia Vera
ii. 1° erythrocytosis (low EPO)
iii. 2° erythrocytosis : inc EPO d/t hypoxia (SaO2<92% or PAO2 <65 mmHg) or abn secretion by neoplastic / other tissues
2. Relative (N RBC mass)
- dehydration, excessive diuresis
141
HbA 93%
HbF 2%
HbA2 5%
Dx?
Beta-thal minor
142
#MC NHL in adults
Follicular lymphoma
143
Intra erythrocytic rings seen in
Malaria
144
Lymphocytes w cytoplasmic projections
Hairy cell leukemia
145
Abn retinoic acid receptor seen in?
AMPL/ AML M3
PML/RAR-a fusion
t(17:15)
Auer rods
146
Paraneoplastic inc in EPO seen w?
» Paraneoplastic Rise to High Hct Levels «
1. Pheochromocytoma
2. RCC
3. HCC
4. Hemangioblastoma
5. Lymphoma
147
Paraneoplastic Marantic endocarditis seen w?
Marantic/ Nonbacterial endocarditis d/t Pancreatic adenoca
148
Paraneoplastic inc in EPO seen w?
» Paraneoplastic Rise to High Hct Levels «
1. Pheochromocytoma
2. RCC
3. HCC
4. Hemangioblastoma
5. Lymphoma
149
Paraneoplastic Marantic endocarditis seen w?
Marantic/ Nonbacterial endocarditis d/t Pancreatic adenoca
