Heme Flashcards
1
Q
steps of hemostatsis
A
- rapid constriction
- platelet adhesion to surface of vessel (vWF binds collagen, platelets bind vWF vis Gp1b)
- platelet degranulation (ADP promotes exposure of GP2b/3a and TXA2 promotes aggregation)
- platelet aggregation (Gp2b/3a uses fibrinogen)
2
Q
vasoconstriction mediated by…..
A
neural stimulation and endothelin released by endothelial cells
3
Q
Gp1b
A
binds platelets to vWF
4
Q
where does vWF come from
A
endothelial cells and platelets
5
Q
WP bodies
A
contain vWF and p-selectin
6
Q
mediators in platelets
A
ADP and TXA2
7
Q
ADP leads to expression of….
A
Gp2b3a
8
Q
Gp2b3a
A
for platelet aggregation, bind fibrinogen
9
Q
TXA2
A
signal for platelet aggregation
10
Q
primary hemostasis disorders
A
involves platelets
- mucosal and skin bleeding
- intracranial bleeding with severe thrombocytopenia
11
Q
petechiae are signs of…
A
thrombocytopenia, not qualitative disorders
12
Q
idiopathic thrombocytopenic purpura
A
- auto IgG against platelet antigens (GPIIb/IIIa)
- most common
- antibodies produced in spleen and consumes platelets
13
Q
ITP in children
A
- after viral infection, self limited
14
Q
ITP in adults
A
- can be secondary (SLE)
- can cause thrombocytopenia in offspring (IgG across placenta)
15
Q
labs in ITP
A
- low platelets
- normal PT/PTT
- increase in megakaryocytes
16
Q
treatment of ITP
A
- steroids
- IVIG (eats other sticks)
- splenectomy
17
Q
microangiopathic hemolytic anemia
A
- platelet microthrombi in small vessels
- consumption of platelets and destruction of RBC
- schistocytes
18
Q
microangiopathic hemolytic anemia seen in…
A
TTP and HUS
19
Q
thrombotic thrombocytopenic purpura
A
- due to decrease in ADAMSTS13 (usually autoantibody)
- increases platelet adhesion leading to microthrombi
20
Q
ADAMSTS13
A
breaks up vWF multimers
21
Q
hemolytic uremic syndrome
A
- caused by ecoli O157
- verotoxin damages endothelial cells
- causes hemolytic anemia
- in kids with undercooked beef
22
Q
clinical findings in TTP and HUS
A
- skin and mucosal bleeding (use up platelets)
- hemolytic anemia
- fever
- renal insufficiency and CNS abnormalities
23
Q
lab findings in TTP/HUS
A
- thrombocytopenia
- normal PT/PTT
- anemia with schistocytes
- increased megakaryocytes on bone marrow
24
Q
bernard-soulier syndrome
A
- genetic GP1b deficiency
- platelet adhesion is impaired
- mild thrombocytopenia with enlarged platelets
25
Glanzmann thrombasthenia
- GIIb/GIIIa deficiency
| - aggregation is impaired
26
aspirin....
irreversibly inactivates cyclooxygenase
27
uremia and platelets
blocks adhesion and aggregation
28
secondary hemostasis
coagulation cascade generates thrombin which converts fibrinogen to fibrin
29
activation of coag cascade requires
1. exposure
2. phospholipid surface
3. calcium
30
clinical features of secondary hemostasis
deep tissue and rebleeding
31
what activates factor 12
subendothelial collagen
32
what activates factor 7
tissue thromboplastin
33
measure heparin with
PTT
34
measure coumadin with...
PT
35
hemophilia A
- factor 8 deficiency
- X-linked
- deep tissue joint bleeding
36
labs in hemophilia A
- high PTT, normal PT
- low factor 8
- normal platlets
37
hemophilia B
- deficiency in factor 9
| - resembles A
38
coagulation factor inhibitor
- most common is factor 8
- distinguished by adding patient serum (mixing study)
- mixing study does not correct
39
Von Willebrand disease
- most common
- most common type is decreased factor
- problem with platelet adhesion
- mucosal and skin findings
40
labs in vWF disease
- high bleeding time
| - PTT is up (vWF stabilizes factor 8)
41
vFW stabilizes factor.....
8
42
ristocetin test
ristocetin causes platelet aggregation
| - abnormal in von willebrand disease
43
treatment of von willbrand
desmopressin
| - increase vWF from WP bodies
44
vitamin K deficiency
- gamma carboxylation of 2,7,9,10 and C,S
| - activated by epoxide reducates in liver
45
vitamin K generated by...
bacteria in gut
| - problems in newborns, long term antibiotics, or malabsorption
46
liver failure hemostasis
- lack of coag factors
- no epoxide reductase of vitamin K
- use PT to measure
47
heparin-induced thrombocytopenia
- heparin forms complex with PF4, antibody forms
- platelets are activated
- increased in thrombosis
48
DIC
- pathologic activation of coag cascade
| - consume platelets and factors leading to bleeding
49
DIC caused by...
something else
- OB complication (tissue thromboplastins)
- sepsis from cytokines
- mucin in adenocarcinoma
- APML (auer rods)
- rattlesnake bite
50
labs in DIC
- low platelets
- high PT/PTT
- low fibrinogen
- hemolytic anemia
- elevated d-dimer
51
d-dimer test
for DIC - fibrin split products
52
fibrinolysis
removal of thrombus by plasmin
| - tPA allows for plasmin activation
53
effects of plasmin
1. cleaves fibrin
2. cleaves plasma fibrinogen (stop future production)
3. destroys coag factors
4. blocks platelet aggregation
54
disorder of fibrinolysis
overactivity results in excessive cleavage of fibrinogen
55
examples of fibrinolysis
1. radical prostatectomy - release or urokinase activates plasmin
2. cirrhosis - antiplasmin not produced
56
presentation of fibrinolysis disorder
- just like DIC
- high PT/PTT
- increased bleeding time
- increased fibrinogen split products, no d-dimes
57
difference between DIC and fibrinolysis disorder
```
DIC = low platelets because they are used up, d-dimer
fibrinolysis = normal platelets, no d-dimer (no clot)
```
58
treatment of fibrinolysis disorder
aminocaproic acid
59
characteristics of thrombus
1. lines of Zahn (RBCs and fibrin)
2. attachment to vessel
- used to distinguish before and after death
60
3 risk factors of thrombosis
1. disruption in blood flow
2. hypercoagulability
3. endothelial damage
61
prostaglandin I2
blocks platelet aggregation, produced to endothelium
62
thrombomodulin
- takes thrombin and allows it to activate protein C
63
causes of endothelial damages
- atherosclerosis
- vasculitis
- high serum homocysteine
64
B12 deficiency and thrombus
- leads to high homocysteine
| - damages endothelium leading to thrombosis
65
cystathionine beta synthase deficiency
- results in high homocysteine levels
| - characterized by thrombosis, mental retardation, lens dislocation and long fingers
66
protein C and S
inactivate 5 and 8 factors
67
protein C and S deficiency
- decrease in negative feedback
| - at risk for warfarin skin necrosis (C and S are destroyed first that can lead to clot)
68
action of warfarin
blocks epoxide reductase
69
factor V Leiden
- factor 5 cant be cleaved by C and S
| - hypercoaguability
70
prothrombin 20210A
- promotes hypercoaguable state
71
ATIII deficiency
- ATIII produced by endothelium
- like heparin
- inactivates coagulation factors
- PTT does not rise with heparin
72
mechanism for heparin
ATIII (doesn't work in ATIII deficiency)
73
cholesterol clefts
athersclortic plaque
74
amniotic fluid embolus
- during labor or delivery
- SOB and neurologic
- fluid loaded with tissue thromboplastin leading to DIC
- squamous cells and keratin debris
75
microcytosis occurs because of...
extra division to maintain hemoglobin concentration
76
four causes of microcyctic anemia
1. iron deficiency (no iron)
2. chronic disease (trapped iron)
3. sideroblastic anemia (no porphyrin)
4. thalassemia (no globin)
77
iron absorption
enterocyte use ferroportin (import) to move iron, transferrin (transports) iron, stored in cell (in) by ferritin
78
iron labs
- serum iron
- transferrin (TIBC)
- % sat
- serum ferritin (stored in macrophages)
79
main causes of blood loss
menorrhagia in women, peptic ulcer disease in males
80
bleeding in elderly
colon/polyps and carcinoma and hook worm in developing world
81
how iron helps get absorbed
acid environment, gastrectomy can make it worse
82
stages of iron deficiency
1. ferritin stores decrease
2. serum iron is decreased
3. normocytic anemia
4. microcytic anemia
83
relationship between ferritin and TIBC
inverse
84
labs in iron anemia
- microcytic, hypochromic anemia
- high RDW
- low ferritin, high TIBC
- low serum iron, low saturation
85
FEP
free erythrocyte protoporphyrin - iron is down so proto is not bound to iron
86
blood smear in iron deficiency
microcytic-normal, central pallor
87
Plummer Vinson syndrome
iron deficiency anemia, esophageal web, glossitis, red tongue
88
chronic disease
- increase in hepcidin (block it from bacteria)
| - suppresses EPO
89
lab findings in chronic disease
- high ferritin, low TIBC
- low serum iron, low saturation
- high FEP
90
sideroblastic anemia
defect in protoporphyrin synthesis
| - leads to macrocytic anemia
91
enzymes involved in proto synthesis
ALAS - requires B6, can be congenital, isoniazid
ALAD - lead poisoning
ferrochelatase - in mitochondria, lead poisoning
92
ringed sideroblasts
iron trapped in the mitochondria
93
isoniazid vitamin deficiency
B6
94
labs in sideroblastic anemia
high ferritin, low TIBC
- high serum iron, high saturation
- high iron overload
95
thalassemia is explained by...
protection from falciparum
96
how many copies of alpha gene
4 - most important, in every globin
97
2 alpha genes deleted
- mild anemia, slightly increased RBC
| - cis is worse for progeny (more common in Asia)
98
3 alpha genes deleted
- severe anemia
| - beta tetramers form HbH
99
HbH
beta tetramers
| - seen on electrophoresis
100
4 alpha genes deleted
- lethal in utero, hydrops fetalis
101
Hb Barts
gamma tetramers
| - seen on electrophoresis
102
beta thal is due to.....
gene mutations, can vary the amount of production
103
beta minor
- increase in HbA2
- asymptomatic with increase in RBC
- target cells
104
target cells
- seen in beta thal (decreased hemoglobin)
| - either decreased in cytoplasm or increase in membrane
105
beta major
- severe form of disease
- no problem in fetus
- alpha tetramers lead to extravascular hemolysis
106
massive erythroid hyperplasia
- expansion of hematopoiesis in other places
| - crew cut and chipmunk cheeks
107
risk of aplastic crisis with...
parvovirus B19 in beta thal,
- infects erythroid precursors
- usually dependent on all red blood cell production
108
HbA2
alpha 2 and delta 2
109
what drives MCV to be big
not enough divisions
110
characteristic of B12 or folate deficiency
- megaloblastic anemia
- hypersegmented neutrophils
- other large cells (only seen in megaloblastic)
111
other causes of macrocytic anemia
alcoholism, liver disease, drugs
112
folate is absorbed in...
jejunum, can't be stored
113
lab findings in folate deficiency
- macrocytic RBCs and hypersegmented neutrophils
- glossitis
- low folate
- high serum homocysteine
- normal MMA
114
pernicious anemia
- destruction of parietal cells
| - loss of IF, can't take up B12
115
other causes of B12
- pancreatitis (separates R binder from intrinsic factor for B12 binding)
- damage to terminal ileum (Crohn's or diphyllobothrium latum)
- vegans
116
labs of B12 deficiency
- macrocytic anemia with hypersegmented neutrophils
- glossitis
- subacute combined degeneration (myelin stops due to high MMA)
- low B12
- high homocystein
- high MMA
117
reticulocyte count
- young red blood cells with bluish cytoplasm
| - should be increased in anemia
118
corrected retic count
multiply by hematocrit/45
119
extravascular hemolysis
involves reticuloendothelial system
120
lab findings in extravascular hemolysis
- anemia with splenomegaly
- jaundice (too much UCBilli)
- bilirubin gallstones
- marrow hyperplasia (bone marrow is fine so it is working hard)
121
intravascular hemolysis
hemoglobin directly in blood, binds to haptoglobin (decreases)
122
labs in intravascular hemolysis
- hemoglobinemia
- hemoglobinuria
- hemosiderinuria
- low haptoglobin
- basically hemoglobin is going directly into blood
123
hereditary spherocytosis
- due to ankyrin, spectrin defects
- blebs of membrane are removed by spleen
- leads to round cells
- trapped in spleen
124
labs in hereditary spherocytosis
- anemia with loss of central pallor
- high RDW
- high MCHC
- splenomegaly, jaundice (extravascular hemolysis)
- gallstones
- aplastic crisis in parvo B19 infection
125
diagnosis of HE
osmotic fragility test
| - in hypotonic solution, nor extra membrane for cell to expand, leads to bursting of cells
126
HE after splenectomy
- spherocytes persist
| - Howell-Jolly bodies (no spleen)
127
extravascular hemolysis
hereditary spherocytosis
| sickle cell
128
sickle cell disease
- hemoglobin S (mutated B)
| - polymerizes when deoxygenated (reversible)
129
situations of sickling
- dehydration
- acidosis
- deoxygenation
130
treatment of sickle cell
hydroxyurea
131
things seen in sickle cell
- extra and intravascular hemolysis
- target cells (dehydrated cells)
- massive erythroid hyperplasia (crew cut, extramedullary hematopoiesis)
132
irreversible sickling
- leads to vaso-occlusion
- dactylitis in children
- autosplenectomy (increase in encapsulated organisms)
- salmonella osteomyelitis
- howell jolly bodies
133
common causes of death in sickle cell
strep pneumo in kids (encapsulated organisms)
| acute chest in adults
134
sickle cell trait
less than 50% HbS, usually don't sickle
- expect in renal medulla
- leads to decrease ability to concentration urine
135
metabisulfite
causes any cell to sickle
| - screens for trait
136
hemoglobin C
in beta chain
- C has lysine
- mild anemia
- have hemoglobin C crystals
137
paroxysmal nocturnal hemogloinuria
- deactivating CDs on RBC block complement (lacking GPi)
- acquired
- due to acidosis activating complement at night
138
findings in PNH
- intravascular hemolysis
| - hemoglobinuria, hemoglobinuria, hemosiderinuria days later
139
tests for PNH
- sucrose for screening
- acidify serum to confirm
- check for CD55
140
death in PNH
thrombosis (platelets lack GPi and get destroyed)
141
other complications in PNH
- iron anemia
| - AML (due to other mutations)
142
G6PD deficiency
- X Linked recessive
- less NADPH produced
- more susceptible to oxidative stress
143
cause of oxidative stress
infection, drugs, fava beans
144
things seen in G6PD
- Heinz bodies (hemoglobin precipitates)
- intravascular hemolysis
- bite cells
- hemoglobinuria
- back pain (nephrotoxic)
145
Heinz prep
screen for G6PD
146
when to due enzyme studies
after everything is resolved
147
IgG hemolysis
- extravascular
- warm
- remove membrane
- leads to spherocytes
- removed by spleen
- associated with lupus and CLL and drugs
148
IgM hemolysis
- intravascular
- cold
- fixes complement killing cells
- mycoplasma pneumoniae and mono
149
diagnosis in Ab hemolysis
Coombs test
| - test for Ab on cell (direct) or in serum (indirect)
150
when is MAHA seen
```
TTP - platelet thrombi
HUS - toxin produced
DIC - platelet and fibrin thrombi
HELLP
aortic stenosis
fake heart valves
```
151
MAHA findings
schistocytes and helmet cells
152
low production anemias
micro/macrocytic anemia
renal failure
- parovirus B19
- aplastic anemia
