Hematology - Sheet1 Flashcards
2
Q
What activates platelets
A
adhesion with vWF, binding thrombin, ADP, TxA2
3
Q
Molecule stored in platelet granules
A
ADP, fibrinogen, VWF, calcium
4
Q
Glanzmann’s thrombasthenia
A
platelets fail to expres 2 proteins for firbinogen receptor Integrin a2bb3
8
Q
Thrombi
A
Thrombi
9
Q
common location venus thrombi
A
around the valve in the vein
10
Q
2 identifying features of thrombus
A
lines of zahn and site of attachment to vessel wall
11
Q
postmortem clot layers
A
very red layer - current jelly and gelatinous yellow layer - chicken fat
13
Q
Inherited Bleeding Disorders
A
Inherited Bleeding Disorders
14
Q
factor for hemophilia A
A
8a
15
Q
Factor for hemophilia B
A
9a
16
Q
Glanzmann thrombasthenia clinical symptoms
A
easy brusing, epistaxis, Menorrhagia
17
Q
Dual function Von Willebrand factor
A
platelet adhesion to endothelium. binds and carries coagulation factor 8 in plasma
18
Q
Weibel-Palade bodies
A
storage granules in endothelial cells that store VWF and P-selecten
19
Q
VWF central role in which disease
A
microcirculatory occlusions in thrombotic thrombocytopenic purpura
20
Q
What proteolyzes VWF
A
ADAMTS13
21
Q
VWF disorder inheritance pattern
A
autosomal dominant
22
Q
VWF disorder typical bleeding
A
brusiing, bleeding after surgery, dental procedures
23
Q
VWF disorder locations without bleeding
A
No muscle or joint bleeding
24
Q
VWF disoder type 1
A
decreased amounts of normal
25
Q
VWF disorder type 2
A
decreased amounts abnormal
26
Q
VWF disorder type 3
A
severely decreased concentration and activity
27
Q
VWF disorder functional measure
A
Use Ristocetin co-factor activity
28
Q
VWF disorder multimer analysis
A
Type 1 has normal gel with less of everything. Type 2 has abnormal gel bc actual protein is messed up
29
Q
PT and aPTT in VWF disorder
A
PT normal. aPTT can be abnormal if factor 8 levels are affected
30
VWF disorder treatment DDAVP
this causes release of vWF from endothelial storage sites.
31
VWF disorder treatment plasma
Plasma from factor 8 concentrates with vWF activity
32
VWF disorder treatment alternatives
provide anti-fibrolytic agents and simple pressure, ice etc.
33
hemophilia delayed bleeding
happens because platelets are functioning normally but can't produce fibrin well so clot dissolves
34
Hemophilia common bleed sites
Joints, knees, elbows, shoulders, ankles, hips
35
Hemophilia PT aPTT
Prolonged aPTT
36
Why can't you measure factor 9 at birth
Factor 9 always low at birth so cannot diagnose neonatal Hemophilia B
37
Primary vs Secondary Prophylaxis Hemophilia
Provide factor infusion before or after first joint bleeds
38
3 Treatment options Hemophilia
Plasma from factor concentrates, recombinant factor, Factor 7 recombinant to bypass the problems
40
Acquired Disorders
Acquired disorders
41
Which factor used to compare liver vs vitamin K problems
Factor 5 bc it is not vitamin K dependent. Helps diagnose long PT
42
Factor 8 response in liver disease
not affected the same. Often elevated bc not made by hepatocytes
43
thrombophlebitis
thrombosis and inflammation in veins near the skin. Can happen w thrombosis from adenocarcinomas
44
DIC initiation hypothesis
exposure of blood to tissue factor
45
lupus anticoagulant effect
causes artificial elongation of aPTT in vitro bc binding to phospholipids.
46
DIC bleeding vs thrombosis
Bleeding normally in acutely ill patients. Thrombosis classic with cancer
47
DIC PT aPTT
both elongated. aPTT less sensitive than PT
48
DIC significant lab
platelet counts are low. prsenece of fibrin degredation (D-dimers).
49
DIC cell pathology
RBC fragments (schistocytes) and thrombocytopenia bc mciroangiopathic hemolytic anemia.
50
Schistocytes
RBC fragments
51
Factor 13 function
cross-links fibrin. Need this before you get D dimers
53
DIC w cancer treatment
heparin to inhibit coagulation
54
DIC bleeding treatment
provide FFP, fibrinogen cryoprecipitate and platelet transfusion
55
antiphospholipid antibodies
includes lupus. some bind to phospholipids, others bind to phospholipid assocated proteins
56
Antiphospholipid antibody syndrome requirements
presence of antibodies at least 2 occasions w Thrombosis, pregnancy morbidity, or thrombocytopenia
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5 Hereditary Thrombophilias
Factor 5 leiden, prothrombin mutation, protein c deficiency, protein s deficiency, antithrombin deficiency
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Most important risk of hereditary thrombophilias
increased risk of venous thromboembolism or VTE
59
heparin mechanism
imrpoves anticoagulant activity of AT
60
Antithrombin deficiency genetics
autosomal dominant
61
antithrombin deficiency Type 2 groups
Thrombin binding site defects, heparin binding site defects, defects affecting thrombin and heparain binding
62
AT deficiency assays
antigen assay measure AT levels. Functional assays measure ability to neutralize thrombin and FXa
63
AT function
forms complexes and inhibits thrombin and FXa
64
Protein C activation
Pro form activated by thrombin that is bound to thrombomodulin on endothelial surface
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Protein S function
Protein S improves function of activated protein C
66
Protein C function
lyses coagulation factors Va and VIIIa
67
Protein C type 1 and type 2 deficiency
Again has to do with total amount and then total function
68
Protein S, 3 Types
Type 1 = amount, type 2 = functional abnormal, type 3 = normal total levels but reduced functional
69
Protein S carrier
half unbound and half bount to C4-binding protein
70
Neonatal Purpura fulminans
severe homozygous protein C deficiency. Purpura and necrosis
71
Neonatal purpura fulminans treatment
anticoagulation and protein C
72
Warfarin induced skin necrosis
Half life of different factors causes initial increased clotting
73
Vitamin K protiens
2,7,9,10 and Protein C adn Protein S
74
Vitamin K protein degredation rate
Protein C,S and factor 7 decline slower than the 2,9,10
75
Warfarin induced skin necrosis mechanism
thrombotic imbalance leads to cutaneous vessel thrombosis = purpuric and necrtoic skin lesions
76
Factor V leiden mechanism
point mutation making factor 5 unaffected by Activated protein C
77
Factor 5 leidin genetics
autosomal dominant
78
Prothrombin mutation mechanism
change in a non-coding region making mRNA more stable and higher levels of prothrombin
79
prothrombin mutation effect
increased levels of prothrombin and significant increase risk of clot
80
post VTE treatment length
3-6 months of anticoagulation
81
best indicator of risk for VTE
having a previous VTE. tips balance away from testing for Hereditary thromphilias
83
Anticoagulant and Antiplatelet agents
anticoagulant and antiplatelet agents
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Anticoagulants
inhibit thrombin or 10a or decrease levels of prothrombin and other zymogens
85
fibrinolytic agents
degrade existing clots
86
antiplatelet agents
inhibit platelet plug formation
87
Anticoagulant list
unfractionated heparin, lmw heparin, direct inhibitors of thrombin/factor10a, coumadin
88
proteins inactivated by unfractionated heparin
2a, 10a, 9a, 11a, 12a
89
Large heparain useful because
have the long pentasaccharide sequence to help inhibit thrombin and factor 10a
90
Unfractionated heparin usage issues
short half-life that is variable. Have peaks and troughs in administration. Only IV leads to steady state levels
91
Unfractionated Heparin uses
acute thromboembolism, prevent thromboembolism, maintain a coronary artery bypass graft
92
unfractionated heparin significant toxicity
osteoporosis, and HIT
93
Heparin induced thrombocytopenia with thrombosis
heparin/PF4 complex binds to platelet Fc. Causes platelet aggregation and destruction. So get thrombocytopenia with thrombosis of platelets being aggregated
94
Test used to monitor unfractionated heparin
use aPTT - want 1.5-2x baseline
95
LMW heparin target
affects 10a more than 2a. Does not affect aPTT as much
96
LMW heparin benefits
half-life longer. less beleding and thrombocytopenia
97
Direct thrombin inhibitors
Lepirudin and Argatroban
98
Lepirudin
recombinant hirudin. for HIT and thrombi prevention after surgery. Renal excretion. comes from active ingredient used by leeches. IV USE
99
Argatroban
active site inhibitor, hepatic excretion IV USE
100
Factor 10a inhibitors
Rivaroxiban, Apixaban, Fondaparinux (indirect)
101
Thrombin 2a inhibitors
Dabigatran (direct) renal excretion
102
Rivaroxiban
Factor 10a inhibitor
103
Apixaban
Factor 10a inhibitor
104
Fondaparinux
Indirect factor 10a inhibitor
105
Dabigatran
Direct 2a inhibitor
106
Warfarin mechanism
inhibits re-use of vitamin K
107
Vitamin K purpose
Vitamin K carboxylation of glutamate
108
Warfarin in the body
bound to albumin
109
Warfarin degraded by
P450
111
International normalized ratio
(Patient PT/average control PT)^ISI
112
Coumadin in first trimester
causes an embryopathy
113
Limitation of oral factor 10 and 2 inhibitors
no quick reversing mechanism currently
114
Fibrinolytic agents
Fibrinolytic Agents
115
Plasmin function
cleaves fibrinogen and fibrin
116
Plasminogen activators
Streptokinase, urokinase, recombinant t-PA
117
Plasminogen activator contradiction
some trauma or surgery that puts you at risk of bleeding or massive hemorrhage
118
Antiplatelet agents
ADP, thrombin receptor antagonists, aspirin, dipyridamole, integrin blockers
119
Platelet receptor blockers
Clopidogrel (plavex) nad Vorapaxar (SCH530348)
120
Platelet receptor blocked
AD P2y12
121
ADP p2y12 receptor antagonists requiring metabolism
Ticlopidine, clopidogrel, prasugrel
122
ADP p2y12 receptor antagonist direct
Cangrelor
123
Platelet signal blockers
Aspirin and dipyridamole
124
Platelet integrin blockers
ReoPro (abiciximab), Integrilin (Epifibatide), Tirofiban (Aggrastat)
125
dipyridamole
increase cAMP and block signal in platelet aggregation
127
hemodynamic disorders
hemodynamic disorders
128
Hyperemia vs congestion
Hyperemia is an active process
129
Hyperemia causes
erythema
130
Congestion causes
cyanosis
131
Liver congestion where does blood back up
in regions such as sinusoids around the central vein. spares periportal regions
132
nutmeg liver
chronic passive congestion of liver.
133
nutmeg liver discoloration
dark red is centriolbular congestion. Periportal fatty change is yellow
134
Direction of clot formation
always towards the heart.
135
Virchow's triad
endothelial injury, hypercoagulability, abnormal blood flow
136
white thrombi
arterial thrombi. more platelets and fibrin w less RBC. Prominent lines of Zahn
137
mural thrombi
a thrombi that is stuck to the wall of the vessel and not really occlusive
138
small/medium artery w arterial thrombi
generally occlusive
139
red thrombi
venous thrombi, lines of zahn not as prominent. more red blood cells bc more about stasis and sitting blood
140
paradoxical embolus
venous thrombus passes to systemic circulation through patent foramen ovale or vsd or patent ductus arteriosus
141
thrombus organization
ingrowth of granulation tissue and smooth muscle cells into thrombus. convert to fibrous tissue
142
pulmonary web
indicates that a prior thrombus had existed
143
white infarct
arterial infarct when solid organ has one blood supply
144
red infarct
hemorrhagic infarct or venous infarct, organ with 2 blood supplies. Or white infarct w/ reperfusion
145
dual blood supply w infarct
if one is blocked and second compromised than you can get tissue with ischemia and blood supply that is not enough to prevent the ischemia
147
Anemia
Anemia
148
Microcytic anemia differential
iron deficiency, anemia of chronic inflammation/chronic disease, thalassemia, sideroblastic anemia
149
iron deficiency anemia presentation
low hemoglobincMicrocytic, hypochromic anemia
150
iron deficiency anemia pathology
pencil cells, , low MCV, high RDW
151
Prussian blue stain
stain when assessing iron. Wil stain iron blue
152
Thalassemia trait unique
have microcytosis without anemia
153
thalassemia presentation
microcytic, hypochromic anemia. Very low MCV
154
Thalassemia pathology
target cells
155
Normocytic anemia differential
hemolytic anemia, hemorrhage/blood loss, sicke cell disease, anemia of chronic inflammation/disease, aplastic anemia
156
hemolytic anemia cause
hereditary spherocytosis
157
hereditary spherocytosis
defect in proteins making RBC cytoskeleton. shortened lifespan RBC
158
Hemolytic anemia presentation
normocytic, normochromic anemia with high reticulocyte count
159
spherocyte
cells that have lost membrane and take spherical shape. Lack central pallor
160
Macrocytic differential
megablastic anemia (B12 deficiency, folate deficiency), liver disease, alcohol, yelodysplastic syndrome
161
B12/folate deficiency effect
disrupt pathway for DNA synthesis. ineffective erythropoiesis
162
megaloblastic anemia pathology
large RBCs. hypersegmented neutrophils
163
Retic count correction in anemia
corrected retic count = reticulocyte x actual Hct/ideal Hct
164
Hemolytic anemia: intravascular hemolysis minfestation
anemia, hemoglobinemia, hemoglobinuria, hemosiderinuria, jaundice
165
Intravascular hemolysis cause
mechanical injury, complement fixation ,intracellular parasites
166
Extravascular hemolysis cause
premature destruction of cells in phagocytes bc alteration akes RBC less deformable
167
megaloblastic anemia cause
impaired synchrony of nuclear and cytoplasmic maturation
168
3 B12 proteins
intrinsic factor, transcobalamin II, R protein
169
Pernicious anemia
intestines cannot properly absorb B12, get an anemia because of failure for DNA production.
170
Megaloblastic anemia signs
tiredness, pallor, jaundice, epithelial esions on gums, gastric mucosa, cervical lesions
171
B12 neurologic problems
demyleination and subacute combine systems disease, paresthesias of hand and feet, spastic ataxia, etc
172
B12 lab assessment
B12 down. Methylmalonic acid and homocystein increase
173
Folate deficiency assessment
Homocystein down more in isolation than in B12
175
Folate deficiency poor nutrition
goat milk anemia, poverty, early birth etc.
176
folate deficiency absorption
nontropical or tropical spruce. disease of small intestine
177
folate deficiency increased requireent
pregnancy, increased cell turnover from chronic hemolytic anemia, exfoliative dermatitis
178
Nitrous oxide exposure
Acute megaloblastic anemia,
179
inborn cobalamin deficiency
Imerslund-grasbeck disease, congenital deficiency of IF, transcobalamin II deficiency
180
inborn error folate metabolism
congenital malabsorption, dyhydrofolate reductase deficiency, N .... transferase deficiency
181
increased LDH
marker of hemolysis. Leaking out of destroyed RBC's. enzyme for converting pyruvate to lactate
182
hyperbilirubinemia
marker for hemolysis from broken down heme
183
increased plasma hemoglobin
marker of intravascular hemolysis as hee leaks into circulation
184
low plasma haptoglobin
marker for intravascular hemolysis bc haptaglobin is depleated to bind hemoglobin and take to spleen
185
hemoglobinuria
sign of intravascular hemolysis bc extra hemoglobin is not picked up and instead comes out in urine
186
extravascular hemolysis causes
intrinsic RBC efects, extracorpuscular defects
187
Intravascular hemolysis causes
problems w hemoglobin, problems with RBC membrane, deficiencies of enzymes
188
hereditary spherocytosis osotic fragility test
red cells placed in hypotonic saline, %lysis measured HS RBC's lyse at greater concentration of hypotonic salinethan normal RBCs
189
G6PD deficiency mechanism
withotu G6PD, hemoglobin more succeptible to oxidative damage.
190
heinz bodies
damaged hemoglobin aggregate to make heinz bodies
191
bite cells
macrophages rmeove heinz bodies from RBC's causes bite cells and inducing hemolysis
192
G6PD deficiency genetics
X chromosome. more males affected
193
G6PD deficiency at risk populations
A variant = african americans. B variant = mediterranean and asian ancestry
194
Warm autoimmune hemolytic anemia
IgG bind to RBC surface at warm temp leading to microspherocytes
195
Warm AIHA test
DIrect Coombs test to see if RBC's coated with IgG
196
causes of warm AIHA
idiopathic autoimmune disorders lupus,lymphoproliferative disorders
197
Cold AIHA
IgM binding below 37 degrees. activate complement that remains and causes lysis of RBCs
198
Kuppfer cells
complement receptor expressing cells in liver that take out RBC's in Cold AIHA
199
Cold AIHA diagnosis
blood reachign room temp will agglutinate.
200
3 mechanisms of drug induced hemolytic anemia
hapten mediated - drug binds RBC and serves as IgG target. neoantigen - drug binds membrane gets new conformation for IgG. Drug alters membrane causing new antigen
