Hemostasis And Transfusion Medicine Flashcards
1
Q
First screening test for hemostatic problems should always be?
A
Patient’s medical history
2
Q
Most detailed platelet function test
A
Platelet aggrgation
3
Q
Laboratory for extrinsic pathway?
For intrinsic pathway?
A
Prothrombin time
Activated partial thromboplastin time
4
Q
What are the routine RBC compatibility testing (3)
A
- ABO compatibility
- Antibody screen
- Crossmatching
5
Q
Oxygen delivery to tissues (DO2) is dependent on 3 factors
A
- Cardiac output
- Regional blood flow
- O2 carrying capacity (o2 content of blood)
6
Q
Cryoprecipitate is created by a controlled thaw of frozen plasma, which allows for precipitation of large molecules such as (2)
A
- Fibrinogen
2. vWf
7
Q
Symptoms of disorders of primary hemostasis present with bleeding where (2)
A
- Skin
2. Mucosa
8
Q
MC HEREDITARY bleeding disorder
A
vWf disease
9
Q
Are now the drug of choice for emergent reversal of warfarin in place of FFP
A
Prothrombin complex
10
Q
Steps of primary hemostasis (4)
A
- Adherence
- Activation
- Stabilization
- Inhibition
11
Q
When the endothelial lining is disrupted to expose the underlying matrix, platelets adhere to ______ via surface integrin receptors ______ and _______.
A
Collagen
GP (Ia/IIa)
GP IV
12
Q
In high shear arterial flow, _______ from endothelial cells from preexisting clots bind to ______.
A
vWf
Integrin Ib/IX
13
Q
In activation, in “outside-in” signaling, a central target is the?
A
Phospholipase C
14
Q
G protein coupled receptors are activated by an array of agonists (
A
- Thrombin
- ADP
- TXA2
- Serotonin
- Epi
- Vasopressin
15
Q
Activated PLC leads to several structural changes in the platelets. Via IP3, ______ is released from storage tubules. It catalyzes release of dense granules & a granules.
A
Calcium
16
Q
These granules contain (3)
A
- ADP
- Serotonin
- More calcium
17
Q
The a granules contain (3)
A
- Factor V
- Fibrinogen
- Platelet factor
18
Q
Is the target antigen for the antibodies causing heparin-induced thrombocytopenia
A
Heparin-PF4 complex
19
Q
Also facilitates rearrangement of the platelet musculoskeleton from discoid to flat and spiky
A
Calcium
20
Q
Furthermore, calcium helps activate ______, which release more arachidonic acid.
A
Phospholipase A2
21
Q
Arachidonic acid, as catalyzed by cyclooxygenase is modified to?
A
Thromboxane A2
22
Q
The activated PLC initiates “inside-out” signaling of GP IIb/IIIa via. This changes the shape of GP IIb/IIIa which permits it to better bind fibrin and vWf.
A
DAG
Protein kinase C
23
Q
Inhibition
Endothelial cells secrete ______, which binds to a surface receptor to signal increased CAMP. Elevated CAMP activates _______, a multisite inhibitor of vWf adherence. Endothelial cells also secrete ______, which at high levels initiates a signaling pathway leading to inhibition of the TXA2 receptor.
A
PGI2
PKA
NO
24
Q
Aspirin and trifusal inhibits
A
COX1 (converts AA to TXA2)
25
ADP, has its P2Y12 recetor blocked by?
Clopidogrel
26
The PAR-1 for thrombin activation is blocked by?
Vorapaxar
27
Formation and stabilization of the platelet plug is blocked by (3), which act at GPIIb/IIIa.
1. Abciximab
2. Eptifibatide
3. Tirofiban
28
A major inhibitory pathway, PGI2, is upragulated by (2)
Dypiridamole
| Cilostazol
29
Thrombin converts?
Fibrinogen to fibrin
30
The process begins when endothelial disruption exposes tissue factor (TF) on underlying cell membranes EXTRINSIC to the circulation.
Extrinsic pathway
31
TF binds both? And is a cofactor for the activation of VII.
VII
| VIIa
32
This form the 1st complex in the extrinsic pathway (4)
1. VIIa enzyme
2. TF
3. Phospholipid (cell membrane)
4. Ca
33
Activates factor X and IX
Tenase
34
Assemble to form the second complex, the prothrombinase (4)
Which converts _____ to _____
1. Xa
2. Va
3. Phospholipid
4. Ca
Prothrombin (II) to thrombin (IIa)
35
Thrombin activates platelets via surface receptors (2), cleaves more ____ to _____ and initiates the intrinsic pathway by cleaving factor ____ to ____. Thrombin also activate _____ to _____. This is carried and stabilized in the plasma by vWf. So low vWf also has a deficiency in what factor?
PAR1
PAR4
V to Va
XI to XIa
VIII to VIIIa
VIII
36
Third complex (4)
1. IXa enzyme
2. VIIIa cofactor
3. Phospholipid
4. Ca
37
Fibrin polymers are cross-linked by what factor?
XIIIa
38
All clotting factors are produced in the liver except for what factor?
VIII (endothelial cells)
39
Plasma half life of most clotting factors?
Except for what clotting factors? (3)
1.5 to 3 days
VIII (6 hours)
V & VIII (8 to 12 hours)
40
Clotting factors have 3 inhibitors
1. TF pathway inhibitor
2. Antithrombin III
3. Protein C-ase
41
Inhibits external tenase by binding to Xa. Produced in endothelial cells, released by heparin
TF pathway inhibitor
42
A serine protease inhibitor or serpin. Inhibits proteases in all clotting pathways.
AT III
43
In tissues, this is the main plasminogen activator
Urokinase
44
PAI 1 is secreted where?
| PA 2?
a granules
| Placenta
45
One of the first platelet function test.
Bleeding time
46
VWf is a factor deficiency with clinical features of what dysfunction, due tonthe central role of vWf in cross-linking them.
Platelet
47
This vWf deficiency is a quantitative deficiency
Type 1
48
This vWf deficiency has decreased activity from a defective protein.
Type 2
49
What the factor deficiency in hemophilia A?
| In hemophilia B?
VIII
| IX
50
Fibrin formation by fibrinolysis generates the fibrin fragments called?
D-dimers
51
This test is used for measuring the clinical effects of bivalirudin and dabigatran.
Ecarin clotting time (ECT)
52
This tests measure the rate, strength and lysis, if any, of clot formation.
TEG
53
The INR’s therapeutic range for warfarin anticoagulation is?
2 to 3
54
What is the clotting factor that declines the fastest when warfarin takes effect?
Protein C
55
What drugs directly inhibit factor Xa? (2)
1. Rivaroxaban
| 2. Apixaban
56
Is a monoclonal antibody that neutralizes dabigatran.
Idarucizumab
57
The plasma must be frozen within how many hours to be labeled as FFP.
6 hours
58
Cryoprecipitate is made from barely thawed FFP, which yields a precipitate rich in?
Fibrinogen
59
How many bags of cryo is equivalent to and adult dose?
5
60
Routine serology with NAT (nucleic acid tests) shortens the window period in a newly infected donor how long for
HIV and HCV?
HepB?
7 to 10 days
| 1 month
61
This serology for this virus is only found in leukocytes.
CMV
62
Autologous donations by the patient can be made in advance of scheduled surgery. Usual minimum hemoglobin or hematocrit level is?
Donation should be made within this time period to permit erythropoeisis before surgery.
11 g/dL
33%
6 weeks
63
In leukoreduction, WBC content is typically removed from 10 to the 9th to less than?
10 to the 6th WBCs/unit
64
Washing cellular components with saline is mostly done to remove what component in patients with allergic transfusion reactions such as those who are IgA deficient?
Plasma
65
This is performed to prevent transfusion GVHD from directed-donor units from relaltives.
The units are exposed to gamma irraditation (2,500 cGy)
Irradiation
66
Platelets are stored at what temperature but this increases the risk of bacterial growth.
Room temperature
67
RBC uses this for preservation. (4)
1. CPDA-citrate (anticoagulant)
2. Phosphate (buffer)
3. 1 to 2 grams D-glucose and adenine (to maintain ATP levels and RBC membrane integrity)
68
What component is depleted in the first 2 weeks and shifts the oxygen hgb dissociation curve to the LEFT.
2,3 DPG
69
By the end of the 42-shelf life,
1. The pH is?
2. Plasma K is due to RBC leakage and hemolysis
3. % Range of RBCs that are nonviable
pH is 6.5
50 mmol/L
15 to 20%
70
RBC testing takes how many minutes?
45 to 60 minutes
71
In emergency cases what blood group can be given?
Uncrossmatched group O RBCs
72
What is the universal donor PLASMA
AB
73
Transfusion guidelines start with hgb level below?
And hct level below?
Hemoglobin goals at what level?
8 g/dL
0.25
7 to 10 g/dL
74
For patients with hgb levels between 7 to 10 g/dL two societies recommend transfusion in these patients (3)
1. Critical non-cardiac end-organ ischemia
2. Active blood loss
3. Clinical condition of tissue hypoxia
75
Patients with neurologic injury showed poor outcome with hgb levels below?
9 g/dL
76
Physiologic compensation for anemia
1. Increased cardiac output
2. Altered microcirculatory blood flow
3. Increased tissue oxygen extraction
77
Anemia causes a shift of the oxygen hemoglobin dissociation to the?
Due to increased levels of 2,3 DPG
Right
78
Isovolumic hemodilution of hematocrit levels less than how much generates and increase in 2,3 DPG.
25%
79
Factors that shift the oxygen hemoglobin dissociation curve to the right thereby decreasing AFFINITY of oxygen for hemoglobin and improving tissue oxygen extraction.
CABET
1. Carboxyhemoglobin
2. Acidosis
3. Inc 2,3 DPG
4. NEUROPHYSIOLOGY
5. Hyperthermia
80
In STABLE patients WITHOUT bleeding, the hemoglobin should rise 1g/dL approximately how much hematocrit for each unit of packed RBCs.
33%
81
AABB Target goal of hemoglobin for patients with acute hemorrhage.
ESA recommends a target hemoglobin between?
8 g/dL
7 to 9 g/dL
82
For stable patients with severe thrombocytopenia, transfusion can be held until counts fall below this level in the ABSENCE of bleeding.
10,000 uL
83
Prophylactic platelet transfusion is necessary for patients with this level who will undergo MAJOR or INVASIVE surgery such as lumbar puncture, liver biopsy, NEURAXIAL ANESTHESIA, or endoscopy with biopsy.
Below 50,000/uL
84
Platelet transfusion start at what level when CVP will be placed.
20,000/uL
85
In preparation for surgery on the EYE or the CNS platelet count should be raised above this level.
100,000/uL
86
Any patient with a critical blood loss or hemorrhagic shock should be transfused with a platelet with a target of?
75,000 to 100,000/uL
87
How many platelet concentrates from whole blood
1 unit contains about how much platelets
Five to eight
3 x 10 to the 11th or 4 x 10 to the 11th
88
Plasma preparation includes
Frozen plasma remains usable for how many days?
1. Fresh frozen (within 8 hours from phlebotomy)
2. Plasma frozen (within 24 hours of collection)
4 days
89
Prior to use of plasma products, each unit must be thawed at what temperature?
It can be stored at what temperature for up to 24 hours as thawed FFP or 5 days as thawed plasma
30 to 37 degrees celsius
4 degree + - 2 degree celsius
90
Does FFP need ABO compatibility testing?
Yes
91
The initial therapeutic dose of plasma averages how much in an attempt to obtain at least 30% factor activity.
10 to 15 mL/kg
92
Riskiest blood component currently in use due TRALI, allergic reactions, and circulatory overload.
Plasma
93
Is created by a controlled thaw of FFP, which allows precipitation of large molecules. It is then centrifuged, the supernatant removed, and the final product resuspended in 10 to 15 mL of plasma.
Cryoprecipitate
94
Cryoprecipitate contains what clotting factors (5)
They are stored at -18 degrees C for up to 12 months
1. Fibrinogen (15 g/L)
2. Fibronectin
3. VWf
4. FVIII
5. FXIII
95
1 dose of cryoprecipitate increases the fibrinogen levels to?
50 g/L
| 2.5 g/L in plasma
96
Threshold for fibrinogen replacement
80 to 100 mg/dL
97
Most common transfusion reaction
Mild fever
98
Most common transfusion-transmitted infection
CMV
99
Clasically present within 4 hours of transfusion with an increase in temperature 1 degree to 2 degrees and may be associated with chills, rigor, anxiety and headache.
Febrile nonhemolytic transfusion reaction
100
Best treatment for allergic reactions from transfusion.
Reduce the rate
101
Overall fatality rate from transfusion reaction is? But is significantly dependent on the VOLUME transfused with fatality risk more than 20% with the infusion of more than?
10%
50 mL
102
Refers to the induction of an immune response to allogenic antigen exposure. Majority of alloimmunization results from transfusion of blood products containing immunogenic antigens on the surface of RBCs.
Alloimmunization
103
Leading cause of transfusion-associated mortality,
TRALI
104
Criteria for TRALI (2)
1. Acute onset hypoxemia within 6 hours of transfusion (PaO2/FiO2 <300 mmHg or O2 sat < 90%
2. No evidence of left atrial hypertension
105
Highest risk associated with TRALI
Plasma donations from Multiparous women
106
Lung volume Measures in treating TRALI (3)
1. Maximize PEEP
2. Avoid volume overload
3. Low Vt
107
Despite the supportive treatment of TRALI, what is the best treatment?
Prevention
108
Hyperkalemia results from high volume transfusion when the rate is?
100 to 150 mL/hr
109
Coagulation factor activity decreases by how much for every 1 degree decrease in core body temperature.
10%
110
Is an autosomal recessive disorder that results from an abnormality of the GP 1b receptor.
Bernard-Soulier syndrome
111
Is an autosomal recessive disorder that results from a defect in the platelet integrin aIIbB3 receptor which, under normal circumstances, allows fibrinogen and other ligands to bind and facilitate plateletlet aggregation.
Glanzmann thrombasthenia
112
vWf us produced where?
| What is its functions (2)?
Endothelial cells and megakaryocytes
| Platelet adhesion and aggregation at the site of vascular injury through GP 1b receptor on the platelet surface.
113
Most common and mildest type of vWD.
What is the most severe
Type 1
Type 3, this is the ONLY type likely to cause spontaneous hemorrhage in joints and soft tissues
114
Treatment for vWD
1. DDAVP (promotes cleavage of vWf from fVIII)
| 2. Factor concentrates
115
Most common hemophilia
A deficiency of what clotting factor?
A
8
116
Hemophilia B also called what disease?
Involves a deficiency in what clotting factor?
Christmas disease
IX
117
Hemophilia C results from a deficiency of what clotting factor?
XI
The only autosomal recessive inheritance pattern
118
Protein C inactivates what clotting factor? And depends on protein S as a cofactor
V
119
There are 2 sources of vitamin K
The absorption of both types depends on?
1. Phylloquinone (green leafy)
2. Menaquinone (GI tract)
Bile salts
120
For vitamin K deficiency, what is the best route for this replacement?
How fast can IV take effect and what dose?
Oral adminstration has the best bioavailability
But can take 24 hours to take effect
6 to 8 hours for IV especially in 5 to 10 mg doses
121
What is the mainstay of replacement therapy for consumption of clotting factors in DIC?
Plasma (10 to 15 mL/kg)
Cryoprecipitate is the product of choice for treatment of overt DIC with consumptive coagulopathy and major bleeding, because it contains fVIII and fibrinogen.
122
This is primarily used for stroke prophylaxis since they increase the production of cAMP, an active inhibitor of platelet aggregation.
Phosohodiesterase inhibitors
123
Is a reversible ADP uptake inhibitor and prime therapeutic agent in this class.
Dypridamole
124
The P2Y12 ADP receptor antagonist such as these 3 drugs, prevent the expression of GP2b/3a on the surface of activated platelets.
Clopidogrel
Prasugrel
Ticagrelor
125
Examples of GP IIb/IIIa inhibitors (3)
Monoclonal antibody
1. Abciximab (longer context sensitive half time 24 to 48 hours)
1. Tirofiban
2. Epitifibatide
126
Target INR for warfarin monitoring?
2 to 3
127
Warfarin monitoring
For patients with INR higher than 5.0 what should be done?
If the INR is 8.0
Warfarin (held for one to two doses)
Administer vitamin k (1 to 3 mg vit k IV) (corrected in 6 to 8 hours)
128
New oral anticoagulant should be discontinued before surgery?
```
24 hrs (minor surgery)
48 hrs (major surgery)
```
129
Two types of heparin
1. UFH
| 2. LMWH
130
This type of heparin indirectly inhibits thrombin and FXa by binding to AT III
UFH
131
Reversal drug of UFH
Protamine
132
Is a type of heparin but specifically inhibits Xa.
LMWH
133
Indirect factor Xa antagonist example
Fondaparinux (no antidote)
134
What heparin is more likely to cause HIT
UFH
135
Adverse effect of warfarin
Gangrenous thrombosis of the limbs
136
Synthetic agents that directly inhibit thrombin. No risk of HIT. (2)
1. Agatroban
| 2. Bilavirudin (rapid onset) (DOC for renal and liver dysfunction)
137
Originally introduced for treatment for diabetes insipidus, but it was also found to improve hemostasis
What is the common side effect?
Desmopressin
Hypotension
