Hemostasis And Transfusion Medicine Flashcards
First screening test for hemostatic problems should always be?
Patient’s medical history
Most detailed platelet function test
Platelet aggrgation
Laboratory for extrinsic pathway?
For intrinsic pathway?
Prothrombin time
Activated partial thromboplastin time
What are the routine RBC compatibility testing (3)
- ABO compatibility
- Antibody screen
- Crossmatching
Oxygen delivery to tissues (DO2) is dependent on 3 factors
- Cardiac output
- Regional blood flow
- O2 carrying capacity (o2 content of blood)
Cryoprecipitate is created by a controlled thaw of frozen plasma, which allows for precipitation of large molecules such as (2)
- Fibrinogen
2. vWf
Symptoms of disorders of primary hemostasis present with bleeding where (2)
- Skin
2. Mucosa
MC HEREDITARY bleeding disorder
vWf disease
Are now the drug of choice for emergent reversal of warfarin in place of FFP
Prothrombin complex
Steps of primary hemostasis (4)
- Adherence
- Activation
- Stabilization
- Inhibition
When the endothelial lining is disrupted to expose the underlying matrix, platelets adhere to ______ via surface integrin receptors ______ and _______.
Collagen
GP (Ia/IIa)
GP IV
In high shear arterial flow, _______ from endothelial cells from preexisting clots bind to ______.
vWf
Integrin Ib/IX
In activation, in “outside-in” signaling, a central target is the?
Phospholipase C
G protein coupled receptors are activated by an array of agonists (
- Thrombin
- ADP
- TXA2
- Serotonin
- Epi
- Vasopressin
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.
Calcium
These granules contain (3)
- ADP
- Serotonin
- More calcium
The a granules contain (3)
- Factor V
- Fibrinogen
- Platelet factor
Is the target antigen for the antibodies causing heparin-induced thrombocytopenia
Heparin-PF4 complex
Also facilitates rearrangement of the platelet musculoskeleton from discoid to flat and spiky
Calcium
Furthermore, calcium helps activate ______, which release more arachidonic acid.
Phospholipase A2
Arachidonic acid, as catalyzed by cyclooxygenase is modified to?
Thromboxane A2
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.
DAG
Protein kinase C
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.
PGI2
PKA
NO
Aspirin and trifusal inhibits
COX1 (converts AA to TXA2)
ADP, has its P2Y12 recetor blocked by?
Clopidogrel
The PAR-1 for thrombin activation is blocked by?
Vorapaxar
Formation and stabilization of the platelet plug is blocked by (3), which act at GPIIb/IIIa.
- Abciximab
- Eptifibatide
- Tirofiban
A major inhibitory pathway, PGI2, is upragulated by (2)
Dypiridamole
Cilostazol
Thrombin converts?
Fibrinogen to fibrin
The process begins when endothelial disruption exposes tissue factor (TF) on underlying cell membranes EXTRINSIC to the circulation.
Extrinsic pathway
TF binds both? And is a cofactor for the activation of VII.
VII
VIIa
This form the 1st complex in the extrinsic pathway (4)
- VIIa enzyme
- TF
- Phospholipid (cell membrane)
- Ca
Activates factor X and IX
Tenase
Assemble to form the second complex, the prothrombinase (4)
Which converts _____ to _____
- Xa
- Va
- Phospholipid
- Ca
Prothrombin (II) to thrombin (IIa)
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
Third complex (4)
- IXa enzyme
- VIIIa cofactor
- Phospholipid
- Ca
Fibrin polymers are cross-linked by what factor?
XIIIa
All clotting factors are produced in the liver except for what factor?
VIII (endothelial cells)
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)
Clotting factors have 3 inhibitors
- TF pathway inhibitor
- Antithrombin III
- Protein C-ase
Inhibits external tenase by binding to Xa. Produced in endothelial cells, released by heparin
TF pathway inhibitor
A serine protease inhibitor or serpin. Inhibits proteases in all clotting pathways.
AT III
In tissues, this is the main plasminogen activator
Urokinase
PAI 1 is secreted where?
PA 2?
a granules
Placenta
One of the first platelet function test.
Bleeding time
VWf is a factor deficiency with clinical features of what dysfunction, due tonthe central role of vWf in cross-linking them.
Platelet
This vWf deficiency is a quantitative deficiency
Type 1
This vWf deficiency has decreased activity from a defective protein.
Type 2
What the factor deficiency in hemophilia A?
In hemophilia B?
VIII
IX
Fibrin formation by fibrinolysis generates the fibrin fragments called?
D-dimers
This test is used for measuring the clinical effects of bivalirudin and dabigatran.
Ecarin clotting time (ECT)
This tests measure the rate, strength and lysis, if any, of clot formation.
TEG
The INR’s therapeutic range for warfarin anticoagulation is?
2 to 3
What is the clotting factor that declines the fastest when warfarin takes effect?
Protein C