2 - Coagulation and Blood Flashcards
What is the end factor of the plasma clotting factor cascade?
Fibrin
Describe Platelet Adherence in Veins
endothelial lining is damaged
Platelets adhere to exposed collagen via surface integrin receptors GPIa/IIa and GP VI receptors
Describe platelet adherence in Arteries
Endothelial lining is disrupted, and in addition to collagen adherence,
vWF from endothelial cells and pre-existing clot adhere to integrin Ib/IX
What is the role of ADP in primary hemostasis?
Platelet Activation
What is the role of COX and cyclooxygenase in primary hemostasis?
Platelet Activation
What is the role of the GP IIb/IIIa receptor in primary hemostasis?
Platelet Stabilization
“Inside-Out” signaling
How are platelets naturally inhibited in their endothelial environment?
Endothelial cells secrete Prostaglandin i2
they also secrete NO which inhibits TxA2 receptor (platelet activation)
What drugs counteract platelet adherence?
None!
Which drug is an ADP antagonist?
What part of primary hemostasis does it inhibit?
Clopidogrel
Platelet Activation
Abciximab, Eptifibatide, and Tirofiban act at which receptor?
Which part of primary hemostasis do they inhibit?
GP IIb/IIIa
Formation and Stabilization of the platelet plug
Are the extrinsic and intrinsic pathways part of primary or secondary hemostasis?
Secondary
What is secondary hemostasis?
The cascade of enzymes that creates fibrin to stabilize the preliminary platelet clot
Activation of _______ initiates secondary hemostasis.
Thrombin
What is the extrinsic pathway?
Why is it called extrinsic?
Initiated when endothelial damage exposes tissue factor (TF) on underlying cell membranes
The TF comes from the cell membrane, which is not part of (extrinsic) the circulation
What is the end product of the extrinsic pathway?
Thrombin (IIa)
What happens after the extrinsic pathway?
Thrombin acts on fibrinogen to form fibrin
Thrombin cleaves factor XI to XIa, which triggers the intrinsic pathway
What is the purpose of the intrinsic pathway?
Produces more Xa
Xa transforms Prothrombin to Thrombin
Thrombin transforms fibrinogen to fibrin
All of the clotting factors are primarily produced in the liver except ________
VIII (8)
Which factors are Vitamin K dependent?
2
7
9
10
What are the three natural clotting inhibitors?
TF Pathway Inhibitor
Anti-thromibn III
Protein C and S
What is tPA?
tissue plasminogen activator
Secreted in the body by endothelial cells to activate plasminogen to plasmin, which breaks down fibrin
What two drugs inhibit fibrinolysis?
How?
Epsilon-Aminocaproic acid (EACA) and TXA
block the binding sites of plasminogen, so it can’t act on fibrin
What is a normal platelet count?
150-400
What is the primary role of vWF?
cross-linking activated platelets to form the plug
What lab evaluates primary hemostasis?
Your platelet count
What labs evaluate secondary hemostasis?
PT/PTT
INR
What is viscoelastic testing
ROTEM
Looks at whole blood clotting and fibrinolysis
What is factor V Leiden?
FVL
most common hypercoaguable mutation
What lab would show how effective apixaban or rivaroxaban are?
AntiXa
Why do DTIs end in “-rudin”?
Because they’re derived from hirudin in LEECHES!!!!
What O2ER is associated with tissue hypoxia?
> 50%
What MixedVO2 and CentralVO2 would indicate tissue hypoxia?
50, 60
What is Cryo?
When is it useful?
Cryo is thawed FFP that has been centrifuged to remove everything but fibrinogen, fibronectin, vWF, F8, and F13
Cryo contains more fibrinogen by volume
Useful when fibrinogen is depleted: DIC, massive hemorrhage
What are the two primary treatment options for patients with vWD?
DDAVP
Factor concentrates
Why does DDAVP help stop bleeding in vWD patients?
Promotes cleavage of F8 into vWF
Is vWD a disease of primary or secondary hemostasis?
Primary
What is the most common form of hemophilia?
Hemophilia A (85%)
How is hemophilia treated?
DDAVP (increases factor 8)
recombinant F8 (but often develop antibodies to it)
Plasma transfusion
PT/PTT are ______ in a patient with Vit K deficiency?
Prolonged
Are PT/PTT accurate measures of bleeding risk in liver disease patients?
No. Often overestimate bleeding risk.
The hemostatic balance is usually (fragilely) maintained by compensation during liver disease
DIC is always associated with _________
a comorbid condition:
infection
inflammation
malignancy
Does DIC result from an abnormality of the intrinsic or extrinsic pathway?
Extrinsic
TF sparks unregulated thrombin production and fibrin development
Which disorders are most associated with DIC?
Sepsis
Malignancy
Obstetric Complications
Name 2 cyclooxygenase inhibitors.
How do they cause anticoagulation?
Aspirin and NSAIDS
Inhibit platelet aggregation
Can aspirin be reversed?
No. Non-competitive inhibitor.
Why are Phosphodiesterase Inhibitors used for stroke prophylaxis?
cAMP is an active inhibitor of platelet aggregation
Name 2 ADP antagonists.
How do they cause anticoagulation?
Clopidogrel, Ticagrelor
Inhibit platelet aggregation
Name 3 GP IIb/IIIa Receptor Antagonists.
How do they cause anticoagulation?
Abciximab, Eptifibatide, Tirofibin
inhibit cross-linkage of fibrinogen (platelet aggregation)
Name 1 Vit K Antagonist.
How does it cause anticoagulation?
Warfarin
Competes with Vit K for carboxylation binding sites
Inhibits synthesis of VitK dependent factors (2, 7, 9, 10, fctrs C and S)
Does heparin inhibit FXa directly or indirectly?
Indirectly by binding to AT-III
Name 2 Parenteral Direct Thrombin Inhibitors
Argatroban and Bivalirudin
Which drug is used to reverse heparin?
How does it work?
Protamine
Derived from fish sperm!
Binds to heparin and forms a stable salt
Name 2 lysine analogues.
TXA and EACA
What is the average blood volume of a male?
Female?
70ml/kg
65ml/kg
