Hemostasis Flashcards
What is the major process in primary hemostasis?
FIRST vessel reflexively constricts
platelets form a plug to minimize blood loss
What is the major process in secondary hemostasis?
Clotting cascade forms a fibrin clot that anchors and stabilizes the platelet plug
______ is central to the hemostatic response because i tis a potent platelet activator and it converts soluble fibrinogen to an insoluble fibrin clot
thrombin
The _________ surface is an important site for assembly and localization of the membrane bound enzyme complexes of coagulation
Activated platelet surfac
Gradual transition to ______ facilitates removal of a clot and wound healing
fibrinolysis
List three pro-thrombotic components
- Platelets/ vWF: formation of hemostatic plug
- Coagulation cascade: thrombin–> fibrin clot formation
- Fibrinolysis inhibitors: soluble protease inhibitors that down regulate fibrinolysis and prevent degradation of the clot
List three anti-thrombotic components
- Intact endothelium
- Fibrinolysis: second enzyme cascade converts plasminiogen to plasmin which lyses the fibrin clot
- Coagulation inhibitors: soluble protease inhibitors that down-regulate the coagulation cascade and remove activated coagulation factors
List three classes of drugs that can be used to prevent hemostasis and their major targets
- antiplatelet drugs: target formation of primary platelet plug
- anticoagulants: prevent formation of fibrin clot
- antifibrinolytics: prevent breakdown of fibrin clot
List the steps in primary hemostasis
- Platelet adhesion: interaction of platelet Gp-Ib with vWF
- Platelet activation: by thrombin, collagen, ADP
- Platelet aggregation: cross linking of activated platelets by fibrinogen binding to Gp IIb/IIIa
- Secretion of platelet granules
- Retraction of the newly formed thrombus
Platelet ______ results in conformational change and activation of Gp IIb/IIIa, granule release, and thrombus contraction
activation
Megakaryocyte differentiation is characterized by _____ in which DNA replication occurs but the nucleus does not divide
endomitosis
The production of platelets is controlled by the cytokine _____
TPO, thrombonpoietin
About 30% of platelets are stored in the spleen and can be released in response to _____
epinephrine
There is usually an ____ relationship between platelet number and mean platelet volume
inverse
Describe the relationship between platelet sequestration, platelet desttruction, and megakaryocyte hyperplasia
As platelets are sequestered, but not destroyed, in a large spleen, there is no compensatory megakaryocyte hyperplasia in the marrow in patients with thrombocytopenia due to hypersplenism. In contrast, when the platelet count is reduced due to rapid destruction, there is megakaryocytic hyperplasia.
Large circulating platelets on the blood smear in a patient with thrombocytopenia suggests:
peripheral destruction of platelets
Rapid platelet production leads to increased size of circulating platelets
List the two hemostatic functions of vWF
- major carrier of VIII, prolongs half life of VIII
- mediates platelet tethering and adhesion to exposed subendothelium
Where is vWF found/ stored
endothelial cells, megakaryocytes, subendothelial connective tissue
wVW is released by endothelial cells in the blood, which can be enhanced by ________
DDAVP
If there is inherited or acquired deficiency of________, large VWF-platelet aggregates can form
in the circulation and occlude small blood vessels causing tissue injury.
ADAMTS13
This causes the disease thrombotic thrombocytopenic purpura (TTP)
_______ promotes vWF unfolding
high shear stress- as in arterial circulation
List platelet agonists that trigger platelet activation
collagen (in ECM) thrombin (generated by TF) epinephrine ADP serotonin TXA2 produced by COX1
Describe the contents of a granules and dense granules
a granules: proteins such as fibrinogen, vWF and factor V that promote clot formation as well as chemokines that recruit inflammatory cells
Dense granules: ADP/ATP and serotonin which activates additional platelets
______ is normally sequestered on the inner membrane of a platelet but is exposed after platelet activation. It enhances the assembly of membrane bound coagulation enzyme complexes
phosphatidylserine
Describe the terms intrinsic pathway and extrinsic pathway
Extrinsic pathway: plasma clotting in response to addition of tissue homogenates- factors “extrinsic to the blood”. Measured by PT
Intrinsic pathway: clotting of plasma in a glass tube using only factors intrinsic to the blood. Measured by aPTT