BL Hemostasis: approach to patients Flashcards
Platelets contain 3 types of granules:
name them and what they contain
○ Dense granules contain ATP, ADP, serotonin, and calcium.
○ α-granules contains proteins essential for platelet function:
- platelet-specific factors for platelet activation,
- growth factors,
- procoagulant proteins (fibrinogen, factor V, von Willebrand factor, etc)
○ Lysosomal granules contain acid hydrolases.
Do platelets have a nucleus? Cytoskeleton?
No nucleus but they do have a mitochondria
Yes cytoskeleton: cytoplasmic framework of monomers, filaments, and tubules that allow shape change with activation.
Thrombopoietin (TPO)
the main growth and maturation factor for megakaryocytes (platelet precursors)
Where are contents of platelet granules pushed out from during platelet aggregation and secretion?
extensive system of internal platelet membrane tunnels, called the surface-connected canalicular system
Primary hemostasis
vessel gets damaged → Adhesion, activation, and aggregation of platelets to form a platelet plug
4 events in the formation of a platelet plug:
- Platelet adhesion
- Platelet activation
- Platelet aggregation
- Fibrin formation and support of local coagulation
Platelet adhesion steps
□ Vessel injury → expose subendothelial components → circulating von Willebrand factor (vWF) sticks to damaged exposed subendothelium.
□ Under high flow → platelets can contact the exposed subendothelium → Glycoproteins (GP1b) on platelet surface are receptors for adhesive proteins (vWF or collagen) present in the vessel wall
□ Other ligands in the subendothelium (collagen, fibrinogen, laminin, fibronectin) also interact with integrins on the platelet surface
here are the ligands. Name their receptors:
GPIa/IIa
GPIIb/IIIa
GPIb alpha
GPIa/IIa - collagen
GPIIb/IIIa - fibrinogen
GPIb alpha - vWF
Platelet activation
Exposed platelets change shape through cytoskeletal activation → becomes more spherical with extended pseudopods and spreading over the exposed subendothelium → Secretion of intracellular alpha and dense granule contents from platelet → activates the platelets (expose ligands for binding to receptors)
Platelet aggregation steps
- Ligands bind receptors (ie. vWF) in high affinity state.
2. Fibrinogen!! binds to ligands and lace the platelets together into an aggregate
Fibrin formation and support of local coagulation
last step of platelet plug formation
□ Thrombin generated through activation of the coagulation cascade then converts fibrinogen to fibrin to stabilize the platelet plug.
Normal platelet count
150,000 and 400,000/uL.
methods of treating ITP
a. Corticosteroids
b. Intravenous immunoglobulin (IVIG)
c. Splenectomy
d. Rituximab (=anti CD 20):
e. TPO (=thrombopoetin):
immune thrombocytopenic purpura (ITP)
most common cause of thrombocytopenia due to increased destruction
- autoantibodies develop which are directed against platelet antigens, leading to their removal by macrophages of the reticuloendothelial system of the liver and spleen
( similar to autoimmune hemolytic anemia)
How do corticosteroids treat ITP
○ Steroids work by dampening proliferation of the B cell clone making the autoantibody. An effect is usually seen within 7 to 10 days of starting treatment.
