Primer 12 - Platelets Flashcards
How long do platelets live?
From eight to ten days.
What is the end product of the coagulation cascade?
Fibrin mesh.
What are the stages of platelet during a blood vessel injury?
- Adhesion.
- Activation.
- Aggregation.
What are 4 factors inside endothelium that are relevant in coagulation?
- von Willebrand Factor (vWF).
- Thromboplastin.
- tPA.
- PGI2.
What is the von Willebrand factor and what does it do?
It is made up of several subunits linked by disulfide bonds, synthesized by endothelial cells and megakaryocytes.
Function: Two.
-Complexes with and stabilizes Factor VIII (deficiency of this leads to increase in PTT).
-Platelet adhesion to vessel wall and other platelets (deficiency leads to increase in bleeding time).
What are the contents of platelets relevant to coagulation?
- vWF.
- Fibrinogen.
- Cyclooxygenase.
- Thromboxane A2.
What happens in adhesion during endothelial damage?
Damage to the endothelium exposes the collagen underneath. The vWF that leaked out of the ruptured endothelium binds to the subendothelial collagen. The exposed side of the vWF attaches to the Glycoprotein Ib (Gp1b) that is on the surface of platelets, leading to platelet adhesion to the injured site.
What happens in activation phase in endothelial damage?
- Secretion of ADP, PDGF, serotonin, fibrinogen, lysosomal enzymes, thromboxane A2, calcium, thrombin.
- Thrombin: Fibrinogen that leads to fibrin.
- Thromboxane A2 that leads to vasoconstriction and platelet aggregation.
What happens in the aggregation phase in endothelial damage?
The activated platelets secrete ADP and on the surface of platelets there is a ADP receptor, triggering the expression of Gp IIb/IIIa from inside the platelet to outside the platelet. Then the glyprotein binds to the free fribrinogen and other platelets binds to that same fibrinogen with their glycoprotein IIb/IIIa receptor, making a series of crosslinks making the plug.
What does Aspirin inhibit?
Inhibits COX, the enzyme that blocks arachidonic acid to thromboxane A2.
What does Ticlopidine, clopidogrel block?
Block the ADP receptor on platelet surface.
What do Abciximab, epitofibatide, tirofiban inhibit?
They inhibit Gp IIb/IIIa directly in the platelet surface.
What labs are going to be abnormal in platelet disfunction?
-Bleeding time.
What are the symptoms of platelet disorders?
- Bleeding from the mucous membranes.
- Epistaxis.
- Petechiae.
- Purpura.
What are four important platelet disorders?
- Immune thrombocytopenia purpura (ITP).
- Thrombotic thrombocytopenic purpura (TTP).
- Bernard-Soulier syndrome.
- Glanzmann thrombasthenia.
What is the treatment for immune thrombocytopenia purpura (ITP)?
- Steriods.
- IV immunoglobulin (IVIG).
- Splenectomy.
What is the underlying pathophysiology of Thrombotic thrombocytopenic purpura (TTP)?
- Deficiency of the metalloprotease called ADAMTS13 (zinc containing enzyme that cleaves the von Willebrand factor multimers into smaller active units). This causes excessive platelet activation/aggregation which in turn causes widespread thrombosis.
- With this widespread thrombosis, it causes consumption of platelets, leading to thrombocytopenia.
- And the activation of coagulation cascade, leads to excessive fibrin mesh, which causes microangiopathic hemolytic anemia.
What is the classic triad of Hemolytic Uric Syndrome?
-a milder form of TTP, causes Hemolysis, Uremia, and Thrombocytopenia.
What is the classic pentad of TTP?
[Neuritic Fever Torched His Kidneys]
-Fever, anemia(hemolysis), thrombocytopenia, renal failure, and neurological symptoms.
