Platelets Flashcards
How are platelets produced?
Fragmentation of Megakaryoctes
What is the precursor to a megakaryocyte?
A megakaryoblast.
Why is TPO low in patients with high platelet counts?
Platelets have a receptor for TPO and remove it from circulation.
What platelet surface glycoprotein facilitates adhesion to collagen?
Glycoprotein Ia
What glycoprotein is deficient in Bernard-Soulier syndrome?
Glycoprotein Ib
What is Bernard-Soulier syndrome?
Mild to moderate mucocutaneous bleeding disorder caused by one of a series of mutations to platelet glycoprotein Ib or GPIX, part of the Ib/IX/V von Willebrand factor receptor complex. The disorder is a defect of platelet adhesion.
What glycoproteins are defective in Glanzmann’s thrombasthenia?
Mutations in Glycoprotein IIb or IIIa.
What is Glanzmann’s thrombasthenia?
Severe mucocutaneous bleeding disorder caused by one or a series of mutations in GP IIb and or IIIa. Normal GP IIb/IIIa recognizes and binds the arginine-glycine-aspartate peptide sequence receptor complex found in fibrinogen and von Willebrand factor. Glanzmann’s thrombasthenia causes a defect of fibrinogen-dependent platelet aggregation.
What are the three types of storage granules contained within the platelets?
- Dense
- α
- Lysosomes
What is contained within the α granules?
- VWF
- PDGF
- clotting factors
What is contained within the dense granules?
- ATP
- ADP
- Serotonin
- Calcium
What is contained within the lysosomes?
Hydrolytic enzymes
How are platelet surface antigen known?
HPA-Human Platelet Antigen
What are the three categories of platelet action?
Adhesion, aggregation, and release reactions. There is also amplification.
Which GP acts to allow direct platelet adhesion to collagen?
GPIa
What is the function of VWF?
- VWF is involved in shear dependent platelet adhesion to vessel wall and to other platelets.
- It also carries Factor VIII
Where is VWF synthesized?
- Platelets
2. Megakaryocytes
Where is VWF stored?
- Weibel-Palade bodies
2. α granules of platelets
How is the VWF stored in Weibel-Palade bodies released?
In the form of large and ultra large multimers the most adhesive and reactive form of VWF.
What cleaves these very adhesive very adhesive ULVWF multimers?
A VWF cleaving metalloprotease ADAMTS
How is platelet aggregation achieved?
By cross-linking of platelets through active GPIIb/IIIa receptors with fibrinogen bridges
What role does ADP released from dense granules play in platelet aggregation?
Plays a major role in positive feedback promoting platelet activation.
What role does TXA2 play in platelet aggregation?
TXA2 is the second major platelet positive feedback loop molecule and is important in secondary amplification of platelet activation to form a stable platelet aggregate.
What are the natural inhibitors of platelet function?
- N.O
- Prostacylin
- The Ectonucleotidase CD39 (ADPase)
How does a megakaryocyte divide?
By endomitosis. Nucleus divides cell does not
After splenectomy what happens to platelet count.
At first increases sharply then falls back down to a normal number
Where is calcium in platelets stored?
Dense tubular system which is analogous to ER
Are dense granular Ca2+ and neucleotides available for platelet metabolic needs?
NO
What is the primary function of platelets?
Form the primary hemostatic plug
What is VWF role during formation of haemostatic plug?
Bind GPIb on platelet to subendothelial connective tissue.
What is the function of ADP during haemostatic plug?
Secreted ADP activates platelets as well as recruits other platelets to the site of injury.
What does secretion of ADP essentially lead to?
Aggregation
What subsequently happens at the site of aggregation?
Formation of a fibrin clot.
What is a secondary function of VWF?
Under a certain amount of shear stress it can facilitate platelet aggregation.
How do platelets aggregate together?
The GpIIb/IIIa receptor on one platelets binds to FIBRINOGEN on 2 platelets
What are the two molecules that generally govern the activity of platelets?
Ca2+ and cAMP
High cAMP affects platelets how?
Turn off the cell.
What are the 2 most potent activators of platelets?
Thrombin and Thromboxane A2 (TXA2)
How does prostacyclin (PGI2) affect platelets?
Potent inhibitor of platelet activation via increasing cAMP
What are the causes of thrombocytopenia?
- Failure of production
- Increased consumption
- Sequestration
- Dilution
Causes of Bone Marrow failure?
- Cytotoxic drugs
- Radiation therapy
- Aplastic Anemia
- Myelodysplastic syndromes
- Myelofibrosis/infiltration diseases
- MM
- Megaloblastic anemia
- HIV infection
What are the causes of selective Megakaryocyte depression?
- Drug toxicity
- Viral infection
- Congenital mutation of c-MPL receptor
- Congenital absent radii
- May-Hegglin anomaly
- Wiscott-Aldrich syndrome
What are the causes of Increased destruction-Immune of platelets?
- Autoimmune-idiopathic, SLE, CLL/lymphoma
- Infection-H pylori, HIV, other viral malaria
- Drug induced-Heparin quinine, quinidine
- Post transfusion
- Feto-maternal alloimmune thrombocytopenia
Thropbopoietin (TPO)
- Hormone Made in liver and kidney
- Regulates Megakaryocytopoiesis.
- Has receptors on Megakaryocytes and Platelets
What is not ordinarily recommended in patients with ITP?
Platelet transfusion
What are the treatment for ITP?
- Corticostreoids
- High dose IVIg
- Immunosuppression
- Rituximab
- Thrombopoietin receptor agonists
- Splenectomy
- IV anti-D immunoglobulin
- Stem cell transplant
What are the causes of reactive thrombocytosis?
- Acute Trauma, surgery, blood loss, chronic iron deficiency
- Splenectomy
- Infections: Osteomyelitis, tuberculosis
- Inflammatory disease: rheumatoid arthritis, chronic ulcerative colitis, vasculitis
- Malignancy: carcinoma, Hodgkin’s disease
