Disorders of primary haemostasis Flashcards
Describe platelet production
Platelets are produced by megakaryocytes (polyploid) and shed into blood stream. Newer platelets are larger and denser than old ones (life span 7-12 days ; 50% removed by spleen 33% by liver, rest is BM and lymph)
Describe platelet structure
Alpha granules- contains coagulation proteins:
- clotting factor V,
- protein S,
- plasminogen activator inhibitor,
- adhesive plasma proteins including: fibrinogen, fibronectin, VWB, …
Delta granules:
- serotonin,
- ADP,
- ATP,
- phosphate,
- Ca2+
Describe platelet normal function
- hemostasis
- inflammation
- antimicrobial host defence
- tumor growth
Briefly describe the platelet receptor GP IIb/IIIa for adhesive proteins? (inside-out/ outside in)
GP IIb/IIIa is a receptor for the ligands collagen, vWF, fibrinogen, and fibronectin
- after platelet activation, “inside-out” signaling process is initiated, GP 2b3a changes conformation and increases it’s affinity for its ligand fibrinogen.
- once fibrinogen binds, another conformational change occurs “outside-in” signaling process is initiated resulting in acceleration of the aggregating process
What is atherothrombosis?
atherothrombosis is when atherosclerotic plaque is ruptured, activating platelets and thrombus formation -> leads to MI and stroke
What is the link between thrombosis and inflammation?
activated platelets in circulation like to bind leukocytes, inducing a pro-inflammatory, pro-adhesive state in endothelial cells
- provides a bridge between endothelial cells and leukocytes
What is bernard soulier syndrome?
Platelet adhesion defect.
- prolonged bleeding time, large platelets (abnormal megakaryopoiesis) and thrombocytopenia
- presents in infancy/ childhood with bleeding/bruising/ nosebleeds and gum bleeding
- key test is aggregometry
What is glanzmanns thrombasthenia
Agrregation deffect
-patients lack GP 2b/3a so no fibrinogen binding occurs and bleeding time is prolonged
- test using ELISA
What is alpha granule storage disease?
Secretion defects (aka gray platelet syndrome)
- disorder caused by absence or reduction of alpha granules in platelets or of the proteins in these granules -> mild bleeding
- diagnosed based on appearance of platelets
What is hermansky pudlak syndrome?
Storage pool disease
- platelet dense granule are not formed , decreased aggregation and secretion,
- moderate bleeding, immunodeficiency, albinism
