Platelets, Platelet Disorders Flashcards
hemostasis
prevention of blood loss
4 mechanisms of hemostasis
1) vascular Constriction
2) Formation of Platelet Plug
3) Formation of a blood clot (coagulation)
4) growth of fibrous tissue to close a vessel hole permanently
Vasoconstriction
- contractile response of vascular smooth muscle
•Sensory impulses from traumatized vessel
•Stimulation of smooth muscle via perivascular nerves results in spasm
•Thromboxane A2 released from platelet dense granules
•May be sufficient to close arterioles and small arteries
thrombus
stable clot
primary hemostasis
platelet aggregation
-vessel injury -> platelet adherence -> activation -> hemostatic plug
(within seconds)
secondary hemostasis
blood coagulation
-hemostatic plug ->fibrin strands -> thrombus -> clot contraction
(minutes-hours)
thrombopoiesis
CFU-Meg->Megakaryocyte->thrombocyte
-IL3, thrombopoietin, GM-CSF, SCF
megakaryocyte
- giant cells with multiple copies of DNA in nucleus
- edges break off to form platelets
platelets
-2-4micrometres in diameter
-lack nuclei -> can’t synthesize new proteins
-live ~10days -> drug consequences
-old plateletes are removed by macrophages in the spleen
aka thrombocytes
-mostly circulate in blood, some stored in spleen
-150,000-400,00/microliter of blood
hyalomere
outside concentric zone of platelet; microtubules maintain shape and contraction
granulomere
inside concentric zone of platelet; 3 types of granules (release prohemostatic and anti-hemostatic substances); few mitochondria
platelet adhesion
- at site of endothelial injury
- mediated by integrins (GlycoProtein receptors)
integrins
integral membrane receptor proteins
aka GlycoProtein receptors
-receptor binding activates platelets
GP lalla
GlycoProtein receptor, binds collagen beneath the vascular bed
GP IbIX
GlycoProtein receptors, binds von willebrand factor on extra-vascular smooth muscle cells
activated platelets
- change shape (spherical -> stellate) and discharge granule contents
- serotonin-> local vasoconstriction
- ADP -> activates other platelets -> amplification
- adhesion activates phospholipase A2 in platelet membrane _> activates other platelets
- activation exposes GP IIbIIIa receptors ->aggregation
phospholipase A2
in platelet membrane -> activates other platelets -> amplification
aspirin
- inhibits platelet activation and aggregation
- irreversible inhibitor of cyclooxygenase enzymes (COX-1)
NSAIDS
- non-steroidal anti-inflammatory drugs (e.g. ibuprofen)
- reversible COX inhibitors
acetaminophen
- tylenol/ paracetamol
- elevated transaminase indicates liver toxicity
platelet aggregation
- Mediated by fibrinogen receptors (GP IIbIIIa)
* GP IIbIIIa receptors become exposed during activation
Bernard-Soulier syndrome
-defective vWf receptor (GPIb-IX) -> inactive platelets
Glanzmann’s disease
defective fibrinogen receptor (GPIIb-IIIa) -> no aggregation
antagonists for thrombosis
Abciximab and Eptifibatide bind to GPIIbIIIa and compete with fibrinogen.They prevent platelet aggregation
plavix
binds/blocks ADP-receptor preventing ADP-activation
aka Clopidogrel
Thrombocytopenia
decrease in platelets; < 150,000/ μl of blood
- purpura, petechia, hemorrhage
- positive tourniquet test is >20 petechiae in area of 3cm diameter of cubital fossa
- increases bleeding time (normal is 2-6min)
purpura
bleeding under the skin causing a purple or red discoloration)
petechiae
minor bleeds under skin),
Primary thrombocytopenic purpura
unknown cause
Secondary thrombocytopenic purpura:
due to a known cause: aspirin overdose, aplastic anemia, malignancies infiltrating BM, infections like dengue fever (hemorrhagic fever).
thrombocytosis
- increase in platelets: >400,000 / μl of blood
- thrombotic (clotting) events- stroke, heart attacks, pulmonary embolism
- may happen after splenectomy bc fewer platelets are removed from circulation
- gangrene
eptifibatide
- protein in rattlesnake
- inhibits GPIIbIIIa -> decrease in aggregation
GPIIbIIIa
fibrinogen receptor, normally hidden but get exposed when platelets are activated
thromboxane A2
produced by activated platelets and has prothrombotic properties
