Normal Platelet Function

Stop bleeding, prevent pathogens from entering blood stream

All of the above

Formation of hemostatic plug and provides phospholipid membrane surface for assembly of key coagulation proteins

Vasoconstriction, blood coagulation proteins, platelet activation/aggregation/adhesion

Up to 10 days

70% in bloodstream, 30% in spleen

False

True

Peripheral zone, Sol-Gel zone, Organelle zone, and Membrane system

• Surface membrane: rich in glycoprotiens for adhesion and aggregation, as well as phospholipids that are a source of thromboxane A2
• Open canalicular system: transports substances in and out of platelets

Cytoskeleton for retaining and changing shape

Mitochondria and lysosomes, contain granules which store critical signalling compounds.

• Alpha: adhesive proteins - fibrinogen, vWF, factors V, VIII, XI, XIII, HMWK1, PAI-1
• Delta (dense): ATP and ADP, calcium, histamine, serotonin, and epinephrine

Calcium store, enzymes for prostaglandin synthesis

Adhesion, aggregation, contraction and secretion (contraction and secretion are the steps of platelet activation)

Triggered by exposure of subendothelial substances, especially collagen. Van willibrand factor binds to collagen and this complex binds to glycoprotein Ib/IX on platelet surface.

Adhere to other platelets via GpIIb/IIIa. This involves vWF and fibrin(ogen)

Activation of platelet causes shape change from discoid to spheroid.

Explosive secretion of platelet granular contents due to calcium influx. This makes the platelet plug a tight mass.

The platelet plug provides surface for assembly of coagulation proteins leading to fibrin formation.

Arachidonate is released by activated platelets and oxygenated into endoperoxides. These are then converted to thromboxane A2 by thromboxane synthesis.

Potent signal for platelet aggregation, vasoconstrictor, increases cytosolic calcium.

It inhibits cyclooxyenase, leading to decreased thromboxane A2 and prostacyclin.

Tissue injury -> exposure of collagen, fibronectin, vitronectin, laminin, and release of tissue factor. Van Willebrand factor binds to collagen. Ib-alpha on platelet can bind to the vWF-collagen complex. The platelet rolls along this complex until it comes to a halt. Gp6 on the platelet binds collagen, triggering activation of the platelet. GpIIb/IIIa is exposed on the platelet, which can bind additional vWF to allow for aggregation of platelets.

ADP and calcium

Negatively charged, such as phosphatidylserine.

Fibrillary collagen (even without thrombin) and fibrin-bound platelets

• an in vivo test of coagulation. Limited use in a few circumstances.
• Time required for bleeding to stop after a cut of defined length and depth is made. 
• Affected by platelet number and function, subendothelial tissue elasticity, coagulation proteins. Prolonged with van Willebrand factor deficiency and ASA ingestion

False - no tight correlation, but a platelet count may still provide diagnostic clues

in vitro assay measuring platelet aggregation in response to various stimuli. Stimuli include: ADP, collagen, arachidonic acid, ristocetin, epinephrine. With some stimuli, response can be biphasic: low doses induce primary wave of activation and higher doses induce aggregation plus release of endogenous ADP, producing a secondary wave.

Centrifuge blood, platelets are suspended. Put platelet portion in aggregometer and add an agonist (ie. ADP, epinephrine). Stir. The machine has a light source and a photometer that counts the amount of light. With agonist, platelets will undergo shape change and aggregate together, meaning more space between the platelets and a higher reading on the photometer as more light can pass through. If the platelets don't aggregate, transmission will not increase.

lowered platelet count (uremia, too much ASA and rare genetic disorders), various marrow failure or injury (aplastic anemia, leukemia), sometimes immunologically mediated, destruction of platelets by prosthetic heart valves, common manifestation of AIDS

• Spontaneous bleeding, prolonged bleeding time
• Bleeding into CNS a concern

• Glanzmann's thrombasthenia: GpIIb/IIIa, autosomal recessive, poor platelet plug formation, treated with transfusions
• Bernard-Soulier Syndrome: GpIb alpha/IX, autosomal recessive, large platelets, mild thrombocytopenia, treated with transfusions

• Gray platelet syndrome: alpha granule, large, gray platelets with light microscopy, abnormal electron microscopy, may respond to DDAVP
• Quebec platelet disorder: abnormal response to epinephrine
• Herman-Pudlak: albinism, dense granules defective, abnormal aggregation with collagen, defective second wave
• Chediak-Higashi: abnormal granules in leukocytes, melanocytes, but not platelets, pyogenic infections, bleeding tendency
• Wiskott-Aldrich: thrombocytopenia, small platelets, X-linked, recurrent infections, Eczema

• ASA: inhibits cyclooxygenase
• Clopidogrel: blocks ADP receptor
• Abcixibam: antibody, blocks GpIIb/IIIa