Move freely through the lumen of blood vessels as part of the circulatory system, maintaining vascular integrity, nourishing the endothelium by platelet components or platelet incorporation into the blood vessel wall.

Platelets are highly reactive cellular effectors hemostasis, immunity, and inflammation.

The anucleate progeny of bone marrow megakaryocyte cells.

About 10% of the platelets are utilized to maintain vascular integrity.

Arrest bleeding at sites of vascular injury by adherence and aggregation at the sites of injury.

When platelets enter the circulation cytoskeletal actin and tubulin processes serve continued roles in platelet function, regulating secretion, aggregation for hemostasis.

For platelets to provide hemostasis platelets must be present in normal numbers, and must function properly.

Fragments of cytoplasm from megakaryocytes in the bone marrow.

Contain ABO antigens on their surface.

Normal count 150-400,000/microL.

Platelet counts vary with age-reduced by as much as 35% in older men and 25% in older women (Balduini CT, Noris P).

Platelet counts are highly heritable.

Mildly elevated platelet counts may be due to older age or ethnicity.

Normal diameter of platelet is 1-4 microL.

70% of platelets are in the circulation and 30% in the spleen.

Responsible for forming a platelet plug, and are a essential component of hemostasis.

Provides a framework for the formation of fibrin clots, secretes cytokines and growth factors.

Platelets express A and B red cell antigens , Class I human leukocyte antigen, and platelets specific antigens on their surface.

Daily production of platelets is 40,000/mL, or approximately 10th to 11power.

Healthy individuals make about 100 billion platelets daily to maintain homeostasis.

Formation and release probably occur via the sinus endothelial cells.

Thrombopoietin controls production and release of platelets.

Flow in the blood stream until exposed to thrombin, collagen, clot mediators and activated platelets.

Supports thrombin generation by assembling activated coagulation factors on their surfaces.

Thrombin activates platelets through 2 protease activated receptors (PARs), PAR-1 and PAR-2.

PAR-1 is activated by lower concentrations than PAR-4, and mediates a more rapid platelet activation response.

Can lead to occlusion of pathologically diseased blood vessels.

Platelets that have been activated and have released loltheir contents and still circulate are known as exhausted platelets and these cells can no longer function to support coagulation.

Platelets are heterogeneous in terms of size, reactivity, circulatory experience in susceptibility to antiplatelet therapy.

Reticulated platelets are young platelets that retain megakaryocyte derived RNA.

Thiazole orange binds RNA selectively and allows detection of reticulated platelets by flow cytometry measurement.

An increased percentage of reticulated platelets predicts cardiovascular death in acute coronary syndromes and is associated with embolize stroke.

Reticulated platelets are relatively resistant to antiplatelet therapy.

Atrial fibrillation increases the percentage of reticulated platelets, so that antiplatelet therapy lacks efficacy in treatment of stroke prevention in this dysrhythmia.

Platelets may actively promote cancer progression by protecting cancer cells from immune surveillance, arresting cancer cells in the microvascular and stimulation of angiogenesis.

Adhesion requires the presence of von Willebrand factor which is present in the subendothelial matrix or absorbed into injured tissue exposed to plasma.

8-10 day survival.

Platelet morphology changes are seen in the Wiskott-Aldrich syndrome with the smallest platelets being present.

The May-Hegglin anomalyis associated with large platelets and Dohle bodies in granulocytes.

The Bernard-Soulier syndrome has the largest platelets and is ref2242ed to as the giant platelet syndrome-actually an artifact of slide preparation. Accounts for the large platelets since the mean platelet volume measurements are normal.

Activation leads to: release of platelet alpha and delta (dense) granules which activate additional platelets, platelet aggregation mediated by von Willebrand factor or fibrinogen, and exposure to negatively charged platelet membrane phospholipids, providing a surface for procoagulant clotting factors.

Once activated, platelets enlarge and flatten, become pointed, and degranulate with the release of thromboxane A2 (TXA2), adenosine diphosphate (ADP), serotonin, calcium, fibrinogen, platelet factor 4, factor V, platelet-derived growth factor thromobospondin and vWF.

Platelets exposed to collagen plus thrombin form coated platelets that express high levels of procoagulant proteins with factor V, fibrinogen, fibronectin, and von Willebrand factor, providing a procoagulant surface supporting further fibrin generation.

Binding of platelets to collagen or to von Willebrand factor leads to partial activation of platelets and the coagulation process is most effectively initiated when enough thrombin is generated on or near the tissue factor bearing cells to trigger full platelet activation and activation of coagulation cofactors on the platelet surface.

When thrombin accumulates on tissue factor bearing cells it is responsible for activation of platelets, activating factor V, VIII, and disassociating factor VIII from von Willebrand factor, and activates factor XI.

Two major platelet receptors involved in platelet adhesion and activation are the von Willebrand factor receptor, glycoprotein Ibα, and GPVI, a signaling collagen receptor.

Following arterial rupture the initial platelet contact to exposed subendothelial collagen requires the binding of platelet membrane Ibα to immobilized von Willebrand factor and the VWF- Ibα interaction results in the slowing of the platelets permitting platelet GPVI to bind to collagen.

Provide a catalytic surface for the coagulation cascade to assemble enzyme complexes which enhance fibrin formation.

Activated during sepsis.

Expression of Toll-like receptors suggests platelets play a role in immune responses and may have a role in infectious inflammation and atherosclerosis.

Survey integrity of blood vessel wall to maintain normal circulation.

Positioned near the endothelial cell layer in arterial flow.

Significant spontaneous bleeding does not occur until the platelet count is 5000 micro/L or less.

Estimated that the daily loss of 7100 platelets/microL/day that are needed to maintain the integrity of the vessel wall.

Decreased platelet production can be seen with viral infections, following drug administration, during of the course of a malignant hematologic disease, after chemotherapy, after radiation, as a result of alcohol toxicity, and vitamins B12 or folic acid deficiency.

Increased platelet destruction can be seen in immunologic conditions such as idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, HELLP syndrome, and antiphospholipid syndrome.

Some viral infections can affect both platelet production and destruction.

Sepsis is the main cause of thrombocytopenia in severely ill or intensive care unit patients.

As many as 40% patients incidentally found to have a platelet count greater than 400,000 per cubic millimeter, in the absence of iron deficiency and benign inflammatory conditions, an occult cancer, most commonly a primary GI, lung, breast, or ovarian cancer.

Platelets actively promote cancer progression by protection of cancer cells from immune surveillance, by negotiation cancer cell arrest in the micro vasculature and promotion of angiogenesis.

Increased thrombopoietic cytokine production by tumor cells and both cells is a major reason for paraneoplastic thrombocytosis.

Paraneoplastic thrombocytosis is mediated by hepatic thrombopoietin synthesis that is increased in response to excessive tumor derived interleukin-6, increasing platelet counts, which in turn promote tumor growth.

Some of the risk for increased ischemic adverse events and death in diabetes may be related to platelet hyperactivity and altered platelet receptor and intracellular signaling pathways, including an up regulation of the P2Y12 pathway.

Patients with diabetes often have persistently high platelet reactivity in the presence of clopidogrel therapy.

Biologic assays for platelet function: light transmission aggregation, impedance whole blood aggregometry, dehydrothromboxane B2 level in urine, platelet function analyzer system, rapid platelet function assay, vasodilator-stimulated phosphoprotein phosphorylation assay.

Platelet function analyzer system and dehydrothromboxane test are specific for aspirin.

Vasodilator-stimulated phosphoprotein phosphorylation assay is specific for clopidogrel and similar compounds.

Platelet dysfunction may be due to many causes including: Medication, herbal supplements, renal failure, genetic abnormalities such as Glanzmann thrombasthenia, Bernard=Soulier syndrome, cardiopulmonary bypass circuit membrane use, extracorporal membrane oxygenation circuits, nonsteroidal anti-inflammatory drugs, aspirin, adenosine diphosphate receptor inhibitors, adenosine reuptake inhibitors, glycoprotein IIb/IIIa inhibitors, thromboxane inhibitors, and beta lactam antibiotics.

Thrombin is the most potent activator of platelets, so in DIC there is increased activation of platelets and they are consumed, resulting in thrombocytopenia.

Fibrin degradation products found in DIC can bind to GPIIB/IIIa and inhibit platelet aggregation.

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