Platelet Formation and Function

• Platelets are part of the formed elements of blood.

Platelet Physical Description

• Platelets are oval/spherical in shape
• They are 3 microns in size, smaller than red blood cells (7-8 microns)
• There are roughly 250,000 platelets per cubic mm of blood.

Thrombopoiesis and Platelet Formation

• Platelets are formed in red bone marrow
• They originate from large precursor cells called megakaryocytes
• Megakaryocytes undergo fragmentation, pinching off bits of cytoplasm to form platelets
• Platelets are considered fragments of cells rather than actual cells, hence the disuse of the term "thrombocytes."

Platelet Components

• Platelets contain many granules
• They have adenosine diphosphate, which promotes platelet aggregation
• Platelet factors (phospholipids) aid in clotting
• Serotonin brings local vasoconstriction
• Platelets contain actin and myosin

Platelet Function

• Platelets aid in hemostasis, a 2 step clotting process, involving activation/aggregation of platelet plug, then blood clotting

Platelet Plug Formation (Stage I)

• Vessel damage initiates the process by tearing endothelial cells of the inner lining, exposing collagen
• Collagen promotes formation of the von Willebrand factor (vWf)
• vWf is a plasma protein secreted by cells and platelets that promote platelet adhesion to endothelial cells
• Platelets adhere, activate, and aggregate, releasing substances that amplify the response
• Chemical mediators are released:
  • Adenosine Diphosphate (ADP) stimulates more platelets to adhere via positive feedback
  • Serotonin acts as a local vasoconstrictor
  • Thromboxane A2 has a positive feedback effect on platelets and promotes platelet adhesion
• Chemical mediators lead to vascular smooth muscle contraction within damaged vessels, causing vasoconstriction
• A platelet plug forms with positive feedback promoting platelet adhesion

Regulatory Mechanisms

• The platelet plug forms only where the vessel is damaged, preventing clotting in nearby regions
• Endothelial cells of undamaged regions synthesize and release:
  • Prostaglandin I (PGI, or Prostacyclin)
  • Nitric Oxide (NO), a vasodilator
• PGI and NO inhibit platelet adhesion, activation, and aggregation

Blood Clotting

• Autocatalysis is involved, with thrombin as the main autocatalyst
• Vasoconstrictor action takes place through:
  • Reflex vasoconstriction in the injury region
  • Compression of the vessel via mass clotted blood (capillary adhesion)
  • Release of vasoconstrictor principle via lysis of platelets (serotonin)

Prothrombin Activation Inhibitors

• Heparin is an intrinsic anticoagulant produced in small amounts in humans, and in large amounts in leeches
• Antithrombin is an intrinsic inhibitor
• Citrates and oxalates are used experimentally, as they chelate calcium and inhibit clotting, since calcium is an important cofactor
• Rhubarb leaves are filled with oxalates and thus humans can only eat the stalks

Clotting Disorders

• Hemophilia is a sex-linked recessive trait on the X chromosome
• The underlying issue of Hemophilia is a deficiency in Factor VIII or others, affecting correct messenger production
• Females are generally not affected by hemophilia

Fibrinolytic System

• Plasminogen (profibrinolysin) converts to plasmin (fibrinolysin), leading to clot lysis
  • Tissue plasminogen activator (TPA) is secreted by endothelial cells to convert plasminogen into plasmin
  • Plasma activators, such as urokinase from kidney cells, activate it
  • Some bacteria produce streptokinase which can lyse clots exogenously
• Doctors may inject antifibrinolytic drugs like E-amino caproic acid to prevent the activation of plasminogen into plasmin in hemophiliac surgery patients

Terminology

• Coumadin (Warfarin) antagonizes Vitamin K, having a depressant effect on clotting factor production and is given to people vulnerable to clot formations
• Thrombus (thrombi) is a clot formed in a blood vessel, possibly from atherosclerosis
• Embolus (emboli) is a detached clot freely floating in a blood vessel
• Embolism is the occlusion of a vessel by a transported clot
• Thromboembolic condition is caused by:
  • Artery narrowing from atherosclerosis, plaque, infection, or trauma
  • Roughened interior activating the intrinsic clotting pathway
• People who have recently had surgery have a higher predisposition to a thromboembolic event
• Normal clotting time is 2-3 minutes, but can last up to 6 minutes
• Serum is the portion of blood after clot, blood cell, and platelet removal, it's plasma without clotting factors

Antigen-Antibody Reactions

• Agglutination is the clumping of donor and recipient red blood cells, often followed by hemolysis
• Antigens:
  • Are substances that induce antibody synthesis
  • Found on the surface of red blood cells
  • Synonymous with agglutinogens
  • An individual is born with these
  • They determine an individual's blood type
• Antibodies:
  • Are protein substances that combine with a certain antigen
  • Found in the plasma
  • Synonymous with agglutinins
  • These are not present at birth and develop over time

ABO Blood Groups

• Blood types are named for agglutinogens present on RBC membranes
  • Type A (41%) has Agglutinogen A, and Agglutinin Anti B
  • Type B (10%) has Agglutinogen B, and Agglutinin Anti A
  • Type AB (4%) is the universal recipient, has Agglutinogen A,B, and no Agglutinin
  • Type O (45%) is the universal donor, has no Agglutinogen, and Agglutinin Anti A, Anti B

Rh Blood Group

• The Rh factor is inherited from the Rhesus Monkey
  • Rh+ has the D agglutinogen in the RBC membrane (85%)
  • Rh- has no factor (15%) and no agglutinins in the plasma