Blood platelets are a nucleate fragments derived from bone marrow megakaryocytes. They are 1.5 – 3.0 μ m in diameter with a volume of ∼ 7 fL. Electron microscopy reveals a fuzzy coat (glycocalix) on the platelet surface composed of membrane glycoproteins (GP), glycolipids, mucopolysaccharides and plasma proteins. The plasma membrane is a bilayer of phospholipids in which cholesterol, glycolipids and glycoproteins are embedded.
Platelets have an elaborate channel system, the open canalicular system, which is composed of invaginations of the plasma membrane. In addition, they have a dense tubular system, a closed – channel network derived from the smooth endoplasmic reticulum; it is the major site of platelet thromboxane synthesis. The discoid shape of resting platelets is maintained by a cytoskeleton consisting of a spectrin membrane skeleton, a microtubule coil, and an actin scaffold.
Platelets contain several organelles: mitochondria and glycogen stores, lysosomes, dense granules and alpha granules. The dense (δ) granules contain calcium, ATP, ADP, magnesium and serotonin.
The alpha (α) granules contain numerous proteins, including β – thromboglobulin ( β TG) and platelet factor 4 (PF4), which are considered platelet – specific, several higher molecular mass coagulation factors, (e.g., fi brinogen, factor V, high molecular weight kininogen, factor XIII), von Willebrand factor (vWF), growth factors (e.g., platelet – derived growth factor, vascular endothelial growth factor), protease inhibitors (e.g., plasminogen activator inhibitor – 1, C1 inhibitor, amyloid – β – protein precursor), thrombospondin, P – selectin, albumin and IgG. The lysosomes contain acid hydrolases and other enzymes.
Platelet function in hemostasis
Following injury to the blood vessel, platelets adhere to exposed subendothelial collagen (adhesion), which involves among other events the interaction of a plasma protein, von Willebrand factor (vWF), and a specific glycoprotein complex on the platelet surface, glycoprotein (GP) Ib – IX – V. This interaction is particularly important for platelet adhesion under conditions of high shear stress (i.e., high blood flow). Glycoprotein VI also contributes to platelet adhesion to collagen under conditions of flow.
Adhesion is followed by recruitment of additional platelets which form clumps, a process called aggregation. This process involves binding of fibrinogen to specific platelet surface receptors — a complex comprised of glycoproteins IIb and IIIa (GPIIb – IIIa, integrin α IIb β 3). Binding of fibrinogen to platelets is a prerequisite for aggregation. On platelet activation, the GPIIb – IIIa complex undergoes a conformational change and acquires the ability to bind fibrinogen.
C. Secretion (release reaction)
Activated platelets release contents of their granules including from dense granule, alpha granules and the lysosomal vesicles. ADP and serotonin released from the dense granules further enhance the platelet activation processes. For example, ADP released from the granules interacts with receptors on platelets to enhance the activation process.
D. Platelet procoagulant activities
Several key enzymatic reactions of blood coagulation occur on the platelet membrane lipoprotein surface. During platelet activation negatively charged phospholipids, especially phosphatidylserine, translocate from the inner aspect of the plasma membrane to the platelet surface. This translocation is an essential step in accelerating specific coagulation reactions that occur on the platelet surface and leading to thrombin generation.
Regulation of platelet number
Platelets are produced from bone marrow megakaryocytes; approximately 1 × 10 11 platelets are produced daily. The normal platelet count is 150,000 – 400,000/ μ L (Atlas Figure 8). Platelets have a life – span in blood of 7 – 10 days. The number of circulating platelets is regulated by thrombopoietin (TPO), which is synthesized in the liver and binds to megakaryocytes and hematopoetic stem cells via the TPO receptor, c – Mpl. Because of this binding, there is an inverse relationship between platelet mass and circulating TPO levels.