Haemostasis

Published on 03/04/2015 by admin

Filed under Hematology, Oncology and Palliative Medicine

Last modified 03/04/2015

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Haemostasis

Blood clotting is a critical defence mechanism which, in conjunction with inflammatory and general repair responses, helps protect the integrity of the vascular system after injury. The complex sequence of events described in detail below is activated within seconds of tissue damage. It is easiest to divide the description of normal haemostasis into a platelet component, with formation of a loose platelet plug at the site of injury, and a coagulation component, where there is generation of a more robust fibrin scaffold (thrombus) around the platelets. This approach facilitates understanding but in practice the two mechanisms are inextricably linked.

The role of platelets

Following damage to a blood vessel there is immediate vasoconstriction to slow blood flow and reduce the risk of exsanguination. The break in the endothelial cell barrier leads to the recruitment of platelets from the circulation to form an occlusive plug. Platelets interact both with the vessel subendothelial matrix (platelet ‘adhesion’) and with each other (platelet ‘aggregation’) (Fig 6.1). The first step in this process, adhesion, does not require platelet metabolic activity. It does, however, lead to the ‘activation’ of platelets.

Fig 6.1 Primary platelet adhesion, activation and aggregation.
vWF, von Willebrand factor.

Platelets are small disc-shaped particles produced in megakaryocyte cytoplasm which have a lifespan of around 10 days. They have no nucleus and no capacity for DNA biosynthesis but do have a complex infrastructure. Pores in the trilaminar platelet membrane connect with an open canalicular system allowing transport of agonists in and discharge of secretions out. The membrane receptors for agonists include:

the glycoprotein (GP) Ia/IIa complex (α₂β₁ integrin) and glycoprotein (GP) VI which are receptors for collagen

the GPIb/IX/V complex, a receptor for vessel wall von Willebrand factor (vWF) and thrombin

the GPIIb/IIIa complex (α_IIbβ₃ integrin), which is an agonist-induced receptor for fibrinogen and vWF (vWF is discussed in more detail on p. 74).

In the platelet cytoplasm are organelles including alpha granules (containing fibrinogen, vWF, thrombospondin and other proteins) and dense granules (containing small molecules such as ADP and calcium).

Platelet activation follows stimulation by agonists such as ADP and thromboxane A₂ interacting with surface receptors, or by direct contact with the vessel wall subendothelial matrix. Platelets convert from a compact disc to a sphere, surface receptors become activated, and cytoplasmic granules secrete their contents. The net effect is the mediation and reinforcement of aggregation and adhesion, and the promotion of further activation. Other circulating platelets adhere to the initial layer and a loose platelet plug is formed.

In addition to the formation of a physical barrier at the site of injury, platelets have a procoagulant action. The coagulation sequence described below completes much more rapidly in the presence of platelets. Following activation, platelets rearrange their membrane phospholipids and shed vesicles from their surface. The platelet surface and vesicles reveal binding sites for coagulation proteins leading to the creation of coagulation complexes (e.g. the ‘prothrombinase complex’) which accelerate formation of factor Xa and thrombin.

Coagulation

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