|Home > Research|
People in Research
Mª Cristina L. Martins
Instituto de Engenharia Biomédica (INEB), Porto, Portugal
Blood compatibility is often referred to as haemocompatibility and is one aspect of biocompatibility. Blood compatibility relates to the specific interactions between biomaterials and circulating blood. Biocompatibility is defined as the ability of a material to perform with an appropriate response related to a specific application .
The human body is equipped with interrelated regulation systems. These systems’ purpose is to heal wounds and to protect against intrusion by foreign organisms. This overall regulation is termed “homeostasis” . When a biomaterial is brought into contact with blood, the first event that occurs is a rapid, almost immediate, adsorption of proteins onto its surface. The performance of the biomaterial is influenced by this film of adsorbed proteins. It can elicit adverse host responses, such activation of plasma enzyme cascades (coagulation, fibrinolytic, kinin and complement systems) and adhesion and activation of platelets and leukocytes [3-6]. These systems coordinate together in order to eliminate the biomaterial by isolation (fibrin) or degradation (phagocytosis combined with liberation of enzymes and reactive radicals) .
Generally, the first proteins to be adsorbed are the relatively abundant plasma proteins, such as albumin, fibrinogen, immunoglobulin G and fibronectin. These are soon replaced by trace proteins, including factor XII (Hageman factor) and high molecular weight kininogen (HMWK). This hierarchical adsorption process is called the “Vroman effect” [7-11]. The small amount of activated factor XII (XIIa) is the key enzyme in initiating the coagulation, fibrinolysis and kinin cascades. Activated factor XII and its fragments (XIIf) can potentially induce activation of the classical pathway of complement system [5, 6] (Figure 1).
Figure 1. Simplified schematic represents contact activation on biomaterials surface. The initial event is the adsorption of factor XII to the biomaterial where it is activated to form factor XIIa. Abbreviations for the following clotting factors are: prekallikrein (PK); kallikrein (K); high molecular weight kininogen (HMWK); factor XII (XII); activated factor XII (XIIa); factor XII fragment (XIIf); factor XI (XI); activated factor XI (XIa). Adapted from Spatnekar and Anderson .
Blood coagulation is a local cascade process whereby soluble plasma proteins become activated in response to vascular injury, leading to the formation of a fibrin clot that arrests blood flow [2, 12]. In the process, thrombin production leads to platelet activation. Platelet aggregates are part of the final clot.
Coagulation can be triggered either by surface-mediated reactions (intrinsic pathway), or by exposure to factors derived from damaged tissue (extrinsic pathway). The two processes join into a common path leading to the formation of an insoluble fibrin gel (Fig. 2) [2, 5, 6, 12].
Figure 2. Simplified schematic represents coagulation by activation of factor XII (intrinsic pathway) and factor VII / tissue factor (extrinsic pathway). Adapted from Spatnekar and Anderson .
The fibrinolytic system is designed to degrade unneeded blood clots by the action of plasmin, a specific protease which cleaves the fibrin networks that were formed during coagulation (Figure 3) [5, 6, 12].
Figure 3. Simplified schematic represents the fibrinolytic system. Adapted from Hanson and Harker .
The plasma kinin system is an enzymatic system that is triggered by activated factor XII.
The activation of prekallikrein into kallikrein by the activated factor XII occurs on the surface of biomaterials and in the fluid phase (Figure 4).
Figure 4. Simplified schematic represents kinin system.
The major function of kallikrein is to amplify the activation of coagulation and the fibrinolytic systems. Kallikrein also cleaves HMWK to produce bradykinin, a potent inflammatory mediator that produces vasodilation during the recruitment of leukocytes .