Pulmonary Embolism and vascular injury: What is the role of thrombin?

Lungs possess dynamic and complex coagulation-thrombolytic and inflammatory sets of innate reactive responses, which generate changes that cause a dramatic alteration in its parenchyma. Clinically, since its steps are reciprocally inter-connected, the pulmonary embolic injury is very complex to describe as one exclusive progression. For example, each step in a coagulation-fibrinolytic-inflammation-integrated pathway produces more side-steps, which later plays an important role in a specific lung damage description. In this clinical review, the enzyme thrombin, an ontogenetically very old and key blood coagulation serine protease is centrally placed as a mediator, activator and up-regulator of postpulmonary embolic damage to reveal its enormous flexibility in post-pulmonary embolism damage and its reparative processes. Additionally, some beneficial aspects of its control throughout its inhibition are discussed. ABBREVIATIONS: ADP adenosine 5 diphosphate; APC activated protein C; APTT activated partial thromboplastin time; ASA Acetylsalicylic acid; AT III antithrombin; C-IINH C-lInhibitor; EC endothelial cells; eNOS endothelial nitric oxide synthase; EPCR endothelial protein C receptor; FDP s fibrin degradation products; fibrin stabilization factor FSF; FM Fibrin monomer; GAG Glycosaminoglycans; GP glycoprotein; HC II Heparin cofactor II; HIT heparin induced thrombocytopenia; HMWK High Molecular Weight Kininogen; LDUH low dose unfractionated heparin; LMWH low molecular weight heparin (s); LV left ventricle ; MAP mean arterial pressure ; MLCK myosin light chain kinase; NO nitric oxide; PA pulmonary artery; PARs Proteinase (or protease)-activated receptors; PC protein C; PAI-l plasminogen activator inhibitor; PE pulmonary embolism; PF 4 platelet factor 4; PLA-2 phospholipase A 2; PN-I Protease Nexin; PT prothrombin time; RBC red blood cell ; RV right ventricle; SMC S s vascular smooth muscle cells ; t-Pa tissue plasminogen activator; TAFI thrombin activatable fibrinolysis inhibitor; TF tissue factor (factor III); TFPI Tissue factor pathway inhibitor; TM Thrombomodulin; TNF tumor necrosis factor; TXA 2 thromboxane A2; VEGF vascular endothelial growth factor ; vWfvon Willebrand factor.