الفهرس 
Physiology of Haemostasis and Blood CoagulationOnly 14 pages are availabe for public view
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Abstract
Perioperative thromboembolism is considered one of the most important causes of morbidity and mortality in the periopoerative period. Three primary influences predispose to thrombus formation, the so-called Virchow triad: (1) endothelial injury; (2) stasis or turbulence of blood flow; and (3) blood hypercoagulability. So a great effort is done in order to understand the normal haemostatic mechanism which will facilitate understanding of pathology of thrombus formation. The coagulation system is considered by many clinicians to consist just of platelets and clotting factors. For some time, however, it has been recognized that many more cellular and molecular components participate in the coagulation process, thereby forming a multifaceted, well-balanced system called haemostasis. Moreover, the coagulation system is not only made for forming clots but is also involved in a variety of defense systems, including tissue repair, defense against micro-organisms, autoimmune processes, arteriosclerosis, tumor growth and metastasis.
This was accompanied by side by side advances in the pharmacology of coagulation. For more than half a century, heparin and warfarin have defined anticoagulant therapy for the short-term and long-term management, respectively, of thrombotic disorders of the venous system. Recently LMWHs, fondparinux and direct thrombin inhibitors have replaced heparin and warfarin in many clinical situations because they are more effective and have less side effects. But the absence of antidote for this drugs limits their use.
New antiplatelet drugs have been approved and replaced aspirin e.g. ticlopidine, dipyridamole and tirofiban. These drugs act by discrete mechanisms, and thus in combination their effects are additive or even synergistic. Their availability has led to a revolution in cardiovascular medicine, whereby angioplasty and vascular stenting of lesions now is feasible with low rates of restenosis and thrombosis when effective platelet inhibition is employed.
The new thrombolytic drugs, Alteplase, seem to be superior to streptokinase in dissolving older clots and, ultimately, may be approved for other applications. Alteplase has a low affinity for free plasminogen in the plasma, but it rapidly activates plasminogen that is bound to fibrin in a thrombus or a haemostatic plug. Thus, alteplase is said to be fibrin selective, and at low doses, it has the advantage of lysing only fibrin, without unwanted degradation of other proteins notably fibrinogen. This contrasts with streptokinase, which acts on free plasminogen and induces a general fibrinolytic state.
The ideal drug for prophylaxis and treatment of thrombotic disease remains an agent that will inhibit thrombosis but not haemostasis.
This great advances increase the need for having guidelines for identifying patients with high risk and low risk for venous thrombosis, guidelines for thromboprophylaxis, guidelines for dealing with patients on regular anticoagulant therapy and for management of cases of acute intraoperative pulmonary embolism. Transoesophageal echocardiography and multidetector CT scan facilitate the diagnosis of acute pulmonary embolism and help rapid initiation of therapy.
Uncontrolled massive haemorrhage is an important cause of morbidity and mortality in surgical and trauma patients. Massive haemorrhage is often characterized by a surgical or vascular component and a coagulopathic component. The surgical/vascular component can be corrected by surgical intervention or embolization, however, coagulopathic bleeding is difficult to control.
Haemostatic agents play an important role in haemostasis. Antifibrinolytic agents have been employed to decrease blood loss during surgical procedures as in dental surgery, subarachnoid haemorrhage and prostatic surgery. These drugs include tranexamic acid and epsilon amino caproic acid. They are as effective as aprotinin in the setting of primary cardiac surgery and is far more cost-effective.
Aprotinin reduces transfusion requirements in many situations. Its use in CABG has been associated with reduction in blood transfusion. It has also an anti-inflammatory effect. However the manufacturer temporarily suspended the worldwide marketing of aprotinin after the results of Mangano and colleagues international cohort study which included increased risks of renal failure, myocardial infarction, and stroke and increased 5-year mortality with aprotinin but not with the lysine analogues.
Recombinant activated factor VII is a welling powerful initiator of haemostasis.
Desmopressin is useful in patients with mild haemophilia or type I von Willebrand’s disease who are undergoing surgery, it has also been used successfully to treat or prevent bleeding in patients with congenital or acquired defects of platelet function, chronic liver disease and uraemia.
Preoperative screening for defects in the coagulation system is recommended especially in major surgery e.g. CABG and liver transplantation. This can be done by proper history taking, clinical examination and investigations. Generally PT, aPTT, platelet count and bleeding time are sufficient.