الفهرس 
Physiology of Coagulation SystemOnly 14 pages are availabe for public view
Abstract
Hemostasis is the process that maintains the integrity of a closed, high-pressure circulatory system after vascular damage. Vessel-wall injury and the extravasation of blood from the circulation rapidly initiate events in the vessel wall and in blood that seal the breach. Circulating platelets are recruited to the site of injury, where they become a major component of the developing thrombus. Blood coagulation, initiated by tissue factor, culminates in the generation of thrombin and fibrin.
The interactions between activated platelets and the clotting cascade, with their subsequent amplification, give rise to a hemostatic response that is rapid and localized to the injury site lead to thrombosis, vascular inflammation, and tissue damage.
Coagulation is modulated by a number of mechanisms: dilution of procoagulants in flowing blood, removal of activated factors through the reticuloendothelial system, and control of the activated procoagulants and platelets by natural antithrombotic pathways. Which play an active role in maintaining the fluidity of blood.
The patient with chronic Kidney Disease is at risk for clot formation, with VTE and stroke occurring more frequently as compared with their age-matched counterparts. In the presence of CKD, several conditions unique to this population influence the risk for thrombosis.
The mechanisms for increased coagulation are multifactorial. Patients with CKD are known to have increased levels of procoagulant factors. Simultaneously, decreases in endogenous anticoagulants and fibrinolytic activity might occur. Commonly used medications, such as erythropoietin stimulating agents, can also increase the risk of thromboembolism.
Drug elimination in the body involves many complex rate processes. The site of excretion is dependent on the solubility, ionization, and protein binding of the substance or its metabolites. The liver and kidneys are the most important sites of drug excretion, which is expressed as ‘clearance’ (renal and non-renal).
Renal disease generally reduces both glomerular filtration and tubular secretion. For drugs that are excreted by the kidneys, renal dysfunction may result in drug accumulation, and dose reduction or a prolongation in the administration interval may be required for such drugs. Dosage adjustment and close monitoring usually based on an estimation of renal function using the glomerular filtration rate.
Many anticoagulation methods have been pursued including low-dose heparin, low-molecular weight heparin, direct thrombin inhibitors, fondaparinux, warfarin and new oral anticoagulants. Data supporting the optimal prophylactic dose of low-molecular weight heparins (LMWH), direct thrombin inhibitors, and fondaparinux in CKD are unclear, but potentially lower than that used in patients with a creatinine clearance (CrCl) over 30 mL/min.
Warfarin can be used in patients with chronic renal impairment without dose adjustments since their metabolism is hepatic. Careful dosing and closer monitoring of the INR in patients with chronic renal impairment to avoid supra therapeutic values and bleeding complications.
The novel oral anticoagulants have a similar or slightly better efficacy and safety profile than the vitamin K antagonists in the general population and in patients with mildly to moderately decreased kidney function. In contrast with warfarin, none of the new oral anticoagulant drugs require routine coagulation monitoring due to their more predictable pharmacological profiles.
The anticoagulant effects of warfarin, apixaban, rivaroxaban, and edoxaban can be reversed by 4-factor prothrombin complex concentrate. Which can replete coagulation factors much faster than fresh-frozen plasma, with less volume overload, which is favorable to patients with advanced CKD and on dialysis who are prone to volume overload.
Clinical indications for systemic anticoagulation in various settings including venous thromboembolism (VTE), atrial fibrillation (AF), acute coronary syndromes (ACS), and heparin induced thrombocytopenia (HIT).
AF and CKD share several common risk factors (e.g., hypertension, diabetes, preexisting cardiovascular disease, obesity, metabolic syndrome). AF is highly correlated with atherosclerotic disease. CKD may increase the risk of AF through several mechanisms. chronic volume overload might lead to left ventricular hypertrophy and dilatation, poor ventricular compliance, and eventually increased left atrial size and pressure, established predictors of AF.
Arterial and venous thromboembolic diseases are prevalent in renal disease, and are associated with high morbidity and mortality. Increased risk of thromboembolic events is due to the alteration of many physiological mechanisms that lead to substantial changes in hemostasis. These are represented by increased atherosclerosis and endothelial damage, alteration in protein C metabolism.
HIT is an adverse immune mediated drug reaction that is associated with a high risk of venous and arterial thrombosis. Risk factors for HIT include duration and type of heparin exposure, patient population, severity of trauma, and gender. Although thrombocytopenia is the most common presenting feature of HIT, in up to 25% of patients with HIT the development of thrombosis precedes the development of thrombocytopenia. The first step in the treatment of HIT is discontinuation of all forms of heparin and LMWH.