الفهرس 
Role of Blood Cells and Coagulation System in Hemostasis and ThrombosisOnly 14 pages are availabe for public view
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Abstract
Stroke is an important cause of death and disability. In about 40% of all ischaemic strokes, no definite cause can be identified, despite extensive ancillary investigations (Lonneke et al., 2010).
Although ischemic stroke occurs mainly in elderly individuals aged 65 years or older,and the incidence of stroke rises exponentially with age, nowadays, it is increasingly found in young individuals, even in children (Visnja et al., 2013).
Traditional risk factors for stroke such as hypertension and diabetes are not very frequent in young adults (Ferro et al., 2010), and so there are an other important causes and risk factors associated with stroke in younger patients as hematologic and coagulation disorders.
Hypercoagulable states likely explain the high percentage of cases of cryptogenic cerebral infarction in young people (Naveed et al., 2006).
Several hematologic disorders and hemostatic defects increase risk of ischemic stroke. A common feature of these disorders is the creation of a prothrombotic state, now commonly referred to as “hypercoagulable state” . Hematologic abnormalities lead to thrombosis in the cerebral vasculature, causing ischemic cerebrovascular events; hematologic abnormalities are estimated to account for about 5% to 10% of all strokes, being higher in young people. There is accumulating evidence that hypercoagulable states play a role in the development of cerebrovascular diseases (Matijevic and Wu, 2006).
Management of cerebrovascular events is guided by the underlying etiology and is well studied for the established causes. However, in a significant proportion (particularly of young individuals) the origin of stroke remains unknown, or can be attributed to so-called “unusual” etiologies. Of these, strokes due to hematological disorders represent a non-negligible entity (Buhler and Mattle, 2009).
Ischemic strokes have been attributed to hematological disorders . Some hematological disorders have been shown to be causal, for others the association with cerebrovascular events is less certain because of the frequent coexistence of other vascular risk factors (Buhler and Mattle, 2009).
The maintenance of hemostasis requires a complex interplay between a large number of checks and balances in the coagulation pathways. Deficiencies of factors inhibiting coagulation (antithrombin III [AT III], protein S, and protein C), increased levels of factors promoting coagulation (factors V and VII), and decreased activity in the fibrinolytic pathway (plasminogen or plasminogen activator deficiencies) have all been implicated in ischemic stroke (Levine et al., 2005).
Numerous conditions are known to predispose to vascular thrombosis including cerebral vascular thrombosis, generally accepted or ”classically” acquired risk factors include advanced age, prolonged immobilisation, surgery, fractures, use of oral contraceptives and hormone replacement therapy, pregnancy, puerperium, Smoking, Obesity elevated cholesterol levels, Sepsis in disseminated infection, heart failure, autoimmune diseases, Diabetes, Uremia, cancer.
In addition to these well-established risk factors, several lines of evidence over the past few decades specify a role of hematologic and coagulation disorders associated with (Ischemic stroke). The most significant breakthrough has been the confirmation of the concept that hypercoagulable conditions are present in a large proportion of patients with ischemic stroke, these include Sickle-cell disease,Thalassemia, Nocturnal paroxysmal hemoglobinuria, Spherocytosis, Polycythemia vera , Anemia, Essential thrombocythemia, Reactive thrombocytosis, Thrombotic thrombocytopenic purpura (TTP), Hemolytic uremic syndrome (HUS), Idiopathic thrombotic thrombocytopenia (ITP), Heparin induced thrombocytopenia (HIT), leukemia, Lymphoma, Myeloma, Waldenstro¨m’s macroglobulinemia, Protein C deficiency, Protein S deficiency, Protein Z deficiency, Antithrombin III deficiency, Heparin cofactor II deficiency, Factor V Leiden mutation (APC), Prothrombin gene mutation (G20210A), Elevated factors V, VII, VIII, VWF, Elevated fibrinogen, Plasminogen deficiency Dysfibrinogenemia, Factor XII (Hageman factor) deficiency, Disseminated intravascular coagulation, Antiphospholipid syndrome, Hyperhomocysteinemia.
This broad list of genetic and acquired factors emphasizes that a single cause of venous thrombosis rarely exist alone and that this condition should be considered as a complex or multifactorial trait. (Naveed et al., 2006).
When ordering tests of coagulation in stroke patients, one should keep in mind whether the results will influence therapy and/or patient outcome. It is generally not advocated to screen all stroke patients for a “hypercoagulable workup” (Levine, 2005).
Extensive hematological evaluation of unselected patients will yield little useful information. Therefore, most stroke patients can be adequately evaluated with a routine hematological testing. A more thorough evaluation is warranted for patients with previous unexplained thrombotic episodes, combined venous and arterial thrombotic events, positive family history of recurrent thromboembolism, or patients with pathological laboratory findings. In patients with hereditary hematological disorders, studies should be extended to close relatives (Buhler and Mattle, 2009).
Many of these patients may benefit from urgent anticoagulation, steroids, chemotherapy, phlebotomy or plasmatic exchanges (Ombeline et al., 2011). Combining antiplatelet agents with anticoagulant therapy generally causes more bleeding complications and does not increase benefits to the patient (Allan, 2005).
If from clinical history, family history and/or laboratory studies, a patient is felt to have a hypercoagulable state, the decision for long term chronic anticoagulation needs to be individualized (Naveed et al., 2006).
The aim of this review is to highlight the significance of these hematologic and coagulation factors in ischemic stroke, and to assess their impact on treatment and long-term prognosis.
This review delineated the existing evidence regarding the association of blood disorders with stroke. we focus on the several hematological and coagulation disorders (the so called hypercoagulable states or thrombophilia) that are associated with ischemic stroke, and summarize the increasing information on the underlying pathophysiological mechanisms, determination of what, where , when and for whom stroke patient, recommended laboratory tests for the workup of hypercoagulable tests should be done, as well as on treatment options.