Diseases of Platelets and Coagulation System PDF

Hemostasis Hemostasis: is a series of events that functions to arrest bleeding from damaged blood vessels and to maintain blood flow to all body tissues. depends on the integrity of – Blood vessels – Platelets – Coagulation factors ** Hemostatic abnormalit...

Hemostasis Hemostasis: is a series of events that functions to arrest bleeding from damaged blood vessels and to maintain blood flow to all body tissues. depends on the integrity of – Blood vessels – Platelets – Coagulation factors ** Hemostatic abnormalities can lead to excessive bleeding or thrombosis  Normal hemostasis comprises a series of regulated processes that maintain blood in a fluid, clot-free state in normal vessels while rapidly forming a localized hemostatic plug at the site of vascular injury. The pathologic counterpart of hemostasis is thrombosis, the formation of blood clot (thrombus) within intact vessels. Coagulation cascade It is a series of enzymatic conversions, turning inactive proenzymes into activated enzymes. Ending in the formation of thrombin which then converts fibrinogen into fibrin. fibrin strengthens the clot.  Steps in Hemostasis Formation of primary platelet plug due to adhesion of platelets to collagen. Conversion into permanent plug supported by fibrin. Intrinsic Pathway HMWK Prekallikeri n XII Surface XIIa Extrinsic Pathway XI XIa VIIa VII TF IX IXa VIII aX Xa Va Prothrombin Thrombin Fibrinoge Fibri n n XIII Cross linked afibrin  Initial Laboratory Tests For Bleeding Abnormalities Platelet count Partial thromboplastin time (PTT). Prothrombin time (PT). Thrombin time(TT). Partial thromboplastin time (PTT): - Screens for the activity of the proteins in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, and fibrinogen). - Recording the time required for clot formation (usually 28 to 35 seconds).  Partial Thromboplastin Time HMWK Prekallikerin Surface XII XIIa XI XIa VIIa VII TF IX IXa VIIIa X Xa Va Prothrombin Thrombin Fibrinogen Fibrin XIIIa Cross linked fibrin Prothrombin time (PT): - Screens for the activity of the proteins in the extrinsic pathway (factors VII, X, II, V, and fibrinogen). - The time to fibrin clot formation (usually 11 to 13 seconds) is recorded.  Prothrombin Time(PT) HMWK Prekallikerin Surface XII XIIa XI XIa VIIa VII TF IX IXa VIIIa X Xa Va Prothrombin Thrombin Fibrinogen Fibrin XIIIa Cross linked fibrin Thrombin time: is a screening coagulation test designed to assess fibrin formation from fibrinogen in plasma. The reference range for the thrombin time is usually less than 20 seconds (15-19 seconds).  Thrombin Time HMWK Prekallikerin Surface XII XIIa XI XIa VIIa VII TF IX IXa VIIIa X Xa Va Prothrombin Thrombin Fibrinogen Fibrin XIIIa Cross linked fibrin  Thrombus A thrombus is a blood clot that consists of platelets, fibrin, erythrocytes, and leukocytes. Can form anywhere in the circulatory system  Virchow’s triad Three conditions promote thrombus formation: - Endothelial injury - Sluggish blood flow - Increased coagulopathy  Embolus The consequences of thrombus formation: Dissolution, occlusion of a blood vessel, recanalization or embolus development. An embolus occurs when a portion or all of the thrombus breaks and travels through the circulatory system, eventually becoming embedded in a smaller vessel.  Diseases of the Platelets Platelets are vital components of the coagulation process. Normal platelet levels range from 150,000 to 350,000 cells/mL3. Thrombocytosis : increased platelet levels (increases the risk of thrombus formation) Thrombocytopenia: decreased platelet levels (increases the risk of bleeding). Diseases of the platelets include issues in quantity and quality of platelets.  Hemophilia A X-linked recessive bleeding disorder. Deficiency or abnormality of clotting factor VIII. The severity of the disorder varies depending on the amount of factor VIII present in the blood. Bleeding is the main symptom of the disease Treatment strategies include replacing clotting factors through transfusions  Von Willebrand’s Disease Most common hereditary bleeding disorder. It results from a deficit of von Willebrand factor. Clinical manifestations include abnormal bleeding.  Disseminated Intravascular Coagulation Life-threatening disorder that occurs as a complication of other diseases (e.g., serious acute infections). Normally, during injury, clotting factors become activated and travel to the injury site to help stop bleeding. In persons with DIC, these factors become abnormally active.  Consequently, small blood clots form within the blood vessels, and can occlude blood supply to tissue and organs. Over time, the clotting factors become used up. When this happens, the person is at risk for serious bleeding. Clinical manifestations of DIC include signs and symptoms of tissue and organ ischemia and/or abnormal bleeding. Management of DIC is complicated but starts with the identification and treatment of the underlying cause and replacement of platelets, coagulation factors to control severe bleeding..  Immune Thrombocytopenic Purpura The immune system destroying its own platelets. Circulating immunoglobulin G reacts with the platelets, which are then destroyed in the spleen and liver. Acute ITP is more common in children. Chronic ITP is more common in adults aged 20–50 and in women. Clinical manifestations take the form of abnormal bleeding.  Thrombotic Thrombocytopenic Purpura Resulting from a deficiency of an enzyme necessary for cleaving(inactivating) von Willebrand factor. This enzyme deficiency leads to increased clotting, which in turn decreases available platelets. TTP is characterized by thrombi, thrombocytopenia, and bleeding. Venous Thrombosis Mostly in superficial or deep veins of the legs. - Superficial vein thrombosis occur when there are varicosities. Manifestations: local congestion, swelling (edema), pain, tenderness, infections of overlying skin and development of varicose ulcers. (Rarely embolize) - Deep vein thrombosis is more serious; it may lead to pulmonary emboli, causes edema, pain and tenderness. Deep Venous Thrombosis (DVT) Occurs with stasis in the venous circulation due to heart failure. Sedentary life style and inactivity (trauma, surgery and burns). Vascular injury with release of clotting factors Conditions associated with DVT include: Cancers, advanced age, prolonged bed rest, post-operative, late pregnancy, and postpartum.