1. Lecture NO- 12- Dr: Dalia Kamal Eldien

2.  Coagulation: Is the process by which blood changes from a liquid to a clot. Coagulation begins after an injury occur to the blood vessel, causing damage the endothelium lining the vessel. It results in hemostasis  Hemostasis: The cessation of blood loss from a damaged vessel, followed by repair, the opposite of hemostasis is hemorrhage.  Blood coagulation involving both a cellular (platelet) and a protein (coagulation factor) component

3.  Hemostasis comprises major events that occur in a set order following the loss of vascular integrity  The initial phase of the process is vascular constriction. This limits the flow of blood to the area of injury.  Next, platelets become activated by thrombin and aggregate at the site of injury, forming a temporary, loose platelet plug.  The protein fibrinogen is primarily responsible for stimulating platelet clumping, Platelets clump by binding to collagen that becomes exposed following rupture of the endothelial lining of vessels adhesion, activated platelets change their shape to accommodate the formation of the plugs.  To insure stability of the initially loose platelet plug, a fibrin mesh (also called the clot) forms and entraps the plug. If the plug contains only platelets it is termed a white thrombus ; if red blood cells are present it is called a red thrombus  Platelets plug at the site of injury is called primary hemostasis. Secondary hemostasis occurs simultaneously

5.  It is involves 12 coagulation factors (designated by Roman numerals as factors I through XII) found in blood plasma and several other blood components. The factors include prothrombin, thrombin, and fibrin, each has a precise role in coagulation, respond in a complex cascade to form fibrin entraps, which strengthen the platelet plug.  Thrombin converts Fibrinogen(soluble protein) to Fibrin monomers(insoluble strands) which polymerize to form a Fibrin clot.  The Fibrin clot acts with activated platelets at the site of the injury to form a blood clot that stabilizes the damaged tissue and prevents further blood loss.  Several coagulation cascade models have been proposed, including the intrinsic and extrinsic pathway

6.  In addition to directly generating active Fibrin, Thrombin activates Coagulation Factor XIII, which stabilizes Fibrin and promotes its polymerization.  Thrombin also activates Coagulation Factors V, VIII, and Protein C. These factors enhance or inhibit Thrombin production through positive or negative feedback.  Finally, the clot must be dissolved in order for normal blood flow to resume following tissue repair. The dissolution of the clot occurs through the action of plasmin

7.  A deficiency in clotting factors or a disorder that affects platelet production or one of the many steps in the entire process can disrupt clotting and severely complicate blood loss from injury, childbirth, surgery, and specific diseases or conditions in which bleeding can occur.

10. Definition:  Coagulation disorders deal with disruption of the body's abili ty to control blood clotting.  When you get injured, your blood normally begins to clot to prevent a massive loss of blood. Sometimes the mechanism that causes the blood to clot fails, resulting in rapid or prolonged bleeding (hemorrhage ) or obstructive clotting (thrombosis).  The most commonly known coagulation disorder is hemophilia, a condition in which patients bleed for long periods of time before clotting. There are other coagulation disorders with a variety of causes.

11.  Many causes are related to protein defects in the plasma. In some diseases, these proteins might be missing completely or they may be low in concentration. The majority of these defects are hereditary (passed from parent to child through genes). However, some may develop due to other medical conditions.  Liver disease  Low red blood cell count  Vitamin K deficiency  Medication side-effects

12.  The most common inherited bleeding disorders are: 1- Hemophilia : caused by a deficiency or lack of certain blood clotting factors, this disorder causes heavy or unusual bleeding  If you have hemophilia, you may bleed for a longer time after an injury than if your blood clotted normally.  Small cuts usually aren't much of a problem. The greater health concern is deep bleeding inside the body, especially in knees, ankles and elbows. That internal bleeding can damage the organs and tissues, and may be life-threatening.  Haemophilia A (clotting factor VIII deficiency) and represents 80% of haemophilia cases  Haemophilia B (factor IX deficiency)  hemophilia is genetic disorder is carried by females but most often affects males

13. 2- Von Willebrand’s disease: the most common inherited bleeding disorder; caused by a deficiency of von Willebrand factor, which helps blood platelets clump together and stick to a blood vessel wall 3- Disseminated intravascular coagulation. This disease accelerates clotting, which can actually cause hemorrhage. 4- Thrombocytopenia is the most common cause of coagulation disorder. It is characterized by a lack of circulating platelets in the blood. This disease also includes idiopathic thrombocytopenia. 5- Factor II, V, VII, X, XII deficiency : relate to blood clotting problems or abnormal bleeding problems

14. The main sign of a bleeding disorder is prolonged or excessive bleeding. The bleeding is normally heavier than normal and unprovoked. Other signs of a bleeding disorder include:  unexplained bruising  heavy menstrual bleeding  frequent nosebleeds

15.  Complete blood count (CBC): to check the amount of blood loss as well as the amount of red and white blood cells.  Platelet Count  platelet aggregation test  Bleeding time: to see how fast your blood vessels close to prevent bleeding  Clotting time

16.  Prothrombin Time (PT) : test measures how well and how long it takes your blood to clot. It normally takes about 25 to 30 seconds. It may take longer if you take blood thinners. Other reasons for abnormal results include hemophilia, liver disease, and male absorption. It is also useful in monitoring those who take medications that affect clotting such as warfarin.  Fibrinogen Level: Fibrinogen is a protein made by the liver. Abnormal results may be a sign of hemorrhage, fibrinolysis, or placental abruption (separation from the uterine wall).  Thrombin Time: measures how well fibrinogen is working. Abnormal results may be due to inherited fibrinogen disorders, liver disease, some cancers, and medications that affect clotting.

18. Thank you