Hemostasis Hemostasis is a sequence of responses that stops bleeding When blood vessels are damaged or ruptured, the hemostatic response must be quick, localized to the region of damage, and carefully controlled in order to be effective Three mechanisms reduce blood loss Vascular spasm Formation of a platelet plug Blood clotting (coagulation)

Hemostasis Vascular spasm occurs as damaged blood vessels constrict Platelets adhere to damaged endothelium to form a platelet plug

Platelet Plug Formation 1 2 3 Red blood cell Platelet Collagen fibers and damaged endothelium Liberated ADP, serotonin, and thromboxane A2 Platelet plug Platelet adhesion Platelet release reaction Platelet aggregation 1 2 Red blood cell Platelet Collagen fibers and damaged endothelium Liberated ADP, serotonin, and thromboxane A2 Platelet adhesion Platelet release reaction 1 Red blood cell Platelet Collagen fibers and damaged endothelium Platelet adhesion Platelet Plug Formation

Hemostasis Clotting (coagulation) is possible because of the presence of several clotting proteins normally dissolved (soluble) in the blood. Coagulation occurs in a cascading fashion whereby one activated clotting protein triggers the next step in the process, which triggers the next, and so on - once activated, the soluble clotting factors become insoluble There are 2 pathways to activate the system

Stages of Clotting PROTHROMBINASE THROMBIN STRENGTHENED FIBRIN THREADS Tissue trauma Tissue factor (TF) Blood trauma Damaged endothelial cells expose collagen fibers (a) Extrinsic pathway (b) Intrinsic pathway Activated XII Ca2+ platelets Platelet phospholipids Activated X Activated PROTHROMBINASE V Prothrombin (II) THROMBIN Loose fibrin threads STRENGTHENED FIBRIN THREADS Activated XIII Fibrinogen (I) XIII (c) Common pathway 1 2 3 + Tissue trauma Tissue factor (TF) Blood trauma Damaged endothelial cells expose collagen fibers (a) Extrinsic pathway (b) Intrinsic pathway Activated XII Ca2+ platelets Platelet phospholipids Activated X Activated PROTHROMBINASE V Prothrombin (II) THROMBIN (c) Common pathway 1 2 + Tissue trauma Tissue factor (TF) Blood trauma Damaged endothelial cells expose collagen fibers (a) Extrinsic pathway (b) Intrinsic pathway Activated XII Ca2+ platelets Platelet phospholipids Activated X Activated PROTHROMBINASE V 1 Stages of Clotting

Hemostasis The extrinsic pathway has few steps and occurs rapidly, often within seconds, once the protein “tissue factor” (TF) leaks into the blood The intrinsic pathway is more complex and occurs more slowly in response to damage to endothelial cells or phospholipids released by activated platelets

Hemostasis Both the extrinsic and intrinsic clotting pathways converge at a common point (pathway) where factor X becomes activated (Xa) In this second stage of blood clotting prothrombin is converted to thrombin which in turn converts soluble fibrinogen to insoluble fibrin threads

Hemostasis The mineral Ca2+ plays an important role throughout the clotting system, and many steps have positive or negative feedback on various other steps to propagate the process, yet maintain control Clot retraction is the consolidation of the fibrin clot. As the clot retracts, it pulls the edges of the damaged vessel closer together, decreasing the risk of further damage – new endothelial cells can then repair the vessel lining

Fibrinolysis Because blood clotting involves amplification and positive feedback cycles, a clot has a tendency to enlarge, creating the potential for impairment of blood flow through undamaged vessels The fibrinolytic system dissolves small, inappropriate clots; it also dissolves clots at a site of damage once the damage is repaired both body tissues and blood contain substances that can activate plasminogen to become plasmin, (the enzyme that actively dissolves clots)

Intravascular Clotting Blood clots sometimes form unexpectedly within the cardiovascular system. Clotting in an unbroken blood vessel (usually a vein) is called thrombosis; the clot itself, called a thrombus Such clots may be initiated by roughened endothelial surfaces of a blood vessel resulting from atherosclerosis, trauma, or infection

Intravascular Clotting Intravascular clots may also form when blood flows too slowly (stasis), allowing clotting factors to accumulate locally and initiate the coagulation cascade Having an undamaged blood vessels with smooth surfaces, good circulation, and non-sticky platelets are important factors that inhibit thrombosis administration of anticoagulants and platelet inhibiting drugs (aspirin-like drugs) can also hinder thrombus formation or reverse a thrombus that has formed

Intravascular Clotting A thrombus may become dislodged and be swept away in the blood. When a blood clot, air bubble, piece of fat or other debris is transported by the bloodstream, it is called an embolus In the worst circumstances (pulmonary embolism or stroke), emboli can obstruct a blood vessel and cause ischemia to the tissue beds distal to the obstruction

Blood Components Blood transfusion is the process of transferring blood or blood products from one person to another Almost all donated blood in the U.S. is separated into its various components to make better use of it Whole blood is fractionated into units of packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and WBCs Albumin, coagulation factors, and antibodies can be individually collected

Plasma vs. Serum If the liquid part of blood is allowed to coagulate it is called serum - serum is just plasma without the clotting factors Serum is stable at room temperature and can be stored on a shelf it is also used for diagnostic testing because it won’t coagulate in the machine and mess it up! The liquid serum in the blood tube is put into testing machines to check a chemistry panels, lipid panels, etc.

Blood Groups Red cells (and all cells in the body) have proteins on their surface which act as antigens or surface markers Even within the same species, the antigens of one individual are not necessarily compatible with those of another. For this reason, before donor blood cells can be transfused to another person the major surface antigens must be determined the most significant of the 100 markers currently known to exist on RBCs are the A and B antigens

Blood Groups In transfusion medicine the presence or absence of the A and B red cell antigens forms the basis of the ABO blood group system Another major red cell antigen is the Rh antigen, which 85% of the population have, and comprises another important blood grouping

Blood Groups For reason that are not totally clear, serum contains anti-ABO antibodies of a type opposite to the ABO antigen on the red cell surface For instance, those with A antigens on their red cells have anti-B antibodies in their serum

Blood Groups By knowing the status of the A antigen, B antigen, and Rh antigen, most of the major blood incompatibility issues can be avoided Type AB individuals are “universal recipients” because they has neither anti-A nor anti-B antibodies in their serum that would destroy transfused RBCs Type O individuals are “universal donors” because their RBCs have no antigens on the cell surface that can potentially react with the recipients serum

Blood Groups Blood typing for ABO status is done using single drops of blood mixed with different antisera Agglutination with an antisera indicates the presence of that antigen on the RBC

Rh Incompatibility Normally, blood plasma does not contain anti-Rh antibodies; individuals whose RBCs have the Rh antigen are said to be Rh+ while those who lack the Rh antigen are Rh- Rh incompatibility can cause problems with any blood transfusion, so it is screened just as carefully as the ABO group perhaps the biggest problem with Rh incompatibility, however, involves mother and child in pregnancy

Rh Incompatibility If blood from an Rh+ fetus sensitizes an Rh- mother during birth, anti-Rh antibodies will form in the blood of that woman. During her next pregnancy those antibodies can cross the placenta to affect the next baby Hemolytic disease of the newborn (HDN) results when an Rh+ fetus develops in the womb of an Rh- woman

Rh Incompatibility To prevent HDN, mothers who are Rh- are given a injection of RhoGAM - a commercially produced anti-Rh antibody – at various points in her pregnancy The administered RhoGAM destroys any Rh+ cells from the baby before the mother’s immune system can become sensitized to them and produce her own anti-Rh antibody. For this same reason, RhoGAM is given to Rh- patients who have abortions or miscarriages

Transfusion Reactions In a blood transfusion, if the recipient receives the wrong blood type, antigen-antibody reactions will cause a rapid destruction (hemolysis) of the donor red blood cells Giving the wrong type blood can cause the patient to develop a fever, develop serious renal failure, or go into shock. The most common cause is clerical error (i.e. the wrong unit of blood being given to the patient)

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