Blood 3

platelet plug formation continued

As more platelets aggregate, they release more chemicals, aggregating more platelets, and so on, in a positive feedback cycle. Within one minute, a platelet plug is built up, further reducing blood loss. Platelets alone are sufficient for sealing the thousands of minute rips and holes that occur unnoticed as part of the daily wear and tear in your smallest blood vessels. Because platelet plugs are loosely knit, larger breaks need additional reinforcement.

thromboembolic disorders, Bleeding disorders, and DIC

Blood clotting is one of nature's most elegant creations, but it sometimes goes awry. The 2 major disorders of hemostasis are at opposite poles. Thromboembolic disorders result from conditions that cause undesirable clot formation. Bleeding disorders arise from abnormalities that prevent normal clot formation. Disseminated intravascular coagulation (DIC) involves both widespread clotting and severe bleeding.

atherosclerosis or inflammation

Conditions that roughen the vessel endothelium, such as atherosclerosis or inflammation, cause thromboembolic disease by allowing platelets to gain a foothold. Slowly flowing blood or blood stasis is another risk factor, particularly in bedridden patients and those taking a long flight in economy-class seats. In this case, clotting factors are not washed away as usual and accumulate so that clot formation finally becomes possible.

Disseminated intravascular coagulation

DIC is a situation in which widespread clotting occurs in intact blood vessels and the residual blood becomes unable to clot. Blockage of blood flow accompanied by serve bleeding follows. DIC is most commonly encountered as a complication of pregnancy or a result of septicemia or incompatible blood transfusions

platelet-derived growth factor (PDGF)

Even as clot retraction is occurring, the vessel is healing. Platelet-derived growth factor (PDGF) released by platelet degranulation stimulates smooth muscle cells and fibroblasts to divide and rebuild the wall. As fibroblasts form a connective tissue patch in the injured area, endothelial cells, stimulated by vascular endothelial growth factor (VEGF), multiply and restore the endothelial lining.

Heparin

Heparin, the natural anticoagulant contained in basophil and mast cell granules, is also found of the surface of the endothelial cells. It inhibits thrombin by enhancing the activity of antithrombin III. Like most other clotting inhibitors, heparin also inhibits the intrinsic pathway.

Blood typing

It is crucial to determine the blood group of both the donor and the recipient before blood is transfused. Because it is so critical that blood groups be compatible, cross matching is also done. Cross matching tests for agglutination of donor RBCs by the recipient's serum, and of the recipients RBCs by the donor serum. Typing for the Rh factors is done in the same manner as ABO blood typing.

ABO blood types

The ABO blood groups are based on the presence or absence of 2 agglutinogens, type A and type B. Depending on which of these a person inherits, his or her ABO blood group will be one of the following: A, B, AB, or O. The O blood group, which has neither agglutinogen, is the most common ABO blood group in white, black, Asian, and native Americans. AB, with both antigens, is least prevalent. The presence of either the A or the B agglutinogen results in group A or B.

Restoring blood volume

When a patient's blood volume is so low that death from shock is imminent, there may not be time to type blood, or appropriate whole blood may be unavailable. Such emergencies demand that blood volume be replaced immediately to restore adequate circulation.

whole blood transfusions

Whole blood transfusions are routine when blood loss is rapid and substantial. In all other cases, infusions of packed red blood cells (whole blood from which most of the plasma has been removed) are preferred for restoring oxygen-carrying capacity. The usual blood bank procedure involves collecting blood from a donor and then mixing it with an anticoagulant, such as certain citrate or oxalate salts, which prevents clotting by binding calcium ions. The shelf life of the collected blood at 4 degrees C is about 35 days. Because blood is such a valuable commodity, it is most often separated into its component parts so that each component can be used when and where it is needed.

prostaglandin (PGI2)

As a rule, platelets do not stick to each other or to the smooth endothelial linings of blood vessels. Intact endothelial cells release nitric oxide and a prostaglandin called prostacyclin (or PGI2). Both chemicals prevent platelet aggregation in undamaged tissue and restrict aggregation to the site of injury.

ADP, Serotonin, and thromboxane A2

However, when the endothelium is damaged and underlying collagen fibers are exposed, platelets adhere tenaciously to the collagen fibers. A large plasma protein called von Willebrand factor stabilizes bound platelets by forming a bridge between collagen and platelets. Platelets swell, form spiked processes, become stickier, and release chemical messengers including the following: -Adenosine diphosphate (ADP): a potent aggregating agent that causes more platelets to stick to the area and release their contents. -Serotonin and thromboxane A2 (a short lived prostaglandin derivative): messengers that enhance vascular spasm and platelet aggression.

Other antigens

Other antigens (such as MNS, Duffy, Kell, and Lewis factors) are mainly of legal academic importance. Because these factors cause weak or no transfusion reactions, blood is not specifically typed for them unless the person is expected to need several transfusions, in which case the many weak transfusion reactions could have cumulative effects. Here we describe only the ABO and Rh blood groups.

thrombopoietin

Platelet formation is regulated by a hormone called thrombopoietin. Their immediate ancestral cells, the megakaryocytes, are progeny of the hemocytoblast and the myeloid stem cell, but their formation is quite unusual. In this line, repeated mitosis of the megakaryoblast occur, but cytokinesis does not. The final result is the megakayocyte (literally "big nucleus" cell), a bizarre cell with a huge, multilobed nucleus and a large cytoplasmic mass.

Phase 2: common pathway to thrombin

Prothrombin activator catalyzes the transformation of the plasma protein prothrombin to the active enzyme thrombin.

transfusion reaction

When mismatched blood is infused, a transfusion reaction occurs in which the donor's red blood cells are attacked by the recipient's plasma agglutinins. (Note that the donor's plasma antibodies may also be agglutinating the host's RBCs, but they are so diluted in the recipients circulation that this does not usually present a serious problem).

fibrinolysis

A clot is not a permanent solution to blood vessel injury, and a process called fibrinolysis removes unneeded clots when healing has occurred. This cleanup detail is crucial because small clots are formed continually in vessels throughout the body. Without fibrinolysis, blood vessels would gradually become completely blocked.

Thrombocytopenia

A condition in which the number of circulating platelets is deficient, thrombocytopenia causes spontaneous bleeding from small blood vessels all over the body. Even normal movement leads to widespread hemorrhage, evidenced by many small purplish spots, called petechiae, on the skin. Thrombocytopenia can arise from any condition that suppresses or destroys the red bone marrow, such as bone marrow malignancy, exposure to ionizing radiation, or certain drugs. A platelet count of under 50,000/ul of blood is usually diagnostic for this condition. Transfusions of concentrated platelets provide temporary relief from bleeding.

Aspirin

A number of drugs, most importantly aspirin, heparin, and warfarin, are used clinically to prevent undesirable clotting in patients at risk for heart attack or stroke. Aspirin is an antiprostaglandin drug that inhibits thromboxane A2 formation (in this way, it blocks platelet aggregation and platelet plug formation). Clinical studies of men taking low-dose aspirin (one aspirin every 2 days) over several years demonstrated a 50% reduction in incidence of heart attack.

Erythroblastosis fetalis

An important problem related to the Rh factor occurs in pregnant Rh- women who are carrying Rh+ babies. The first such pregnancy usually results in the delivery of a healthy baby. But when bleeding occurs as the placenta detaches from the uterus, the mother may be sensitized by her baby's Rh+ antigens that pass into her bloodstream. If so, she will form anti-Rh antibodies unless treated with RhoGAM before or shortly after she has given birth. (the same precautions are taken in women who have miscarried or aborted the fetus). RhoGAM is a serum containing anti-Rh agglutinins. By agglutinating the Rh factor, it blocks the mother's immune response and prevents her sensitization.

Bleeding disorders

Anything that interferes with the clotting mechanism can result in abnormal bleeding. The most common causes are platelet deficiency (thrombocytopenia) and deficits of some procoagulants, which can result from impaired liver function or certain genetic conditions.

factors preventing undesirable clotting

As long as the endothelium is smooth and intact, platelets are prevented from clinging and piling up. Also, antithrombic substances-- nitric oxide and prostacyclin--secreted by the endothelial cells normally prevent platelet adhesion. Additionally,vitamin E quinone a molecule formed in the body when vitamin E reacts with oxygen, is a potent anticoagulant.

Antigens

At least 30 groups of naturally occurring RBC antigens are found in humans, and many variants occur in individual families rather than in the general population. The presence or absence of each antigen allows each persons blood cells to be classified into several different blood groups. Antigens determining the ABO and Rh blood groups causes vigorous transfusion reactions (in which the foreign erythrocytes are destroyed) when they are improperly transfused. For this reason, blood typing for these antigens is always done before blood is transfused.

Phase 1: 2 pathways to prothrombin activator

Clotting may be initiated by either the intrinsic or the extrinsic pathway. In the body both pathways are usually triggered b the same tissue-damaging events. Clotting of blood outside the body (such as in a test tube) is initiated only by the intrinsic pathway. Before we examine the "why" of these differences, lets see what these pathways have in common.

anticoagulants

Factors that inhibit clotting are called anticoagulants. Whether or not blood clots depends on a delicate balance between clotting factors and anticoagulants. Normally, anticoagulants dominate and clotting is prevented, but when a vessel is ruptured, procoagulant activity in that area increases dramatically and a clot begins to form. Clot formation is normally complete within 3 - 6 minutes after blood vessel damage.

coagulation continued

Figure 17.14 illustrates the way clotting factors act together to form a clot. The coagulation sequence looks intimidating at first glance, but 2 things will help you cope with its complexity. First, realize that in most cases, activation turns clotting factors into enzymes by clipping off a piece of the protein, causing it to change shape. Once one clotting factor is activated, it activates the next in sequence, and so on, in a cascade. 2 important exceptions to this generalization are fibrinogen and calcium, as we will see below.

plasma expanders

Fundamentally, blood consists of proteins and cells suspended in a salt solution. Replacing lost blood volume essentially consists of replacing that isotonic salt solution. Normal saline or a multiple electrolyte solution that mimics the electrolyte composition of plasma (for example, Ringer's solution) are the preferred choices. You might think that it would be important to add materials to mimic the osmotic properties of albumin in blood, and indeed this has been widely practiced. However, studies have shown that plasma expanders such as purified human serum albumin's, hetastarch, and dextran provide no benefits over much cheaper electrolyte solutions and are associated with significant complications of their own. Volume replacement restores adequate circulation but cannot, of course, replace the oxygen-carrying capacity of the lost RBCs. Research on ways to replace the capability by using artificial blood substitutes is ongoing.

universal donor and universal recipients

Group O RBCs bear neither the A nor the B antigen, so theoretically this blood group is the universal donor. Indeed, some laboratories are developing methods to enzymatically convert other blood types to type O by clipping off the extra (A- or B- specific) sugar molecule. Since group AB plasma is devoid of antibodies to both A and B antigens, group AB people are theoretically universal recipients and can receive blood transfusions form any of the ABO groups. However, these classifications are misleading, because they do not take into account the other agglutinogens in blood that can trigger transfusion reactions.

heparin

Heparin is also prescribed as an anticoagulant drug, as is warfarin, an ingredient in rat poison. Administered in inject able form, heparin is the anticoagulant most used in the hospital (for preoperative and postoperative cardiac patients and for those receiving blood transfusions). Taken orally warfarin is a mainstay of outpatient treatment to reduce the risk of stroke in those prone to atrial fibrillation, a condition in which blood pools in the heart. Warfarin works via a different mechanism than heparin-- it interferes with the action of vitamin K in the production of some procoagulants

Erthyroblastosis fetalis continued

If the mother is not treated and becomes pregnant again with an Rh+ baby, her antibodies will cross through the placenta and destroy the baby's RBCs, producing a condition known as hemolytic disease of the newborn, or erythroblastosis fetalis. The baby becomes anemic and hypoxic. In severe causes, brain damage or even death may result unless transfusions are done before birth to provide the fetus with more erythrocytes for oxygen transport. Additionally, one or 2 exchange transfusions are done after birth. The baby's Rh+ blood is removed, and Rh- blood is infused. Within 6 weeks, the transfused Rh- erythrocytes have been broken down and replaced with the baby's own Rh+ cells.

embolus

If the thrombus breaks away from the vessel wall and floats freely in the bloodstream it becomes an embolus. An embolus ("wedge") is usually no problem until it encounters a blood vessel too narrow for it to pass through. Then it becomes an embolism, obstructing the vessel. For example, emboli that become trapped in the lungs (pulmonary embolisms) dangerously impair the ability of the body to obtain oxygen. A cerebral embolism may cause a stroke.

Blood transfusions in the early 80's

In addition, the dependance of patients with hemophilia on blood transfusions or factor injections has caused other problems. In the past, many became infected by the hepatitis virus and, beginning in the early 1980's, by HIV, a blood transmitted virus that depresses the immune system and causes AIDS. New infections are now avoided as a result of new testing methods for HIV, availability of genetically engineered clotting factors, and hepatitis vaccines.

Vascular Spasm

In the first step, the damaged blood vessels respond to injury by constricting (vasoconstriction). Factors that trigger this vascular spasm include direct injury to vascular smooth muscle, chemicals released by endothelial cells and platelets, and reflexes initiated by local pain receptors. The spasm mechanism becomes more and more efficient as the amount of tissue damage increases and is most effective in the smaller blood vessels. The spasm response is valuable because a strongly constricted artery can significantly reduce blood loss for 20-30 minutes, allowing time for platelet plug formation and blood clotting to occur.

fibrin stabilizing factor

In the presence of calcium ions, thrombin also activates factor XIII (fibrin stabilizing factor), a cross-linking enzyme that binds the fibrin strands tightly together, forming a fibrin mesh. Cross-linking further strengthens and stabilizes the clot, effectively sealing the hole until the blood vessel can be permanently repaired.

Platelet plug formation

In the second step, platelets play a key role in hemostasis by aggregating (sticking together), forming a plug that temporarily seals the break in the vessel wall. They also help to orchestrate subsequent events that lead to blood clot formation.

plasma proteins

Most clotting factors are plasma proteins synthesized by the liver. They are numbered I to XIII according to the order of their discovery; hence, the numerical order does not reflect their reaction sequence. All (except tissue factor) normally circulate in blood in inactive form until mobilized. Although vitamin K is not directly involved in coagulation, this fat-soluble vitamin is required for the synthesis of 4 of the clotting factors.

hemostasis

Normally blood flows smoothly past the intact blood vessel lining (endothelium). But if blood vessel wall breaks, a whole series of reactions is set in motion to accomplish hemostasis, or stoppage of bleeding. Without this plug-the-hole defensive reaction, we would quickly bleed out our entire blood volume from even the smallest cuts.

preventing clots from becoming to big

Once the clotting cascade has begun, it continues until a clot is formed. Normally, 2 homeostatic mechanisms prevent clots from becoming unnecessarily large: (1) swift removal of clotting factors and (2) inhibition of activated clotting factors. For clotting to occur in the first place, the concentration of activated procoagulants must reach certain critical levels. Clot formation in rapidly moving blood is usually curbed because the activated clotting factors are diluted and washed away. For the same reasons, further growth of a forming clot is hindered when it contracts blood flowing normally.

other mechanisms that block the final step

Other mechanisms block the final step in which fibrinogen is polymerized into fibrin. They work by restricting thrombin to the clot or by inactivating it if it escapes into the general circulation. As a clot forms, almost all of the thombin produced is bound onto the fibrin threads. This is an important safeguard because thrombin also exerts positive feedback effects on the coagulation process prior to the common pathway. Not only does it speed up the production of prothrombin activators by acting indirectly through factor V, but it also accelerates the earliest steps of the intrinsic pathway by activating platelets. By binding thrombin, fibrin effectively acts as an anticoagulant preventing the clot from enlarging and thombin from acting elsewhere.

agglutinogens (antigens)

People have different blood types, and transfusion of incompatible blood can be fatal. RBC plasma membranes, like those of all body cells, bear highly specific glycoproteins at their external surfaces, which identify each of us as unique from all others. These glycoproteins serve as antigens, which are anything the body perceives as foreign, including bacteria and their toxins, viruses, cancer cells, or mismatched RBCs. One person's RBC proteins may be recognized as foreign is transfused into someones with a different red blood cell type, and the transfused cells may be agglutinated (clumped together) and destroyed. Since these RBC antigens promote agglutination, they are more specifically called agglutinogens.

PF3 and prothrombin activator

Pivotal components in both pathways are negatively charged membranes, particularly those on platelets containing phosphatidlyserine also known as PF3 (platelet factor 3). Many intermediates of both pathways can be activated only in the presence of PF3. The intermediate steps of each pathway cascade toward a common intermediate, factor X. Once factor X has been activated, it complexes with calcium ions, PF3, and factor V to form prothrombin activator. This is usually the slowest step of the blood clotting process, but once prothrombin activator is present, the clot forms in 10 to 15 seconds.

Platelets continued

Platelets are essential for the clotting process that occurs in plasma when blood vessels are ruptured or their lining is injured. By sticking to the damaged site, platelets form a temporary plug that helps seal the break. Platelets age quickly because they are anucleate, and they degenerate in about 10 days if they are not involved in clotting. In the meantime, they circulate freely, kept, mobile but inactive by molecules (nitric oxide, prostacyclin) secreted by endothelial cells lining the blood vessels.

Platelets

Platelets are not cells in the strict sense. About 1/4 the diameter of a lymphocyte, they are cytoplasmic fragments of extraordinarily large cells (up to 60 um in diameter) called megakaryocytes. In blood smears, each platelet exhibits a blue-staining outer region and an inner area containing granules that stain purple. The granules contain and impressive array of chemicals that act in the clotting process, including serotonin, Calcium a variety of enzymes, ADP, and platelet-derived growth factor (PDGF)

Symptoms and treatment of hemophilia

Symptoms of hemophilia begin early in life. Even minor tissue trauma causes prolonged bleeding into tissues that can be life threatening. Commonly, the person's joints become seriously disabled and painful because of repeated bleeding into the joint cavities after exercise or trauma. Hemophilia's are managed clinically by transfusions of fresh plasma or injections of the appropriate purified clotting factor. These therapies provide relief for several days but are expensive and inconvenient.

plasmin, plasminogen and tPA

The crucial natural "clot buster" is a fibrin-digesting enzyme called plasmin, which is produced when the plasma protein plasminogen is activated. Large amounts of plasminogen are incorporated into a forming clot, where it remains inactive until the blood vessel causes the endothelial cells to secrete tissue plasminogen activator (tPA). Activated factor XII and thrombin released during clotting also serve as plasminogen activators. As a result, most plasmin activity is confined to the clot, and any plasmin that strays into the plasma is quickly destroyed by circulating enzymes. Fibrinolysis begins within 2 days and continues slowly over several days until the clot is finally dissolved.

Extrinsic pathway

The extrinsic pathway is: 1. triggered by exposing blood to a factor found in tissues underneath the damaged endothelium. This factor called tissue factor (TF) or factor III. 2. Called extrinsic because the tissue factor it requires is outside of blood 3. Faster because it bypasses several steps of the intrinsic pathway. In severe tissue trauma, it can promote clot formation in 15 seconds.

autologous transfusions

The risk of transfusion reactions and transmission of life-threatening infections (particularly HIV) from pooled blood transfusions has increased public interest in autologous transfusions. In autologous transfusions, the patient predonates his or her blood, and it is stored and immediately available if needed during or after an operation. They are particularly sought by people considering elective surgery who are in no immediate danger. Iron supplements are given, and as long as the patient's postoperative hematocrit is at least 30%, one unit (400-500 ml) of blood can be collected every 4 days, with the last unit taken 72 hours prior to surgery.

Phases 1, 2 and 3

The second strategy that will help you cope is to recognize that coagulation occurs in 2 phases, each with a specific end point: Phase 1: 2 pathways to prothrombin activator. A complex substance called prothrombin activator is formed Phase 2: Common pathway to thrombin. Prothrombin activator converts a plasma protein called prothrombin into thrombin, an enzyme. Phase 3: Common pathway to the fibrin mesh. Thrombin catalyzes the joining of fibrinogen molecules present in plasma to a fibrin mesh, which traps blood cells and effectively seals the hole until the blood vessel can be permanently repaired.

hemophilia

The term hemophilia refers to several different hereditary bleeding disorders that have similar signs and symptoms. Hemophilia A, or classical hemophilia result from a deficiency of factor VIII (antihemophiliac factor). It accounts for 77% of cases. Hemophilia B results from a deficiency of factor IX. Both types are X-linked conditions and so occur primarily in males. Hemophilia C, a less severe form of hemophilia seen in both sexes, is die to a lack of factor XI. The relative mildness of this form, as compared to the A and B forms, reflects the fact that the procoagulants (factor IX) that factor XI activates may also be activated by factor VII.

Coagulation - procoagulants

The third step, coagulation or blood clotting, reinforces the platelet plug with fibrin threads that act as a "molecular glue" for the aggregated platelets. The resulting blood clot (fibrin mesh) is quite effective in sealing larger breaks in a blood vessel. Blood is transformed from a liquid to a gel in a multistep process that involves a series of substances called clotting factors, or procoagulants.

Rh factor

There are 50 different types of Rh aggultinogens, each of which is called an Rh factor. Only 3 of these, the C, D, and E antigens are fairly common. The Rh blood typing system is so named because the Rh antigen (agglutinogen D) was originally identified in rheus monkeys. Later, the same antigen was discovered in humans. Most Americans (about 85%) are Rh+ (Rh positive), meaning that their RBCs carry the D antigen. As a rule, a person's ABO and Rh blood groups are reported together, for example, O+, A-, and so on.

transfusion reaction continued

These events lead to 2 easily recognized problems: (1) The oxygen carrying capability of the transfused blood cells is disrupted, and (2) the clumping of red blood cells in small vessels hinders blood flow to tissues beyond those points. Less apparent, but more devastating, is the consequence of hemoglobin escaping into the bloodstream. Circulating hemoglobin passes freely into the kidney tubules, causing cell death and renal shutdown. If shutdown is complete (acute renal failure), the person may die.

Phase 3: common pathway to fibrin mesh

Thrombin catalyzes the transformation of the soluble clotting factor fibrinogen into fibrin. The fibrin molecules then polymerize (join together) to form long, hairlike, insoluble fibrin strands. (notice that, unlike other clotting factors, activating fibrinogen does not convert it into an enzyme, but instead allows it to polymerize.) The fibrin strands glue the platelets together and make a web that forms the structural basis of the clot. Fibrin makes plasma become gel-like and traps formed elements that try to pass through it.

antithrombin III and protein C

Thrombin not bound to fibrin is quickly inactivated by antithrombin III, a protein present in plasma. Antithrombin III and protein C, another protein produced in the liver, also inhibit the activity of other intrinsic pathway procoagulants.

effects of transfusion reactions

Transfusion reactions can also cause, fever, chills, low blood pressure, and rapid heartbeat, nausea, vomiting, and general toxicity, but in the absence of renal shutdown, these reactions are rarely lethal. treatment of transfusion reactions is directed toward preventing kidney damage by administrating fluid and diuretics to increase urine output, diluting and washing out the hemoglobin.

antibodies (agglutinins)

Unique to the ABO blood groups is the presence in the plasma of preformed antibodies called agglutinins. The agglutinins act against RBCs carrying ABO antigens that are not present on a person's own RBCs. A newborn lacks these antibodies, but they begin to appear in the plasma within 2 months and reach adult levels between 8 and 10 years of age. A person with neither the A nor the B antigen (group O) possesses both anti- A and anti-B antibodies, also called a and b agglutinins. Those with group A blood have anti-B antibodies, while those with group B have anti-A antibodies. Neither antibody is produced by AB individuals.

Rh factor continued

Unlike the ABO system antibodies, anti-Rh antibodies are not spontaneously formed in the blood of Rh- (Rh negative) individuals. However, if an Rh- person receives Rh+ blood, the immune system becomes sensitized and begins producing anti-Rh antibodies against the foreign antigen soon after the transfusion. Hemolysis does not occur after the first such transfusion because it takes time for the body to react and start making antibodies. But the second time, and every time thereafter, a typical transfusion reaction occurs in which the recipient's antibodies attack and rupture the donor RBCs.

formation of platelets

When formed, the megakaryocyte presses up against a sinusoid (the specialized type of capillary in the red marrow) and sends cytoplasmic extensions through the sinusoid wall into the bloodstream. These extensions rupture, releasing the platelet fragments like stamps being torn from a sheet of postage stamps and seeding the blood with platelets. The plasma membranes associated with each fragment quickly seal around the cytoplasm to form the grainy, roughly disc-shaped platelets, each with a diameter of 2-4 um. Each micro-liter of blood contains between 150,000 and 400,000 of the tiny platelets.

Impaired liver functions

When the liver is unable to synthesize its usual supply of procoagulants, abnormal, and often severe, bleeding occurs. The causes can range from an easily resolved vitamin K deficiency (common in newborns and after taking systemic antibiotics) to nearly total impairment of liver function (as in hepatitis or cirrhosis). Liver cells require vitamin K for production of the clotting factors, and dietary deficiencies are rarely a problem because bacteria that reside in the large intestine produce vitamin K. However, vitamin K deficiency can occur if fat absorption is impaired, because vitamin K is a fat soluble vitamin that is absorbed into the blood along with fats. In liver disease, the nonfunctional liver cells fail to produce not only procoagulants, but also bile that is required for fat and vitamin K absorption.

clot retraction and serum

Within 30 to 60 minutes, the clot is stabilized further by a platelet-induced process called clot retraction. Platelets contain contractile proteins (actin and myosin), and they contract in much the same manner as muscle cells. As the platelets contract, they pull on the surrounding fibrin strands, squeezing serum (plasma minus the clotting proteins) form the mass, compacting the clot and drawing the ruptured edges of the blood vessel more closely together.

thrombus

Despite the body's many safeguards, undesirable intravascular clotting, called "hemostasis in the wrong place" by some, sometimes occurs. A clot that develops and persists in an unbroken blood vessel is called a thrombus. If the thrombus is large enough, it may block circulation to the cells beyond the occlusion and lead to death of those tissues. For example, if the blockage occurs in the coronary circulation of the heart (coronary thrombosis), the consequences may be death of heart muscle and a fatal heart attack.

3 steps of hemostasis

The hemostasis response is fast, localized, and carefully controlled. It involves many clotting factors normally present in plasma as well as some substances that are released by platelets and injured tissue cells. During hemostasis, 3 steps occur in rapid sequence: (1) vascular spasm, (2) platelet plug formation and (3) coagulation, or blood clotting. Blood loss at the site is permanently prevented when fibrous tissue grows into the clot and seals the hole in the blood vessel.

blood loss of the body

The human cardiovascular system is designed to minimize the effects of blood loss by (1) reducing the volume of the affected blood vessels, and (2) stepping up the production of red blood cells. However, the body can compensate for only so much blood loss. Losses of 15-30% causes pallor and weakness. Loss of more than 30% of blood volume results in severe shock, which can be fatal.

initial events

The initial event, agglutination of the foreign red blood cells, clogs small blood vessels throughout the body. During the next few hours, the clumped red blood cells begin to rupture or are destroyed by phagocytes, and their hemoglobin is released into the bloodstream. (when the transfusion reaction is exceptionally severe, the RBCs are lysed almost immediately).

differences in pathways

The intrinsic and extrinsic pathways usually work together and are interconnected in many ways, but there are significant differences between them.

Intrinsic pathway

The intrinsic pathway is: 1. triggered by negatively charged surfaces such as activated platelets, collagen, or glass (this is why this pathway can initiate clotting in a test tube) 2. Called intrinsic because the factors needed for clotting are present within (intrinsic to) the blood. 3. Slower because it has many intermediate steps.