CH 35 Blood Types Rh Factor Blood Transfusions & CH 36 Hemostasis Blood Coagulation

Question 1

Blood Antigen Systems

There are at least 30 types of antigens and hundreds of other rare types found on the membranes of red blood cells (RBCs). There are two antigen systems that cause these life-threatening reactions—the ABO system and the Rh system. The other surface antigens are used for determining parentage. Antigens are also called _____________because they cause RBC
agglutination.

Answer 1

agglutinogen

Question 2

ABO Blood Types
Blood types are determined by the presence of the surface antigens. There are four major blood types named after their type of surface antigens:

1. type A—A antigens are present
2. type B—B antigens are present
3. type AB—both A and B antigens are present
4. type O—no surface antigens present

Answer 2

KNOW THESE BASICS

Question 3

Genetic Determination of Blood Type
• Two genes, one from each of the chromosomes inherited from the mother and father, determine the
child’s blood type.

Relative frequency of the different blood types:

O BLOOD IS 47%
A BLOOD IS 41%
B BLOOD IS 9%
AB BLOOD IS 3%

Answer 3

KNOW THIS

Question 4

Rh Factor System

Antigen D is what the Rh factor is based on because it causes the most serious antigen-antibody reaction.

• If you have antigen D—your are Rh____________
• If you do not have antigen D—you are_____________

Answer 4

positive (Rh+)

Rh negative (Rh-)

Question 5

Just as in the ABO system, plasma antibodies develop if the surface antigen is NOT present.

• Therefore, ____ has the D antigen so it does not develop antibodies.
• _____ does not have the D antigen so develops anti-D
antibodies.

Answer 5

Rh+

Rh-

Question 6

Transfusion Reactions

I. Reactions From Mismatched Blood Types

When blood types are mismatched, the RBCs agglutinate (clump) as a result of the agglutinins (antibodies) binding to the surface antigens. Each agglutinin can attach to two or more RBCs at one time causing the cells to “clump”. These clumps can cause _________ in the small blood vessels throughout the circulatory system.

Answer 6

blockages

Question 7

Within a few hours to a few days, the membranes of the RBCs destroyed by the antibodies (________) OR they are phagocytized by WBCs. Either way, hemoglobin molecules are released into the plasma which results from the hemolysis of the RBCs.

Answer 7

hemolysins

Question 8

____________ hemolysis is from the immediate destroying the cell membrane by the hemolysins while ____________ hemolysis results from phagocytosis by the WBCs. Immediate is far less common than agglutination followed by delayed hemolysis because there has to be a high number of hemolysins available to activate immediate.

Answer 8

Immediate

delayed

Question 9

Example of mismatched blood type reaction:

Donor blood = type A—has plasma anti-B antibodies (agglutinins) Recipient blood = type B—has RBCs with type B surface antigens. The transfused blood from the donor will begin to agglutinate in the recipient—the
recipient’s plasma agglutinins will agglutinate with the mismatched donor’s RBCs. This is called a ______ _______

Answer 9

transfusion reaction.

Question 10

Transfusion reaction is going to cause either immediate or delayed hemolysis in which ___ is released from the destroyed RBCs and enters the blood plasma. As Hb is broken down, the __________( porphyrin) parts become bilirubin which is excreted by the liver in bile. If the concentration of bilirubin rises high enough, it causes the skin and internal tissues to take on a yellow color from the bile pigment—this is jaundice.

Answer 10

Hb

non-iron

Question 11

Kidney shutdown seems to result from three causes:

1. An increase of_________released into circulation from the hemolysis of the RBCs. This causes powerful renal vasoconstriction—less blood entering the kidneys.
2. With hemolysis, there is a decrease in circulating RBCs so this along with the vasoconstriction and presence of a high number of toxins it causes __________ shock.
3. With excess _____in circulation, they leak through the glomerular membrane into the renal tubules and causes a blockage of the tubules.

**These three factors together cause acute renal shutdown and the person could die within one week to 12 days unless treated by dialysis (an artificial kidney).

Answer 11

toxins

circulatory

Hb

Question 12

Rh Transfusion Reactions

With repeated exposure to Rh+ blood transfusions, the person who is Rh- will become more strongly “_________” (immunized) to the Rh factor and the transfusion reactions will become more severe similar to mismatched ABO transfusion reactions.

Answer 12

sensitized

Question 13

______ _________ (Hemolytic Disease of the New Born) This is a disease that begins during fetal formation and is characterized by the agglutination and phagocytosis of the fetus’s RBCs.

In most cases, this condition is caused by an Rh-
mother and an Rh+ father. The baby inherits the Rh+ factor from the father and the mother develops anti-Rh (anit-D) agglutinins (antibodies) from exposure to the fetus’s Rh+ surface antigens. The mother’s anti-Rh agglutinins diffuse through the placenta into the fetus’s blood circulation and causes RBC agglutination.

Answer 13

Erythroblastosis Fetalis

***In the first pregnancy, the mother does not develop enough anti-Rh agglutinins to cause any harm to the fetus.
• In the second pregnancy, about 3% of babies exhibit signs of the disease.
• In third pregnancy, incidence increases to about 10%

Question 14

Clinical Picture of Erythroblastosis Fetalis

The cause of death from the disease is usually severe anemia but those infants who survive exhibit permanent mental impairment and damage to motor areas of
the brain because of precipitation of bilirubin in the neuronal cells which destroys the cells—condition is called ___________

Answer 14

kernicterus.

Question 15

Treatment of Erythroblastosis

• Replacement of the newborn’s Rh+ blood with Rh-
blood—about 400 ml of Rh- blood are infused over a 1½ to 2 hour period while the Rh+ blood is removed.

• This procedure is repeated several times in the first few
_______ of life in order to keep ________ levels low and prevent kernicterus.

• It takes at least 6 weeks for the infants own Rh+ RBCs to replace the infused Rh- cells and destroy the anti-Rh
agglutinins from the mother.

Answer 15

weeks

bilirubin

Question 16

_______________—(a) the stoppage or arrest of bleeding (b) the prevention of blood loss

When a blood vessel is ________ or_________, hemostasis occurs through several mechanisms:

1. vasoconstriction—vascular spasm of affected blood vessel
2. platelet aggregation—for formation of platelet plug
3. thrombin and fibrin synthesis—for formation of fibrous
   (mesh) tissue
4. blood coagulation—for formation of blood clot

Answer 16

Hemostasis

severed or ruptures

Question 17

Vasoconstriction

1. Immediately following a cut or rupture, the trauma to the blood vessel wall causes the _________ muscle lining the vessel to contract—this instantaneously reduces the flow of blood from the damaged vessel.
2. This contraction primarily results from vascular spasm (local myogenic spasm)—the more severely the vessel is damaged, the __________degree of vascular spasm.
3. Secondarily, contraction is sustained by activation of local _________ substances (autacoid factors) that work like hormones to maintain vasoconstriction.
4. A third mechanism that assists with vasoconstriction are nervous system _________ initiated by pain receptors in the vessel or nearby tissue.

Answer 17

smooth

greater

vasoconstrictor

reflexes

Question 18

Formation of the Platelet Plug–1

Platelets (___________) are formed in the bone
marrow from _____________ which are large cells but fragment into platelets either in the bone marrow
or shortly after entering blood circulation.

Answer 18

thrombocytes

megakaryocytes

Question 19

Formation of the Platelet Plug—2

Platelets contain many active factors such as
___________ proteins (actin & myosin), mitochondria to
produce ATP & ADP, endoplasmic reticulum to store
Ca2+, and a growth factor that helps repair vessel
damage.
• They have a surface ________ that prevents
adherence to normal endothelium but is highly
attracted to injured endothelial cells and to exposed
collagen.
• Also contain glycoprotein that activate multiple
stages of the blood-clotting process.

Answer 19

contractile

glycoprotein

Question 20

. Mechanism of the Platelet Plug—1

__________—platelets are attracted to the damaged
vascular surface and begin to stick (adhere) to the
exposed sub-endothelial collagen.

Answer 20

Adhesion

Question 21

Mechanism of the Platelet Plug—2

Adhesion of platelets initiates platelet activation
where the platelets (1) swell, (2) take on irregular
shapes with pseudopods protruding from their
surfaces, (3) they become sticky to adhere to the
collagen and to a protein called ___ ________ factor,
and (4)secrete ADP and _______________A2.

Answer 21

von Willebrand

thromboxane

Question 22

Mechanism of the Platelet Plug—3

___________—the ADP and thromboxane in turn
activate other nearby platelets to stick to the original
activated platelets. This increasing number of
platelets sticking together is called platelet
___________________
• All these platelets form a loose platelet plug and in the
next stage, the fibrin strands provide a mesh for blood
coagulation forming a stronger plug and eventually a
_______ __________

Answer 22

Aggregation

aggregation.

blood clot.

Question 23

Blood Coagulation x 7

1 • The third mechanism of hemostasis is the formation of the blood clot.
2 • The clot begins to develop within a few seconds of the vascular wall being damaged.
3 • Activator substances are released from the damaged ____________cells, the platelets and blood proteins are attracted to the injury.
4 • After the platelets agglutinate,________ fibers provide the mesh for blood cells to adhere.
5 • Within 3 to 6 minutes after the injury to the vessel, the entire opening in the vessel is filled with a clot.
6 • Within 20 minutes to an hour, the platelets and the clot retract (clot retraction) closing the injured site even more.
7 • The clot becomes a completely fibrous tissue within 1 to 2 weeks because of _________ activity.

Answer 23

endothelium

fibrin

fibroblast

Question 24

Blood Coagulation Details

It is thought that over 50 substances are found in the blood and in the tissues that either:

(a) promote coagulation—called ______________ OR
(b) inhibit coagulation—called ___________

Under “normal, healthy” conditions, the anticoagulants dominate so that circulating blood flows through the blood vessels without clotting.

• When blood vessels are severed, procoagulants in the area become “activated”
and override the anticoagulants so that a clot can form.

Answer 24

PROcoagulants

ANTIcoagulants.

Question 25

General Mechanism of Blood Coagulation–1
• There are essentially 3 steps involved in blood clot formation:

1. In response to (a) damage to the blood vessel and (b)
   trauma to the blood itself, a cascade of chemical
   reactions occur involving over a dozen blood clotting
   factors that form substances called ________activators.
   Extrinsic pathway is initiated by vessel trauma
   Intrinsic pathway is initiated by blood trauma

Answer 25

prothrombin

Question 26

General Mechanism of Blood Coagulation–2
• There are essentially 3 steps involved in blood clot formation:

2. These prothrombin activators (thromboplastin) along
   with Ca2+ catalyze the conversion of prothrombin into
   __________

Answer 26

thrombin.

Question 27

General Mechanism of Blood Coagulation
• There are essentially 3 steps involved in blood clot formation:

3. Thrombin is a protein enzyme that removes 4
   peptides from ____________forming one fibrin
   monomer which then polymerizes with other
   monomers to form long fibrin fibers. These cross- linked fibrin polymers constitute the____________ of the
   blood clot.

Answer 27

fibrinogen

reticulum

Question 28

QUICK FACTS:

Prothrombin is a plasma protein (α2-globulin) formed in the liver. If the liver fails to produce prothrombin, in a day or two, prothrombin concentration falls low enough that normal _________ ____________cannot occur.
• Prothrombin is an unstable protein and splits easily into smaller substances such as _________
• The liver requires vitamin __ to activate prothrombin and other clotting factors.

Answer 28

blood coagulation

thrombin.

K

Question 29

Positive Feedback Cycle of Clot Formation X 4

1• Once a blood clot begins developing, it initiates a positive feedback to promote more and more clotting until the blood leakage stops.
2• Thrombin itself perpetuates the cycle by acting with _____and ______ ___ to continually have a proteolytic effect on prothrombin thus causing other clotting factors to form prothrombin activators which then converts prothrombin into more thrombin.
3• The rate limiting factor in blood coagulation is usually the formation of ________activator and NOT the subsequent chemical (clotting factors) reactions.
4• Although prothrombin activator is the rate limiter, the subsequent reactions in either the intrinsic or extrinsic pathways cannot occur without __________

Answer 29

Ca2+

Factor V (Labile Factor)

prothrombin

Ca2+ (factor IV).

Question 30

Interaction Between Extrinsic and Intrinsic Pathways

1• Endothelium (tissue) damage initiates the ________
pathway.
2• Blood cell damage and platelets coming into contact with sub-endothelium collagen initiates the ________ pathway.
3• Initiation of blood coagulation processes begins in both pathways simultaneously.
4• However, the ________ pathway is more explosive; with
severe tissue trauma, evidence of clotting in this pathway
can occur in as little as 15 seconds.
5• The speed of clotting in the _______pathway is slower
(requires 1 to 6 minutes to cause clotting) as it requires
additional activating steps before reaching the “common
pathway”.
6• The common pathway is where prothrombin is converted to thrombin and the following steps until cross-linked fibrin polymers are formed.

Answer 30

extrinsic

intrinsic

extrinsic

intrinsic

Question 31

Clot Retraction

• Platelets are necessary for clot formation to occur.
Therefore, if clot formation fails to occur, there are not
enough circulating blood platelets.

Platelets contribute to clot retraction in 2 ways:

1. Platelets entrapped in the clot release fibrin-stabilizing
   factor which causes more and more __________ bonds
   between adjacent fibrin fibers.
2. Platelets contribute to clot contraction by activating
   actin, myosin, and thrombosthenin which are all contractile proteins. These helps compress the fibrin meshwork into a more compact mass. As the clot retracts, it pulls the edges of the damaged blood vessel together which further contributes to _________

Within a few minutes of clot formation, fluid is expressed from the clot. This fluid is called________
________ does NOT contain fibrinogen or all of the clotting
factors so it cannot coagulate (clot).

Answer 31

cross-linked

hemostasis.

serum.

serum.

Question 32

Anticoagulants —Intravascular Anticoagulants

Prevention of blood clotting under normal conditions:

1. a protein called _________ is bound to the endothelial membrane and when thrombomodulin
   binds to thrombin (forming a thrombomodulin-thrombin complex), it slows the clotting process by removing thrombin.
2. If the endothelium becomes damaged, the smoothness,glycocalyx coating and thrombomodulin
   layers are lost which sets up activation of the platelets and clotting factors. Fibrin fibers and __________ are two powerful anticoagulants.

Heparin has to combine with antithrombin III to have an anticoagulant effect. Herparin increases the ability of
antithrombin III to remove ___________ by a thousand-fold (very powerful). The concentration of heparin in the blood is low so intravascular levels are not high enough to be effective. Heparin is produced by the mast cells that produce basophils so the basophils also release a small amount of heparin. The normal level of heparin is useful in the lungs and liver because these areas are susceptible to small embolic clots from slow flowing blood.

Answer 32

thrombomodulin

Antithrombin III

thrombin

Question 33

Lysis of Blood Clots

Over time (the amount of time depends on the amount of damage), the clot is dissolved and replaced with normal tissue. ___________is the process of dissolving the clot. Plasminogen (a plasma protein) is activated by t
-PA and other factors and becomes ________. Plasmin
digests the fibrin fibers, fibrinogen, prothrombin and
other blood clotting factors. WBCs, through phagocytosis, remove products of clot dissolution

Answer 33

Fibrinolysisis

plasmin

Question 34

Excessive Bleeding Conditions

1. vitamin ____ contributes to adding a carboxyl group onto five clotting factors. Without vitamin ___, sufficient coagulation cannot occur.
2. Hemophelia—a bleeding disorder that occurs almost exclusively in males. In 85% of the cases, hemophelia
   is caused by an abnormality or deficiency of clotting Factor VIII (called ______________).
3. ___________—is caused by platelet deficiency. Like hemopheliacs, they have a tendency to bleed but in this case, they are tiny bleeds in the venules or capillaries. As aresult, the skin has many small purplish blotches (called thrombocytopenic purpura).

Answer 34

k

k

hemophilia A

Thrombocytopenia

Question 35

Thromboembolic Conditions

1. Thrombus—an abnormal blood clot, usually caused by roughened ___________ tissue (resulting from atherosclerosis or infection) which initiates the clotting process. Also, a thrombus can form as blood flows slowly through vessels and significant quantities of thrombin and other procoagulants are present.
2. Emboli originating in the larger arteries on _____side of the heart flow to the periphery and can plug smaller arteries or arterioles in the brain, kidneys, etc.
3. Emboli originating in the venous system or ______ side of the heart flow to the lungs causing an pulmonary embolism.

Answer 35

endothelial

left

right

Question 36

Femoral Venous Thrombosis (Deep Vein Thrombosis)

Blood clotting often begins when blood flow is blocked for many hours—complete bed rest, crossing the legs, propping the legs over an arm of a chair or sofa, etc The clot grows in the direction of the slow moving blood flow and can sometimes grow the entire length of the leg veins

If the clot is large enough to occlude both pulmonary arteries at the same time,_____ _______occurs. If only one pulmonary artery is occluded, death could still occur within hours to days because the clot can continue to grow while lodged in the pulmonary artery.

Answer 36

sudden death

***Treatment with t-PA can save the life.

Question 37

Anticoagulants for Clinical Use

Anticoagulant drugs have been developed to combat the coagulation of some thromboembolic conditions. Two common ones are:
1. ________—derived from various animal tissues and prepared in almost a pure form. A small amount changes clotting time from the normal 6 minutes to more
than 30 minutes. This change in clotting time immediately slows further development of the thromboembolic condition. The enzyme heparinase
dissolves the injected heparin in 1½ to 4 hours.
2. __________— the most widely known are Coumadin and Warfarin and decrease the amount of active
prothrombin and other clotting factors. Warfarin
decreases the availability of vitamin K. After administration of warfarin , coagulant activity decreases to 50% of normal by the end of 12 hours and to about 20% of normal at the end of 24 hours. The decrease in coagulation activity is not immediate, it takes time for the
prothrombin and other clotting factors to degrade. Normal cogagulation returns in 1 to 3 days after discontinuing coumarin therapy

Answer 37

Heparin

Coumarins