1. 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)

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

3. Platelet Plug Formation1 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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)

10. 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

11. 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

12. 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

13. 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

14. 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.

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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)

24. End of Chapter 19
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