Blood and Blood Clotting

BLOOD & clotting

Specific Objectives

1.       describe the mechanisms that contribute to blood clotting  

2.       identify the stages involved in blood clotting

3.       describe how chemicals called serotonin and Thromboxane A2 (released by platelets) play a role in Haemostasis

4.       describe the terms used to describe the difference between stationary versus moving blood clots

5.       describe the similarities and differences between the extrinsic and the intrinsic pathways of blood clotting

6.       describe the role of vitamin K in blood clotting

7.       list the 4 common blood types of the ABO blood group system

8.       describe which antibodies are found circulating in each of the respective ABO blood types (if any)

9.       Describe the Rh antigen.

10.   distinguish between the terms Rh negative and Ph positive  

11.   describe the complications that can occur when there is a mismatch between a mother who is Rh positive and a baby who is Rh negative , and what if anything that can be done to prevent problems.

Definition: The sequence (cascade) of reactions that prevent blood loss from a broken vessel.

 It's a fast, localized, and carefully controlled process. It occurs within seconds to minutes of the injury. Has three phases:

1. Vascular spasms – constriction of damaged blood vessels. Triggers include:

-          Direct injury to vascular smooth muscle

-          Presence of chemicals released by endothelial cells and platelets especially serotonin.

-          Reflexes initiated by local pain receptors

2. Platelet plug formation – sealing the vessel walls .Platelets adhere to exposed collagen fibers, become sticky, and form spiked processes. Attachment to collagen fibers activates the release of several chemicals including:

-          Serotonin – enhances the vascular response

-          Adenosine diphosphate (ADP) – attract platelets to site of injury

-          Thromboxane A2 – stimulates positive feedback cycle

-          PGI₂ limits the platelet plug formation to the site of injury

3. Coagulation or blood clotting – Blood clotting (coagulation) is normally complete within 3-6 minutes after blood vessel damage. In summary blood is transformed from a liquid to a gel. Consists of three crucial steps:

-          Formation of prothrombin activator. Step 1 can be divided into Two Separate mechanisms, called the Intrinsic Pathway and the Extrinsic Pathway. Intrinsic Pathway is initiated from damage from within the blood vessel (e.g., damage to endothelial lining exposes Collagen Fibers that, in turn, activate clotting factors within or intrinsic to the blood).  Platelets participate. Extrinsic Pathway-activated by chemicals released from damaged tissue, that is by factors Outside (Extrinsic to) the blood.

 Note:  Extrinsic Pathway has Fewer Steps than the intrinsic pathway, and, thus, is more rapid than the intrinsic pathway (e.g., in cases of Severe Tissue Trauma, the Extrinsic mechanism may clot blood within 15 seconds).
       :  a typical cut on the skin will activate both the Extrinsic and the intrinsic pathways.  How?  Well, damaged tissues in the area of the cut will activate the extrinsic pathway.  Also blood vessel damage inside the skin will exposes collagen fibers that activate clotting factors Intrinsic to the blood (the intrinsic pathway).
Disease Atherosclerosis might put one at risk for activation of the intrinsic pathway.  Narrowing of blood vessels----> increased Blood Pressure ----> increased risk of damaging blood vessels from within.  Thus, there is increased risk of blood clot formation of person with "hardening of arteries."
-The liver synthesizes many of the clotting factors present within the blood.  Almost all of these clotting factors exist in an inactive form until they are acted upon by something else.  Clotting Factor X is common to both intrinsic and extrinsic pathways.
 --exists in an inactive form until acted upon by intrinsic or extrinsic pathway.
Extrinsic pathway:  tissue factor TF, clotting factor VII activate---> Activated Factor X.
Intrinsic pathway:  platelet Factors XII, XI, IX, and VIII act on Factor X (inactive) ---> Activated Factor X.

-          Conversion of prothrombin to the active enzyme called thrombin

-          Activation of Fibrinogen to Fibrin by thrombin. Which forms a mesh that traps blood cells and seals the hole until the blood vessel can be permanently repaired.

Anticoagulants inhibit clot formation (e.g. Heparin, warfarin)

-unneeded clots are removed when healing has occurred (within 2 days of clot formation) by Fibrinolysis to prevent vessel blockage. Plasmin is the active digesting enzyme responsible for Fibrinolysis and is confined to the clot

Vitamin K is necessary for the synthesis of 4 clotting factors prothrombin (II), VII, IX, and X)

Calcium is also necessary for proper blood clotting.  Chelators like EDTA and Citrate Phosphate Dextrose will bind up the calcium in a test tube, and prevent the blood from clotting.  Useful in "blood banking" clinics.

Factors Limiting Clot Growth or Formation:

-          Size of clot is limited by the rapid removal of clotting factors and inhibition of activated clotting factors

-          Heparin is released in small amounts to inhibit thrombin activity

-          Unwanted clotting is prevented by the secretion of antithrombic substances (PGI₂ and heparin) secreted by endothelial cells; vitamin E is also a potent anticoagulant

Fibrinolysis – removal of unneeded clots when healing has occurred (within 2 days of clot formation)

• Prevents vessel blockage
• Plasmin is the active digesting enzyme responsible for Fibrinolysis
• Plasmin action is confined to the clot

Mechanism - plasminogen (a plasma protein) is activated by many factors & becomes Plasmin. Which then breaks down fibrin meshwork & phagocytic WBCs remove products of clot dissolution

        Factors Limiting Clot Growth or Formation

o   Size of clot is limited by the rapid removal of clotting factors and inhibition of activated clotting factors

o   Heparin is released in small amounts to inhibit thrombin activity

o   Unwanted clotting is prevented by the secretion of antithrombic substances (PGI₂ and heparin) secreted by endothelial cells; vitamin E is also a potent anticoagulant

Clinical Disorders of Haemostasis – Can be due to improper clot formation or the inhibition of natural clot formation

1.      Thromboembolytic Conditions – result from undesired clot formation:

• Thrombus – a stationary blood clot.  a clot that develops in an unbroken vessel. can block circulation and kill viable tissues
• Embolus – a mobile "moving" blood clot in the bloodstream. Dangerous if it encounters narrow vessels. if it lodges in lungs, called a Pulmonary Embolism.
• Embolism – clot obstructing a vessel
• Disseminated Intravascular Coagulation (DIC) – bacterial toxins cause clotting in healthy tissue; the remaining blood in the system is unable to clot and patient experiences heavy bleeding.

 Treatment: aspirin, heparin, and dicumarol are used to prevent unwanted clotting

2.      Bleeding Conditions – normal clot formation is inhibited

• Thrombocytopenia – due to a platelet deficiency

§  Seen in patients with bone marrow disorders; people exposed to ionizing radiation (ex. X-rays); and certain drugs

§  Spontaneous bleeding occurs in these individuals and Haemostasis cannot occur because of platelet deficiency

§  As a consequence of this, the patient may experience bruising and the formation of purplish spots on the skin.

• Liver Impairment – causes are reduction in the production of procoagulants needed for the clotting response.

• Vitamin K deficiency – due to lack of vitamin K in the diet (rare) or because antibiotic use has disrupted the intestinal flora responsible for making vitamin K. Prothrombin Synthesis in the liver requires the presence of Vitamin K.

-          Disruption in fat absorption, especially in the intestines – Vitamin K is fat-soluble and any disruption involving lipids or fat will impair vitamin K absorption

-          Disruption in bile production or a bile duct obstruction - The salts present in bile are critical for vitamin K absorption in the intestines; imbalances or disruptions will also impair vitamin K absorption

-          prolonged antibiotic therapy (decreases bacteria that make Vitamin K)

• Hemophilias - genetic 'defect' that leads to inability to produce certain clotting factor(s). Temporary treatment is by infusion with whole blood.
• Anticoagulant therapy (e.g., heparin--acts as an anti-thrombin; coumadin--interferes with liver's utilization of Vitamin K; that is, coumadin is a vitamin K antagonist).  Note:  another name for Coumadin is Warfarin or Dicumarol.

Transfusions and Blood Typing

·         The word "antigen" means Antibody Generating. A person will produce antibodies against blood group antigens that are foreign (not on the surface of one's own red blood cells). For some 80% of the population, the ABO blood group antigens are also present in salivary secretions (saliva).

·         Antigens (agglutinogens) present on the surface of red blood cells can cause adverse reactions in transfusion recipients. They are glycolipids or glycoproteins.

·         Prior to receiving transfusions a patient's blood type must be determined and the blood they receive must match to avoid complications

·         The following agglutinogens are screened in all cases: ABO and Rh

ABO Blood Typing

determined by the presence or absence of AB agglutinogens (Antigens) on RBC cell membranes. An individual with type AB:

• Both the A and B antigens are present on RBC cell membrane
• Antibodies against A and B antigens are not produced in the individual
• AB individuals can receive A, B, AB, or O blood transfusions (Universal Recipient)
• AB individuals can only donate to AB individuals

• An individual with type A:
• Only the A antigens are present on the RBC cell membrane
• Antibodies against B antigens are produced in the individual
• A individuals can receive A or O blood transfusions
• A individuals can only donate to A or AB individuals

• An individual with type B:
• Only the B antigens are present on the RBC cell membranes
• Antibodies against A antigens are produced in the individual
• B individuals can receive B or O blood transfusions
• B individuals can only donate to B or AB individuals

• An individual with type O:
• Neither A nor B antigens are present on the RBC cell membranes
• Antibodies against A and B antigens are produced in the individual
• O individuals can only receive O blood transfusions
• O individuals can donate to A, B, AB, and O individuals (Universal Donor)

Rh factor Blood Typing

determined by the presence or absence of at least 8 different types if Rh agglutinogens.

• An Rh⁺ individual:
• Rh agglutinogens are present on the RBC cell membrane
• No antibodies are formed against the Rh antigens in the individual
• Individuals can receive blood from Rh⁺ and Rh^- individuals, provided they have the correct ABO blood group

• An Rh^- individual:
• Rh agglutinogens are absent on the RBC cell membrane
• No antibodies are formed against Rh antigens unless the individual has prior exposure to them (ex. Transfusion Rh⁺ blood or delivery of an Rh⁺ baby to an Rh^-mother)
• Rh^- individuals can only receive Rh^- blood transfusions
• Rh^- can donate to Rh^- and Rh⁺ individuals (because of the absence of the Rh antigen on the RBC cell membrane), provided they have the correct ABO blood group

Pregnancy and Rh^- Individuals

• If the fetus of an Rh^- mother is Rh⁺, the mother will produce large amounts of antibodies to the Rh antigen when the placenta detaches and the fetal blood is mixed with the maternal blood.  This first pregnancy will not be affected. 

Following delivery (live or dead), the mother must receive a shot containing antibodies against the Rh antigen. This will inhibit an immune response against an Rh⁺ fetus in future pregnancies.  This will prevent severe birth defects in the fetus and improve chances of a successful pregnancy; Hemolytic Disease of the Newborn (HDN).

Plasma and Blood Volume Expanders

• Clinical use:  colloidal or isotonic salt solutions are used in emergency situations in which the patient is experiencing severe blood loss and immediate blood transfusions are not available.  Plasma and blood volume expanders will only bring the blood volume back to normal, not increase the levels of the formed elements.
• Colloid solutions – e.g. Dextran and purified human serum albumin – used to replenish plasma volume
• Isotonic salt solutions – e.g. Normal saline, Ringer's solution – used to increase blood volume by increasing water volume

1. Define and classify the various forms of Anemia
2. Explain the roles of Vitamin K, B12, EPO

Created by Musango 28/03/11