Chapter 4: Platelets Flashcards
1
Q
What are platelets?
A
Small, granulated, non-nucleated round or oval bodies of about 2-4 microns in diameter.
2
Q
Platelets diameter
A
2-4 microns
3
Q
What is the normal platelet count in blood?
A
300,000 mm^3
4
Q
Platelet life span
A
8 days
5
Q
What produces platelets?
A
They are produced in the bone marrow by giant cells called megakaryocytes.
6
Q
How are myeloid stem cells formed?
A
The pluripotent uncommitted stem cells under the effect of interleukins are transformed into myeloid stem cells.
7
Q
What can the myeloid stem cells develop into?
A
Myeloid stem cells are cells in the bone marrow that are capable into developing into:
1. Monocytes
2. Macrophages
3. Neutrophils
4. Basophils
5. Eosinophil
6. Erythrocytes
And/or
7. Megakaryocytes under proper stimulation
8
Q
What is differentiated into megakaryocytes?
A
The myeloid stem cells under the effect of thrombopoietin (produced by the liver and kidneys) are differentiated into megakaryocytes.
9
Q
What are functions of thrombopoeitin?
A
- Helps myeloid stem cells differentiate into megakaryocytes.
- Facilitate megakaryocytes maturation.
10
Q
What is the percentage of platelets that pass to the blood?
A
70% of the platelets extruded from the bone marrow pass to the blood.
11
Q
What is the percentage of platelets stored?
A
30% of the platelets are stored in the spleen.
12
Q
What is the effect of splenectomy on the platelet count?
A
It increases the platelet count (thrombocytosis).
13
Q
Structure of platelets
A
Platelets are active cells that have many functional characteristics of whole cells even though they have no nucleus and can’t reproduce.
They consist of a plasma membrane, a cytoplasm, and granules.
14
Q
Platelets Plamsa membrane
A
- Coat of Glycoprotein: on the plasma membrane surface to prevent adherence of platelets to normal epithelium but helps adherence to injured epithelium.
- it contains receptors for collagen and vessel wall Von-Willebrand factor. - Phospholipids
- Open canalicular system: serves as a pathway for extracellular calcium uptake and release of Intracellular substances.
15
Q
Platelets Cytoplasm
A
Contains many active structures:
1. Contractile actin and myosin: enable the activated platelets to change shape.
2. Microtubules
3. Mitochondria
4. Lysosomes
5. Residuals of endoplasmic reticulum
6. Golgi apparatus
7. Glycogen granules and enzymes
16
Q
Granules present inside the platelets
A
Dense and alpha granules
17
Q
Dense granules of platelets
A
Contain non protein substances secreted by platelets as:
1. Serotonin
2. ADP
3. Calcium ions
18
Q
Alpha granules
A
Contain secreted proteins as clotting factors:
1. Fibrinogen stabilizing factor (XIII)
2. Platelet derived growth factor (PDGF)
3. Platelet activation factor (PAF)
19
Q
What is Hemostasis?
A
Prevention of blood loss after injury. Whenever a blood vessel is cut or ruptured, a series of changes occur to stop blood loss.
20
Q
What are the steps of hemostasis?
A
- Constriction of blood vessel.
- Formation of temporary Hemostatic plug.
- Conversion of temporary platelet clot to definitive clot by fibrin threads produced by the process of coagulation.
- Clot is dissolved to resume normal blood flow after tissue repair. The dissolution of the clot occurs through the action of plasmin.
21
Q
constriction of a blood vessel
A
The constriction of a blood vessel occurs immediately after an injury and may be so marked that the lumen is completely closed.
22
Q
What are causes of vasoconstriction?
A
- Local myogenic contraction due to direct trauma.
- Nervous reflexes initiated by pain from the traumatized vessel.
- Local humoral factors from platelets such as serotonin, ADP, and thromboxane A2.
23
Q
Formation of temporary Hemostatic plug
A
Injury stimulates the platelets to form a mechanical plug to seal the vascular injury.
1. Cut is small: the platelet plug can stop blood loss.
2. Cut is large: blood clot is needed to be added to stop bleeding.
24
Q
How do normal platelets circulate in the blood?
A
Normal platelets circulate freely in the blood and do not adhere to the endothelial surface.
25
What happens when a vascular surface is injured?
Platelets adhere to the exposed subendotheliel collagen of the injured blood vessel.
26
What does the platelet adhesion depend on?
1. Glycoprotein receptors on the platelets membrane for collagen and Von- willebrand factor.
2. Von-willebrand factor (vWF) , which is a glycoprotein present in the subendothelial tissue. it is also present in the plasma bound to factor VIll.
27
What initiates platelet activation?
The binding of platelets to collagen.
28
What proves that the platelets are activated?
Platelets swell, change their shape, put out pseudopodia, and discharge the content of the granules.
29
What is the activation of platelets enhanced by?
By ADP and thrombin.
30
What are released contents of dense granules functions?
1. Calcium: release of more granules.
2. ADP: activation, aggregation, and fusion of platelets.
3. Serotonin: reinforce and maintain vasoconstriction of the injured blood vessel.
31
What are the released content of alpha granules functions?
1. Coagulation factor XIII: stabilization of fibrin clot.
2. Platelet derived growth factor (PDGF): stimulates wound healing and repair by stimulation of growth and multiplication of vascular endothelium smooth muscles and fibroblasts.
3. Platelet activation factor (PAF): platelet aggregation.
32
Is Ca++ an independent or dependent reaction?
Dependent reaction.
33
what is thromboxane A2 released from?
Activated platelets.
34
What is thromboxane A2 (TxA2) produced from?
Arachidonic acid in the membrane of the platelets by cyclooxyrgenase enzyme.
35
What is the function of TxA2?
It increases free Ca++ in the cytoplasm of the platelets which will lead to:
1. Vasoconstriction
2. Induction of release reaction
3. Powerful platelet aggregation
36
How is prostacyclin produced?
It is produced from arachidonic acid in the wall of blood vessels by the action of cyclooxygenase enzyme.
37
What are the functions of prostacyclin?
1. Powerful vasodilator.
2. Inhibits the release and aggregation of platelets.
3. Since it’s actions are opposite to TxA2, prostacyclin seems to keep the platelet plug localized to the site of injury.
38
What causes more platelets to aggregate at the site of injury?
Released ADP and TxA2.
39
Explain the self-propagating process.
Released ADP and TxA2 cause more platelets to aggregate at the site of injury. This leads to further release reaction which liberates more ADP, and thromboxane A2, causing more aggregation.This self-propagating process results in the formation of the platelet plug.
40
What forms the platelet plug?
The self-propagating process.
41
Aggregation is also stimulated by?
Platelet activating factor (PAF).
42
What is the platelets pro coagulant activity?
Platelets act as catalysts for coagulation. The membrane phospholipids (platelet factor 3) is exposed providing an ideal surface for concentration and activation of coagulation factors.
43
Why is aspirin used as a preventive measure against myocardial infarction?
Aspirin inhabits cyclooxygenase enzyme, thus reduces the production of both TxA2 and prostacyclin. However, the endothelial cells produce new cyclooxygenase in a matter of hours, whereas platelets cannot manufacture the enzyme. Therefore, administration of small amounts of aspirin for prolonged periods reduces clot formation and has been of value in preventing myocardial infarction.
44
What is the cause of irreversible fusion of aggregated platelets at the site of injury?
1. High concentration of ADP and thrombin.
2. Enzymes liberated during the platelet realms reaction.
45
What is blood coagulation?
Formation of blood clot by intrinsic and extrinsic pathways to stop bleeding.
46
What are coagulation factors?
Plasma proteins mainly beta globulins that are synthesized by the liver.
47
How can you recognize coagulation factors?
By capital Roman numerals, the first four are usually referred to by names.
48
What are coagulation factors?
They are inactive enzymes, which when activated lead to a chain of proteolytic reactions activating other factors.
49
What are the three groups of coagulation factors?
Fibrinogen group, prothrombin group, and contact group.
50
Fibrinogen
Factor I(fibrinogen), factor V, factor VIII, factor XIII.
They are activated by thrombin.
51
Prothrombin group
Factor II (prothrombin), factor VII, factor IX, factor X.
All need vitamin k for synthesis in the liver.
52
Contact group
Factor XI, Factor XII
Activated by contact to electro-negativity charged surface.
53
What is Mechanism of Coagulation?
Process by which loose aggregation of platelets in the temporary plug is bound together and converted into a definitive clot by fibrin threads.
54
What is a blood clot composed of?
Mesh work of fibrin threads run in all directions entrapping blood cells, platelets, and plasma.
55
What is the purpose of the fibrin adhesion?
They adhere to damaged surfaces of blood vessels to prevent blood loss.
56
What is the process of the clotting mechanism?
It involves a cascade of reactions in which clotting factors are activated.
57
Intrinsic pathway of coagulation can occur in vivo or vitro?
Both Vivo and vitro.
58
How is the intrinsic pathway initiated?
By the conversion of inactive factor XII to active factor XIIa. This activation occurs when blood is exposed to the collagen fibers present beneath the blood vessel endothelium.
59
What is the activation of XII catalyzed by?
By circulating proteins, high molecular weight kininogen and plasma kallikrein.
60
How can factor XII be activated in vitro?
It can be activated in vitro by exposing the blood to electro-negatively charged wettable surfaces like glass.
61
What activates factor XI?
XIIa
62
What activates factor IX?
Factor XIa
63
How is factor VIII activated?
It is activated when it’s separated from von willebrand factor by the proteoglycan action of thrombin.
64
The complex is formed between what factors?
Factors IXa and VIIIa
65
What activates factor X?
The complex of IXa, VIIIa, phospholipids (PL) of aggregated platelets, and Ca++.
66
What converts prothrombin to thrombin?
Factor Xa ,in the presence of (PL), Ca++, and active factor V.
67
What catalyzes the conversion of soluble fibrinogen polymer to insoluble fibrin monomer threads?
Thrombin catalyzes the conversion of soluble fibrinogen polymer to insoluble fibrin monomer threads. Fibrin threads will be arranged spontaneously into loose mesh.
68
What converts the loose fibrin threads into tight strands?
Fibrin stabilizing factor XIII of platelets.
69
What activates factor XIII?
Thrombin in the presence of Ca++ ions.
70
What is the net result of the intrinsic pathway of coagulation?
The net results is the formation of clot that closes and adheres to the injured vessel wall.
71
Check book for diagram 😊
You can find a test version on notability ❤️
72
Does the extrinsic system occur in vivo or vitro?
Vivo
73
What releases thromboplastin?
Tissue phospholipid TPL is released by tissue trauma either vascular or extravascular.
74
What activates factor VII?
Thromboplastin TPL
75
What activates factors IX and X?
TPL and factor VIIa.
76
What system is initiated when a blood vessel is injured?
Both systems simultaneously.
77
Which system is more rapid? The extrinsic or intrinsic pathway?
The extrinsic system is very rapid ( 15 seconds) and extensive, while the intrinsic system is slow (1-6 minutes).
78
What happens when a critical amount of thrombin is formed?
A vicious cycle develops.
79
How does the extrinsic system activate the intrinsic system?
1. Activated factor VII (extrinsic) activates factor IX (intrinsic) as well as factor (X).
2. The extrinsic system leads to the formation of thrombin more rapidly. Once thrombin is formed, it activates factors VIII and V leading to the activation of the intrinsic system.
80
What reactions is Ca++ needed for in blood clotting?
It is required for all reactions except for the first two in the intrinsic system.
81
Serum in blood clotting.
Serum is the squeezed out plasma remaining after a clot retraction. It is devoid of fibrinogen, factors V and VIII. It contains excess serotonin released from the platelets.
82
What are limiting reactions?
The tendency of blood to clot is balanced in vivo by limiting reactions that tend to prevent clotting inside the blood vessels and to break down any formed clots.
83
What are types of limiting reactions?
General and specific limiting reactions.
84
General limiting reaction
1. Smooth vascular endothelium thus there are no activation of factor XII or platelets.
2. Removal of some activated clotting factors and their inactivation in the liver.
3. Presence of heparin, which is a naturally occurring anticoagulant.
85
What is heparin.
Naturally occurring coagulant.
86
What are types of specific limiting reactions?
1. The interaction between thromboxane A2 and prostacyclin.
2. Antithrombin III.
3. Fibrinolytic system.
87
The interaction between thromboxane A2 and prostacyclin.
The interaction between platelet-aggregating and vasoconstrictor effects of thromboxane A2 versus the antiaggregator prostacyclin and vasodilator effects of prostacyclin. This interaction causes a clot to form at the site of injury but keeps the vessel lumen free of clot.
88
Antithrombin III
It inhibits the activated clotting factors. This action is facilitated by heparin. The clotting factors that are inhibited are active forms of factors: 9,10,11, and 12. Translate later.
89
What produces thrombomodulin?
All endothelial cells, except for cerebral microcirculation, produce thrombomodulin.
90
What is thrombomodulin?
A thrombin binding protein.
91
What activates protein C?
Thrombin binding to thrombomodulin forms a complex that activates protein C.
92
What is are the functions of Protein C and it’s cofactor protein S?
APC and protein S will:
1. Inactivate factors V and VIII.
2. Inactivate inhibitor tissue plasminogen activator (TPA), which activates TPA.
3. Increase the formation of plasmin.
93
What activates plasmin (fibrinolysin)?
Activated TPA and thrombin activate the inactive precursor plasminogen into plasmin.
94
What is the function of plasmin?
Plasmin lyses fibrin and fibrinogen into fibrinogen degradation products FDP which inhibit thrombin.
95
Is TPA available for clinical use?
Human TPA is now produced by recombinant DNA techniques and is available for clinical use.
96
How is TPA used for clinical use?
If given as soon as after the onset of myocardial infarction (within 6 hours), it lyses the clots in the coronary arteries.
97
What are other fibromyalgia substances used in treatment of myocardial infarction?
Streptokinase and urokinase bacterial enzymes.
98
What are anticoagulants?
Substances used in either vivo or vitro to prevent blood clotting.
99
What are types of anticoagulants?
Vivo and Vitro coagulants.
100
Vitro
Anticoagulants used to prevent clotting outside the body.
101
What are methods of vitro anticoagulants?
1. Heparin
2. Precipitation of Ca++ by oxalate ions or deionization of Ca++ by citrate. The latter is used to prevent blood clots of the blood used for transfusion.
3. Collecting blood in unwettable silicone tubes to prevent activation of factor XII and platelets.
102
Vivo coagulants
Used to prevent clotting inside the body.
They include: heparin and Coumadin derivatives (warfarin, dicumarol).
103
Origin of heparin
Mast cells and basophils
104
Origin of dicumarol
Plants
105
Heparin mode of action
Facilitates the action of antithrombin III which blocks the activity of 9a, 10a, 11a, 12a.
106
Dicumarol mode of action
Competitive inhibition of vitamin k in the liver, so it inhibits the formation of prothrombin and factors VII, IX, and X.
107
Heparin site of action
In vivo and vitro
108
Dicumarol site of action
Vivo
109
Heparin onset
Rapid onset
110
Dicumarol onset
Slow onset
111
Heparin duration
Short duration
112
Dicumarol duration
Long duration
113
Heparin administration
Injection
114
Dicumarol administration
Orally
115
Heparin antidote
Protamine 1% or blood transfusion.
116
Dicumarol antidote
Vitamin k or blood transfusion.
117
What are abnormalities in hemostasis?
1. Conditions that cause excessive bleeding.
2. Conditions that cause excessive intravascular clotting.
3. Conditions that cause excessive bleeding and intravascular clotting.
118
Conditions that cause excessive bleeding
1. Thrombocytopenic purpura
2. Vitamin K deficiency
3. Hemophilia
119
Conditions that cause excessive intravascular clotting
Thromboembolic conditions
120
Conditions that cause excessive bleeding and intravascular clotting
Disseminated intravascular coagulation (DIC).
121
Thrombocytopenic purpura
1. Deficiency of platelets ( symptoms appear when count is less than 50,000 mm3).
2. Presence of many subcutaneous hemorrhages called petechiae and prolongation of bleeding time.
122
Bleeding time
Time needed for bleeding to stop without clotting.
Normal bleeding time is 1-3 minutes.
It depends on the platelet count and function.
123
Vitamin K deficiency
- A fat soluble vitamin synthesized by the intestinal bacterial flora.
- needed for the formation of the factors II, VII, IX, X by the liver.
- deficiency leads to decrease in the formation of these factors, thus a prolongation of coagulation time.
124
Vitamin K deficiency is due to?
1. Absence of intestinal bacterial floral which occurs in new born infants.
2. Treatment with antibiotics for long periods in adults.
3. Obstruction of biliary ducts which leads to absence of bile needed for absorption of the vitamin.
125
Hemophilia
Sex linked recessive disease characterized by a tendency for severe bleeding after mild trauma. It is carried by female but manifested almost always in males.
It cause prolongation of the whole coagulation time.
126
Coagulation time
Time needed for blood to clot.
Around 3-10 minutes.
127
Coagulation time diseases
The coagulation time is prolonged in both extrinsic and intrinsic disease such as:
- vitamin k deficiency.
- hemophilia.
- liver diseases.
128
Prothrombin time
Test for extrinsic system factor VII.
Normal time is 15 seconds and is prolonged in vitamin K deficiency.
129
Activated partial thromboplastin time (APTT)
Test for intrinsic factors XII XI IX VIII.
Normal time is 30 to 40 seconds and is prolonged in hemophilia.
130
What are three types of hemophilia?
Hemophilia A, B and C.
131
Hemophilia A
85% of the cases of hemophilia. Classic hemophilia with deficiency in factor VIII.
132
Hemophilia B
Deficiency of factor IX.
133
Hemophilia C
Deficiency of factor XI.
134
Thromboembolic conditions
Results in slow blood flow.
Occurs in leg veins due to long bed rest after operations, varicose veins, and atherosclerosis due to the roughness of the vascular endothelium.
135
Disseminated intravascular coagulation
1. Characterized by wide spread clotting accompanied with bleeding tendency due to consumption of many clotting factors.
2. Due to massive thromboplastin production from traumatized tissue.
3. It may be caused by the retention of a dead fetus in the uterus for weeks or septicemia.
