Blood Coagulation
Fernandez, Shaina
Ho, Mary
Hua, Huy
Kim, Bo
Blood
Blood
- Blood: is a specialized fluid of connective tissue that consists of two components
- Plasma: fluid, makes up 55% of the whole blood; consists of 92% water, 7% proteins (albumin, globulins and fibrinogen) and 1% other solutes
- Formed elements: consists of
- Red Blood Cells or erythrocytes- makes up 99.9% of formed element; transport oxygen
- White Blood Cells or leukocytes- body’s defense against disease; 2 major types:
- Granulocytes: neutrophils, eosinophils and basophils
- Agranulocytes: leukocytes and monocytes
Platelets
Platelets
- Platelets or thrombocytes- involved in blood clotting; activated by local changes in the environment, and releases clotting factors and other chemicals (platelet thromboplastin factor) and just like RBCs and WBCs, they are generated in the bone marrow.
- Thrombocytopenia- lower than normal number of platelets
- Thrombocytosis- higher than normal number of platelets
Other Factors
Other Factors
- Blood: is a specialized fluid of connective tissue that consists of two components
- Plasma: fluid, makes up 55% of the whole blood; consists of 92% water, 7% proteins (albumin, globulins and fibrinogen) and 1% other solutes
- Formed elements: consists of
- Red Blood Cells or erythrocytes- makes up 99.9% of formed element; transport oxygen
- White Blood Cells or leukocytes- body’s defense against disease; 2 major types:
- Granulocytes: neutrophils, eosinophils and basophils
- Agranulocytes: leukocytes and monocytes
Definition
Definition
- Hemostasis: homeostatic regulation of blood
- In regards to clotting...
- process of blood clotting after injury called coagulation cascade which involves many clotting factors (specialized proteins used in clotting) and the presence of Calcium ions
- Regulation of hemostatic coagulation process will be explained later
Abnormalities
Abnormalities
- Deficiencies or denaturization of factors described above will lead to abnormal bleeding of injuries
- Abnormal can mean increased amount of time taken to coagulate
- Normal coagulation time ranges from 25-30 seconds
Coagulation Cascade
Coagulation Cascade
Cascade Part 1
Cascade Part 1
- Clotting process is triggered by XII (also known as Hageman Factor), a plasma protein
- Once activated, Factor XII goes on to react with Factor XI (also known as Plasma Thromboplastin)
- When activated, Factor XI becomes XIa
- XIa activates Factor IX (also known as Christmas Factor)
- Activated Factor IX, when in the presence of Calcium ions and phospholipids, will react with Factor VIII (also known as anti-hemophilic factor, AHF)
- The reaction between Factor IX and Factor VIII forms the Tenase complex
- Reaction is dependent on phospholipid released from platelets
- Intrinsic vs. Extrinsic Pathway
- Difference between the pathways lies in steps before activation of Factor X used to convert prothrombin into thrombin
- Both pathways converge during coagulation cascade during activation of Factor X so that steps after this activation are the same
Cascade Part 2
Cascade Part 2
- Tenase Complex activates Factor X (Stuart-Prower Factor)
- When activated, Factor X becomes Xa
- Activated Factor Xa, when in the presence of Calcium ions and phospholipids, reacts with Factor V (also known as Proaccelerin or Labile Factor)
- The reaction between Factor Xa and Factor V forms Prothrombinase Complex
- Reaction is dependent on phospholipid release from platelets.
- Prothrombinase Complex convert prothrombin to thrombin
- Thrombin converts fibrinogen to fibrin
- Reaction involves splitting polypeptides into monomers which, in turn, will repolymerize forming fibrin clots.
- When thrombin levels are high, the amount of fibrin clots produced is reduced
- Happens through the destruction of Factor V and Factor VIII
- Excess thrombin formed during the coagulation cascade is neutralized by antithrombins
Intrinsic Pathway
Intrinsic Pathway
- Intrinsic: starts with Factor XII, HMW kininogen, prekallekerin, and Factor XI > activates XI to XIa > XIa acts with Factor VIII > formation of Tenase Complex > converts Factor X to Factor Xa > proceed to normal coagulation cascade
Extrinsic Pathway
Extrinsic Pathway
- Extrinsic: activated when tissue factors (also known as thromboplastin) and plasma coagulants combine allowing the tissue factors to “unlock” and bind to Factor VIIa > Factor VIIa and Calcium ions activate Factor X to Factor Xa > proceed to normal coagulation cascade.
- Considered the main pathway for hemostasis
- Tissue Factors/Thromboplastin are glycoprotein receptors in the transmembrane of diverse cells, especially platelets which are one of the main components in the blood clotting process.
Recap
Recap
- Coagulation defined
- 3rd step in hemostasis
- 2 main pathways: Intrinsic & Extrinsic
- Common pathway
- End result of the pathways
- Regulation mechanisms
Mechanisms
Mechanisms
Regulation Mechanism:
- Ensures optimal coagulation and prevents widespread thrombosis
- Prostacyclin
- Anticoagulants
- Tissue Factor Inhibitor
- Antithrombin III protein
- Activated Protein C and Protein S
- Thrombomodulin
- Endothelial cell receptor
- Fibrinolytic System
- Antithrombin
Intrinsic Factors
Intrinsic
Intrinsic Factors
- Collagen
- Von Willebrand factor (vWF)
- Kininogen & Kallinkrein
- Calcium ions (IV)
- Anti-hemophilic factor (VIII)
- Plasma thromboplastin component (IX)
- Plasma Thromboplastin antecedent (XI)
- Hageman factor (XII)
Extrinsic, Common, & Cofactors
Extrinsic & Common
Extrinsic Factors
- Thromboplastin/Tissue factor (III)
- Proconvertin (VII)
Common Pathway Factors
- Vitamin k
- Fibrinogen (I)
- Prothrombin (II)
- Proaccelerin (V)
- Stuart Prower factor (X)
- Fibrin-stabilzing factor (XIII)
Cofactors
- Calcium
- Phospholipid
- Vitamin K
Interactive
Interactive Activities
Instructions
Instructions
1) Divide into groups of four.
2) One person from each group will either use their mobile device or laptop and go to website: kahoot.it
3) Enter the room code displayed on the screen
4) Upon seeing the question posted on the board, one person will answer it by matching the same symbol corresponding to the answer.
5) The group that answers the most questions correctly will receive a prize (ties will result in best two out of three in rock paper and scissors)
KAHOOT
Kahoot
https://create.kahoot.it/l/#user/375e8075-97da-4bf6-a1ca-e967d1447b83/kahoots/created
References
References
- Crampton, L. (2017, June 27). How Blood Clots: Platelets and the Coagulation Cascade. Retrieved from https://owlcation.com/stem/How-Does-Blood-Clot-and-What-Causes-Coagulation
- Hougie, C. (1970). Mechanisms of Blood Clotting. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1501996/pdf/califmed00137-0107b.pdf
- Morfini, M., Coppolo, A., Franchini, M., and Minno, G. (2013 Sep) Clinical Use of Factor VIII and Factor IX Concentrations Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853992/
- Orfeo, T., Brufatto, N., Nesheim, M.E., Xu, H., Butenas, S., and Mann, KG. (2004 May 7). The Factor V Activation Paradox. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/14982929
- Palta, S., Saroa, R., and Palta, A. (2014 Oct) Overview of the Coagulation System
- Sarode, R. Components of Blood. The Merck manual online. Retrieved from The Merck Manuals Online Medical Library database.
- Silverthorn, D. U., Johnson, B. R., Ober, W. C., Ober, C. E., & Silverthorn, A. C. (2016). Human Physiology: An Integrated Approach (7th ed.). Pearson Education Limited.
- Singh, A. P. (2017, November 20). Hemostasis Mechanism and Regulation. Retrieved from https://medcaretips.com/hemostasis-mechanism-and-regulation/
- World Federation of Hemophilia (Ed.). (2014, May). What are rare clotting factor deficiencies? Retrieved from https://www.wfh.org/en/page.aspx?pid=662
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A Special Note