Hematology: Blood Coagulation

1. Sources of Error in the Ivy Bleeding Time Test:

• Inaccurate Incision Size: too shallow or too deep.
  • Shallow Incision: may not produce enough bleeding for accurate measurement of clotting time.
  • Deep Incision: can damage larger blood vessels, leading to prolonged clotting time.
• Excessive Blotting of Blood from the Incision: This can disrupt the newly formed platelet plug, resulting in increased bleeding and prolonged clotting time.
• Abnormal Blood Vessels in the Forearm: For example, narrowed, blocked, or deformed blood vessels can lead to prolonged bleeding time.
• Puncturing a Deeply Situated Blood Vessel: This can cause prolonged bleeding time.

Note:

• It is advisable to make the incision on the anterior surface of the forearm, avoiding areas with hair and easily visible blood vessels.
• A standardized incision tool should be used to ensure the correct size and depth of the incision.
• Blotting should be done gently to avoid disrupting the platelet plug.
• It is essential to carefully check the condition of the blood vessels in the forearm before performing the Ivy Bleeding Time test.

2. Factors Involved in Activating the Coagulation and Hemostasis Process:

• Endothelium and Subendothelial Layer of Blood Vessels: These are the surfaces directly exposed to blood, playing a crucial role in the initial stages of hemostasis.
  • Endothelial Surface: Produces factors that activate platelets and intrinsic clotting factors.
  • Subendothelial Surface: Contains collagen and other factors that facilitate platelet adhesion and the release of coagulation-activating substances.
• Platelets: Small blood cells that participate in the initial hemostasis process and form the platelet plug.
  • Adhesion: Platelets adhere to collagen in the subendothelial layer, mediated by von Willebrand factor (vWF) in plasma and glycoproteins on the platelet membrane.
  • Release: Platelets release coagulation-activating substances, vasoconstrictors, and platelet aggregation agents, including ADP, serotonin, thromboxane A2, etc.
  • Aggregation: Platelets bind to each other, forming a platelet plug that serves as temporary hemostasis.
• Plasma Clotting Factors: These are proteins with enzymatic activity that participate in the intrinsic and extrinsic coagulation pathways.
  • Intrinsic: Factors XII, XI, IX, VIII, X, V, II, I, XIII.
  • Extrinsic: Factors VII, X, V, II, I, XIII.
• Tissue Factor: A lipoprotein released from damaged tissue cells, activating the extrinsic coagulation pathway.
• Calcium Ions: A crucial electrolyte involved in various stages of coagulation, including:
  • Binding to phospholipids and vitamin K-dependent proteins.
  • Activation of factor XIIIa.
  • Stabilizing the complex of von Willebrand factor and factor VIII.

3. Coagulation and Hemostasis are Manifestations of Physiological and Biochemical Processes:

• Coagulation: The physical change of blood due to the conversion of fibrinogen (soluble protein) into fibrin (fibrous protein).
• Hemostasis: The process of stopping bleeding from a wound, involving the following stages:
  • Initial Hemostasis: Temporary hemostasis achieved by vasoconstriction and platelet plug formation.
  • Plasma Coagulation: Formation of a blood clot, leading to permanent hemostasis.
  • Fibrinolysis: Breakdown of the blood clot, restoring blood flow.

4. The Coagulation and Hemostasis Process is an Interplay of Three Components:

• Blood Vessel Wall: The site of injury and activation of the coagulation process.
• Blood Cells: Includes platelets and plasma clotting factors.
• Plasma Proteins: Enzymes involved in the coagulation process.

5. Enzyme Reactions Can Be Regulated by Negative Feedback Factors:

• Physiological Inhibitors: Help control the coagulation process, allowing activation only at the site of injury, preventing widespread coagulation.

Note: Physiological inhibitors are crucial for maintaining a balance between coagulation and fibrinolysis, preventing thrombosis and abnormal bleeding.

6. Imbalance in Coagulation and Hemostasis Leads to Consequences:

• Thrombosis: Formation of blood clots within blood vessels, obstructing blood flow.
• Bleeding: Excessive and difficult-to-stop bleeding due to a deficiency in clotting factors or impaired platelet function.

7. When the Vessel Wall is Injured, the Subendothelial Layer Exposed to Blood Activates:

• Platelets: Adhere to collagen, releasing coagulation-activating substances.
• Contact Factors: Factors XII, XI, prekallikrein, kininogen.

8. Platelet Function in Coagulation and Hemostasis:

• Vasoconstriction: Helps repair minor damage to the vessel wall.
• Formation of the Platelet Plug: This is the initial hemostasis process, sealing small wounds.
• Participation in the Coagulation Process: By releasing coagulation-activating substances and providing a surface for the activation of clotting factors.
• Influence on Fibrinolysis: By releasing substances that activate and inhibit fibrin breakdown.

Note:

• Platelets are essential in maintaining the integrity of the vessel wall and controlling the hemostasis process.
• Platelet responses, including adhesion, release, and aggregation, are regulated by activating and inhibiting factors, ensuring efficient and safe coagulation.

9. Platelet Adhesion Depends on:

• von Willebrand Factor: Present in plasma, it binds to glycoprotein Ib on the platelet membrane, facilitating platelet adhesion to collagen.

Note: Deficiency in von Willebrand factor reduces platelet adhesion, leading to bleeding.

10. Factors Influencing the Release of Platelet Granules:

• Collagen: Activates platelets to release coagulation-activating substances, vasoconstrictors, and platelet aggregation agents, including ADP, serotonin, thromboxane A2, etc.
• Thrombin: A product of the coagulation process, activates platelets, leading to the release of coagulation-activating substances and vasoconstrictors.

11. How Collagen and Thrombin Affect the Release of Platelet Granules:

• Collagen: Activates platelets to synthesize prostaglandins, leading to the formation of thromboxane A2. Thromboxane A2 reduces platelet cAMP, triggering the release of platelet granules.
• Thrombin: Binds to thrombin receptors on the platelet membrane, activating signaling pathways leading to the release of platelet granules.

12. Platelet Release Reactions are Inhibited by:

• Prostacyclin (PGI2): Synthesized in the subendothelium, it increases platelet cAMP, inhibiting the release of platelet granules.

Note: PGI2 plays a crucial role in preventing widespread coagulation, maintaining blood vessel patency.

13. The Platelet Granules Released are:

• ADP: Activates platelet aggregation, causing platelets to swell and adhere to each other.
• Serotonin: A vasoconstrictor, reducing blood loss from the wound.
• Fibrinogen: Precursor of fibrin, participating in coagulation.
• Lysosomes: Degrading enzymes, helping to break down damaged tissues.
• Platelet Factor 4 (Heparin Antagonist): Neutralizes heparin, an anticoagulant.
• Epinephrine: A vasoconstrictor, reducing blood loss from the wound.
• Prostaglandin Derivatives, Thromboxane A2: Vasoconstrictors and coagulation activators.

14. Substances That Induce Platelet Aggregation:

• ADP: Causes platelets to swell and their membranes to adhere tightly to each other.
• Thromboxane A2: A chemical mediator that activates thromboxane A2 receptors on the platelet membrane, leading to platelet aggregation.

Note:

• ADP and thromboxane A2 are the most significant substances involved in platelet aggregation.
• Other platelet aggregation agents may act through ADP and thromboxane A2 pathways.

15. Zymogen of Transglutaminase:

• Factor XIII: An enzyme that binds fibrin molecules together, forming a stable blood clot.

Note: Deficiency in factor XIII makes the blood clot unstable and prone to breakdown, leading to bleeding.

16. Nature of Clotting Factors:

• Glycoproteins: Functionally, clotting factors can be grouped differently depending on their roles:
  • Zymogens: Proteins capable of transforming into active enzymes.
  • Cofactors: Proteins without enzymatic activity but supporting the activity of other clotting enzymes.
  • Substrates: Proteins acted upon by clotting enzymes to be converted into products.

Note: Clotting factors are crucial in controlling the coagulation process, ensuring the efficient and safe formation of the blood clot.

17. Zymogen is:

• Proteins capable of transforming into active enzymes.

18. Zymogens of Serine Proteases:

• Prekallikrein: A precursor of kallikrein, an enzyme that activates factors XII and XI.
• Factors XII, XI, IX, X, VII, II: Precursors of clotting enzymes, activated by other factors.

19. Contact Factors:

• XI, XII, prekallikrein, and kininogen: Factors involved in the intrinsic coagulation pathway, activated when blood comes into contact with negatively charged surfaces.

Note: Contact factors are crucial in initiating the intrinsic coagulation pathway.

20. Classification of Clotting Factors:

• Stable Factor Group:
  • Not Vitamin K-dependent: Factors XI, XII, prekallikrein, and kininogen.
  • Do not Require Calcium: Factors XI, XII, prekallikrein, and kininogen.
  • Stable in Stored Plasma: Factors XI, XII, prekallikrein, and kininogen.
• Prothrombin Group:
  • Includes Factors II, VII, IX, X.
  • Vitamin K-dependent: Factors II, VII, IX, X.
  • Require Calcium for Activation: Factors II, VII, IX, X.
  • Except for II, not consumed during coagulation (present in serum), stable in stored plasma: Factors VII, IX, X.
• Fibrinogen Group:
  • Includes Factors I, V, VIII, XIII.
  • Interact with Thrombin: Factors I, V, VIII, XIII.
  • Consumed during coagulation (not present in serum): Factors I, V, VIII, XIII.
  • Factors V and VIII lose activity in stored plasma: Factors V, VIII.

Note: Classifying clotting factors based on their properties helps understand the role of each factor in the coagulation process.

21. Clotting Factors Present in Serum:

• VII, IX, X

Note: Serum is plasma without fibrinogen.

22. Clotting Factors NOT Present in Serum:

• I, V, VIII, XIII

23. Factors that Lose Activity in Stored Plasma:

• V, VIII

Note: Factors V and VIII degrade quickly during storage, so stored plasma no longer has the activity of these two factors.

24. Thrombin Interacts with Factors:

• I, V, VIII, XIII

Note: Thrombin is a crucial enzyme in the coagulation process, activating other factors and forming fibrin.

25. The Fibrinogen Group Includes:

• I, V, VIII, XIII

26. Function of Factor XIII:

• Stabilization of Fibrin: Factor XIIIa binds fibrin molecules together, forming a stable blood clot.

27. The Coagulation Process is Initiated by:

• A lipoprotein called Tissue Factor or Extrinsic Thromboplastin: Released from damaged tissue cells.

Note: Tissue factor is the activator of the extrinsic coagulation pathway.

28. Both the Lipid and Protein Portions of Tissue Factor are Necessary for Coagulation, But the Specificity Lies in the Lipid Portion:

• INCORRECT: The specificity of tissue factor lies in the protein portion and not the lipid portion.

Note: The protein portion of tissue factor has the ability to bind with other clotting factors, activating the coagulation process.

29. Tissue Factor Has Enzymatic Activity:

• INCORRECT: Tissue factor does not have enzymatic activity, but it functions as a cofactor in the activation of factors VII and X.

Note: Tissue factor does not have enzymatic activity, but it binds with other clotting factors, helping activate them.

30. Tissue Factor Does Not Have Enzymatic Activity But Functions as a Cofactor in the Activation of Factors VII and X:

• CORRECT

31. The Role of Calcium Ions in Coagulation and Hemostasis:

• Facilitates the Binding of Vitamin K-dependent Proteins to Phospholipids: This helps form the prothrombinase complex, activating prothrombin into thrombin.
• Intervenes in Reactions Independent of Vitamin K: Such as the activation of factors XI, XII, prekallikrein.
• Essential for the Manifestation of Factor XIIIa Enzymatic Activity: Helps stabilize the blood clot.
• Essential for the Stability of Factor V and the Complex of von Willebrand Factor and Factor VIII:C: Helps maintain the activity of these factors.

Note: Calcium ions are a crucial electrolyte, participating in multiple stages of the coagulation process.

32. Calcium Ions Do Not Intervene in Reactions Independent of Vitamin K:

• INCORRECT: Calcium ions do participate in reactions independent of vitamin K, such as the activation of factors XI, XII, prekallikrein.

Note: Calcium ions are a crucial electrolyte, participating in multiple stages of the coagulation process, including reactions independent of vitamin K.

33. The Coagulation and Hemostasis Process Has How Many Stages:

• 1. Initial Hemostasis (Vascular-Platelet Stage): Includes vasoconstriction and platelet plug formation.
• 2. Plasma Coagulation: Includes the intrinsic and extrinsic coagulation pathways, leading to fibrin formation.
• 3. Fibrinolysis: The breakdown of the blood clot.

34. Platelets Adhere to the Subendothelial Layer Through:

• von Willebrand Factor: Binds to glycoprotein Ib on the platelet membrane.
• Platelet Glycoprotein Ib: Binds to von Willebrand factor.

Note: These two factors facilitate platelet adhesion to collagen in the subendothelial layer, triggering the coagulation process.

35. The Initial Hemostasis Process Includes the Following Stages:

• Vasoconstriction: Reduces blood loss from the wound.
• Platelet Adhesion: Platelets adhere to collagen, triggering the coagulation process.
• Release Reaction: Platelets release coagulation-activating substances, vasoconstrictors, and platelet aggregation agents.
• Platelet Aggregation: Platelets bind to each other, forming a platelet plug that serves as temporary hemostasis.
• Activation of Coagulation: Platelets provide a surface for the activation of clotting factors, initiating the plasma coagulation process.

36. Platelet Factor 3 Is of What Nature:

• Phospholipid: Released from platelets, it helps activate factors X and prothrombin.

Note: Platelet factor 3 is one of the crucial factors in the coagulation process, acting as a catalyst for the activation of other clotting factors.

37. The Initial Platelet Plug Only Provides Temporary Hemostasis in Small Blood Vessels. Hemostasis in Larger Damaged Vessels Requires the Formation of a Blood Clot:

• CORRECT

Note: The blood clot provides permanent hemostasis, stopping bleeding from the wound.

38. Clotting Factors Not Found in Blood:

• Factor 3 (Tissue Factor or Thromboplastin): A lipoprotein released from damaged tissue cells.

39. The Intrinsic Coagulation Pathway is Activated by:

• Contact of Blood with Negatively Charged Surfaces:
  • Subendothelial structures in vivo.
  • Glass or kaolin in vitro.

Note: Negatively charged surfaces activate factor XII, initiating the intrinsic coagulation pathway.

40. The Extrinsic Coagulation Pathway is Activated by:

• Tissue Factor: Released from damaged tissue cells, it activates factor VII, initiating the extrinsic coagulation pathway.

41. Fibrinogen is a Proenzyme:

• INCORRECT: Fibrinogen is a substrate for the enzyme thrombin, being converted to fibrin.

Note: Fibrinogen does not have enzymatic activity but is the substrate acted upon by clotting enzymes.

42. Fibrinogen is a Cofactor:

• INCORRECT: Fibrinogen is a substrate for the enzyme thrombin, being converted to fibrin.

Note: Fibrinogen does not have enzymatic activity but is the substrate acted upon by clotting enzymes.

43. All Enzymes, Except Factor XIII, Are Serine Proteases, Meaning They Have the Ability to Hydrolyze Peptides:

• CORRECT

Note: Factor XIII is a transglutaminase, binding fibrin molecules together, forming a stable blood clot.

44. One Gram Molecule of Activated Factor XI Can Continuously Activate Factors IX, X, and Prothrombin to Form 10^7 Gram Molecules of Fibrinogen:

• INCORRECT: One gram molecule of activated factor XI can continuously activate factors IX, X, and prothrombin to form 2.10^8 gram molecules of fibrinogen.

Note: Each activated molecule of factor XI can activate a significant amount of other clotting factors, resulting in high coagulation efficiency.

45. The Plasma Coagulation Process Is Divided into How Many Periods:

• 1. Formation of Activated Thromboplastin (Prothrombinase Complex) Through Two Pathways, Intrinsic and Extrinsic: The intrinsic pathway is activated by factor XII, while the extrinsic pathway is activated by tissue factor.
• 2. Formation of Thrombin: Prothrombin is activated by the prothrombinase complex into thrombin.
• 3. Formation of Fibrinogen: Thrombin activates fibrinogen into fibrin.

46. The Main Factors Determining the Activation and Inhibition of the Contact Stage of Coagulation:

• XII, prekallikrein, XI, high-molecular-weight kininogen (HMWK), and C1 inhibitor (CI):
  • Factors XII, prekallikrein, XI, and HMWK activate the intrinsic coagulation pathway.
  • C1 inhibitor inhibits the activation of the intrinsic coagulation pathway.

Note: The balance between activating and inhibiting factors helps control the coagulation process, preventing widespread coagulation.

47. Damaged Vessel Walls Activate Factors:

• The Contact Factor Group XII, XI, prekallikrein, HMWK activates factor IX: initiating the intrinsic coagulation pathway.

48. Factors Involved in the Activation of Factor X:

• The Participation of a Complex Including:
  • Enzyme (Factor IXa): Activated by factor XIa.
  • A Cofactor (Factor VIII:C): Activated by thrombin.
  • Calcium Ions: Facilitating the binding of clotting factors to phospholipids.
  • Platelet Phospholipids: Providing a surface for the activation of factor X.

49. Role of Platelet Factor 3:

• Activation of Factor X: Catalyzes the reaction between factor IXa, factor VIII:C, calcium ions, and phospholipids.
• Activation of Prothrombin: Along with factor Xa, factor V, calcium ions, and phospholipids, forming the prothrombinase complex, activating prothrombin into thrombin.

50. Role of Factor IXa:

• It Not Only Has Enzymatic Activity on Factor X but Can Also Activate Factor VII: Creating a connection between the intrinsic and extrinsic pathways.

Note: Factor IXa connects the intrinsic and extrinsic coagulation pathways, enhancing coagulation efficiency.

51. The Relationship Between the Intrinsic and Extrinsic Coagulation Pathways:

• Tissue Damage, Activators of Tissue Factors Activating Coagulation to Form Fibrin, Will Accelerate the Intrinsic Pathway by Activating Cofactors VIII and V: The extrinsic pathway activates the intrinsic pathway, enhancing coagulation efficiency.

52. Immediately Upon Vessel Wall Injury, the Vessel Constricts Due to Mechanisms:

• 1. Neural Reflex Triggered by Pain.
• 2. Local Vasoconstriction, Directly Initiated by Vessel Wall Injury.
• 3. Humoral Factors from Damaged Tissues and Platelets (Thromboxane A2, Serotonin, and Epinephrine).

Note: Vasoconstriction is the body’s first response to injury, reducing blood loss from the wound.

53. Significance of Vasoconstriction:

• This Immediate Vasoconstriction Limits Blood Loss from the Damaged Vessel.

Note: Vasoconstriction is the first stage of the hemostasis process, controlling the amount of blood loss from the wound.

54. All Platelets Produced Circulate in Blood:

• INCORRECT: Only 60-75% of platelets circulate in the blood after being released from the bone marrow, the rest are stored in the spleen.

Note: The spleen is a platelet reservoir, providing a supply of platelets to the blood when needed.

55. Significance of Platelet Plug Formation:

• Platelet plug formation is of particular importance in sealing small wounds in small blood vessels, which happen hundreds of times each day.

Note: The platelet plug is the initial stage of hemostasis, sealing small wounds and preventing blood loss from the wound.

56. The Extrinsic Prothrombinase Complex is Formed by:

• Factor III (Tissue Thromboplastin, consisting of phospholipids and lipoprotein) is secreted from the surface of damaged tissue cells outside the vessel wall.
• Factor III enters the blood, activating factor VII.
• Factor VIIa (activated VII) together with tissue thromboplastin activates factor X.
• Factor Xa combines with phospholipids (from tissues) and factor V in the presence of Ca2+ to form the prothrombinase complex.

Note: The prothrombinase complex is an enzyme complex that activates prothrombin into thrombin, a crucial step in the extrinsic coagulation pathway.

57. Factor XIIa Activates Factor XI, This Reaction Requires Kininogen and Prekallikrein:

• CORRECT

Note: Factor XIIa activates factor XI, requiring kininogen and prekallikrein.

58. Factor VIIa in the Extrinsic Pathway Also Participates in the Activation of Factor IX:

• CORRECT

Note: Factor VIIa activates both factors X and IX, connecting the intrinsic and extrinsic coagulation pathways.

59. Calcium Ions Act in Which Stage of the Intrinsic Coagulation Pathway:

• Formation of Factor IXa: Calcium ions facilitate the binding of factor IXa to phospholipids, activating factor X.

Note: Calcium ions are a crucial electrolyte, participating in multiple stages of the coagulation process.

60. The Prothrombinase Complex Consists of:

• Xa, Va, PL, and Ca++:
  • Factor Xa is the primary enzyme of the complex.
  • Factor Va is a cofactor, enhancing the activity of factor Xa.
  • PL is phospholipid, providing a surface for prothrombin activation.
  • Ca++ is a crucial electrolyte, facilitating the binding of clotting factors to phospholipids.

61. Once Prothrombinase is Formed, It Converts Prothrombin into Thrombin in Just a Few Seconds:

• CORRECT

Note: The prothrombinase complex is a potent enzyme, quickly converting prothrombin into thrombin.

62. Thrombin is a Protein-cleaving Enzyme; It Can Also Act on Prothrombin to Increase Thrombin Formation:

• CORRECT

Note: Thrombin has a positive feedback effect, enhancing the coagulation process.

63. Significance of Blood Clot Formation:

• The blood clot seals the damaged vessel wall, preventing blood loss.

Note: The blood clot is the final product of the coagulation process, providing permanent hemostasis.

64. In the Coagulation Process, the Extrinsic and Intrinsic Pathways are Initiated Simultaneously. However, the Intrinsic Pathway Proceeds Faster:

• INCORRECT: The extrinsic pathway proceeds faster, with a time of 15s, while the intrinsic pathway takes 1-6 minutes.

Note: The extrinsic pathway is faster because it involves the presence of tissue factor, a direct activator of the coagulation process.

65. Significance of Blood Clot Retraction:

• Blood clot retraction pulls the edges of the damaged vessel wall together, sealing the wound more tightly and stabilizing bleeding.

Note: Blood clot retraction compresses the blood clot, sealing the wound and preventing blood loss.

66. Blood Clots Formed at Small Wounds in the Vessel Wall Are Invaded by Fibroblasts, Which Then Form Connective Tissue, Helping to Heal the Wound:

• CORRECT

Note: Wound healing involves the restoration of damaged tissue.

67. Larger Blood Clots or Blood Clots in Blood Vessels Are Dissolved Under the Influence of the Fibrinolytic System:

• CORRECT

Note: The fibrinolytic system removes blood clots, ensuring the patency of blood vessels.

68. When a Blood Clot Forms, Plasminogen is Also Trapped Within It:

• CORRECT

Note: Plasminogen is a precursor of plasmin, an enzyme that breaks down fibrin.

69. Plasminogen is Converted to Plasmin by:

• The Action of Tissue Plasminogen Activator (t-PA): An enzyme secreted by endothelial cells and damaged tissues, activating plasminogen to plasmin.

Note: t-PA is a crucial plasminogen activator, helping control fibrin breakdown.

70. What is the Function of Plasmin:

• Breaks down fibrin, fibrinogen, factor V, factor VIII, and many other proteins.

Note: Plasmin has broad degradative activity, removing blood clots and maintaining blood vessel patency.

71. t-PA is Secreted From:

• Damaged tissues or endothelial cells secrete it about one day (or later) after the blood clot is formed.

Note: t-PA is released late to ensure safe and efficient fibrin breakdown.

72. Thrombin and Factor XIIa Do Not Play a Role in Activating Plasminogen into Plasmin:

•