| Which of the following tests could be used to distinguish whether an abnormal screening coagulation test result (PT or aPTT) is caused by a factor deficiency or an inhibitor?. | View Page |
| The term that describes the process by which fibrin strands are broken down, then removed from an established clot is: | View Page |
| Which of the following mechanisms involve a series of interrelated chemical processes that lead to the formation of durable fibrin strands? | View Page |
| All of the following processes occur during primary hemostasis except: | View Page |
| Primary Hemostasis – Platelet Function Platelets have three primary functions: Maintenance of Vascular Integrity – Platelets contain chemicals within their granules that are vital to the normal growth and maintenance of the vascular system. Platelet Plug Formation – Platelets are the fundamental components of the physical barrier that initially fills the breach in the compromised vessel. Stabilization of the Platelet Plug – Inherent platelet stickiness acts as a strong bond between the platelet and the exposed subendothelium, as well as between platelets themselves. Fibrin strands will weave in amongst the bound platelets that make up the platelet plug, further compressing and solidifying the structure and creating a fibrin clot. | View Page |
| Primary Hemostasis – Platelet Kinetics Kinetic Processes Specific to Platelets. Adhesion – When platelets adhere to exposed collagen, they take on a characteristic “spiny” shape. Their inherent stickiness, and the aforementioned spiny shape serve to compliment each other during this process. Von Willebrands Factor (vWF) is absorbed by surface receptors on both the platelet and exposed subendothelial tissue, thereby linking the platelets to the tissue. Release – This process occurs prior to aggregation. Platelets dump the contents of their granules (ADP, Serotonin, & Calcium), which aids the upcoming aggregation process by acting as a chemical signal. Aggregation – Platelets physically bind to each other, not just to the exposed subendothelial walls and collagen of the breached vessel. Platelet aggregation requires sufficient chemical signal stimulation. Stabilization (technically part of secondary hemostasis as fibrin is a product of secondary hemostasis)– This process strengthens the platelet plug with the addition of interwoven fibrin strands, ultimately producing a fibrin clot. The durable fibrin clot is the ultimate goal of hemostatic processes. | View Page |
| All of the following are activities associated with platelets except: | View Page |
| Summary of Primary Hemostasis In summation, we have covered the following sequence of events which comprise primary hemostasis. The process begins with damage to a vessel wall, as blood flows outside the vasculature. The body responds with vasoconstriction, decreasing blood flow to the affected area. Platelets begin sticking to the damaged vessel walls. As the platelets stick, they release chemicals which signal other platelets to respond. As other platelets arrive, they begin sticking to one another, clumping together, forming a plug to fill in the breach. This plug, while strong, is a temporary fix, and must be reinforced with fibrin strands to effectively fill the breach during the vessel repair process. Construction of the fibrin strands occurs during secondary hemostasis, our next topic to be covered. | View Page |
| Overview of Secondary Hemostasis Secondary hemostasis is the series of interrelated chemical processes which lead to the formation of durable fibrin strands, as well as being involved in their incorporation into the existing platelet plug, creating a fibrin clot. The fibrin strands themselves are manufactured through the interaction of various coagulation factors, via a process known as the coagulation cascade. After strand construction, these fibrin monomers are woven into the framework of the platelet plug, adding greater strength and stability. Once woven into the platelet plug, and further stabilized with covalent cross-linking, a fibrin clot (the end goal of secondary hemostasis) is achieved. The fibrin clot is more durable than the platelet plug, and is more of a long term fix, allowing time for continued vascular repair. | View Page |
| Secondary Hemostasis – Fibrin Formation via the Coagulation Cascade The formation of fibrin involves three interconnected biochemical pathways; the intrinsic, extrinsic, and common pathways. These pathways allow for the interaction of coagulation factors via a finely tuned sequence of chemical processes, where the factors themselves control the activity of the pathway. Most coagulation factors are stimulated and activated by the preceding factor , hence the term, "coagulation cascade." Since factor activation requires the activation of a preceding factor, a deficiency in the functionality or availability of any factor would seriously impact the effectiveness of the coagulation process. Factor deficiencies do occur, however, and often lead to impaired vascular repair and depressed hemostatic activity. | View Page |
| Secondary Hemostasis – The Common Pathway Thrombin, after its conversion from prothrombin, catalyzes the conversion of fibrinogen into a fibrin monomer. Additionally, thrombin triggers the conversion of factor XIII into factor XIIIa which forms covalent bonds that crosslink and stabilize the fibrin monomers. Finally, thrombin feeds back into the intrinsic and common pathways, accelerating the action of factors XI, V, and VIII. | View Page |
| The Fibrinolytic System There is a very close relationship between the formation of fibrin, and its eventual degradation, or lysis. A fibrin clot serves as a temporary seal, intended to prevent continued blood loss from the damaged vessel while repair activities are performed. The breakdown of the clot begins almost as soon as the clot is formed! The process by which fibrin is broken down and removed from the clot, ultimately leading to complete dissolution of the clot, is called fibrinolysis. | View Page |
| The Fibrinolytic System Fibrin strands woven into the clot structure are cleaved into soluble fibrin fragments, and then removed by macrophages. The action of fibrinolysis also serves to restore blood flow into the area that had been sealed off, helping to promote further healing. Fibrinolysis is mediated by a proteolytic enzyme called plasmin. Plasminogen is the inactive precursor form of plasmin that is found in plasma. Plasmin takes on fibrinolytic properties after activation, digesting both fibrin and fibrinogen. Inhibitors act to control the process, serving as a check and balance system for fibrinolytic activities. | View Page |
| Which of the following statements is incorrect? | View Page |
| Fibrin/Fibrinogen Degradation Products and D-dimers The presence of D-dimers in plasma or whole blood indicates that fibrin has been formed and degraded (fibrinolysis). Plasmin can also degrade intact fibrinogen, generating fibrinogen degradation products that are detected in fibrin/fibrinogen degradation products (FDP) assays. D-dimers and FDP can become elevated whenever the coagulation and fibrinolytic systems are activated. The presence of D-dimer confirms that both thrombin and plasmin have been generated since it can only be produced as the result of the plasmin degradation of fibrin. This makes the test for D-dimers more specific for fibrinolysis than the FDP test that also detects the products of the direct proteolysis of fibrinogen (fibrinogenolysis).The D-dimer test can be useful in the diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE), two forms of venous thromboembolism (VTE). When the test is being used for this purpose, it is important that D-dimer levels are accurately measured and accurately reported because of the serious nature of this clinical decision. If the test is positive in a patient suspected to have DVT or PE, clinicians proceed with further diagnostic tests. If the test is negative, depending on the clinical situation and the sensitivity of the D-dimer assay, DVT or PE is considered unlikely and further diagnostic tests for DVT or PE might not be pursued. D-dimer is a sensitive, but not specific, diagnostic test for disseminated intravascular coagulation, and an indicator of increased risk of future myocardial infarction in patients evaluated for chest pain. | View Page |
| Match the forms of poikilocytosis on the left with the physiological/environmental condition associated with their formation on the right: | View Page |
| Match the forms of poikilocytosis on the left with the physiological/environmental condition associated with their formation on the right: | View Page |
| Schistocytes Schistocytes are red cell fragments which are formed when fibrin strands come in contact with circulating red cells. The strands cut a small piece from the original cell. This is the same mechanism which causes the formation of keratocytes. A schistocyte can be seen in the center of this field. | View Page |
| Prekeratocyte or Blister Cells The cell in the center of this slide is sometimes referred to as a prekeratocyte or blister cell. Notice the cell appears to have a blister or pseudo vacuole extending around the flat edge. This cell has freed itself from a fibrin strand, and when the vacuole bursts, one or more projections may be visible. Survival time in circulation for these cells is very short. | View Page |
| Keratocytes Keratocytes are cells which have been damaged due to contact with fibrin strands. Since the cut is incomplete, however, no hemoglobin has been lost from the cell. Keratocytes have one or two projections which may vary in length from a short point to a longer string. These projections are formed when red cells come in contact with fibrin strands during circulation.
Two keratocytes can be seen in this field. The one in the center to the left of the platelet has a lightly-stained projection. The keratocyte in the lower part of the screen is more pronounced. A knizocyte can be seen in the upper left portion of the field. | View Page |