Missed Lecture Material

• How is thrombin-mediated tissue repair activated?


  Increased vascular permeability and increased adhesion of leukocytes to endothelial cells
• Activation of thrombin induces the activation of what?

  Leukocytes, specifically neutrophils & monocytes
• What does PDGF stand for?

  Platelet Derived Growth Factor
• Thrombin also mediates the release of PDGF and stimulates the proliferation of what three components?

  Fibroblasts, smooth muscle cells, and endothelial cells
• What three alternative roles does thrombin serve that all happen at the same time?

  Act as a procoagulant, act in tissue repair, and serve as an anti-coagulant
• Thrombin acts a procoagulant, acts in tissue repair, and serves as an anticoagulant which all happen at the same time, just different rates
• How does thrombin serve as a procoagulant?

  Activates fibrinogen(main substrate), activates XI, VI, and V as a feedback loop, activates XIII to help stabilize the clot, and promotes secretion of serotonin(vasoconstriction)
• The fibrinolytic system refers to fibrin lysing which is the breaking down of the clot
• What leads to fibrin lysis?


  Activation of fibrinolysis
• Fibrin-lysing is the process of gradual enzymatic cleavage of fibrin into fragments which are then removed by macrophages.
• TPA stands for what?


  Tissue Plasminogen Activator
• What does TPA do?

  Activates plasminogen to plasmin
• Where do we derive TPA?

  TPA is derived from damaged endothelial cells
• The fibrinolytic system is mediated by what enzyme?

  Mediated by enzyme plasmin which act primarily on fibrin
• Can we have plasmin runnning through the vessels ?

  NO
• Clot formation is fast, plasmin activation is fast, and the dissolution of clot is slow & precise
• What are disorders of primary hemostasis?

  Abnormalities that result in bleeding that range from hemorrhage to longer bleeding time
• Why do we see bleeding in disorders of primary hemostasis?

  Because of defects in the formation of an adequate platelet plug
• Which is the most commonly encountered group of platelet abnormality?

  Quantitative
• Thrombocytopenia is the decrease of platelets while Thrombocytosis is the increase of platelets
• Thrombocytopenia results from which 3 distinct mechanisms?

  Deficient platelet production, abnormal distribution of platelets, and increased destruction of platelets
• How can we get deficient platelet production?

  Spontaneous(anemia) or as a result of injury to bone marrow (radiation, chemo, BM replacement)
• About 1/3 of platelets pool in the spleen
• Splenomegaly can cause an abnormal distribution of platelets
• Splenomegaly can cause decreased circulation of platelets, affect plate function, and affect platelet distribution in the body
• What can cause an increased destruction of platelets?

  Immune-mediated(which can be idiopathic or secondary to underlying disease) or Immune Thrombocytopenic Purpura(ITP)
• We see little red splotches that indicate bruising very easily in Immune Thrombocytopenia Purpura(ITP).
• Disorders of primary hemostasis that are derived via qualitative deal with an affect toward the quality/function of platelet
• Disorders of primary hemostasis can be derived via congenital. They are?

  1. Platelet surface membrane defects
  2. Platelet release or secretion defects
  3. Platelet coagulation activity defects
  4. Defects associated with abnormal protein interaction
• Platelet surface membrane defects on GPIB would affect by preventing adhesion
• Platelet surface membrane defects on GPIIbIIIa would affect the attachment of fibrinogen, thus, no fibrin strands
• Glanzmann’s Thrombasthenia is a rare bleeding disorder where platelets don’t function properly since they lack/have defective receptors for the clotting factor, factor VIII
• Can von Willebrand Disease(vWD) affect secondary hemostasis?

  Yeah, effects vary based on the amount of inherited deficiency of vWF that are categorized into 3 types
• vWF can be found in endothelial cells and alpha granules of platelets
• Type I vWD is an autosomal dominant disorder which makes up 70% of all cases, and results in decrease of vWF and mild bleeding
• Type II vWD has variable inheritance which is characterized to affect the structure of vWF, makes up most of the other cases, and usually results in mild bleeding
• Type III vWD is autosomal recessive which makes it a very rare disorder that results in absent levels of vWF as well as severe bleeding
• Purpura is a vascular disorder caused by abnormalities of the skin, connective tissue, or blood vessels.
• Primary purpura results from skin fragility, but Secondary Purpura results from another disease process