Ch. 24 Coagulation

  1. Purpura
    Bleeding into skin, organs or membranes.
  2. Petechia
    Small, pinpoint bleeding into skin
  3. Qualitative Platelet Disorder
    • Something wrong with platelets but platelet counts usually normal.
    • EXAMPLE: Wiscott-Aldrich syndrome, Bernand-Soulier Syndrome, Glanzemann's, Thrombasthenia, Aspirin ingestion.
  4. Quantitative Platelet Disorder
    • Low production
    • High Destruction or Consumption
    • Common Causes: Cancer treatment, Damage to the bone marrow by miscellaneous drugs or toxins, 80% of hospitalized alcoholics mild thrombocytopenia, Vitamin B12 and Folic Acid deficiency, autoimmune diseases, leukemias.
  5. Bacterial Sepsis
    A bacterial infection of the blood
  6. Thrombocytosis
    • Increased platelets
    • Acute blood loss, infections, inflammation
  7. Vitamin K
    • Makes the body system avoid excessive blood flow.
    • People without Vitamin K prone to excessive bleeding and bruising.
    • Group 2 (2,7,9,10)
  8. Hemophilia
    Refers to a group of bleeding disorders in which it takes a long time for a blood clot to form.
  9. Hypercoagulable states
    • DVT, PE, Strokes, and Heart attacks
    • High procoagulants
    • Low Fibrinolysis
    • Low natural anticoagulants activity (ATIII, Protein C)
  10. Circulating anticoagulants
    Usually auto antibodies directed against plasma coagulation proteins.
  11. Inhibitors
    • Can have specificity against a specific protein or non-specificity against multiple different proteins.
    • Lupus inhibitors
    • Factor VIII inhibitors
  12. Trousseau's Syndrome:
    Term used for venous thrombosis of upper and lower extremities associated with: visceral cancer.
  13. Recombinant technology:
    Artificial DNA sequence resulting from the combining 2 other DNA sequences in a plasmid.
  14. Lupus inhibitor
    • Non-specific anti-phospholipid antibodies. Found in 10% SLE
    • Associated: HIV, Medications, Cancers
  15. Autoantibodies:
    Directed against plasma coagulation proteins.
  16. ADAMTS-13
    • vWF proteins are normally broken down into smaller, inactive fragments by an enzyme.
    • Deficiency: accumulation of vWF multimers (Abnormally large vWF molecules)
    • Causes: Genetic, others acquired
  17. vWF
    • Synthesized by megakaryocytes and vascular endothelium
    • 95% of Factor VIII composed of vWF
    • Stabilizes Factor VIII and promotes platelet adhesion
  18. Traveler's Thrombosis
    • Types of clotting disease
    • Hypercoagulable conditions
  19. Coumadin (warfarin) therapy
    • Oral, slow
    • 72 hours
    • Effects Group 2 (2,7,9,10) because it's a Vitamin K inhibitor.
  20. Heparin therapy
    • IV
    • Inhibits thrombin by enhancing ATIII
    • Fast Acting
    • 1/2 life= 1 hour
  21. DIC (Disseminated Intravascular Coagulation)
    • Excessive thrombin activation and clotting
    • Procoagulant activity exceeds anticoagulant activity.
    • All hemostasis system activated.
  22. Von Willebrand's Disease
    • Genetically acquired but not sex linked.
    • Males and Females
    • More common than Hemophilia A
    • Factor VIII lowered.
    • Abnormal platelet function
    • 85%: Vascular endothelial cells
    • 15%: Platelet alpha granules
  23. Hemophilia A
    • Factor VIII Absent/decreased synthesis
    • 85% of Hemophilias
    • 66% cases acquired from inheritance of defective X chromosome
    • 33% acquired from spontaneous mutations
    • Females are carriers
  24. Hemophilia B
    • Factor IX deficiency
    • Christmas disease
    • Sex linked, Genetically acquired
    • 20% spontaneous mutations
  25. Hemophilia C
    • Factor XI deficiency
    • Genetically acquired, non-sex linked males and females affected.
    • Most common in E.European Jews
  26. Hypercoagulopathy Syndrome
    ATIII: Decreased

    Protein C: Decreased
  27. Deep Vein Thrombosis/Pulmonary Embolisms
    Types of clotting diseases
  28. ITP
    Idiopathic Thrombocytopenia Purpura
    • Auto-immune anti platelet antibodies
    • Chronic=Adults
    • Acute-transient=Children
    • Treatment: Steroids, splenectomy, plasmapheris (REMOVES ANTIBODIES)
  29. (TTP)
    Thrombotic Thrombocytopenia Purpura
    • vWF proteins are normally low into smaller inactive fragments by an enzyme.
    • Synthesized by megakaryocytes and vascular endothelium.
    • Def. of ADAMTS-13 enzyme promotes an accumulation of vWF multimers.
    • High plasma BUN, Creatinine
    • Low LDH
    • High Bilirubin
    • Low Haptoglobin (RBC Hemolysis)
  30. (HUS) Hemolytic Uremic Syndrome
    • Related to TTP but with renal failure associated from vascular ischemia (blockages to renal blood vessel)
    • ADAMTS-13
  31. Bernard-Soulier Syndrome
    • Qualitative Platelet
    • Dohle Bodies with large platelets
    • Missing platelet GP receptors (Ib, V, IX) with impaired platelet.
  32. Alport's Syndrome
    • Qualitative platelet disorder
    • PFA: Increased
    • Genetic disorder
    • End stage kidney disease
  33. Glanzmann's Thrombasthenia
    • PFA: Increased
    • Missing platelet GP receptors (IIb/IIIa) with impaired platelet adhesion.
  34. Heparin Induced Thrombocytopenia
    • Seen in 1% of heparinized patients.
    • Thrombocytopenia begins 5-7 days after therapy.
    • Heparin mediated immune platelet destruction
    • Heparin interacts with platelet antigens.

    Treatment: Discontinue heparin
  35. Post-transfusion pupura
    • Most common in post partum females
    • Anti-platelet antibodies from previous pregnancies or transfusions
    • Thrombocytopenia 5-10 days post transfusion.
  36. Vascular Disorders
    Bleeding into skin, organs, membranes
  37. Petechia
    Small, pinpoint bleeding into skin
  38. Endothelial damage can occur from:
    • Bacterial toxins
    • Malignancies (Trousseau's Syndrome)
    • Antibody-Antigen reactions
    • Trauma
    • OB complications
    • Diabetes
    • DIC
  39. Platelets
    • 150-450 (103/mm3)
    • Decreased plts: Thrombocytopenia
    • Increased plts: Thrombocytosis

    • >100: for normal clot formation
    • < 50: abnormal bleeding and bruising
    • < 20: Cerebral bleeding (death)
    • < 10: Spontaneous bleeding (Death)
  40. Symptoms of Quantitative and Qualitative Platelet Disorders
    • Petechaie,
    • purpura
    • epistaxsis (nosebleeds)
    • Cerebral hemorrhage
    • Excessive surgical bleeding
  41. Qualitative Platelet Disorder
    Wiscott-Aldrich Syndrome
    • Defective platelet dense granule storage
    • Abnormally small platelets
  42. Bernard-Soulier Syndrome
    (dohle bodies, large platelets)
    • Missing platelet GP receptors (Ib, V, IX)
    • Impaired platelet adhesion
  43. Glanzmann's Thrombasthenia
    Missing platelet GP receptors (IIb,IIIa) with impaired platelet adhesion
  44. Aspirin Ingestion
    • Aspirin inhibits platelet function
    • Aspirin inhibits the synthesis of naturally occuring substances (Thromboxane A2) that promote platelet aggregation.
  45. Quantitative Platelet Disorder
    (Decreased production)
    • Common cause: Cancer treatment (Therapeutic irradiation and chemotherapy)
    • Damage to the bone marrow by miscellaneous drugs or toxins
    • 80% of hospitalized alcoholics have mild thrombocytopenia.
    • Vitamin B12 and Folic Acid deficiency
    • Viral infections (EBV, HIV, Mumps, Chicken pox, others)
    • Autoimmune diseases
    • leukemias
    Heparin Induced Thrombocytopenia
    • Heparin mediated immune platelet destruction.
    • Heparin interacts with platelet antigens
    • Seen in 1% of heparinized patients
    • Thrombocytopenia begins 5-7 days after therapy
    • Checked for platelet counts

    Treatment: stop heparin
  47. Immune complex formation
    • Ab-ag complexes (immune complexes) attach to platelets
    • Removal of platelets from the peripheral blood
    • Associated with: Sepsis (bacteria in the blood) and drugs
  48. Post-Transfusion Purpura (PTP)
    • Most common in post partum females
    • Anti-platelet antibodies from previous pregnancies or transfusions
    • Thrombocytopenia 5-10 days post transfusion
    • (Exposed to antigen in child birth make antibodies)
  49. (ITP)
    Idiopathic (Immune) Thrombocytopenic Purpura
    • Auto-immune anti platelet antibodies
    • Thrombocytopenia (low platelets)
    • Cause: UNKNOWN (perhaps associated with viral infections)
    • Acute to transient symptoms in children
    • Chronic=Adults

    • Treatment: Splenectomy, Steroids, Plasmapheresis (removes antibodies)
    • Titer: way of measuring concentration
  50. (TTP) Thrombotic Thrombocytopenia Purpura
    • vWF is synthesized by megakaryocytes and vascular endothelium.
    • Deficiency of ADAMTS-13 promotes an accumulation of vWF multimers (abnormally large vWF molecules
    • vWF multimers adhere to the endothelium lining and promote platelet adhesion and aggregation.

    • Causes of ADAMTS-13 deficiencies:
    • Genetic, Acquired
  51. Clinical findings and treatment of TTP
    • Thrombocytopenia
    • Microangiopathic (abnormal circulation in blood vessels) hemolytic anemias (schistocytes)
    • High: Plasma BUN and Creatinine (Renal failure), LDH, Bilirubin,
    • Low: Haptoglobin (RBC hemolysis)
    • Vascular occlusions (renal and neurological damage)

    Treatment: Plasmaphoresis to remove vWF multimers from the plasma. Support patient with Platelet transfusions
  52. ADAMTS-13
    • Keep blood vessels clear of vWF.
    • Weeds keep growing and platelets get stuck because ADAMTS-13 can't cut it down.
  53. (HUS)
    Hemolytic Uremic (renal failure) Syndrome
    • Type of TTP, but with renal failure associated from vascular ischemia
    • (Blockages to renal blood vessels)
  54. Hypersplenism
    • Enlarged spleen
    • Abnormal increased removal of platelets from the peripheral blood.
    • Treatment: Splenectomy
  55. Thrombocytosis
    (Increased platelets)
    • Acute blood loss
    • Infection
    • Inflammation
    • Pathological thrombocytosis can be associated with thrombotic events (clotting)
  56. Disorders of the coagulation Proteins
    General Causes
    • Vitamin K deficiency=Decreased group II (2,7,9,10)
    • Liver disease=all coagulation proteins are decreased.
    • Hemophilia
    • Autoimmune antibodies against coagulation proteins.
    • Excessive consumption and depletion of coagulation proteins.
    • 30-40% of circulating proteins is still sufficient to produce normal clotting.
    • There must be a significant factor deficiency before the PT/PTT tests are abnormally elevated.
  57. Hemophilia
    Genetic deficiencies of coagulation protein synthesis
  58. Hemophilia A
    Classic Hemophilia (genetic disorder inherited)
    • Absent or decreased synthesis of Factor VIII
    • Most common hemophilia (85% of all hemophilias)
    • 66% of cases acquired from inheritance of a defective X chromosome.
    • 33% of cases acquired from spontaneous mutation of X chromosome.
    • Disease is almost found in 1/10,000 males.
    • Females are carriers (carry the defective gene, but don't have symptoms of the disease)
    • Found in all ethnic groups.
  59. Hemophilia A
    Caused by decreased or absent VIII:C component of the Factor VIII molecule.
  60. High Molecular Weight
    • vWF (Von Willebrand Factor)
    • VIII:RCo (Platelet aggregation)
    • VIII: Ag (Antigenic site)
  61. Low Molecular Weight
    • VIII: C (procoagulant)
    • VIII: Ag (Antigenic Site)
  62. Genetic Inheritance of Hemophilia A
    • Males: XY sex Chromosomes
    • Females: XX sex chromosomes

    • The genetic mutation responsible for defective Factor VIII synthesis is on the X chromosome, not the Y
    • A male with a defective X chromosome inherits the disease because he has no genetic capacity to synthesize Factor VIII.
    • A female with a defective X chromosome is a carrier of the disease and has no symptoms because she still has an additional normal X chromosome that can still synthesize Factor VIII.

    • All daughters of a hemophiliac father will be carriers.
    • Sons of female carriers have a 50% chance of being hemophiliacs.
    • Daughters of female carriers have a 50% chance of becoming carriers.
    • For practical considerations, females can transmit the disease but cannot become hemophiliacs themselves
  63. Symptoms of Hemophilia
    • Easy bleeding and bruising, even from normal activities.
    • The absence of normal clotting often results in painful and crippling bleeding into joints.
    • Normal cuts and injuries can be life threatening.
  64. Recombinant DNA
    • An artifical DNA sequence resulting from the combing of DNA sequence in a plasmid.
    • Proteins that are produced by different genetically modified organisms following insertion of the relevant DNA into their genome.
    • As this recombines the DNA of 2 different organisms.
  65. Lab Test of Hemophilia A
    • PT: Normal
    • PTT: Increased (only measures Factor 8)
    • FIB: Normal
    • PFA: Normal
    • Plt #: Normal
    • D-dimer: =
    • FDP:=
  66. Von Willebrand's Disease
    • Defective or absent vWF.
    • 95% of Factor 8 is composed of the vWF
    • vWF stabilizes Factor 8 and promotes platelet adhesion.
    • Genetically acquired, but not sex linked (males and females affected)
    • More common than Hemophilia A
    • VWF synthesis (85% endothelial cells + 15% platelet alpha granules)
    • vWF is an adhesive protein that binds with platelet GP IIb/IIIa receptors (its the rope that ties onto the platelets)
    • Affects 1-2% of population
    • 80% mortality if untreated
    • Factor 8 activity is decreased in both Hemophilia A and VWD
  67. Effects of defective/absent vWF
    • Unstable Factor 8 is removed from the plasma.
    • Poor platelet adhesion
  68. Clinical effects of VWD
    • Bleeding from abnormal platelet adhesion.
    • Bleeding from decreased Factor 8 activity
  69. Hemophilia A vs. vWD
    • Normal platelet function
    • Abnormal
  70. Lab Tests of vWD
    • PT: normal
    • PTT: Increased (decreased Factor 8)
    • FIB: normal
    • PFA: Prolonged (Decreased plt. function)
    • Plt #: normal
    • D-dimer: =
    • FDP: =
  71. Hemophilia B
    (on X chromosome)
    • Factor 9 deficiency
    • X-mas disease
    • Sex linked, genetically acquired like Hemophilia A
    • 20% are spontaneous mutations
    • Frequency: 1/30,000 males
    • Similar symptoms as Hemophilia A,but usually not as severe
  72. Hemophilia C
    • Factor 11 deficiency
    • Genetically acquired, non sex-linked, Males and Females affected
    • Frequency: 1/100,000
    • Most common in Eastern European Jews
    • 8% frequency among Israeli Ashkenazi Jews
  73. Disorders of excessive activation and consumption
    Balance between clotting and bleeding
  74. If there is excessive activation of procoagulants
    • Too much clotting
    • The coagulation factors get used up=Bleeding
  75. Excessive activation of the fibrinolytic system
    • Abnormal activation without fibrin formation (Primary fibrinolysis)
    • Activation with fibrin formation (Secondary fibrinolysis)
  76. (DIC)
    Disseminated Intravascular Coagulation
    • Excessive thrombin activation and clotting
    • Pro-coagulant activity exceeds anticoagulant activity
    • All components of the hemostasis system are activated: (Pro-coagulants, Platelets, Vascular System, Fibrinolysis )
  77. Common causes of excessive activation:
    • Childbirth (33%)
    • Malignancies (33%)
    • Bacterial infections
    • Trauma=Burns, surgery, injuries
    • Snake bites
    • RBC hemolysis
  78. Symptoms of DIC
    • Petechia/Purpura
    • Bleeding/cozing from surgical incesions
    • IV
    • Needle sticks
    • coagulation proteins and platelets are depleted in excessive clotting.
    • Excessive fibrinolysis produces increased FDP
    • Increased FDPs inhibit platelet aggregation/adhesion
    • Excessive clotting depletes the natural anticoagulant activity
  79. The root cause of DIC
    • excessive clotting
    • Treatment: Stop the clotting= Anticoagulant therapy (Heparin)
    • Can be supported with blood transfusions until the root cause is controlled (RBCs, Platelets, FFP)
  80. DIC Lab Tests
    • PT: Increased
    • PTT: Increased
    • FIB: Decreased
    • PFA: Prolonged (Decreased Platelet Function)
    • Plt #: Decreased
    • Blood smear: Schistocytes
    • FDP: +
    • D-Dimer: + (most specific indicator)
    • ATIII and PC: Decreased
  81. Hypercoagulable conditions
    (excessive clotting)
    General Causes
    • Increased procoagulants
    • Decreased fibrinolysis
    • Decreased natural anticoagulant activity (ATIII and Protein C)
    • Damaged vascular systems and stasis
    • 300,000 annual deaths in US hospitals
    • More deaths from clotting than bleeding
  82. Type of clotting diseases
    • DVT: Deep Vein Thrombosis
    • PE: Pulmonary Embolisms
    • Strokes and heart attacks from vascular occlusions
    • Traveler's thrombosis
  83. Lab tests associated with causes/detection of Increased clotting
    ATIII: Decreased

    Protein C: Decreased

    FDP: +

    D-dimer: +

    Treatment: Warfarin, Heparin, Aspirin. DVT and PE involves the use of "clot busting" drugs, usually plasminogen activators (TPA). Plasminogen activated plasmin. Activated plasmin dissolves fibrin.
  84. Circulating anticoagulants
    • Substances that inhibit plasma coagulation proteins
    • Circulating anticoagulants (inhibitors) are usually auto antibodies directed against plasma coagulation proteins.
    • Found in 1% of the population
    • Inhibitors can have specificity against a specific protein or non-specificity against multiple different proteins.
    • Most circulating anticoagulants only cause bleeding disorders when they are associated with another coagulation disorder
  85. Lupus Inhibitors
    • Non-specific anti-phospholipid (components of membranes) antibodies
    • Found in 10% of Systemic Lupus Erythromatosis
    • Also associated with HIV, cancers, and medications
  86. Factor 8 Inhibitor
    (most common one)
    • Anti-factor 8 antibody
    • Found in 10-15% of Hemophilia A patients
    • Hemophilia A patients with less than 1% activity often have anti-factor 8
Card Set
Ch. 24 Coagulation