Co mep bruising COMEP

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Co mep bruising COMEP

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  • The limitations of heparin and warfarin have prompted the development of new anticoagulant drugs for prevention and treatment of venous and arterial thromboembolism. The coagulation system, as illustrated in a simplified manner on this slide, is triggered by the tissue factor (TF)/factor VIIa complex, which activates FIX and FX. Activated FIX converts small amounts of prothrombin to thrombin, which is sufficient to amplify coagulation by activating factors V and VIII, platelets, and platelet-bound factor XI. Coagulation is propagated when FIXa binds to FVIIIa on the surface of activated platelets, forming intrinsic tenase, which, in turn, activates FX. Activated FX binds to activated factor V to form prothrombinase, which converts prothorombin (Factor II) to thrombin (Factor IIa). In the final step, thrombin converts fibrinogen to fibrin. New anticoagulants on the near- and intermediate-term horizon affect the propagation and fibrin formation stages of the coagulation pathway. This segment will review the most imminent new agents. Reference Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost. 2005;3:1843-1853.
  • The limitations of heparin and warfarin have prompted the development of new anticoagulant drugs for prevention and treatment of venous and arterial thromboembolism. The coagulation system, as illustrated in a simplified manner on this slide, is triggered by the tissue factor (TF)/factor VIIa complex, which activates FIX and FX. Activated FIX converts small amounts of prothrombin to thrombin, which is sufficient to amplify coagulation by activating factors V and VIII, platelets, and platelet-bound factor XI. Coagulation is propagated when FIXa binds to FVIIIa on the surface of activated platelets, forming intrinsic tenase, which, in turn, activates FX. Activated FX binds to activated factor V to form prothrombinase, which converts prothorombin (Factor II) to thrombin (Factor IIa). In the final step, thrombin converts fibrinogen to fibrin. New anticoagulants on the near- and intermediate-term horizon affect the propagation and fibrin formation stages of the coagulation pathway. This segment will review the most imminent new agents. Reference Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost. 2005;3:1843-1853.
  • The limitations of heparin and warfarin have prompted the development of new anticoagulant drugs for prevention and treatment of venous and arterial thromboembolism. The coagulation system, as illustrated in a simplified manner on this slide, is triggered by the tissue factor (TF)/factor VIIa complex, which activates FIX and FX. Activated FIX converts small amounts of prothrombin to thrombin, which is sufficient to amplify coagulation by activating factors V and VIII, platelets, and platelet-bound factor XI. Coagulation is propagated when FIXa binds to FVIIIa on the surface of activated platelets, forming intrinsic tenase, which, in turn, activates FX. Activated FX binds to activated factor V to form prothrombinase, which converts prothorombin (Factor II) to thrombin (Factor IIa). In the final step, thrombin converts fibrinogen to fibrin. New anticoagulants on the near- and intermediate-term horizon affect the propagation and fibrin formation stages of the coagulation pathway. This segment will review the most imminent new agents. Reference Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost. 2005;3:1843-1853.
  • The limitations of heparin and warfarin have prompted the development of new anticoagulant drugs for prevention and treatment of venous and arterial thromboembolism. The coagulation system, as illustrated in a simplified manner on this slide, is triggered by the tissue factor (TF)/factor VIIa complex, which activates FIX and FX. Activated FIX converts small amounts of prothrombin to thrombin, which is sufficient to amplify coagulation by activating factors V and VIII, platelets, and platelet-bound factor XI. Coagulation is propagated when FIXa binds to FVIIIa on the surface of activated platelets, forming intrinsic tenase, which, in turn, activates FX. Activated FX binds to activated factor V to form prothrombinase, which converts prothorombin (Factor II) to thrombin (Factor IIa). In the final step, thrombin converts fibrinogen to fibrin. New anticoagulants on the near- and intermediate-term horizon affect the propagation and fibrin formation stages of the coagulation pathway. This segment will review the most imminent new agents. Reference Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost. 2005;3:1843-1853.
  • Type of bruise – lumpy or flat, immediate or delayed, bruises, purpura or petechiae Location – soft tissue – subcut or muscle haematoma legs & arms, trunk, back etc
  • The limitations of heparin and warfarin have prompted the development of new anticoagulant drugs for prevention and treatment of venous and arterial thromboembolism. The coagulation system, as illustrated in a simplified manner on this slide, is triggered by the tissue factor (TF)/factor VIIa complex, which activates FIX and FX. Activated FIX converts small amounts of prothrombin to thrombin, which is sufficient to amplify coagulation by activating factors V and VIII, platelets, and platelet-bound factor XI. Coagulation is propagated when FIXa binds to FVIIIa on the surface of activated platelets, forming intrinsic tenase, which, in turn, activates FX. Activated FX binds to activated factor V to form prothrombinase, which converts prothorombin (Factor II) to thrombin (Factor IIa). In the final step, thrombin converts fibrinogen to fibrin. New anticoagulants on the near- and intermediate-term horizon affect the propagation and fibrin formation stages of the coagulation pathway. This segment will review the most imminent new agents. Reference Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost. 2005;3:1843-1853.
  • Co mep bruising COMEP

    1. 1. Bruising (and bleeding conditions) CoMEP 14 th & 27 th April 2010
    2. 2. Specific Learning Objectives <ul><li>Understand basics of physiological haemostasis </li></ul><ul><li>Recognise and differentiate ‘normal’ and pathological bruising patterns and likely underlying aetiologies </li></ul><ul><li>Be able to take a bleeding history with the aim of differentiating acquired & congenital and platelet/vascular & coagulation factor disorders </li></ul><ul><li>Understand the appropriate investigative strategies [and interpretation of their results] for bruising/bleeding patients </li></ul>
    3. 3. Specific Learning Objectives <ul><li>Understand & recognise the common causes of acquired bleeding disorders [drugs and co-morbid disease] </li></ul><ul><li>Understand the basics of the more common congenital bleeding disorders – prevalence, inheritance pattern, clinical and laboratory diagnostic features and treatment </li></ul>
    4. 4. What physiological mechanisms come into play when a blood vessel is damaged?
    5. 6. von Willebrand factor in Primary Haemostasis
    6. 7. Defective Primary Haemostasis <ul><li>Thrombocytopenia </li></ul><ul><li>Dysfunctional platelets [anti-platelet agents] </li></ul><ul><li>Defective platelet - vessel wall interaction </li></ul><ul><li>Vessel wall disorder </li></ul><ul><li>severe VWD </li></ul>Prolonged Bleeding Time
    7. 10. Petechiae and Purpura
    8. 11. Vasculitic Purpura
    9. 12. Senile Purpura
    10. 13. Bleeding Disorder Symptoms Immediate bleeding Delayed bleeding controlled by pressure not controlled by pressure Purpura & petechiae Muscle & joint bleeds Mucosal bleeding Large ecchymoses Epistaxis, menorrhagia Haematuria Bleed after venepuncture Bleed after im injection Post-traumatic bleeds Post-traumatic bleeds GI & CNS bleeds GI & CNS bleeds Platelet / Vascular Defects Clotting Factor Defects
    11. 14. Fibrin Fibrinogen Extrinsic Activation Intrinsic Activation Xa IIa TF/VIIa X IX IXa VIIIa Va II XIa XIIa XI XII Collagen, HMWK, PK Common Pathway Coagulation Pathways
    12. 15. Fibrin Fibrinogen Extrinsic Activation Intrinsic Activation Xa IIa TF/VIIa X IX IXa VIIIa Va II XIa XIIa XI XII Collagen, HMWK, PK Common Pathway Coagulation Pathways
    13. 16. Fibrin Fibrinogen Extrinsic Activation Intrinsic Activation Xa IIa TF/VIIa X IX IXa VIIIa Va II XIa XIIa XI XII Collagen, HMWK, PK Common Pathway Coagulation Pathways – lab assays APTT TCT PT Ca 2+ and phospholipid also required
    14. 17. Current & New Anticoagulant Agents Adapted from Weitz JI et al. J Thromb Haemost. 2005;3:1843-1853. Fibrin Fibrinogen Indirect Xa inhibitors Fondaparinux Danaparoid LMWH, UFH Xa Inhibitors : Rivaroxaban Apixaban IIa Inhibitors Ximelagatran Dabigatran ORAL PARENTERAL Xa IIa TF/ VIIa X IX IXa VIIIa Va II Antithrombin Indirect IIa inhibitors UFH, [LMWH] Warfarin FDPs, D-dimer Antithrombin Plasmin
    15. 18. Bleeding Disorder Symptoms Immediate bleeding Delayed bleeding controlled by pressure not controlled by pressure Purpura & petechiae Muscle & joint bleeds Mucosal bleeding Large ecchymoses Epistaxis, menorrhagia Haematuria Bleed after venepuncture Bleed after im injection Post-traumatic bleeds Post-traumatic bleeds GI & CNS bleeds GI & CNS bleeds Platelet / Vascular Defects Clotting Factor Defects
    16. 19. Key aspects of bleeding history <ul><li>Type, location & size of bruising </li></ul><ul><li>Precipitating factors </li></ul><ul><li>Length of bleeding following lacerations & shaving cuts </li></ul><ul><li>Post-op bleeding </li></ul><ul><li>Epistaxis </li></ul><ul><li>Gum bleeding </li></ul><ul><li>Dental extractions </li></ul><ul><li>GI bleeding </li></ul><ul><li>Menorrhagia </li></ul><ul><li>Is the bleeding history only recent or is it life long </li></ul>
    17. 20. Coagulation Pathway Disorders <ul><li>Congenital </li></ul><ul><ul><li>Haemophilia A Factor VIII deficiency </li></ul></ul><ul><ul><li>Haemophilia B Factor IX deficiency </li></ul></ul><ul><ul><li>von Willebrands disease Deficient or abnormal vWF </li></ul></ul><ul><li>Acquired </li></ul><ul><ul><li>Heparins </li></ul></ul><ul><ul><li>Warfarin (and new oral anticoagulants) </li></ul></ul><ul><ul><li>Liver disease </li></ul></ul>
    18. 21. Fibrin Fibrinogen Extrinsic Activation Intrinsic Activation Xa IIa TF/VIIa X IX IXa VIIIa Va II XIa XIIa XI XII Collagen, HMWK, PK Common Pathway Coagulation Pathways – Haemophilia APTT TCT PT Isolated deficiency of Factors VIII, IX, XI or XII [intrinsic pathway] causes prolonged APTT with normal PT
    19. 22. Case 1 <ul><li>35y male </li></ul><ul><li>Attends A&E following altercation in pub </li></ul><ul><ul><li>Has received punches to face and kicks to right leg </li></ul></ul><ul><ul><li>O/E no bleeding or bruising </li></ul></ul><ul><ul><li>No fractures on X-rays </li></ul></ul><ul><li>Informs staff he has haemophilia B </li></ul>What would you do next?
    20. 24. Haemophilia A <ul><li>Classical haemophilia </li></ul><ul><li>Factor VIII deficiency </li></ul><ul><ul><li>severe  1iu/dl </li></ul></ul><ul><ul><li>moderate 2 - 5 iu/dl </li></ul></ul><ul><ul><li>mild 6 - 40 iu/dl </li></ul></ul><ul><li>Incidence 1/20,000 [1/10,000 males] </li></ul><ul><li>X-linked inheritance </li></ul><ul><li>Prolonged APTT </li></ul>
    21. 26. Treatment of coagulation factor deficiency <ul><li>Education - patients and doctor </li></ul><ul><li>Desmopressin [DDAVP] </li></ul><ul><li>Replacement therapy </li></ul><ul><ul><li>FFP / Cryoprecipitate </li></ul></ul><ul><ul><li>plasma derived factor concentrate </li></ul></ul><ul><ul><li>recombinant produced factor concentrate </li></ul></ul><ul><li>Gene therapy </li></ul>
    22. 27. Case 2
    23. 28. Case 2 <ul><li>48y female </li></ul><ul><ul><li>pyrexia + rigors </li></ul></ul><ul><ul><li>? acute abdomen </li></ul></ul><ul><ul><li>paracolic abscess at laparotomy </li></ul></ul><ul><li>Post-op -> ICU </li></ul><ul><li>Haematology Results </li></ul><ul><ul><li>Hb 94 g/l PT 21s (NR 11-15) </li></ul></ul><ul><ul><li>WBC 16.0 x10 9 /l APTT 41s (NR 26-37) </li></ul></ul><ul><ul><li>Platelets 78 x10 9 /l D-dimer 4200 (NR <500) </li></ul></ul>
    24. 29. Disseminated Intravascular Coagulation Systemic activation of coagulation Intravascular deposition of fibrin Depletion of platelets and coagulation factors Thrombosis of small and midsize vessels and organ failure Bleeding
    25. 30. DIC - Laboratory Investigations <ul><li>LOOK FOR UNDERLYING CAUSE </li></ul><ul><ul><li>sepsis, trauma, cancer, obstetric disaster </li></ul></ul><ul><li>Coagulation PT, APTT, Fibrinogen </li></ul><ul><li>D-dimers </li></ul><ul><li>FBC + film platelets, RBC fragments </li></ul><ul><li>Coag Factors ? </li></ul>
    26. 31. DIC - Treatment <ul><li>TREAT UNDERLYING CAUSE </li></ul><ul><li>FFP +/- platelets if bleeding or high risk for bleeding </li></ul><ul><li>? Heparin 300-500u/h if thrombotic phenotype </li></ul><ul><li>? AT III concentrate (reduces mortality 56% -> 44%) </li></ul><ul><li>? Protein C concentrate (meningococcal sepsis) </li></ul><ul><li>? Activated Protein C </li></ul>
    27. 32. Case 3 - Confused lady in A&E <ul><li>80y female found behind door of ground floor sheltered housing </li></ul><ul><li>GCS = 9 </li></ul><ul><li>right sided weakness with dysphasia </li></ul><ul><li>irregular pulse </li></ul><ul><li>urinalysis clear </li></ul><ul><li>Sent for CT head </li></ul>
    28. 34. Case 3 <ul><li>FBC </li></ul><ul><ul><li>Hb 11.8 g/dl </li></ul></ul><ul><ul><li>WBC 12.7 x10 9 /l </li></ul></ul><ul><ul><li>Plts 191 x10 9 /l </li></ul></ul><ul><li>Coagulation </li></ul><ul><ul><li>PT 97s (INR 7.6) </li></ul></ul><ul><ul><li>APTT 72s (APTTr 1.9) </li></ul></ul><ul><ul><li>TCT 12s (NR 9-12s) </li></ul></ul>
    29. 35. Bleeding complications with warfarin <ul><li>fatal haemorrhage 0.25 - 0.64% per year </li></ul><ul><li>major haemorrhage 1.1 - 2.7% per year </li></ul>Achieved INR major bleeds (% per year) minor bleeds < 2 1.5 11 2 - 3 2.5 12 3 - 4 2.5 15 4 - 5 4 20 5 - 6 5 34  6 9 96 van der Meer et al., Arch Int Med 1993
    30. 36. What can we do when INR is too high? <ul><li>Stop warfarin or reduce dose </li></ul><ul><li>Give Vitamin K 1 ( oral or iv ) </li></ul><ul><li>Give coagulation factors (II, VII, IX, X) </li></ul>
    31. 37. Decline of INR after warfarin cessation when INR >6 Days % INR > 4 Hylek et al. 2000
    32. 40. Warfarin - Life threatening bleeding <ul><li>Stop warfarin </li></ul><ul><li>5mg intravenous Vit K 1 </li></ul><ul><li>Intravenous factor concentrate </li></ul><ul><ul><li>Prothrombin Complex Concentrate (Beriplex or Octaplex) </li></ul></ul>Irrespective of INR
    33. 41. Case 4 – 64y male 4 days after commencing warfarin for PE
    34. 42. Case 5 <ul><li>24y female attends GP having noted petechial rash on legs </li></ul><ul><ul><li>Suffered a short epistaxis previous week </li></ul></ul><ul><ul><li>also gum bleeding after brushing teeth </li></ul></ul><ul><li>PMH </li></ul><ul><ul><li>? Recent viral URTI </li></ul></ul><ul><ul><li>uncomplicated tonsillectomy age 12y </li></ul></ul><ul><li>DH – C-OCP </li></ul>What lab test would you do next?
    35. 43. Case 5 – blood results <ul><li>FBC </li></ul><ul><ul><li>Hb 98 g/L </li></ul></ul><ul><ul><li>WBC 18.7 x10 9 /l </li></ul></ul><ul><ul><li>Plts 25 x10 9 /l </li></ul></ul><ul><li>Coagulation </li></ul><ul><ul><li>PT 14s (INR 1.2) </li></ul></ul><ul><ul><li>APTT 32s (NR 25-35s) </li></ul></ul><ul><ul><li>TCT 12s (NR 9-12s) </li></ul></ul>What most likely diagnosis? Any other tests?
    36. 44. Case 5 – blood results <ul><li>FBC </li></ul><ul><ul><li>Hb 98 g/L </li></ul></ul><ul><ul><li>WBC 18.7 x10 9 /l </li></ul></ul><ul><ul><li>Plts 25 x10 9 /l </li></ul></ul><ul><li>Coagulation </li></ul><ul><ul><li>PT 14s (INR 1.2) </li></ul></ul><ul><ul><li>APTT 32s (NR 25-35s) </li></ul></ul><ul><ul><li>TCT 12s (NR 9-12s) </li></ul></ul>What most likely diagnosis? Any other tests?
    37. 45. Case 6 <ul><li>44y male brought to A&E confused and tremulous </li></ul><ul><ul><li>He is icteric and admits to alcohol intake >60 units/week for some years </li></ul></ul><ul><ul><li>He has many medium sized bruises on limbs and trunk </li></ul></ul><ul><ul><li>Abdominal examination reveals hepatosplenomegaly [liver 5cm bcm, spleen 3cm bcm] </li></ul></ul><ul><li>PMH </li></ul><ul><ul><li>Several previous similar admissions </li></ul></ul><ul><ul><li>Stabbing age 21y and # fibula age 24y without excessive bleeding </li></ul></ul><ul><li>DH – nil </li></ul>What lab test would you do next?
    38. 46. Case 6 – blood results <ul><li>FBC </li></ul><ul><ul><li>Hb 110 g/L </li></ul></ul><ul><ul><li>WBC 4.0 x10 9 /l </li></ul></ul><ul><ul><li>Plts 55 x10 9 /l </li></ul></ul><ul><li>Coagulation </li></ul><ul><ul><li>PT 23s (=INR 1.2) </li></ul></ul><ul><ul><li>APTT 43s (NR 25-35s) </li></ul></ul><ul><ul><li>TCT 12s (NR 9-12s) </li></ul></ul>What are the possible mechanisms for this patients coagulopathy? <ul><li>U&E </li></ul><ul><ul><li>Na 127 umol/L </li></ul></ul><ul><ul><li>K 4.0 umol/L </li></ul></ul><ul><ul><li>Urea 2.7 umol/L </li></ul></ul><ul><ul><li>Creat 91 umol/L </li></ul></ul><ul><li>LFTs </li></ul><ul><ul><li>bili 76 u/L </li></ul></ul><ul><ul><li>Alt 143 u/L </li></ul></ul><ul><ul><li>Ast 100 u/L </li></ul></ul>
    39. 47. Case 6 – Coagulopathy in liver disease <ul><li>Poor coagulation factor synthesis in liver </li></ul><ul><li>If Vit K deficient (poor diet +/- obstructive component to jaundice) </li></ul><ul><li>Poor clearance of activated coagulation factors </li></ul><ul><li>DIC </li></ul><ul><li>Hypersplenism (  low WBC and Plts) </li></ul><ul><li>Reduced thrombopoietin synthesis (  low Plts) </li></ul>
    40. 48. Summary <ul><li>Establish type, duration and distribution of bruising & bleeding </li></ul><ul><li>Is it platelet/vascular of coagulation factor deficiency pattern? </li></ul><ul><li>Determine if acquired or congenital </li></ul><ul><li>Establish drug history and co-morbid disease </li></ul><ul><li>What is the pattern of coagulation screen abnormality? </li></ul>

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