高亮:Traumatic Brain Injury Associated Coagulopathy

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  • DDimer < 0.5 PT 10.2-15.0 Fibrinogen 214-474 INR of 1.0 indicates 100% and an INR of 1.4-1.6 indicates 40%. I will use an INR of 1.2 to indicate 60% prothrombin activity

Transcript

  • 1. Dept. of Neurosurgery. Huashan Hospital. Fudan University. Shanghai Neurosurgical emergency center Liang Gao ( 高亮 ) Traumatic Brain Injury Associated Coagulopathy
  • 2.  
  • 3. Case File
    • 20 year old, female, student.
    • Suffered from traffic accident and loss of consciousness immediately, transferred to local hospital 30’ later, CT scan showed brain swelling, right occipital bone fracture.2009/06/30
    • PE: 3mm, light reflex(+), babinski sign (+) ,GCS13. a
  • 4. 2009.06.30 2:17PM
  • 5. 2009.06.30 2:17PM
  • 6.  
  • 7. DIAGONOSIS
    • Mild TBI
    • Right skull base fracture
    • Small subdural hemorrhage
    • t-SAH
  • 8. DIAGNOSIS- Marshall classification
    • Computed tomography classification system of head injury
    • Diffuse injury I No visible pathology seen on CT
    • Diffuse injury II Cisterns are present with shift 0-5 mm. No high- or mixed-density lesion >25 cc.May include bone fragments and foreign bodies
    • Diffuse injury III (swelling) Cisterns compressed or absent. Shift 0-5 mm. No high- or mixed-density lesion >25 cc
    • Diffuse injury IV (shift)-Shift >5 mm. No high- or mixed-density lesion >25 cc
    • Evacuated mass lesion -Any lesion surgically evacuated
    • Nonevacuated mass lesion-High- or mixed-density lesion >25 cc not surgically evacuated
    HIGH RISK !!!!!
  • 9. 2009.07.01
    • Coma, GCS decrease to 9, pupil diameter 3mm in both sides, light reflex (+), babinski sign in both sides (+);
  • 10. 2009.07.01 18:15PM
  • 11. 2009.07.02 11:12PM
  • 12. 2009.07.02 11:12PM
  • 13. Initial management
    • GCS decreased to 7
    • Pupil 3mm, light reaction(+)
    • Dehydration
    • DIC management
  • 14. 2009.07.03 10:41AM
  • 15.
    • Continuous CSF drainage via lumbar puncture !???
    • GCS decreased to 3.
    • Pupils 1mm, light reaction (+/-)
    • Ventilator support
  • 16. Traumatic Coagulapathy
    • Mechanism
    • Diagnosis
    • Management????
  • 17. 2009.07.04 0:45AM
  • 18. 2009.07.07 10:12AM
  • 19. 2009.07.09 0:04AM
  • 20. Transfer to Shanghai 2009.07.10
    • GCS3, High fever, support with ventilalar
    • SOS
    • Reasons
    • ?????
  • 21. 二 00 九年七月十三日
  • 22. 二 00 九年七月十三日
  • 23. 2009.07.20
  • 24. 2009.08.20
  • 25.  
  • 26.  
  • 27.  
  • 28.  
  • 29. Coagulopathy and TBI
    • Concepts of hemostasis
    • Coagulopathy in traumatic brain injury
    • Review some treatments for TBI associated coagulopathy
  • 30. Coagulopathy and TBI
    • Primary hemostasis
    • Initial clot
    • Function of platelets
    • Secondary hemostasis
    • Thrombin generation via the coagulation cascade
    • Cross-linking of fibrin
    • Fibrinolysis
    • Activation of Plasminogen to Plasmin
    • tPA
  • 31. Coagulation Cascade
  • 32. Cell-based Model of Hemostasis Components Endothelial Injury Tissue Factor release Thrombin generation Platelet activation Coagulation factor activation Mathews Neurocritical Care , 2006
  • 33. Coagulopathy and TBI
    • Coagulopathy is common in TBI
    • Dilutional
    • Pre-existing coagulation abnormalities
    • Anticoagulant use
    • Warfarin, ASA, NSAIDS, Plavix
    • Hypothermia (30-34 degrees)
    • Increased fibrinolysis
    • Thrombocytopenia
    • Impaired platelet function
  • 34. Coagulopathy Score SCORE PT(S) aPTT ( S ) Platelet Fibrinogen ( mg/dl ) D-dimer (ng/ml ) 1 <13.5 28~41 > 150 > 180 < 1000 2 >=13.5 <28, >41 ≦ 150 ≦ 180 < 2000 3 >15 ≦ 24, ≧ 46 ≦ 100 ≦ 150 <4000 4 >18 ≧ 61 ≦ 60 ≦ 100 ≧ 4000
  • 35. Scoring system for diagnosing DIC Prothrombin Index: the percentage of the present prothrombin complex to its normal level
  • 36.  
  • 37.  
  • 38. Time course of coagulopathy in isolated s-TBI
  • 39. Coagulopathy and TBI
    • Coagulopathy is more frequent in TBI
    • Review of 276 Isolated head injury on CT had a 17% rate of coagulopathy.
    • Coagulopathy is highly associated with poor outcome in TBI.
    • Review of 8K TBI pts revealed elevated INR to be a powerful independent prognostic sign of poor outcome.
    • Coagulopathy is highly associated with DTICH.
    • Murray, Steyerberg et al, J Neurotrauma, 2007
    • Zehtabchi,Sinert et al, Resuscitation, 2008
  • 40. Coagulopathy and TBI
    • TBI induced coagulopathy
    • Injury mediated release of Tissue Factor
    • Related to amount of tissue injured
    • Fibrinolysis abnormalities
    • Hypocoagulable state
    • Increase in size of intracranial hemorrhage
    • Hypercoagulable state
    • Increase in microthrombosis causing local ischemia
  • 41. TBI and Platelet Dysfunction
    • Compared to non - TBI trauma and healthy volunteers, TBI patients had:
    • Platelet count lower (180 vs 230 and 256)
    • Longer bleeding time (674 s vs 350/320 s)
    • Diminished platelet function using thromboelastography
  • 42. TBI and Hypoperfusion
    • Challenge to concept that TF release is source of TBI coagulopathy.
    • Prospective cohort study (n=39)
    • AIS of brain ,Protein C, Thyromodulin (Anticoagulants) PT, PTT,ABG(BD>6)
    • Cohen, Pittett et al, J of Trauma, Dec 2007
  • 43. TBI and Hypoperfusion
    • 28 of 39 with normal BD
    • None developed coagulopathy
    • 11 of 39 with BD >6
    • Elevated INR
  • 44. TBI and Hypoperfusion
    • Increasing brain AIS had little effect on PT/PTT.
    Cohen, Pittett et al, J of Trauma, 2007
  • 45. TBI and Hypoperfusion
    • Increasing brain AIS had little effect on Protein C or Thrombomodulin .
    Cohen, Pittett et al, J of Trauma, 2007
  • 46. TBI and Hypoperfusion
    • Increasing base deficit had significant effect on PT/PTT.
    Cohen, Pittett et al, J of Trauma, 2007
  • 47. TBI and Hypoperfusion
    • Increasing base deficit had significant effect on Protein C and Thyromodulin (anticoagulants).
    Cohen, Pittett et al, J of Trauma, 2007
  • 48. TBI and Hypoperfusion
    • Hypoperfusion may be significant contributor to coagulopathy in TBI.
    • Give additional support to hypotension worsens outcome in why TBI.
    • Adequate and early resuscitation field as well as the ED is critical.
  • 49. Warfarin and TBI
    • TBI in patients using warfarin.
    • ICH in warfarin users had 48% mortality.
    • Compared to ICH w/o warfarin mortality of 10%.
  • 50. Warfarin and TBI
    • All trauma patients on warfarin were quickly evaluated and treated by protocol with 4-6 units FFP .
  • 51. Warfarin and TBI
    • Protocol driven warfarin reversal decreased time to INR correction (INR <1.6).
  • 52. Warfarin and TBI
    • Protocol driven warfarin reversal decreased incidence of ICH progression .
  • 53. Warfarin and TBI
    • Protocol driven warfarin reversal decreased mortality from 48% to 10% .
    Both deaths in the treatment group had >10 hour delay in initiation due to transfer issues
  • 54. Warfarin-related hemorrhage
  • 55. Warfarin-related hemorrhage
    • Warfarin doubles ICH mortality.
    • Warfarin increases risk of hematoma expansion. Bleeding continues
    • over a longer period.
    Flibotte et al. Neurology , 2004
  • 56. Warfarin and TBI
    • Increasing use of warfarin for stroke prevention in elderly
    • Less studied than warfarin-related non- traumatic ICH
    • Progression of hematoma common, even when initially small
    • Progression increases mortality risk
    • Reversal seems to decrease progression
    • No randomized trials
    • What’s the smallest amount of traumatic intracranial hemorrhage that doesn’t need to be reversed? Location specific ?
  • 57. Warfarin and TBI Ivascu Journal of Trauma 2005
  • 58. FFP REVERSAL PROTOCAL INR corrected within 24 hours (< 1.4) – Shorter median time to FFP initiation (90 v. 210 min) – 12 of 69 (17%) not reversed by 24 hours This experience neither unique nor acceptable Logistics of FFP or reversal agent itself?
  • 59. Coagulopathy Reversal
    • Principle :
    • any intracranial hemorrhage in patient on warfarin (with INR > 1.4) should be considered “life-threatening”.
    • Goal – normalize coagulation
    • – (not hypercoaguable)
    • – Practical approach: normal INR ASAP
  • 60. Warfarin Reversal Agents
    • Warfarin
    • – Vitamin K antagonist
    • – Vit K is cofactor in g –carboxylation of coagulation factors II, VII, IX, X (and Pro C & S)
    • Options
    • – Directly compete by giving Vitamin K
    • – Replace native coagulation factors (FFP, PCC)
    • – Bypass central part of coagulation cascade (rVIIa)
    • Schulman. Anticoagulants and their reversal. Transfusion Medicine Reviews 21;2007
    • Steiner. Intracerebral hemorrhage associated with oral antiocoagulant therapy. Stroke 37;2006
  • 61. Vitamin K
    • Oral or parenteral
    • Plasma half-life 1.5-3 hours
    • Full effect at 12-24 hours after administration
    • Dose – 10 mg oral, sc, or IV
    • Cost -cheap
    • Utility for urgent warfarin reversal – poor
    • Due to short duration of other replacement agents should be given as part of all reversal protocols
  • 62. Fresh Frozen Plasma
    • “ Standard approach”
    • All coagulation factors in non-concentrated form
    • Must do: ABO compatibility testing, Thawing (~20 min)
    • Difficult to give enough volume to correct INR > 5
    • Volume load (800-3500 ml for full correction)
    • Cost – moderate, ~200 cc unit
    • Utility for urgent warfarin reversal – poor due to logistics (time and volume)
    • Should still probably be given as part of all reversal protocols because it contains all factors
  • 63. Prothrombin Complex Concentrate
    • Dry preparation – ~20 min to reconstitute; no compatibility testing or thawing
    • At least 16 different preps worldwide
    • Some with relatively less VII or IX
    • Dose – various recs 30-50 IU/kg; single bolus dose (~50 ml)
    • Cost – expensive
    • Utility for urgent warfarin reversal – good
    • Problems – availability; risk of thrombosis;
    • viral reduction does not eliminate prions
  • 64. rFVIIa
    • Off-label use
    • Works in non-warfarin ICH?
    • Rapid reconstitution, low volume
    • Dose - ???, reports have used 5-320 µg/kg
    • Cost – very expensive
    • Utility for urgent warfarin reversal – good
    • • Problems – risk of thrombosis, INR correction without eliminating bleeding risk (thromboelastography better?)
  • 65. rFVIIa in TBI
    • Level I trauma, retrospective, 4 years.
    • 681 severe TBI patients.
    • 63 initially coagulopathic (INR >1.4) .
    • 29 received rFVIIa vs. 34 no rFVIIa.
    • Mean age, ISS, GCS, INR
    Stein, Scalea et al, J Trauma, 2008
  • 66. rFVIIa in TBI
    • Time to intervention (median)
    • rFVIIa 144 minutes
    • no rFVIIa 446 minutes (p = 0.0003)
    Stein, Scalea et al, J Trauma, 2008
  • 67. rFVIIa in TBI
    • FFP given prior to intervention (median)
    • rFVIIa 2
    • no rFVIIa 6 (p = 0.0006)
    Stein, Scalea et al, J Trauma, 2008
  • 68. rFVIIa in TBI
    • Mortality in isolated TBI
    • rFVIIa 33.3%
    • no rFVIIa 52.9% (p = 0.24)
    Stein, Scalea et al, J Trauma, 2008
  • 69. rFVIIa in TBI
    • Thromboebolic comlictions
    • rFVIIa --6
    • no rFVIIa --6 (p= 0.759 )
    Stein, Scalea et al, J Trauma, 2008
  • 70. Guidelines for Warfarin Reversal
    • US - Chest 133 (Suppl 175S), 2008:
    • In patients with life-threatening bleeding “hold warfarin therapy and give FFP, PCC, or rVIIa supplemented with vitamin K (10 mg by slow IV infusion). Repeat, if necessary, depending on INR (Grade 1c).”
  • 71. Reversing heparin
    • Unfractionated heparin
    • – Acts at IIa/Xa
    • – Protamine 1 mg per 100 U heparin received within last 2 hours (max 50 mg)
    • Low molecular weight heparin
    • – Acts at Xa
    • – No direct reversal agent
    • Protamine 1 mg per 1 mg enoxaparin received within past 8 hours (max dose 50 mg)?
    • Check factor Xa level
    • -rFVIIa? Few case reports
    • Direct thrombin inhibitors (e.g argatroban)
    • – No reversal agent
  • 72. Antiplatelet Agents
    • Extremely widely used agents – ASA, clopidogrel, ASA + DP
    • ICH – the word is still out
    • – Studies conflict regarding impact on hematoma growth and outcome---- Independent predictor of death, likely due to hematoma enlargement
    • --No effect on outcome or hematoma expansion in
    • CHANT placebo group
    • TBI – even less known than with ICH
    • – May be associated with ongoing bleeding and ↑ mortality, esp in elderly
    • – Everybody’s afraid of clopidogrel and surgery
    Saloheimo Stroke 2006; Neurology 2009
  • 73. Antiplatelet agents – What to Do?
    • You get to pick
    • 1. Nothing
    • 2. Give platelet transfusion
    • 3. Give DDAVP
    • 4. Give rFVIIa
    • 5. Check platelet function assay and do 2/3/4 if abnormal
    • 6. Check bleeding time and do 2/3/4 if abnormal
    • 7. Rescan and do 2/3/4 if hematoma expands
    • 8. Check platelet function assay (PFA-10 )
  • 74. TBI-induced Coagulopathy
    • TBI-initiated consumptive coagulopathy (DIC)
    • – Balance between thrombosis and hemostasis
    • – Acutely, hemostasis and prevention of ongoing bleeding is priority
  • 75. INR & TBI craniotomy
    • Methods: We performed a 2-year (2005-2006) retrospective study of adult blunt trauma patients with traumatic brain injury who presented coagulopathic (international normalized ratio [INR] >1.3) and required emergent craniotomy. We compared patients who did (rFVIIa group) and did not (no-rFVIIa group) receive rFVIIa to correct coagulopathy before craniotomy .
    Brown et al. Recombinant Factor VIIa for the Correction of Coagulopathy Before Emergent Craniotomy in Blunt Trauma Patients. Journal of Trauma-Injury Infection & Critical Care,2010
  • 76. INR & TBI craniotomy
    • METHODS: The clinical and laboratory features of a prospectively followed up case-series of 15 patients with traumatic ICB (mainly isolated SDHs) and coagulopathy (INR) >1.3 treated with rFVIIa in our institution are presented, along with a review of the literature regarding the role of rFVIIa in neurosurgical patients with ICB.
    • RESULTS: All 15 patients suffered a SDH (4 of 15 had a combined ICB) and coagulopathy (mean INR, 2.34 +/- 0.83; thrombocytopenia rate, 20%), which was attributed to anticoagulants in 46.7%. The mean INR decreased to 1.5 +/- 0.14 after standard therapy and 0.92 +/- 0.1 after rFVIIa therapy.
    Bartal C. J Trauma. 2007 Oct;63(4):725-32.
  • 77. rFVIIa INR & emergency Craniotomy
    • METHODS: nine patients with coagulopathy requiring urgent neurosurgical intervention were reviewed retrospectively. Each patient was given a dose ranging from 40 to 90 microg/kg of rFVIIa before undergoing surgery. Pre-rFVIIa coagulation and post-rFVIIa coagulation parameters were obtained. Once correction of the coagulopathy was verified, each patient underwent the appropriate neurosurgical procedure. 20 minutes after infusion of the medication showed normalization of values.
    Park P. Neurosurgery. 2003 Jul;53(1):34-8;
  • 78. INR & TBI craniotomy
    • METHODS: The trauma registry was used to identify patients with severe TBI who were admitted during a 4-year period and were coagulopathic at admission (international normalized ratio, INR >/=1.4) and required a neurosurgical procedure.
    Stein. J Trauma. 2008 Mar;64(3):620-7;
  • 79. Coagulopathy & PLT
    • PLT
  • 80. 谢谢!