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Haemostatic resuscitation

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Haemostatic resuscitation

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Haemostatic resuscitation

  1. 1. HAEMOSTATIC RESUSCITATION Joshua Ho SCGH ED CME Aug 23, 2018
  2. 2. THE FORMAT Context / definitions / theory Resuscitation process / trials / monitoring our therapy / MTP / the practical things I WILL be asking questions, please don’t fall asleep If you give ANY answer, you get chocolate If you give the correct answer, you won’t get more chocolate, you just look smarter
  3. 3. DISCLAIMER: MY EXPERIENCE
  4. 4. THE ED EXPERIENCE
  5. 5. HAEMOSTATIC RESUSCITATION Rapid correction of haemostasis-impairing factors such as: Hypothermia Hypocalcaemia Acidosis Resuscitation with a balanced combination of blood products, which in combination, resembles whole blood, so as to avoid the dilutional coagulopathy observed in the “traditional methods” The goal is to ensure adequate tissue perfusion without worsening coagulopathy Component of ”Damage Control Resuscitation” Also permissive hypotension Also damage control surgery
  6. 6. THE THEORY SIDE OF THINGS Not only because “exams”, but sometimes it’s nice when things at least have the appearance of making sense.
  7. 7. WHAT’S IN THE BLOOD? Cells Red cells White cells Platelets Plasma proteins Alpha globulins Beta globulins Gamma globulins Coagulation factors Water and electrolytes
  8. 8. RED CELLS Functions: 1. Oxygen carrier (Hb) 2. CO2 carrier (carbamino compounds) 3. Intracellular buffer
  9. 9. PLATELETS Functions: 1. Vascular constriction a. Autocoid factors 2. Formation of platelet plug a. Adhesion b. Secretion c. Aggregation d. Procoagulant activity 3. Coagulation process a. Clot retraction b. Fibrin stabilizing factor
  10. 10. COAGULATION FACTORS Classical theory vs. cell based theory Serine proteases Common pathway Calcium important co-factor
  11. 11. FIBRINOLYSIS
  12. 12. PLASMA PROTEINS Albumin 55% Globulins 38% Alpha 1: antitrypsin, TBG, transcortin Alpha 2: haptoglobin, caeruloplasmin Beta: beta 1 transferrin, beta lipoprotein Gamma: immunoglobulin Fibrinogen fractions 7% Complement Coagulation factors Functions: 1. Colloid oncotic pressure 2. Enzymatic functions 3. Coagulation 4. Transport and carriage 5. Buffering action 6. Acquired and innate immunity 7. Amino acid pool
  13. 13. ELECTROLYTES AND MORE Water 93% Electrolytes Glucose Lipids complexed with proteins Plasma proteins
  14. 14. HOW DO WE REPLACE THESE PRODUCTS? Does anyone really know?
  15. 15. QUESTIONS TO ASK OURSELVES. What products should we use? How much do we need? How quickly do we need to replace it? What ratio of products is best? How do we know we’re correcting anything? What are the down sides?
  16. 16. PACKED RED CELLS Each 250ml bag has a HCT of 0.6 ACPD additives Stored at 4 degree celcius 28 day storage Biochemical changes 2,3 – DPG
  17. 17. FRESH FROZEN PLASMA Plasma from a single donation Rapidly frozen to -30 degrees celsius after separation from red cells 200 – 300mls containing all plasma proteins (>0.7IU/ml of factor VIII) Needs thawing before transfusing 10 – 20mls/kg will raise coagulation factor levels 12 – 15%
  18. 18. PLATELETS Either derived from multiple donors or apheresis from a single donor 200 – 300mls of plasma containing around 240 x 109 per unit of platelets Stored at 22 degrees for 5 days Expected increment > 20 x 109/L
  19. 19. CRYOPRECIPITATE Thawing FFP at 4 degrees then frozen Comes from a pool of 4 – 5 donors Thawed to 37 degrees right before use 100 – 250mls of fibrinogen at >140mg/unit, factor VIII >70IU/unit and vWF in high concentrations Each unit is 20 – 40mls 10 units of cryoprecipitate expected to raise fibrinogen
  20. 20. FIBRINOGEN CONCENTRATE Freeze dried lyophilized preparations of fibrinogen (number of brands) 900 – 1400mg per vial Quickly reconstituted No crossmatch required 4g (eg 4 vials) usually increases fibrinogen levels 1g/L
  21. 21. NOVO SEVEN Indicated for the use in the context of surgery for patients with: Haemophilia A or B with inhibitors Congenital Factor VII (FVII) deficiency Glanzmann’s thrombasthenia who have decreased or absent response to platelet transfusions Adults with acquired haemophilia Off label use in all other cases Incidence of thrombosis: 0.2% in patients with congenital haemophilia 4% in people with acquired haemophilia
  22. 22. COLLOIDS Colloid solution as 4% or 20% Prepared from pooled human plasma 40g/L or 200g/L Is expensive in other countries but “free” in Australia SAFE trial and head injuries
  23. 23. CRYSTALLOIDS Haemodilution decreases concentration of clotting factors and leads to coagulopathy 75% of crystalloid volume distributes to interstitial space No contribution to oxygen transport Exacerbation of acidosis with saline
  24. 24. TRANEXAMIC ACID Aminocaproic acid analogue Competitively inhibits plasminogen activation Intravascular thrombosis Use in trauma Use in obstetrics
  25. 25. CALCIUM Many blood products contain citrate Essential co-factor in coagulation cascade Excitation contraction coupling Aim for ionized calcium >1.1mmol/L
  26. 26. REVERSAL AGENTS Dabigatran Rivaroxaban / Apixaban Warfarin Heparins Aspirin / Ticagrelor / Clopidogrel
  27. 27. A FEW STUDIES PROMMTT PROPPR CRASH-2
  28. 28. PROMMTT STUDY (2013) Multi-centered prospective cohort study with 905 patients Early death of patients receiving more red cells than platelets / plasma within the first 6 hours (mortality increased 3 – 4x) Those receiving 1:1 transfusion of plasma/platelets to red cells tended to survive Survival benefit was concentrated on first 6 hours Of those who survived beyond 24 hours, no mortality difference at 30 days
  29. 29. PROPPR TRIAL (2015) Multi-centered RCT 680 patients randomized to 1:1:1 or 1:1:2 (plasma: platelets: red cells) 4% improvement in absolute mortality with 1:1:1, but underpowered Statistically significant mortality improvement from exsanguination within the first 24 hours with the 1:1:1 group (9.2% vs 14.6%)
  30. 30. CRASH 2 TRIAL (2010) Multi-centered international RCT with 20,211 patients in total 1g of TXA given in first 3 hours of trauma followed by 1g over the following 8 hours All cause mortality improvement was significant but small (14.5% vs 16%) Larger improvement in patients who received it within 1 hour of trauma Increase in mortality for those who received it AFTER 3 hours TXA group had lower rate of thrombosis and myocardial infarction
  31. 31. MONITORING OUR THERAPY Traditional Coagulation Studies ROTEM / TEG
  32. 32. INR / PROTHROMBIN TIME Measures integrity of extrinsic and final common pathways of coagulation cascade Factors II, V, VII, X and Fibrinogen Calcium and thromboplastin added Time for fibrin clot formation measured 9.5 to 13.5 seconds usually INR is lab dependent and is PT converted to a ratio
  33. 33. ACTIVATED PARTIAL THROMBOPLASTIN TIME A more sensitive version of thromboplastin time with narrower reference range Evaluates the intrinsic and common pathways Factors II, V, VIII, IX, X, XI, XII and Fibrinogen Calcium and phospholipid emulsion added to sample time to clot formation observed Reference range 30 – 40 seconds
  34. 34. FIBRINOGEN LEVELS Hypofibrinogenaemia Hyperfibrinolysis Level <1.5 needs replacement Dosing for replacement on the MTP
  35. 35. PLATELET COUNT Some suggestion of keeping platelet count >10 x 109/L for bleeding prophylaxis As part of MTP regardless of platelet count >50 x 109/L for procedural cover or in DIC >100 x 109/L in intracranial haemorrhage Does not reflect platelet inactivation!
  36. 36. HAEMOGLOBIN Late marker in the acutely bleeding patient Not apt to wait for a Hb nor use Hb alone as a transfusion trigger Generally keep >7g/dL in patients without IHD If bleeding, keep >10g/dL Higher targets may be necessary if continuous haemodynamic compromise until definitive surgical haemostasis achieved
  37. 37. DIRECT ORAL ANTICOAGULANTS Levels are available for all 3 DOACs Perhaps more relevance now that Idarucizumab exists Prothrombinex is an option Call the haematologists
  38. 38. TEG / ROTEM Thromboelastography and rotational thromboelastometry Global tests of haemostasis performed on whole blood as a POC Assesses kinetics of clot formation, strength and dissolution Used to manage bleeding and assess response to interventions made Cup rotates vs pin rotates
  39. 39. MASSIVE TRANSFUSION PROTOCOLS Available in both trauma bays.
  40. 40. THE PRACTICAL SIDE OF THINGS Because that’s what really matters in the end.
  41. 41. IN MY SCENARIO
  42. 42. IN THE ED SCENARIO
  43. 43. WHAT NEEDS TO HAPPEN? Airway, breathing and circulation; primary survey Large central venous access for massive transfusions Arterial access for repeated ABGs and ROTEMs FAST scan and trauma survey Designated communicator with the laboratory Designated runner to obtain blood products Lots of checking of blood products Managing traffic with presence of inpatient teams
  44. 44. THE CONSIDERATIONS Pre-allocated trauma team roles Badges with team member’s name and said role Limited physical space around the patient available Communication barrier with high decibels and unfamiliar faces Decision on when the patient is ”stable enough” to get to CT / OT / NIISWA / ICU
  45. 45. PEOPLE TO NOT FORGET When things start to look like they’re getting under control.
  46. 46. THE FAMILY MEMBERS
  47. 47. THE REST OF THE DEPARTMENT
  48. 48. NON-ED STAFF
  49. 49. REFERENCES https://www.blood.gov.au/system/files/documents/companion-25-pbm-guidelines.pdf https://www.novosevenrt.com/safety-profile.html https://derangedphysiology.com/main/required-reading/trauma-burns-and- drowning/Chapter%203.0.3/haemostatic-resuscitation-and-massive-transfusion https://wjes.biomedcentral.com/track/pdf/10.1186/1749-7922-7-S1-S3 https://archsurg.jamanetwork.com/article.aspx?articleID=1379768 https://secure.jbs.elsevierhealth.com/action/getSharedSiteSession?rc=1&redirect=https% 3A%2F%2Fwww.thelancet.com%2Fjournals%2Flancet%2Farticle%2FPIIS0140- 6736%252810%252960835-5%2Ffulltext http://jama.jamanetwork.com/article.aspx?articleid=2107789 http://scghed.com/2015/04/scgh-massive-transfusion-protocol/ http://scghed.com/2016/03/roles-in-the-resuscitation-room/ http://rebelem.com/ten-trauma-resuscitation-commandments/

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