Massive transfusion protocol

its sometime difficult to decide in urgent clinical scenarios - Trauma,active bleeding, surgery: What ; when ; how and why to transfuse? answering some of these queries here is my presentation especially made for PG students (will help in answer writing)

1. AIM FOR STABLE PATIENT NOT STABLE HEMOGLOBIN MASSIVE TRANSFUSION PROTOCOL DR AKSHAYA TOMAR DEPT OF IMMUNOHEMATOLOGY AND BLOOD TRANSFUSION AFMC PUNE

2. 81% of all the trauma-related deaths occur within the initial 24-hour period. Most of them are hemorrhage related Most (99%) of the patients receiving <10 RBC units within the first 24 h survived, whereas only 60% of patients who received >10 RBC units within the first 24 h survived (J OF TRAUMA 2011) INTRODUCTION

3. MORTALITY IN TRAUMA

4. DEFINITION IN ADULTS PEDIATRICS

5. MTP CAN ALSO AGGRAVATE COAGULOPATHY- BALANCED APPROACH NEEDED Dec Fibrinogen synthesis and inc degradation Dec propagation phase of coagulation : thrombin Decreases FVII/TF interaction Dec platelets count and function

6. • In the past, trauma patients were given colloid or crystalloid fluid initially . • Blood products were administered after 2 litre of fluid resuscitation, usually guided by laboratory results to keep haemoglobin >10 g/dl, platelet count >50000, and INR ≤1.5. • Using these guidelines, blood loss continued because of delay in laboratory turn around time and dilutional coagulopathy . UNDERSTANDING TIC HELPED US!

7. Recent studies with consideration of resuscitation, and better understanding the pathophysiology of ETIC has led to early use of RBCs, plasma, and platelets and reduced crystalloid use . UNDERSTANDING TIC HELPED US!

8. Administration of RBC:plasma:platelets at 1:1:1 ratio was first proposed by the US military and subsequently supported by military and then civilian studies. The rationale for the 1:1:1 ratio is that it more closely resembles whole blood Retrospective review of patients receiving MT at a US combat hospital demonstrated reduced mortality from 66% to 19% when the RBC:Plasma ratio decreased from 8:1 to 2:1.38 1:1:1

9. randomized trial to evaluate ratios, MT patients receive either a 1:1:1 (higher ratio) or a 2:1:1 (lower ratio) RBC: Plasma: Platelet Outcome studied : survival & LOHS More patients in 1:1:1 group achieved hemostasis and fewer experienced death (no significant differences in mortality at 24hrs or at 30 days)

10. Improved patient outcomes when compared with physician/lab driven protocols Addresses coagulopathy ( Fundamental in triad of ‘DEATH’ ) Improves communication among departments, improves availability of blood products, reduces delay in obtaining blood products MTP is a way to assure good patient care by having a standard protocol on specific actions to take for each service involved . HOW DOES IT HELP

11. COMPONENTS OF MTP

12. PREDETERMINED TRANSFUSION PACKAGES

13. Identifying patients at risk early is a key difference between damage control resuscitation and MTP driven resuscitation. Patients can arrive in relatively stable condition Non lab markers determining need for MTP SBP<90mm Hg Positive Focused abdominal sonography in trauma HR>120 bpm DIAGNOSTIC DILEMMA – everyone can identify a bleeding patient… right?

14. Liver laceration with hemorrhage Emergent abdominal aortic aneurysm Pelvic fracture with overwhelming blood loss Massive gastrointestinal hemorrhage Coronary artery bypass grafting Uterine rupture SPECIFIC INJURY PATTERNS LINKED WITH MTP

15. WB transfusion compared with COMPONENTS use reduced pulmonary and tissue oedema , which decreased the ventilation time and also allowed closure of the abdomen with minimal delay. Patients who received both fresh whole blood and component therapy had better clinical outcomes However, concern for transfusion transmitted infections and TA GvHD remains WHOLE BLOOD Vs BLOOD COMPONENTS- UNSETTLED DEBATE

16. LIMITED data In the majority of institutions, a single MTP is used for both adult and pediatric patients Published literature showed no improvement in overall mortality with institutional MTP when compared to transfusion as recommended by treating clinician PEDIATRIC MTP

17. • Group O RBCs and AB plasma products should be given until the patient’s blood type can be determined. • Use of D-positive products in D-negative or D-unknown patients • Thawed plasma units • Prothrombin complex concentrate (PCC) • Fibrinogen concentrate/CRYO • Tranexamic acid given early in the resuscitation process (<3 h from injury to treatment, preferably within 1 h from injury). • When to consider rFVIIa ? CONSIDERATIONS IN MTP

18. Time is important Group O PRBC/AB plasma can be used (without pretransfusion testing) Test patient sample ASAP (for further demands) Helps to preserve inventory/ reduces typing discrepancies which can occur after multi unit transfusions BLOOD COMPONENT

19. ‘MINUS IS PLUS HERE’ We can use of D-positive products for men and women past childbearing age (usually >50 yr old), and after a set number of D-negative RBC units Frequency of anti-D formation after transfusion of D positive blood products to a D-negative patient is 20% for RBCs and , 4% for platelets (likely lower for apheresis platelets) ACROSS THE D BARRIER!

20. 20 min to thaw Many institution keep around 20 AB thawed plasma for emergent use, shelf life 5 days Only 4% of the population is of AB group, hence this approach is challenging THAWED PLASMA

21. Invented for congenital coagulation disorder/ warfarin reversal/active bleeding PCC can be three-factor, such as Profilnine SD (lacking factor VII), or four-factor, such as Kcentra . No prospective RCT to prove efficacy in MTP Depends on institutional protocol & resource available PROTHROMBIN COMPLEX CONCENTRATE(PCC)

22. Shown to reduce overall mortality related to bleeding in Trauma/ Peri - operative settings Generally used in conjunction with PCC Not yet recommended by US FDA FIBRINOGEN CONCENTRATE

23. There are a few studies addressing the need for cryoprecipitate and some suggest that transfusing with adequate amounts of FFP will obviate the need for cryoprecipitate. Most studies suggest checking fibrinogen levels in patients who continue to demonstrate coagulopathic hemorrhage with maintenance of a level greater than 100 mg/ dL WHAT ABOUT CRYOPPT

24. 1 unit of cryo 2500mg/150ml 1 unit of FFP 400mg/250ml 1 unit of PRBC <100mg 6 units of WB derived PC 480mg 1 unit of Apheresis derived PC 300mg 1 unit of whole blood 1000mg RELATIVE AMOUNT OF FIBRINOGEN

25. Reduce mortality in trauma patients in both civilian and military settings, especially if given early in the resuscitation process (<3 h from injury to treatment, preferably within 1 h from injury) In the military setting, the MATTERs study, mortality in the TXA group was lower than in the group not receiving TXA (Military Application of Tranexamic Acid in Trauma Emergency Resuscitation) TA should be considered for use in bleeding trauma patients No effect on total transfusion rates however TRANAEXEMIC ACID (TXA)

26. rFVII

27. LAB MONITORING IN MTP

28. Oxygen carrying capacity & Delivery Hemostasis Metabolic status Electrolytes WHAT ALL NEEDS TO BE MONITORED?

29. No test can judge the hemostasis accurately in bleeding patient Disadvantages of conventional assays: PT, aPTT , and fibrinogen levels, are likely not available in real-time fashion Do not detect some haemostatic abnormalities, such as platelet dysfunction, hyperfibrinolysis , and FXIII deficiency Do not quantify the relative contribution of pro-coagulant and anti-coagulant factors Do not predict the future needs in MTP CONVENTIONAL COAGULATION Vs THROMBOELASTOGRAPHY

30. Short turn around time (15-20min) ; aids in decision making at an early stage Detects hyperfibrinolysis (clot strength) It assesses all phases of coagulation even platelet role in primary hemostasis It gives result in real time settings/POC such that existing temperature and metabolic status effects can be taken into account ADVANTAGES OF TEG

31. Frequent pathophysiological consequence of severe injury as well as resuscitation 66% of trauma patients presents in ER with hypothermia Classified into Mild : 36°C to 34°C Moderate : 33.9°C to 32°C Severe : below 28°C HYPOTHERMIA

32. Body temperatures less than 33°C produces coagulopathy (functionally equivalent to factor conc. < 50%) Thrombin generation on platelets is reduced by 25% at 33°C and platelet adhesion was reduced by 33% Other clinical effects Cardiac dysrythmias Increased systemic vascular resistance Left shift in oxygen Hb dissociation curve HYPOTHERMIA

33. Clinical effects not seen until pH < 7.2 Effects : Decreases cardiac contractility and cardiac output Reduces activity of coagulation cascade Causes platelet dysfunction ACIDOSIS

34. WHEN TO INITIATE AND STOP SCORING SYSTEMS

35. Clinician discretion can sometimes lead to delay or failure of resuscitation Scoring helps in accurately identifying patients in need of large volume replacement It also aids in restricting unnecessary transfusion and its adverse effects also save this precious resource for the more needy one (PBM) WHY SCORING?

36. SCORING SYSTEMS

37. Surgical control of bleeding Hemodynamically stable Correction of acidosis and coagulopathy Signs of sufficient end organ perfusion Improvement in mental status Improvement in urine output WHEN TO STOP

38. MTP ADMINISTRATION

39. Lab based component replacement POOLED/10 UNITS

40. Speed of transfusion is important during MTP especially when exsanguination occurs at a rate greater than transfusion Pressurized tubing or specialized pressurized rapid transfusers can augment flow Blood and fluid warming is important as to not to exacerbate hypothermia. Adjunctive techniques of warming including forced air devices, blankets,and high operating room temperatures BLOOD ADMINISTRATION METHODS

41. ACHIEVING HEMOSTASIS

42. Significant role Coagulation Platelet adhesion Cardiac and smooth muscle contractility In the setting of hemorrhagic shock Rapid infusion of blood products + decreased hepatic clearance of citrate ( hypoperfusion /hypothermia) Causes hypocalcemia A threshold ionized calcium [ iCa ] <0.9 mmol /L proposed as a trigger for intravenous calcium CALCIUM NEEDED?

43. HOW TO GO ABOUT IT?

44. COMPLICATIONS OF MT THEY DO OCCUR AND CAN BE FATAL

45. Problems secondary to volume resuscitation Inadequate : Hypoperfusion lactic acidosisSIRSMODSDIC Overzealous resuscitation : TACO / Interstitial edema Dilutional problems Dilutional coagulopathy Low colloidal osmotic pressure : Interstitial edema Problems related to stored blood Citrate toxicity ( hypoperfused liver) Hyperkalemia / magnesemia (existing acidosis worsen this) Hypothermia Acidosis IMMEDIATE

46. Respiratory complications : TRALI SIRS Sepsis Thrombotic complications TRIM LATE COMPLICATIONS

47. Placement of refrigerators in urgent care centers and emergency rooms Stocking up O blood group RBCs and AB plasma Maintaining target response time of <30 min once request initiated(un crossmatched /IS X match) prescribe blood and blood products early to allow for delivery time lag and thawing time (30 min for FFP) Collect blood sample for cross match early as colloids may interfere with cross matching HOW CAN WE IMPROVE OUR MTP – ROLE OF HOSPITAL TRANSFUSION COMMITTEE

48. IT INVOLVES ALL OF US WORK AS A TEAM