MASSIVE TRANSFUSION PROTOCOLS by DR JUVERIA.pptx

Presentation on massive transfusion protocols.

1. MASSIVE BLOOD TRANSFUSION PROTOCOLS DR. N. SATYANARAYANA DR. SHAHZEB ZAMAN DR. JUVERIA MAHJABEEN

2. MASSIVE TRANSFUSION Transfusion of greater than 10 units of pRBC's within 24hours, an estimated blood loss of greater than 150ml/hr or transfusion of greater than 5 units of whole blood in 3hours after initiating treatment . Improved outcomes are noted with the administration of whole blood or whole blood equivalents in the ratios of 1:1:1 for RBC's, plasma and platelets.

3. When should the Massive Transfusion Protocol be initiated? There are no simple criteria for this. Ultimately, initiation of a massive transfusion protocol is based on clinical judgement, considering the following factors: How unstable is the patient? How rapidly is the patient bleeding? What is the expected trajectory of this type of bleeding? Is the patient definitely in  hemorrhagic  shock? (If doubt exists about whether the patient is in  hemorrhagic  shock, echocardiography may be useful to confirm the presence of hypovolemia.) The  hemoglobin  level takes hours to fall after bleeding.   Consequently, checking the hemoglobin has little role in determining need for MTP. Hypotension is usually a  late  manifestation of hemorrhage . Worsening hypotension and vasopressor requirement should prompt consideration for MTP.

4. RABT Score The Revised Assessment of Bleeding and Transfusion   (RABT) Score – 1 point each Shock index > 1.0 Pelvic Fracture Positive FAST Penetrating Injury

5. ASSESSMENT OF BLOOD CONSUMPTION(ABC) ABC Score can be used to predict the need for massive transfusion. 4 variables can be assessed quickly, non-invasively and without lab support: If positive response to 2 or more variables             then activate MASSIVE TRANSFUSION PROTOCOL. PENETRATING MECHANISM OF INJURY YES/NO 2.   POSITIVE FAST EXAMINATION YES/NO 3.   SYSTOLIC BLOOD PRESSURE          SBP< 90mmHg YES/NO 4. HEART RATE > 120 beats per minute YES/NO

6.           In general, the criteria that warrant activation of an MTP include : An ABC score of 2 or more points Persistent hemodynamic instability Active bleeding requiring surgery or angioembolization Blood transfusion in the trauma bay

7. EQUIPMENTS 2 most essential components for an MTP are : Availability of blood products Establishment of suitable intravenous(IV) or intraosseous access Catheters with large diameters and shorter length have the highest flow rates  Assemble and insert large-bore catheters typically ranging from 14-18 gauge, either peripherally or centrally(IV) or through intraosseous access.

8. Additional equipment or resources that may be necessary include: Effective communication with blood banks regarding the evolving situation of massive blood loss. Sufficient number of personnel for timely sample collection and the procurement of blood and blood products. A blood warmer. A blood refrigerator within the resuscitation bay stocked with universal donor products, ideally comprising a minimum of 8 units of O-negative PRBCs and 8 units of thawed group AB or low titer anti-B group A plasma.

9. Inclusion of in-line fluid warmers and surface warmers. Continuous core temperature monitors. An invasive arterial blood pressure monitor. Adequate supply of colloid and crystalloid infusion sets.  IV calcium preparations. Point-of-care testing for various bodily functions, including arterial blood gas (ABG), hemoglobin , electrolytes, lactate, and thromboelastography (TEG). Rapid infusion pumps or pressure bags to expedite the fluid infusion rates.

10. INTRA-VENOUS ACCESS

11. INTUBATION Patients with exsanguinating hemorrhage will often need to be intubated (e.g., to facilitate endoscopic control of bleeding). Intubating a patient who is extremely under-resuscitated may precipitate hemodynamic collapse. It is often best to obtain access, give one round of massive transfusion (e.g., 6 units PRBCs, 6 units of platelets, and 6 units of FFP), and establish a reasonable blood pressure  prior  to intubation (“resuscitate before you intubate”).

12. 2:1:1  OR  1:1:1  BLOOD PRODUCT RATIO ? Rather than basing transfusion decisions on clinical judgment or laboratory tests, the concept of developing ratios of FFP and/or platelet concentrates with PRBCs has evolved. A 1:1:1 ratio would be transfusion of 1 unit of plasma, and one-sixth unit of platelets to 1 unit of RBCs. A 1:1:2 ratio would be transfusion of 1 unit of plasma, and one-sixth unit of platelets to every 2 units of RBCs. The convention of onesixth unit of platelets results from the common allocation of platelet products in 1 unit (apheresis) from a single donor or 1 pool (pooled) from six donors in a “six pack.” More recently in the randomized control trial Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study,  found that among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio versus a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days.

13. MONITORING HEMOSTASIS DURING MASSIVE TRANSFUSION PT APTT VISCOELASTIC TESTING --- 1. Thromboelastography(TEG)                                                        2. Thromboelastometry(ROTEM)                                                        3. ROTEM FIBTEM assay

14. VISCOELASTIC TESTING The unique aspect of viscoelastic monitors lies in their ability to measure the entire spectrum of clot formation in whole blood from early fibrin strand generation through clot retraction and fibrinolysis. The early TEG developed by Hartert in 1948 has evolved into two independent viscoelastic monitors: the modern TEG (TEG 5000 Thromboelastograph Hemostasis Analyzer System, Haemoscope , Braintree, MA) and ROTEM (TEM Systems, Durham, NC)

15. Massive Transfusion Protocol Checklist ✅ LABS (order them, but don't delay treatment while you wait) Type & crossmatch. CBC, INR, PT, PTT, fibrinogen (TEG if available). Electrolytes, Ca/Mg/Phos, ionized calcium. VBG or ABG if concern for significant acidemia .

16. Activate MTP and communicate with blood bank Triggers for initiation & termination are clinical. Designate a specific person to call the blood bank immediately. Consider additional fibrinogen (e.g., cryoprecipitate)  Consider 1:1:1:1 ratio of PRBC : FFP : Platelets : Cryo . Fibrinogen may be especially important in obstetric hemorrhage .

17. Calcium  1-2 gram Ca chloride or 3-6 grams Ca gluconate per MTP round (6 units PRBC). Follow ionized Ca if possible, target normal to mildly elevated ionized  Ca (e.g., ~1-3 mM). Tranexamic acid  Consider 1 gram IV, if difficulty achieving hemostasis . May continue infusion at a rate of 1 gram over 8 hours – especially in obstetric or early traumatic hemorrhage . IV Desmopressin Consider in renal failure, thrombocytopenia, or antiplatelet drugs. Dose is 0.3 mcg/kg (max 21 mcg) IV.

18. Review anticoagulant medications & consider reversal Warfarin reversal   Dabigatran reversal Xaban reversal Thrombolysis reversal Heparin reversal Antiplatelet reversal

19. A) WARFARIN REVERSAL : - VITAMIN K : 10mg IV, over 3 0 minutes - PCC or FFP B) DABIGATRAN REVERSAL : - IDARUCIZUMAB (PRAXBIND) : 5grams, given as two separate doses of 2.5grams each, 15 mins apart. C) FACTOR XA INHIBITORS (RIVAROXABAN, EPIXABAN, EDOXABAN, FONDAPARINUX) : - 4 – Factor PCC - ANDEXANET ALFA (K-CENTRA)

20. D) THROMBOLYTICS (t-PA) : - TRANEXAMIC ACID : 1gram IV, loading dose, followed by one gram infusion over the next hour - CRYOPRECIPITATE : start by giving 10units - FFP - PLATELET TRANSFUSION E) HEPARIN AND LMWH REVERSAL : BY PROTAMINE SULPHATE - IF HEPARIN GIVEN WITHIN <30 MINS : 1mg PROTAMINE per 100units HEPARIN - IF HEPARIN GIVEN 30-60 MINS AGO : 0.5-0.75mg PROTAMINE per 100units HEPARIN - IF HEPARIN GIVEN 60-120 MINS AGO : 0.375-0.5mg PROTAMINE per 100units HEPARIN - IF HEPARIN GIVEN 2-6 HRS AGO : 0.25-0.375mg PROTAMINE per 100units HEPARIN

21. F) ANTI-PLATELET REVERSAL DDAVP(DESMOPRESSIN) : 0.3-0.4 mcg per kg, infuse over 20-30 minutes TRANEXAMIC ACID EXOGENOUS PLATELET TRANSFUSION FRESH FROZEN PLASMA : IF INR 2-3.9 : 10cc/kg 4-6 : 12-15cc/kg >6 : 15-20cc/kg ONE UNIT OF FFP : 250-300 ml, so 10-20cc/kg equates to ~3-6 units of FFP.

22. Avoid acidosis   For intubated patients, adjust ventilator to optimize pH. Avoid hypothermia   Use warmed fluids if possible. Follow temperature, consider pre-emptive warming (e.g., with heated air blankets). Hemodynamics   Target lower than typical MAP, pending source control. Stop MTP when patient is hemodynamically stable.

23. SOURCE CONTROL Control of the bleeding source is obviously critical. Emphasis may be placed on the fastest strategy (e.g., surgical packing or interventional radiology, rather than definitive surgical repair). Close coordination with many consultants will usually be required (e.g., gastroenterology, interventional radiology, surgery).

24. Post-MTP lab evaluation: Labs Electrolytes, including ionized calcium Complete blood count INR, PTT, fibrinogen Examination Check patient's temperature Echocardiography to evaluate volume status

25. LETHAL TRIAD OF SEVERE BLOOD LOSS COAGULOPATHY HYPOTHERMIA ACIDOSIS INCREASED LACTIC ACID DECREASED CARDIAC PERFORMANCE DECREASED COAGULATION

26. PERI-OPERATIVE HEMOSTATIC CHANGES Blood loss upto 30% - fluid resuscitation alone Loss of one blood volume – dilution of coagulation factors to 30% of normal Loss of two blood volumes – dilution of coagulation factors to less than 15% of normal THROMBIN GENERATION is affected due to :  Reduced clot strength is monitored by viscoelastic blood monitoring using thromboelastography Ability of fibrin to polymerize is affected Severe hemodilution Decrease in procoagulant levels Thrombocytopenia Decrease in fibrinogen and factor 13

27. MASSIVE TRANSFUSION COAGULOPATHY In life-threatening haemorrhage, as seen in trauma patients, transfusion of fixed ratios of RBCs, FFP, and platelets should be administered. the Army Surgeon General established a clinical policy of 1:1:1 (plasma/ FFP:platelets:RBCs ) for combat casualties expected to receive massive transfusion.  The current military resuscitation practice is to use a balanced approach, using 1:1:1 as the primary resuscitation fluid for the most seriously injured casualties.

28. CAUSES OF BLEEDING IN THE SETTING OF MASSIVE TRANSFUSION COAGULOPATHY

29. DILUTIONAL COAGULOPATHY Dilutional thrombocytopenia is the primary cause of bleeding due to decreased platelets in stored blood. Transfusion of approximately 15 to 20 units causes significant dilution of blood volumes, leading to critical decreases in platelet count to approximately 20,000 to 30,000/mm3 , far below the recommended platelet target goals in actively bleeding patients.

30. FIBRINOLYSIS Vascular endothelial damage and stress responses cause stimulation of tissue plasminogen activator( tPA ) release which initiates fibrinolysis . Plasmin interferes with platelet function as it : This occurs with contact activation due to tissue injury and hemostatic activation.       Degrades fibrinogen and vWF Cleaves glycoprotein 1b receptors from platelets Creates degradation products(FDPs) that bind gp 2b/3a receptors and prevent platelet-fibrinogen cross-linking (similar to action of gp2b/3a receptor inhibitor – abciximab)

31. HYPOFIBRINOGENEMIA Normal fibrinogen levels :  200-400mg/dL Fibrinogen levels in pregnancy : 400-600mg/dL When these levels fall to as low as 80-100mg/dL                                 No role of FFP/plasma transfusion                Cryoprecipitate (or) fibrinogen concentrates can be used

32. DISSEMINATED INTRAVASCULAR COAGULATION Major causes of microvascular bleeding are : Dilutional Thrombocytopenia : seen with replacement of >1.5-2 litres blood volume and platelet counts of <50,000/ mL Coagulation factor deficiency : due to consumption coagulopathy

33. ROLE OF RED CELLS Modulation of biochemical and functional responsiveness of platelets by the red cells occurs by : Red cells have ADP that activates platelets. These activate platelet cyclo-oxygenase . They increase the generation of thromboxane A2. These may directly increase the thrombin burst through exposure of pro-coagulant phospholipids.

34. DIAGNOSIS OF DIC Platelet counts, PT, aPTT Potassium levels pH Calcium levels D- Dimer test

35. TREATMENT OF COAGULOPATHY DURING MASSIVE TRANSFUSION

36. POST-PARTUM HEMORRHAGE 

37. DAMAGE CONTROL RESUSCITATION (a) early and increased use of plasma, platelets, and RBCs while minimizing crystalloid use;  (b) hypotensive resuscitation strategies;  (c) avoiding hypothermia and acidosis that may compound coagulopathy;  (d) use of adjuncts such as calcium, THAM ( trishydroxymethyl aminomethane, an alternate alkalizing agent to sodium bicarbonate), and tranexamic acid and off-label uses of procoagulation agents; and (e) early definitive hemorrhage control