Massive Transfusion. MPQC Spring Summit April 29, Roger Belizaire MD PhD
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1 Massive Transfusion MPQC Spring Summit April 29, 2015 Roger Belizaire MD PhD
2 Take home points 1. Blood is always available. Requests for massive transfusion or emergency release typically only require a patient name, MRN and location. 2. The blood bank will help prepare for complicated or high-risk patients (e.g., patients with RBC alloantibodies or specific coagulopathies). 3. There are unique changes in hematologic and coagulation parameters during pregnancy, and it is unclear if post-partum hemorrhage and coagulopathy are identical to hemorrhage and coagulopathy in trauma. 4. The pathophysiology of post-partum coagulopathies are poorly understood and the optimal role for blood product transfusion (i.e., which products and when) has not been studied adequately. 5. Massive transfusion for post-partum hemorrhage should address all hematologic and coagulation deficiencies, including cryoprecipitate for fibrinogen replacement.
3 What are the goals of transfusion? Red blood cells: Increase oxygen-carrying capacity in the blood to facilitate oxygen delivery to tissues Platelets: Prevent (or stop) bleeding in the setting of thrombocytopenia or platelet dysfunction Plasma: Replenish coagulation factors to promote hemostasis Cryoprecipitate: Replenish fibrinogen to promote hemostasis
4 When is transfusion indicated? Red blood cells: Hb 7g/dL (or symptomatic anemia) Caveat: Largely based on ICU and orthopedic surgery patients who were not acutely bleeding Platelets: <10000/microliter (or bleeding in the setting of thrombocytopenia or platelet dysfunction) Caveat: Prophylactic threshold, largely based on heme/onc patients Plasma: Unclear, no RCTs (outside of specific clinical scenarios, e.g., TTP or coagulation factor deficiencies) Cryoprecipitate: Unclear, no RCTs (outside of specific clinical scenarios, e.g., bleeding in the setting of hypofibrinogenemia or factor XIII deficiency)
5 When is transfusion indicated in the obstetric setting? Red blood cells: Hb 7-8g/dL Platelets: < /microliter Plasma: PT/aPTT >1.5x normal Cryoprecipitate: < mg/dL Based on consensus, expert opinion or extrapolation from other clinical situations No RCTs
6 When is massive transfusion indicated? When massive blood loss has occurred or is anticipated to occur
7 How is blood loss measured?
8 Take home point #1 There will be blood. The blood bank does not question the clinical indication for massive transfusion (or emergency release).
9 Take home point #2 The blood bank can/should help prepare for deliveries with anticipated massive blood loss (e.g., placenta accreta/increta/percreta) or complicated blood product needs (e.g., antigen-negative RBCs or specific coagulation factors)
10 We have a bleeding patient. Her MRN is Please activate the massive transfusion protocol. A B C D 6U RBCs 8U RBCs 4U RBCs 4U RBCs 6U Plasma 4U Plasma 2U Plasma Please order 1 dose Plts 1 dose Cryo Followed by 10U RBCs RiaSTAP is available on the crash cart 4U RBCs 2U Plasma 1 dose Plts 1 dose Cryo (per hour) 10U Plasma 1 dose Plts Please consider using Amicar or TXA
11 We have a bleeding patient. Her MRN is Please activate the massive transfusion protocol. A B C D 6U RBCs 8U RBCs 4U RBCs 4U RBCs 6U Plasma 4U Plasma 2U Plasma Please order 1 dose Plts 1 dose Cryo Followed by 10U RBCs RiaSTAP is available on the crash cart 4U RBCs 2U Plasma 10U Plasma 1 dose Plts 1 dose Plts 1 dose Cryo (per hour) Please consider using Amicar or TXA Hospital A (General) Hospital A (OB) Hospital B (General/OB) Hospital C (General/OB)
12 We have a bleeding patient. Her MRN is Please activate the massive transfusion protocol. A B C D 6U RBCs 6U Plasma 1:1 8U RBCs 4U Plasma 2:1 4U RBCs 2U Plasma 2:1 4U RBCs Please order 1 dose Plts 1 dose Cryo RiaSTAP is available on the crash cart Followed by 4U RBCs 2U Plasma 10U RBCs 10U Plasma 1 dose Plts 1:1 1 dose Plts 1 dose Cryo (per hour) Please consider using Amicar or TXA Hospital A (General) Hospital A (OB) Hospital B (General/OB) Hospital C (General/OB)
13 Does the ratio of plasma to RBCs affect clinical outcomes in trauma?
14 Does the ratio of plasma to RBCs affect clinical outcomes? Retrospective study by Borgman et al., patients at US Army combat hospitals (all massively transfused, i.e., 10 RBC units over 24 hours) Grouped by low, medium and high plasma:rbc transfusion ratios Compared mortality Median survival 2hrs. 38hrs. Does survival increase the likelihood of receiving a higher plasma:rbc ratio?
15 PROPPR RCT (1:1 vs. 1:2 Plasma:RBC) 680 trauma patients at 12 level I centers in North America 338 randomized 1:1 Plasma:RBC 342 randomized to 1:2 Plasma:RBC No statistically significant differences between groups Primary outcomes: Mortality at 24-hours (95% power to detect 10% difference) and 30-days (92% power to detect 12% difference)
16 PROPPR RCT (1:1 vs. 1:2 Plasma:RBC) Holcomb et al., JAMA, 2015
17 PROPPR RCT (1:1 vs. 1:2 Plasma:RBC) No statistically significant difference in 24-hour (or 30-day) mortality between groups Holcomb et al., JAMA, 2015
18 Can we apply the results of PROPPR to obstetric patients? Maybe not how well does traumatic bleeding and coagulation in young male patients model severe post-partum hemorrhage? Etiologies of post-partum hemorrhage Uterine atony or genital tract trauma Uterine rupture Uterine inversion Retained placenta Placental abruption Placenta accreta/increta/percreta Alterations in hematologic parameters and coagulation during pregnancy Expansion of plasma volume and RCM Thrombocytopenia (gestational vs. ITP vs. pre-eclampsia vs. TTP/HUS) Increase in coagulation factors VII, VIII, IX, X, XII, vwf and fibrinogen Decrease in protein S and increased activated protein C resistance Decreased fibrinolysis (due to decreased tpa and increased TAFI and PAI)
19 More or less plasma? Compared to the plasma of a pregnant patient, donor plasma is relatively poor in coagulation factors and fibrinogen Should the threshold for plasma transfusion depend on the etiology of bleeding and the likelihood of a consumptive coagulopathy?
20 How should coagulation be monitored during management of post-partum hemorrhage? Goal: Transfuse the appropriate products and avoid unnecessary transfusions PT/aPTT: low sensitivity, long TAT Fibrinogen (Clauss): high sensitivity for hemorrhage progression (<200mg/dL), long TAT TEG/ROTEM: point-of-care whole blood coagulation testing (i.e., clot formation, fibrinogen, platelets and fibrinolysis); shown to reduce blood loss and blood component use in cardiac surgery patients (Ak et al., 2009)
21 Fibrinogen replacement Increase in fibrinolysis coincident with placental separation, potentially leading to sharp decline in fibrinogen levels Replacement (recommended at < mg/dL) traditionally with cryoprecipitate, which contains predominantly fibrinogen, factor VIII, factor XIII and vwf Must be thawed prior to issue Expires 4-6 hours after thaw Fibrinogen concentrate (e.g., RiaSTAP) ~20mg/mL (vs. 10mg/mL cryo or 2mg/mL plasma) Lyophilized, stable RT 30 months Ongoing RCT (FIB-PPH) examining fibrinogen concentrate for initial management of post-partum hemorrhage
22 Anti-fibrinolytics Rationale: CRASH-2 RCT comparing tranexamic acid (TXA) to placebo >20000 bleeding trauma patients at >250 hospitals in 40 countries Statistically significant reduction in mortality with no increase in thrombotic events WOrld Maternal ANtifibrinolytic (WOMAN) Trial patients with diagnosed post-partum hemorrhage Effect of early TXA on mortality, hysterectomy, need for surgical intervention and transfusion
23 Take home points 1. Blood is always available. Requests for massive transfusion or emergency release typically only require a patient name, MRN and location. 2. The blood bank will help prepare for complicated or high-risk patients (e.g., patients with RBC alloantibodies or specific coagulopathies). 3. There are unique changes in hematologic and coagulation parameters during pregnancy, and it is unclear if post-partum hemorrhage and coagulopathy are identical to hemorrhage and coagulopathy in trauma. 4. The pathophysiology of post-partum coagulopathies are poorly understood and the optimal role for blood product transfusion has not been studied adequately. 5. Massive transfusion for post-partum hemorrhage should address all hematologic and coagulation deficiencies, including cryoprecipitate for fibrinogen replacement.
24 Future directions Quantitation of blood loss Understanding of coagulopathies in conventional trauma vs. postpartum hemorrhage Using the most effective blood product and minimizing unnecessary transfusions Real-time monitoring of coagulation at the bedside (via TEG/ROTEM) Goal-directed transfusion therapy Evaluation of the utility of fibrinogen concentrates (FIB-PPH RCT) Evaluation of the utility use of anti-fibrinolytics (WOMAN RCT) Minimizing blood loss and reducing the need for transfusion
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