Comparison of Platelet Mass Index to Platelet Count as Transfusion Trigger in Neonatal Extracorporeal Membrane Oxygenation.

BACKGROUND: Platelet transfusions are routinely administered to neonates in intensive care units when there are concerns of bleeding, including high-risk situations like Extracorporeal Membrane Oxygenation (ECMO). Most platelets in ICUs are transfused prophylactically for thrombocytopenia based solely on the platelet count. Platelet Mass Index (PMI) has been proposed as an alternative to platelet count (PC) as a transfusion trigger. The objective of this study was to determine the relationship between PMI and platelet-specific maximal clot firmness (PMCF) in Rotational thromboelastometry (ROTEM), which gives an indication of platelet contribution to clot firmness and to investigate whether PMI may be a better choice as a trigger for platelet transfusions than PC. METHODS: Retrospective review of medical records of neonates with congenital heart disease placed on ECMO support in the cardiovascular intensive care unit (CVICU) from 2015 to 2018 was conducted. Platelet count (PC), platelet mean volume (PMV), ROTEM parameters along with demographic data including gestation age, birth weight, gender and survival were collected. Mixed effects linear models with a first order autoregressive covariance structure were used to assess the associations of PMI, PC, and MPV against PMCF. In addition, generalized estimating equations with a first order auto-regressive covariance structure were used to compare odds of transfusion using PC versus PMI triggers. RESULTS: A total of 92 tests on consecutive days were obtained for 12 ECMO patients (5 male, GA = 38.1 ± 1.6 weeks, BW = 3.1 ± 0.4 kgs, mean ± SD). A variation of 40.1% in PMCF was explained by platelet count (p < 0.001) while 38.5% of the variation in PMCF was explained by PMI (p < 0.001). If the platelet transfusion trigger was PC < 100 x 103 platelets/µL vs. PMI < 800. Using the PC trigger yielded significantly higher odds of transfusion compared to the PMI trigger (odds ratio = 1.31, 95% confidence interval: 1.18 - 1.45, p < 0.001). CONCLUSIONS: While our study failed to demonstrate a superior correlation of PMI with PMCF than PC, our study did reveal that using PMI as transfusion trigger would result in significantly less platelet transfusions, when compared with the current practice of using PC as a trigger.

Massive Transfusion Protocols in Obstetric Hemorrhage: Theory versus Reality.

OBJECTIVE: Massive transfusion protocols are widely implemented in obstetrical practice in case of severe hemorrhage; however, different recommendations exist regarding the appropriate ratios of blood product components to be transfused. We report our extensive experience with massive component transfusion in a referral center in which the standard massive transfusion protocol is modified by ongoing clinical and laboratory evaluation. STUDY DESIGN: A retrospective chart review of all patients who had massive transfusion protocol activation in a level 4 referral center for obstetrical practice was performed from January 2014 to January 2020. Data collected included the etiology of obstetrical hemorrhage, number of blood products of each type transfused, crystalloid infusion, and several indices of maternal morbidity and mortality. Data are presented with descriptive statistics. RESULTS: A total of 62 patients had massive transfusion protocol activation, of which 97% received blood products. Uterine atony was found to be the most common etiology for massive hemorrhage (34%), followed by placenta accreta spectrum (32%). The mean estimated blood loss was 1,945 mL. A mean of 6.5 units of packed red blood cells, 14.8 units of fresh frozen plasma and cryoprecipitate, and 8.3 units of platelets were transfused per patient. No maternal deaths were seen. CONCLUSION: The ratios of transfused packed red blood cell to fresh frozen plasma/cryoprecipitate and of packed red blood cell to platelet units varied significantly from the fixed initial infusion ratio called for by our massive transfusion protocol resulting in universally favorable maternal outcomes. When rapid laboratory evaluation of hematologic and clotting parameters is available, careful use of this information may facilitate safe modification of an initial fixed transfusion ratio based on etiology of the hemorrhage and individual patient response. KEY POINTS: · Massive transfusion protocols in obstetrics follow fixed ratios of blood products.. · Actual usage of blood components is different than the standardized protocols.. · We recommend to modify the initial fixed transfusion ratio according to clinical response..

Blood transfusion is associated with increased mortality for neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation support.

BACKGROUND AND OBJECTIVES: Blood transfusion is frequently needed to maintain adequate haemostasis and improve oxygenation for patients treated with extracorporeal membrane oxygenation (ECMO). It is more so for neonates with immature coagulation systems who require surgical intervention such as congenital diaphragmatic hernia (CDH) repair. There is growing evidence suggesting an association between blood transfusions and increased mortality. The aim of this study is to evaluate the association of blood transfusions during the peri-operative period of CDH repair, among other clinical parameters, with mortality in neonates undergoing on-ECMO CDH repair. MATERIALS AND METHODS: We performed a single centre retrospective chart review of all neonates with CDH undergoing on-ECMO surgical repair from January 2010 to December 2020. Logistic regression was used to investigate associations with survival status. RESULTS: Sixty-two patients met the inclusion criteria. Platelet transfusions (odds ratio [OR] 1.42, 95% confidence interval [CI]: 1.06-1.90) in the post-operative period and ECMO duration (OR 1.17, 95% CI: 1.05-1.30) were associated with increased mortality. Major bleeding complications had the strongest association with mortality (OR 10.98, 95% CI: 3.27-36.91). Gestational age, birth weight, Apgar scores, sex, blood type, right versus left CDH, venovenous versus venoarterial ECMO and duration of ECMO before CDH repair and circuit change after adjusting for ECMO duration were not significantly associated with survival. CONCLUSION: Platelet transfusion in the post-operative period and major bleeding are associated with increased mortality in CDH neonates with surgical repair. The data suggest a need to develop robust plans for monitoring and preventing coagulation aberrancies during neonatal ECMO support.

Age-based difference in activation markers of coagulation and fibrinolysis in extracorporeal membrane oxygenation.

OBJECTIVE: Coagulation system activation in extracorporeal membrane oxygenation results in hemostatic derangements. Thrombin generation markers like prothrombin fragment 1+2 and thrombin-antithrombin complex are sensitive markers of hypercoagulability. Plasmin-antiplasmin complex is a sensitive marker for fibrinolysis. D-dimers reflect thrombin generation and fibrinolysis. The aim was to identify the extent of hemostasis activation during extracorporeal membrane oxygenation by measuring thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer. DESIGN: Prospective cohort study. SETTING: Tertiary care academic center. PATIENTS: Children placed on extracorporeal membrane oxygenation from April 2011 to January 2013. INTERVENTIONS: Prothrombin fragment 1+2, thrombin-antithrombin complex, plasmin-antiplasmin complex, and D-dimer were measured on days 1 and 5 of extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Data presented as median (interquartile range); nonparametric tests were done using SPSS. Twenty-nine children (52% < 30 d old [neonates], median extracorporeal membrane oxygenation length 151 hr) were studied. Complications included thrombosis in 14%, bleeding in 45%, and thrombosis and bleeding together in 10%. Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels were high on day 1 and remained increased on extracorporeal membrane oxygenation. In neonates, all levels were higher on day 5 compared with day 1: thrombin-antithrombin complex (55.6 µg/L [30.7-76.0] vs 18.7 µg/L [10.9-34.6]; p = 0.03), prothrombin fragment 1+2 (2,038 pmol/L [1,093-4,018.5] vs 377.5 pmol/L [334.3-1,103.0]; p = 0.00), plasmin-antiplasmin complex (2,160 µg/L [786-3,090] vs 398 µg/L [296.8-990.8]; p = 0.00), and D-dimer (3.0 µg/mL [1.9-11.5] vs 1.5 µg/mL [0.6-2.9]; p = 0.01). Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels did not correlate with anti-Xa activity or heparin dose. In bleeders older than 30 days, plasmin-antiplasmin complex stayed elevated on day 5, but in patients with no bleeding complications, plasmin-antiplasmin level showed a declining trend. In neonates, plasmin-antiplasmin levels increased over the course of extracorporeal membrane oxygenation irrespective of bleeding. CONCLUSION: Despite our best efforts at adequate anticoagulation with unfractionated heparin, neonates showed persistent increase in coagulation activation on extracorporeal membrane oxygenation. Fibrinolysis activation may contribute to bleeding in patients older than 30 days. Different anticoagulation protocols should be individualized based on age.