A Pilot Study To Examine The Effect Of Extracorporeal Membrane Oxygenation (ECMO) On Plasma Factor XIII Levels

Background Children with acute, severe cardiopulmonary compromise may require support with ECMO. Adequate anticoagulation without inducing life-threatening hemorrhage plays a critical role in the management of these patients. Recent data from adult studies suggest that patients undergoing cardiac bypass for coronary artery bypass grafting (CABG) often have reduced Factor XIII levels (FXIII). This relative FXIII deficiency may be predictive of hemorrhage or severe blood loss. Such studies have never been conducted in the pediatric population. Our primary objective will be to determine if a relative deficiency in FXIII occurs in children undergoing ECMO and to determine any time dependency of these changes. Our secondary objective will be to determine if blood loss and/or transfusion requirements during ECMO correlates with FXIII levels. Methods Single center ongoing study utilizing a prospective design involving pediatric patients (ages 0-18) undergoing ECMO. Samples for FXIII, D-Dimers, Fibrinogen and Thrombin Time are being drawn at designated time points as follows: prior to or during ECMO cannulation, 2 hours, 24 hours, 3-5 days and 14-21 days after initiation of ECMO and 1-3 days after discontinuation of ECMO. Mixed effects analysis of covariance (ANCOVA) will be used for data analysis. Results To date, fifteen patients have been enrolled and analyses have been conducted for n=7 patients with a total of 36 time points of data. Figure 1a and 1b show the mean and standard deviation (SD) of FXIII and Fibrinogen, respectively. Figure 1c shows the mean ratio of FXIII to Fibrinogen. Error bars represent 1 SD around the mean (central point). Conclusion and Significance This is the first pediatric study evaluating FXIII activity in children undergoing ECMO. Firm conclusions cannot be drawn with the interim analyses conducted to date. If variations in FXIII are found, our results will provide important information towards determining if children undergoing ECMO could potentially benefit from FXIII replacement, in turn minimizing bleeding complications and/or transfusion requirements often encountered with this treatment modality. Disclosures: No relevant conflicts of interest to declare.

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The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649883 ◽

1995 ◽

Vol 74 (04) ◽

pp. 1064-1070 ◽

Cited By ~ 76

Author(s):

Marco Cattaneo ◽

Alan S Harris ◽

Ulf Strömberg ◽

Pier Mannuccio Mannucci

Keyword(s):

Cardiac Surgery ◽

Blood Loss ◽

Meta Analysis ◽

Postoperative Blood Loss ◽

Controlled Trials ◽

Double Blind ◽

Double Blind Placebo ◽

Transfusion Requirements ◽

The Mean ◽

Excessive Blood Loss

SummaryThe effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials, with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (>1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

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Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia

Blood ◽

10.1182/blood.v96.7.2479 ◽

2000 ◽

Vol 96 (7) ◽

pp. 2479-2486 ◽

Cited By ~ 87

Author(s):

István Balogh ◽

Gabriella Szôke ◽

Levente Kárpáti ◽

Ulla Wartiovaara ◽

Éva Katona ◽

...

Keyword(s):

Protective Effect ◽

Venous Thrombosis ◽

Factor Xiii ◽

Coagulation Factor ◽

Wild Type ◽

Thrombin Cleavage ◽

Plasma Factor ◽

Thrombin Activation ◽

A Subunit ◽

The Mean

Abstract Val34Leu polymorphism of the A subunit of coagulation factor XIII (FXIII-A) is located in the activation peptide (AP) just 3 amino acids away from the thrombin cleavage site. This mutation has been associated with a protective effect against occlusive arterial diseases and venous thrombosis; however, its biochemical consequences have not been explored. In the current study it was demonstrated that the intracellular stability and the plasma concentration of FXIII of different Val34Leu genotypes are identical, which suggests that there is no difference in the rate of synthesis and externalization of wild-type and mutant FXIII-A. In contrast, the release of AP by thrombin from the Leu34 allele proceeded significantly faster than from its wild-type Val34 counterpart. By molecular modeling larger interaction energy was calculated between the Leu34 variant and the respective domains of thrombin than between the Val34 variant and thrombin. In agreement with these findings, the activation of mutant plasma FXIII by thrombin was faster and required less thrombin than that of the wild-type variant. Full thrombin activation of purified plasma FXIII of different genotypes, however, resulted in identical specific transglutaminase activities. Similarly, the mean specific FXIII activity in the plasma was the same in the groups with wild-type, heterozygous, and homozygous variants. Faster activation of the Leu34 allele hardly could be associated with its presumed protective effect against venous thrombosis. No such protective effect was observed in a large group of patients with familial thrombophilia.

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Reversal of Trauma-Induced Bleeding and Anticoagulation with a Dabigatran-Specific Antidote (idarucizumab) As Assessed By Shed and Washed Blood Tests in a Pig Model of Supratherapeutic Anticoagulation and Trauma

Blood ◽

10.1182/blood.v124.21.4268.4268 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4268-4268

Author(s):

Oliver Grottke ◽

Markus Honickel ◽

Johanna Schurer ◽

Joanne van Ryn

Keyword(s):

Blood Loss ◽

Research Funding ◽

Anticoagulant Activity ◽

Alternative Methods ◽

Thrombin Time ◽

Wound Site ◽

Shed Blood ◽

Time Points ◽

Superficial Wound ◽

Dose Dependent

Abstract Background: The most frequent side effect associated with anticoagulant therapy is bleeding. Testing reversal strategies in patients is difficult due to the unpredictability, rarity and heterogeneity of these events. Currently methods to reverse this bleeding are being tested in a variety of clinical settings in volunteers by using reversal of anticoagulation as a marker of reversal of bleeding in patients. However, the limitation of volunteer studies is the lack of understanding between the assay being used to measure anticoagulation and if its reversal has any relevance for bleeding reversal in patients. A marker of bleeding that was safe to use in volunteers and also relevant for predicting reversal of bleeding in a patient would be advantageous. Objective: The feasibility of two markers of bleeding - fibrin formation (fibrinopeptide A, FPA) in blood as it exits a wound and blood loss measured via a washed blood method, both at a superficial wound site - were tested in pigs under high dabigatran anticoagulation. Reversal of dabigatran anticoagulation and bleeding following trauma injury were evaluated with idarucizumab and outcomes compared to the markers of bleeding from superficial wound. Methods: After ethical approval dabigatran etexilate (30 mg/kg p.o. twice daily, n=24) or placebo (n=6, no dabigatran anticoagulation) was administered to male pigs for 3 days. On Day 4, the pigs were anesthetized and given a 90 min infusion of active dabigatran. A standardized blunt liver injury (0 min) was performed and animals underwent hemorrhagic shock, 15 min later were randomized to receive idarucizumab (30, 60 or 120 mg/kg) or vehicle. Blood loss was measured at defined time points over 4 hrs post injury. At the same time points a standardized cut was made on the inner side of the ear using an adult Surgicutt® device, one cut for each method. Shed blood was collected from the wound site as it emerged over 4 min, placed in protease inhibitor solution and processed for FPA measurement by ELISA. For washed blood method, blood as it exited the wound in 10 sec intervals was diluted in saline into 96 wells and measured photometrically. AUC over 15 min was recorded as blood loss. Blood samples were collected over time to measure active dabigatran by diluted thrombin time (dTT). Data shown as mean ± SE. Results: Cumulative blood loss was 630 ± 56 mL in the placebo group and 2977 ± 129 mL in the dabigatran-treated group. There was a dose-dependent reduction in blood loss by 47% (1586 ± 253 mL), 64% (1064 ± 40 mL) and 62% (1140 ± 44 mL) following treatment with 30, 60 and 120 mg/kg idarucizumab (p<0.001). Dabigatran plasma levels were 1228 ± 320 ng/mL prior to injury with no significant differences between groups. Dabigatran activity decreased within 5 min of idarucizumab administration, with a dose-dependent reduction over 240 min and was completely inhibited with 120 mg/kg. FPA in blood from the wound in dabigatran-treated groups was decreased ~74% vs non-anticoagulated group (211.2 ± 86 vs 53.7 ± 13 ng/mL). FPA increased by 2.6-fold (136.3 ± 96 ng/mL), 1.4-fold (103.9 ± 59 ng/mL) and 6.2-fold (251.9 ± 139 ng/mL) over baseline following 30, 60 and 120 mg/kg idarucizumab, respectively. At 240 min, FPA levels were 12%, 25% and 52% of non-anticoagulated animals with increasing idarucizumab doses and correlated with levels of dabigatran at 240 min. Washed blood loss (AUC) in dabigatran-treated animals was increased ~7-fold prior to injury vs non-anticoagulated groups (2110 ± 420 vs 309.1 ± 11.2 OD*sec). There was a dose-dependent reduction in washed blood loss by 2.5% (1682 ± 688 OD*sec), 48% (889 ± 304 OD*sec), and 79% (370 ± 97 OD*sec) 30 min following 30, 60 and 120 mg/kg idarucizumab vs dabigatran-treatment (1724 ± 298 OD*sec). Washed blood loss was comparable to the non-anticoagulated group (186 ± 59 vs 281 ± 201 OD*sec) with 120 mg/kg idarucizumab after 240 min, also correlating with lack of dabigatran anticoagulant activity. Conclusions: This study shows that bleeding and its reversal with a dabigatran-specific antidote can be evaluated using alternative methods that measure FPA levels in shed blood and washed blood loss at non-trauma superficial wound sites. The reversal of blood loss and FPA generation correlated with reversal of bleeding from a trauma wound. These methods may serve as potential markers in experimental bleeding and trauma models to sensitively assess blood loss and to also monitor reversal agents. Disclosures Grottke: Boehringer Ingelheim : Consultancy, Research Funding; CSL Behring: Research Funding. Honickel:Boehringer Ingelheim : Travel support Other. Schurer:Boehringer Ingelheim Pharma GmbH & Co KG: Employment. van Ryn:Boehringer Ingelheim Pharma: Employment.

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A prospective study to evaluate the effects of acute normovolemic hemodilution on perioperative homologous transfusion requirements in patients undergoing major surgery

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20201314 ◽

2020 ◽

Vol 8 (4) ◽

pp. 1303

Author(s):

Ajay Kumar ◽

Shalendra Singh ◽

Parmeet Bhatia ◽

Bhavna Hooda ◽

Priya Taank

Keyword(s):

Blood Loss ◽

Major Surgery ◽

Acute Normovolemic Hemodilution ◽

Autologous Transfusion ◽

Hemodynamic Stability ◽

Homologous Blood Transfusion ◽

Group I ◽

Transfusion Requirements ◽

Normovolemic Hemodilution ◽

The Mean

Background: Acute Normovolemic Hemodilution (ANH) and autologous transfusion can mitigate the harmful effects of banked blood intraoperatively. This study was planned to evaluate its effects on perioperative transfusion requirement, hemodynamic stability and safety profile.Methods: Hundred patients were randomized to Group 1, where assigned patients received ANH and autologous transfusion after hemostasis; and Group II where assigned patients received homologous transfusion. In group I, 350 to 700 ml of patient's blood was collected before induction of anaesthesia and was kept in the operation theatre at room temperature. This was followed by rapid infusion of calculated Hetastarch. Intraoperative blood loss, amount of transfused blood, serial haemoglobin (Hb) assessment, and change in hemodynamics were carefully monitored. The blood was reinfused once hemostasis was secured at the end of surgery.Results: It was observed that hemodynamic stability was maintained in both the groups during and after haemodilution. There was no significant change in bleeding and clotting time due to haemodilution. The mean intra-operative blood loss in both groups was comparable. 350 mL and 700 mL blood withdrawn in 27 and 23 patients and 500mL and 1000 mL HES infused respectively. There was an average fall in the mean Hb level by 1.74 gm % and in the mean haematocrit (Hct) level by 6.4 % after haemodilution. The mean 12th and 24th hour Hb and Hct levels were comparable. The requirement of homologous blood transfusion in group I was significantly low (p<0.0001). Need for homologous transfusion was 0.72 per patient treated in the Group I.Conclusions: Acute normovolemic hemodilution is a simple, safe and effective modality to reduce perioperative transfusion of banked blood and should be considered in patients undergoing surgical procedures where major blood loss is expected.

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Initial Canadian experience with robotic simple prostatectomy: Case series and literature review

Canadian Urological Association Journal ◽

10.5489/cuaj.2750 ◽

2015 ◽

Vol 9 (9-10) ◽

pp. 626 ◽

Cited By ~ 12

Author(s):

Nathan Y. Hoy ◽

Stephan Van Zyl ◽

Blair A. St. Martin

Keyword(s):

Blood Loss ◽

Operating Time ◽

Case Series ◽

Transfusion Rate ◽

Complication Rates ◽

Intraoperative Blood Loss ◽

Transfusion Requirements ◽

Simple Prostatectomy ◽

Significant Difference ◽

The Mean

Introduction: Robotic-assisted simple prostatectomy (RASP) has been touted as an alternative to open simple prostatectomy (OSP) to treat large gland benign prostatic hyperplasia. Our study assesses our institution’s experience with RASP and reviews the literature.Methods: We performed a retrospective chart review from January 2011 to November 2013 of all patients undergoing RASP and OSP. Operative and 90-day outcomes, including operation time, intraoperative blood loss, length of hospital stay (LOS), transfusion requirements, and complication rates, were assessed.Results: Thirty-two patients were identified: 4 undergoing RASP and 28 undergoing OSP. There was no difference in mean age at surgery (69.3 vs. 75.2 years; p = 0.17), mean Charlson Comorbidity Index (2.5 vs. 3.5; p = 0.19), and mean prostate volume on TRUS (239 vs. 180 mL; p = 0.09) in the robotic and open groups, respectively. There was a significant difference in the mean length of operation, with RASP exceeding OSP (161 vs. 79 min; p = 0.008). The mean intraoperative blood loss was significantly higher in the open group (835.7 vs. 218.8 mL; p = 0.0001). Mean LOS was shorter in the RASP group (2.3 vs. 5.5 days; p = 0.0001). No significant differences were noted in the 90-day transfusion rate (p = 0.13), or overall complication rate at 0% with RASP vs. 57.1% with OSP (p = 0.10).Conclusions: Our data suggest RASP has a shorter LOS and lower intraoperative volume of blood loss, with the disadvantage of a longer operating time, compared to OSP. It is a feasible technique and deserves further investigation and consideration at Canadian centres performing robotic prostatectomies.

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Fatal Bleeding Caused by Congenital Factor XIII Deficiency and Development of An Inhibitor in a Hispanic Male

Blood ◽

10.1182/blood.v112.11.4515.4515 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4515-4515

Author(s):

Filipe R. Lorenzo ◽

Derrick Haslem ◽

Josef T. Prchal ◽

Charles Greenberg

Keyword(s):

Factor Xiii ◽

Factor Xiiia ◽

Bleeding Complications ◽

Factor Xiii Deficiency ◽

Catalytic Core ◽

Fatal Bleeding ◽

Plasma Factor ◽

A Chain ◽

Hispanic Male ◽

Congenital Factor

Abstract We report a case of fatal bleeding in a patient with mild congenital Factor XIII deficiency who also developed an inhibitor that interfered with fibrin stabilization. Plasma Factor XIII circulates as a tetramer composed of two A-chain and two B-chains and is bound to fibrinogen. After thrombin cleaves the A-chain at Arg 37, the B-chain dissociate producing Factor XIIIa. Factor XIIIa catalyzes covalent linkages between the fibrin molecules aligned in the fibrin clot. Factor XIIIa makes the fibrin resistant to disruption by urea and plasmin. Factor XIIIa levels greater than 1 % are needed to covalently stabilize a clot. We studied a 39 year old Hispanic male that presented with altered mental status, headache and a large left frontal parietal hemorrhage. Ultimately, he became non-responsive and was intubated. He had no major bleeding history but did have frequent nosebleeds. Routine blood counts and coagulation laboratory tests were normal. However, a qualitative Factor XIII assay was abnormal and the clot dissolved in 5M Urea. Furthermore, a 1:1 mixing study did not correct the defect suggesting the presence of an inhibitor. A small dose of cryoprecipitate was administered to the patient and this corrected the clot stability defect. Four days later, the defect recurred and 150 ml of cryoprecipitate was administered and despite correction of the fibrin stabilizing abnormality the patient died. Two of his sisters had a history of repeated hemorrhagic miscarriages in Mexico a finding consistent with congenital Factor XIII deficiency. DNA sequencing of the factor XIII a-chain gene was performed from the propositus’ mononuclear cells. A reverse transcription was done using an oligo(dT) 12–18 primer followed by nested PCR amplification and a heterozygous missense mutation was observed at codon 35 (G226T; Val35Leu). This mutation was than confirmed in propositus’ platelet cDNA. The Val35Leu substitution is close to the thrombin cleavage site, the G226T substitution is in the catalytic core domain. This case demonstrates that in some cases of Factor XIII deficiency there is residual Factor XIIIa activity in the mutant molecule that can prevent serious bleeding. However, patients may develop autoantibodies that further interfere with Factor XIII function and may suffer serious bleeding complications. Additional cases of Factor XIII deficiency may exist in patients that have mild bleeding problems.

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Efficacy of Intravenous Tranexamic Acid in Reducing Perioperative Blood Loss and Blood Product Transfusion Requirements in Patients Undergoing Multilevel Thoracic and Lumbar Spinal Surgeries: A Retrospective Study

Frontiers in Pharmacology ◽

10.3389/fphar.2020.566956 ◽

2020 ◽

Vol 11 ◽

Author(s):

Alexandre B. Todeschini ◽

Alberto A. Uribe ◽

Marco Echeverria-Villalobos ◽

Juan Fiorda-Diaz ◽

Mahmoud Abdel-Rasoul ◽

...

Keyword(s):

Retrospective Study ◽

Postoperative Complications ◽

Blood Loss ◽

Spinal Fusion ◽

Spinal Surgery ◽

Blood Product ◽

Control Group ◽

Blood Product Transfusion ◽

Transfusion Requirements ◽

The Mean

Introduction: Acute perioperative blood loss is a common and potentially major complication of multilevel spinal surgery, usually worsened by the number of levels fused and of osteotomies performed. Pharmacological approaches to blood conservation during spinal surgery include the use of intravenous tranexamic acid (TXA), an anti-fibrinolytic that has been widely used to reduce blood loss in cardiac and orthopedic surgery. The primary objective of this study was to assess the efficacy of intraoperative TXA in reducing estimated blood loss (EBL) and red blood cell (RBC) transfusion requirements in patients undergoing multilevel spinal fusion.Materials and Methods: This a single-center, retrospective study of subjects who underwent multilevel (≥7) spinal fusion surgery who received (TXA group) or did not receive (control group) IV TXA at The Ohio State University Wexner Medical Center between January 1st, 2016 and November 30th, 2018. Patient demographics, EBL, TXA doses, blood product requirements and postoperative complications were recorded.Results: A total of 76 adult subjects were included, of whom 34 received TXA during surgery (TXA group). The mean fusion length was 12 levels. The mean total loading, maintenance surgery and total dose of IV TXA was 1.5, 2.1 mg per kilo (mg/kg) per hour and 33.8 mg/kg, respectively. The mean EBL in the control was higher than the TXA group, 3,594.1 [2,689.7, 4,298.5] vs. 2,184.2 [1,290.2, 3,078.3] ml. Among all subjects, the mean number of intraoperative RBC and FFP units transfused was significantly higher in the control than in the TXA group. The total mean number of RBC and FFP units transfused in the control group was 8.1 [6.6, 9.7] and 7.7 [6.1, 9.4] compared with 5.1 [3.4, 6.8] and 4.6 [2.8, 6.4], respectively. There were no statistically significant differences in postoperative blood product transfusion rates between both groups. Additionally, there were no significant differences in the incidence of 30-days postoperative complications between both groups.Conclusion: Our results suggest that the prophylactic use of TXA may reduce intraoperative EBL and RBC unit transfusion requirements in patients undergoing multilevel spinal fusion procedures ≥7 levels.

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Blood Loss and Transfusion Requirements in Liver Transplantation: Experience with the First 75 Cases

Anaesthesia and Intensive Care ◽

10.1177/0310057x9402200604 ◽

1994 ◽

Vol 22 (6) ◽

pp. 666-671 ◽

Cited By ~ 9

Author(s):

P. L. Mcnicol ◽

G. Liu ◽

I. D. Harley ◽

P. R. Mccall ◽

G. M. Przybylowski ◽

...

Keyword(s):

Liver Transplantation ◽

Blood Loss ◽

Red Blood Cells ◽

Blood Cells ◽

Surgical Techniques ◽

Fresh Frozen Plasma ◽

Transfusion Requirements ◽

Fresh Frozen ◽

The Mean ◽

Frozen Plasma

The blood loss data and transfusion requirements including blood bank, salvaged washed red cells, fresh frozen plasma and cryoprecipitate were analysed for the first 75 cases of liver transplantation performed at the Austin Hospital between June 1988 and October 1992. The mean blood loss was 8.8 litres (standard deviation 14.1) with a median value of 4.0 litres. Blood product use expressed as mean number of units (SD) was bank red blood cells 7.1 (12.7), washed red blood cells 3.9 (5.9), fresh frozen plasma 7.1 (9.1), platelets 5.1 (7.4), and cryoprecipitate 1.7 (5.1). These results demonstrate that liver transplantation can be performed without imposing excessive demands on blood transfusion services. Management should include surgical techniques to minimize bleeding and use of autologous transfusion. Use of component therapy (FFP, platelets and cryoprecipitate) should not be empirical. It should be selective on the basis of clinical bleeding assessment and guided by results of the laboratory coagulation profile and changes in thrombelastographic (TEG) parameters.

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Sonic Estimation of Elasticity Via Resonance Sonorheometry to Predict Thrombotic Risk in Patients with Cancer

Blood ◽

10.1182/blood.v128.22.4996.4996 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4996-4996 ◽

Cited By ~ 2

Author(s):

Erin McLoughlin ◽

Elisa Ferrante ◽

Francesco Viola ◽

Hillary S. Maitland

Keyword(s):

Lung Cancer ◽

High Risk ◽

Thrombin Time ◽

Thrombotic Risk ◽

Time Points ◽

High Risk Patients ◽

Upper Limit ◽

Risk Patients ◽

The Mean ◽

D Dimer

Abstract Venous thromboembolic (VTE) disease is associated with significant morbidity and mortality and is one of the leading causes of death in patients diagnosed with a malignancy. The actual reported incidence of VTE in patients with malignancy varies greatly and depends on the type and stage of cancer, type of treatment, and patient-specific factors. This study is designed to assess the efficacy of a novel ultrasound-based technology, Sonic Estimation of Elasticity via Resonance (SEER) Sonorheometry, in predicting thrombosis and identifying high-risk patients. Treatment naïve patients with a new diagnosis of a solid tumor malignancy were eligible for inclusion in the study. Baseline conventional measures of hemostasis (D-Dimer, fibrinogen, thrombin time, PT/INR, PTT, and platelet count) were measured within the first cycle of chemotherapy and at 6 months for all patients. The HemoSonics' Quantra Hemostasis Analyzer (Quantra) is a point of care device that uses SEER Sonorheometry to measure key parameters of clot formation including clotting time, clot stiffness, and platelet and fibrinogen contributions to clot stiffness. A research use only (RUO) version of the Quantra was utilized to collect data within the first cycle of chemotherapy and at 6 months. Patients were monitored for the development of a venous thromboembolism. In order to determine the feasibility of using this technology/device on a larger scale, our ongoing enrollment goal for this pilot study is 20 patients. Seven patients with lung cancer (non-small cell lung cancer n=5, small cell lung cancer n=2), 4 patients with squamous cell carcinoma of the head and neck, and 1 patient with gastric adenocarcinoma have been enrolled to date. At the initial and 6-month time points, the mean values for INR, PT, PTT, thrombin time, and platelet count were normal. The mean D-dimer and mean fibrinogen were elevated at both time points. The D-dimer decreased by 7.1 percent over the 6 months while the mean fibrinogen increased by 7.7 percent over the same time period. The mean clotting time increased by 19.2% from 2.6 minutes to 3.1 minutes (95% CI, 2.1-4.1), however it remained within the normal limits of the assay. The mean values for the remaining Quantra parameters increased above the upper limit of normal for the assays over the 6-month time frame. Clot stiffness, fibrinogen and platelet contribution increased by 79.2, 83.3, and 84.0% respectively. Specifically, the mean fibrinogen contribution increased from 5.4 to 9.9 hecto-Pascals (hPa) (95% CI, 3.3-16.5) at 6 months, exceeding the upper limit of normal of 7.0 hPa. The mean platelet contribution to the clot increased from 18.2 to 33.5 hPa (95% CI, 20.6-46.5), exceeding the upper limit of normal of 30 hPa. The mean clot stiffness increased from 24 to 43 hPa over the 6-month interval; the upper limit of normal for the assay is 37 hPa. To date, there have been no documented occurrences of venous thromboembolism in our patient population. Thromboprophylaxis can be considered for certain high risk patients, however it is not currently recommended as a part of therapy for solid tumors. Additionally, identifying patients at high risk for thrombosis is difficult as no specific biomarkers have been shown to reliably predict VTE risk. SEER Sonorheometry and the Quantra will potentially allow for the ability to identify high risk patients based on parameters that more closely mimic in vivo hemostasis. The number of patients enrolled to date only allows for the observation of potential trends but there is a consistent increase in the clot stiffness as well as platelet and fibrinogen contributions in the patients' hemostatic balance as time progresses. Compared to using D-Dimer for predicting thrombotic risk, which is elevated at both time points, the Quantra parameters tended to be normal at the initial time point and increase over the 6 months to levels that exceeded the upper limit of normal for the assays. While this data suggests a trend toward increasing hypercoagulability with progressive chemotherapy cycles, more data is needed to confirm and understand the significance of these trends and to determine if SEER Sonorheometry and the Quantra can be used to identify those patients at highest risk for thrombosis. Disclosures Ferrante: Hemosonics: Employment. Viola:Hemosonics: Employment, Other: Shareholder.

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Adjuvant instant pre-operative renal artery embolization facilitates the radical nephrectomy and thrombectomy in locally advanced renal cancer with venous thrombus: A retrospective study of 54 cases

10.21203/rs.3.rs-28801/v1 ◽

2020 ◽

Author(s):

Guangxin Tang ◽

xiaoxu chen ◽

Jianwei Wang ◽

Wei He ◽

Zhihong Niu

Keyword(s):

Blood Loss ◽

Renal Artery ◽

Locally Advanced ◽

Operation Time ◽

Artery Embolization ◽

Venous Thrombus ◽

Estimated Blood Loss ◽

Transfusion Requirements ◽

Renal Artery Embolization ◽

The Mean

Abstract Background: The role of renal artery embolization (RAE) in the therapeutic armamentarium is always controversial. The present study aimed to assess the safety and the surgical outcomes of the instant renal artery embolization (I-RAE) prior to nephrectomy and thrombectomy in locally advanced renal cell carcinoma patients with venous thrombus.Methods: We performed a retrospective analysis of 54 patients treated with nephrectomy and thrombectomy between Jan 2012 and Jan 2019. Twenty-four patients were treated by I-RAE before surgery. Thirty patients were performed surgery alone (Non-RAE). The patient demographics, operation time, blood loss, transfusion requirements, complications and other surgical parameters were analyzed between the two groups.Results: The mean tumor size in I-RAE group was significantly larger than that in the Non-RAE group (11.1cm versus 7.9cm; p = .001). The mean estimated blood loss was significantly lower in I-RAE group compared to Non-RAE group (596ml versus 827ml; p = .015), and the patients in the Non-RAE group were more likely to receive blood transfusion (RBC units, 4U versus 6U, p = .025; plasma volume, 200ml versus 400ml, p = .01). No differences were found in operative duration, ICU stay, perioperative complications and length of postoperative hospitalization. Conclusions: The adjuvant instant pre-operative renal artery embolization (I-RAE) is a safe technique. It facilitates the nephrectomy and thrombectomy by reduction of blood loss, transfusion requirements and complication of delayed operation, providing the urologists with a reliable option for locally advanced RCC with tumor thrombus.

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