Abstract Number: PB1118
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Management of Bleeding and Trauma
Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei (PMP) is associated with excessive bleeding and acquired fibrinogen deficiency. The FORMA-05 study indicated that human fibrinogen concentrate (HFC) is non-inferior to cryoprecipitate for achieving hemostatic efficacy in bleeding patients with acquired fibrinogen deficiency undergoing CRS for PMP.
Aims: This sub-analysis of the FORMA-05 study explores interoperative and postoperative coagulation profiles in patients undergoing CRS for PMP.
Methods: FORMA-05 was a single-center, prospective, randomized, controlled Phase 2 study. Patients undergoing CRS with predicted intraoperative blood loss ≥2L received either HFC (4g), or cryoprecipitate (2 pools of 5 units, approximately 4.0-4.6g fibrinogen), repeated as needed. Plasma fibrinogen concentration (Clauss assay) and FIBTEM A20 were measured hourly intraoperatively, while factor XIII (FXIII), factor VIII (FVIII), von Willebrand Factor (VWF) and endogenous thrombin potential (ETP) were measured every two hours. Post-surgery, all parameters were measured at 6, 12, 24 and 48 hours, and 10 days.
Results: The analysis included 45 patients randomized to receive HFC (n=22) or cryoprecipitate (n=23). Table 1 shows the intraoperative and postoperative changes in ETP, FXIII, FVIII and VWF. Table 2 shows the changes in FIBTEM A20 and fibrinogen concentration. Both groups had comparable plasma fibrinogen levels at baseline and 1 hour after surgery start, while from 2 hours after surgery start, intraoperative and postoperative mean values appeared numerically higher with HFC than cryoprecipitate. Activated partial thromboplastin time, prothrombin time and platelet count were maintained throughout surgery in both groups.
Conclusions: The FORMA-05 coagulation parameter analyses showed broad overlap between HFC and cryoprecipitate with satisfactory maintenance of clot quality, FXIII and thrombin generation parameters in both treatment groups. Together with the FORMA-05 efficacy results, this demonstrates HFC can correct for loss, consumption and dilution of fibrinogen in patients undergoing CRS for PMP.
| Parameter | Treatment group | Baseline mean (SD) | Intra-operative 2 h after surgery start, mean (SD) | Intra-operative 6 h after surgery start, mean (SD) | End of surgery mean, (SD) | 2 days after end of surgery, mean (SD) | 10 days after end of surgery, mean (SD) |
| Endogenous thrombin potential (nmol/L/min) | HFC | 1514.5 (430.6) | 1673.5 (340.1) | 1310.7 (171.2) | 1225.4 (220.7) | 1263.4 (176.9) | 1426.2 (260.4) |
| Endogenous thrombin potential (nmol/L/min) | Cryoprecipitate | 1639.1 (339.1) | 1690.2 (320.2) | 1260.7 (342.2) | 1346.4 (243.6) | 1385.6 (301.6) | 1357.0 (349.5) |
| Factor XIII:C (%) | HFC | 121.86 (27.32) | 80.09 (27.60) | 53.31 (16.16) | 55.28 (22.28) | 48.05 (16.86) | 65.54 (18.58) |
| Factor XIII:C (%) | Cryoprecipitate | 115.55 (29.52) | 71.63 (23.63) | 60.27 (15.26) | 62.97 (13.42) | 50.60 (13.44) | 65.00 (14.31) |
| Factor VIII:C (%) | HFC | 152.21 (53.61) | 155.50 (90.60) | 130.70 (50.14) | 121.89 (54.50) | 278.84 (57.74) | 313.88 (84.16) |
| Factor VIII:C (%) | Cryoprecipitate | 136.73 (40.90) | 123.61 (50.68) | 120.63 (48.36) | 116.99 (39.50) | 242.78 (54.59) | 331.19 (102.22) |
| Von Willebrand factor antigen (IU/dL) | HFC | 144.43 (65.58) | 144.07 (61.05) | 145.01 (50.99) | 138.52 (54.51) | 253.97 (59.91) | 320.41 (88.32) |
| Von Willebrand factor antigen (IU/dL) | Cryoprecipitate | 140.95 (49.59) | 137.56 (52.21) | 167.56 (52.61) | 174.21 (56.23) | 260.46 (72.54) | 301.54 (92.71) |
[Table 1]
| Parameter | Treatment group | Baseline mean (SD) | Intra-operative 2 h after surgery start, mean (SD) | Intra-operative 6 h after surgery start, mean (SD) | End of surgery mean, (SD) | 2 days after end of surgery, mean (SD) | 10 days after end of surgery, mean (SD) |
| FIBTEM A20 (mm) | HFC | 29.77 (10.65) | 18.59 (6.05) | 13.06 (3.80) | 11.67 (2.69) | 28.10 (4.28) | 50.10 (11.70) |
| FIBTEM A20 (mm) | Cryoprecipitate | 26.04 (12.09) | 15.30 (6.94) | 10.60 (4.21) | 11.48 (3.78) | 29.32 (5.89) | 54.27 (14.23) |
| Plasma fibrinogen concentration (g/L) | HFC | 4.79 (1.31) | 3.20 (0.72) | 2.34 (0.61) | 2.21 (0.52) | 5.47 (0.83) | 6.62 (1.48) |
| Plasma fibrinogen concentration (g/L) | Cryoprecipitate | 4.50 (1.50) | 2.67 (0.98) | 1.91 (0.54) | 2.08 (0.56) | 5.24 (0.82) | 6.48 (1.69) |
[Table 2]
To cite this abstract in AMA style:
Roy A, Sargant N, Solomon C, Kruzhkova I, Knaub S, Mohamed F. Comparison of Coagulation Parameters Associated with Fibrinogen Concentrate and Cryoprecipitate for Treatment of Bleeding in Patients Undergoing Cytoreductive Surgery for Pseudomyxoma Peritonei: Results from the FORMA-05 Study [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/comparison-of-coagulation-parameters-associated-with-fibrinogen-concentrate-and-cryoprecipitate-for-treatment-of-bleeding-in-patients-undergoing-cytoreductive-surgery-for-pseudomyxoma-peritonei-resul/. Accessed January 28, 2022.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/comparison-of-coagulation-parameters-associated-with-fibrinogen-concentrate-and-cryoprecipitate-for-treatment-of-bleeding-in-patients-undergoing-cytoreductive-surgery-for-pseudomyxoma-peritonei-resul/