In Vitro Comparison of Recombinant and Plasma-Derived von Willebrand Factor Concentrate for Treatment of Acquired von Willebrand Syndrome in Adult Extracorporeal Membrane Oxygenation Patients

Abstract

BACKGROUND: Coagulopathic bleeding is common during adult extracorporeal membrane oxygenation (ECMO), and acquired von Willebrand syndrome is a contributing factor. We compared ECMO patient blood samples that were treated in vitro with recombinant von Willebrand Factor concentrate and plasma-derived von Willebrand Factor concentrate. Our hypothesis was that recombinant von Willebrand Factor (vWF) would have greater efficacy in increasing vWF function. Secondarily, we hypothesized that recombinant vWF would have less impact on thrombin generation. METHODS: Thirty ECMO patients and 10 cardiac surgical controls were enrolled in the study. ECMO patient blood samples were treated in vitro with low-and high-dose recombinant vWFs and low-and high-dose plasma-derived vWFs. Whole blood ristocetin-induced platelet aggregation (RIPA), plasma ristocetin cofactor activity (RCo), and thrombin generation were compared between ECMO patient blood samples and control blood samples and between vWF-treated ECMO patient blood samples and nontreated samples. RESULTS: ECMO patient blood samples had severely reduced median RIPA compared to control samples 2 ohms (1-12 [25th-75th percentile]) vs 20 ohms (11-42) (P < .001). Treatment of ECMO patient blood samples with high-dose recombinant vWF significantly increased median RIPA to 10 ohms (2-15) (P < .001), while low-dose recombinant vWF and low-and high-dose plasma-derived vWFs did not significantly increase RIPA; 6 ohms (3-14), 4 ohms (1-13), and 6 ohms (2-10), respectively (P = .25, >.99, and >.99). Treatment with high-dose recombinant vWF and low-and high-dose plasma-derived vWFs significantly increased median plasma RCo to 4.7 international units (IU)/mL (3.7-5.9), 3.3 IU/mL (2.7-4.8), and 3.9 IU/mL (3.4-5.3), respectively, compared to controls 1.8 IU/mL (1.5-2.3) (all P < .001). Treatment with low-and high-dose plasma-derived vWFs significantly increased mean endogenous thrombin potential (6270.2 ± 2038.7 and 6313.1 ± 1913.3) compared to nontreated samples (5856.7 ± 1924.6) (P = .04 and .006), whereas treatment with low-and high-dose recombinant vWFs had no significant effect on mean endogenous thrombin potential (5776.1 ± 2087.3 and 5856.2 ± 1946.4) (P > .99 for both comparisons). CONCLUSIONS: In vitro treatment of ECMO patient blood samples with high-dose recombinant vWF was superior to low-dose recombinant vWF and plasma-derived vWF in terms of improving RIPA. In addition, recombinant vWF treatment did not increase endogenous thrombin potential, which may reduce overall thrombotic risk if it used to treat acquired von Willebrand syndrome in ECMO patients. (Anesth Analg 2022;134:312-21) KEY POINTS• Question: Does in vitro treatment of extracorporeal membrane oxygenation (ECMO) patient blood samples with recombinant and plasma-derived von Willebrand Factor (vWF) concentrate equally improve ristocetin-induced platelet aggregation (RIPA)? • Findings: In vitro treatment of ECMO patient blood samples with high-dose recombinant vWF concentrate, but not low-dose recombinant or plasm...

The effect of recombinant versus plasma-derived von Willebrand factor on prolonged PFA closure times in ECMO patients with acquired von Willebrand syndrome – an observational study

“…The rVWF contains ultra-large (UL) VWF multimers because it has not been in contact with ADAMTS13. Our findings are in line with a recently published comparison of rVWF and pVWF in ECMO patients that showed a better effect of rVWF on ristocetin-induced platelet aggregation (RIPA) [ 33 ].…”

Forget-Me-Not: The Primary Hemostasis Defect in Extracorporeal Membrane Oxygenation May Require Unique Treatment

“…We recognize that future clinical trials are needed to improve clinical diagnosis of acquired vWS, determine optimal vWF concentrate dosing, as well as its efficacy and safety in ECMO patients. We also believe based on our prior in vitro work 5…”

“…We recognize that future clinical trials are needed to improve clinical diagnosis of acquired vWS, determine optimal vWF concentrate dosing, as well as its efficacy and safety in ECMO patients. We also believe based on our prior in vitro work 5 that vWF concentrate may have an important role in treating coagulopathic bleeding during ECMO and is worth further study in Phase 1 clinical trial.…”

“…4 Treatment with both plasma-derived and recombinant vWF concentrate improves in vitro platelet adhesion with recombinant vWF having a greater effect because of its ultra-large multimer content. 5 Although, treatment with vWF concentrate carries risk, it is also more likely to restore primary hemostasis than allogeneic transfusion alone. We recognize that future clinical trials are needed to improve clinical diagnosis of acquired vWS, determine optimal vWF concentrate dosing, as well as its efficacy and safety in ECMO patients.…”

Shear-induced acquired von Willebrand syndrome: an accomplice of bleeding events in adults on extracorporeal membrane oxygenation support

“…In clinical practice ( 72 ), a 40 IU/kg dose of VWF concentrate can effectively improve VWF function in adult ECMO patients with AVWS. Meanwhile, this team ( 73 ) further demonstrated an in vitro test that high-dose (0.8 IU/ml) recombinant VWF may have an obvious effect on normal VWF function in ECMO patients and a minimal thrombotic risk compared to plasma-derived VWF concentration. So, we can choose the optimal type of VWF concentration according to the actual situation in clinical practice.…”