Von Willebrand Factor Concentrate Administration for Acquired Von Willebrand Syndrome- Related Bleeding During Adult Extracorporeal Membrane Oxygenation

Mazzeffi, Michael; Bathula, Allison; Tabatabai, Ali; Menaker, Jay; Kaczorowski, David J.; Madathil, Ronson J.; Galvagno, Samuel M.; Pasrija, Chetan; Rector, Raymond; Tanaka, Kenichi A.; Herr, Daniel

doi:10.1053/j.jvca.2020.06.083

Cited by 17 publications

(14 citation statements)

References 21 publications

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“…All patients, except 1, had peripheral cannulation. The median day of blood sampling was ECMO day 7 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), median pump speed was 3258 (2901-3556) revolutions per minute, and median ECMO circuit blood flow was 4.1 liters per minute (3.5-5). Mean platelet count was 134 ± 83 10 9 /L.…”

Section: Resultsmentioning

confidence: 99%

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

Mazzeffi

Henderson

Krause

et al. 2022

Anesthesia &Amp; Analgesia

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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...

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Section: Resultsmentioning

confidence: 99%

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

Mazzeffi

Henderson

Krause

et al. 2022

Anesthesia &Amp; Analgesia

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“…If their values are low (ratio <0.7) and bleeding is severe, treatment with desmopressin or VWF concentrate is appropriate. 111 VWF concentrate can be given as a 40 IU per kg dose, but caution should be exercised if a plasma-derived concentrate is used because factor VIII can increase thrombotic risk. 111 There are case series and multiple case reports of using recombinant-activated factor VII in ECMO patients with severe bleeding, but caution should be exercised, particularly in patients with minimal cardiac ejection, as fatal intracardiac or intrapulmonary thrombosis can occur.…”

Section: Consensus Statementmentioning

confidence: 99%

“…111 VWF concentrate can be given as a 40 IU per kg dose, but caution should be exercised if a plasma-derived concentrate is used because factor VIII can increase thrombotic risk. 111 There are case series and multiple case reports of using recombinant-activated factor VII in ECMO patients with severe bleeding, but caution should be exercised, particularly in patients with minimal cardiac ejection, as fatal intracardiac or intrapulmonary thrombosis can occur. [112][113][114] The optimal hemoglobin target during ECMO is not known, but using a transfusion threshold of 8 g/dL is associated with comparable outcomes when compared to 10 g/dL.…”

Section: Consensus Statementmentioning

confidence: 99%

Intraoperative Management of Adult Patients on Extracorporeal Membrane Oxygenation: An Expert Consensus Statement From the Society of Cardiovascular Anesthesiologists—Part II, Intraoperative Management and Troubleshooting

Mazzeffi

Rao

Dodd‐o

et al. 2021

Anesthesia &Amp; Analgesia

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In the second part of the Society of Cardiovascular Anesthesiologists Extracorporeal Membrane Oxygenation (ECMO) working group expert consensus statement, venoarterial (VA) and venovenous (VV) ECMO management and troubleshooting in the operating room are discussed. Expert consensus statements are provided about intraoperative monitoring, anesthetic drug dosing, and management of intraoperative problems in VA and VV ECMO patients.

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“…Critically ill patients with COVID-19 require ECMO relatively often if an acute respiratory distress syndrome develops [ 36 ]. It has recently been shown that pVWF concentrates were able to enhance VWF activity in ECMO-induced aVWS patients [ 37 ]. The mean VWF ristocetin cofactor activity to antigen ratio increased after treatment but was not normalized.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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Background Extracorporeal membrane oxygenation (ECMO) is applied in patients with respiratory or cardiopulmonary failure, but bleeding is a frequent complication contributing to the high mortality rates in this patient collective. A major factor predisposing patients to bleeding events is an acquired von Willebrand syndrome (aVWS). So far, specific treatment options for this phenomenon are lacking. In hereditary von Willebrand disease (VWD), treatment with recombinant or plasma-derived von Willebrand factor (rVWF or pVWF) is common practice. Closure time measured by the Platelet Function Analyser-200 (PFA-200) is an established assay to detect defects in primary hemostasis and the method is useful to monitor the effect of hemostatic therapy. The aim of this study was to assess the effect of recombinant (rVWF) vs. plasma-derived von Willebrand factor (pVWF) on closure times measured by PFA in blood obtained from ECMO patients with aVWS. Methods Blood was sampled from thirteen patients receiving extracorporeal membrane oxygenation and three patients with hereditary VWD. Diagnosis of aVWS was made by conventional coagulation parameters and by multimeric structure analysis. PFA analysis of blood spiked with rVWF or pVWF was performed. Results Thirteen patients receiving ECMO were recruited. Ten patients survived and three patients suffered major bleeding complications. PFA closure times in ECMO patients with aVWS spiked with rVWF were significantly shorter at all concentrations than with pVWF (e.g., rVWF vs. pVWF: 1 U/ml: 150.4 ± 21.7 s vs. 263.8 ± 11.7 s; 4 U/ml: 97.8 ± 9.8 s vs. 195.8 ± 15.4 s, p<0.001). PFA closure times were also significantly shorter in three patients with hereditary VWD treated with rVWF compared to pVWF (e.g., 1 U/ml rVWF vs. pVWF: 73.7±1.33 s vs. 231.3±43.4 s, p<0.01) Conclusion In summary, this study shows that rVWF compared to pVWF more effectively reduced PFA closures times in blood samples of ECMO patients with aVWS. Higher doses of VWF are needed to normalize PFA closure time in blood samples of patients with ECMO-induced aVWS compared to hereditary VWD. These data support the use of PFA-200 to monitor hemostatic effects in a future clinical trial involving ECMO patients with aVWS.

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Von Willebrand Factor Concentrate Administration for Acquired Von Willebrand Syndrome- Related Bleeding During Adult Extracorporeal Membrane Oxygenation

Cited by 17 publications

References 21 publications

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

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

Intraoperative Management of Adult Patients on Extracorporeal Membrane Oxygenation: An Expert Consensus Statement From the Society of Cardiovascular Anesthesiologists—Part II, Intraoperative Management and Troubleshooting

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

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