Acquired von Willebrand syndrome in ECMO patients: A 3-year cohort study

Panholzer, Bernd; Bajorat, Tido; Haneya, Assad; Kowalski, Dorothee; Juhl, David; Rocke, Angela; Shneyder, Maria; Kuta, Piotr; Clausnizer, Hartmut; Junker, Ralf; Kowalski, A.; Tulun, Aysun; Al-Suraimi, Akram; Cremer, Jochen; Kalbhenn, Johannes; Zieger, Barbara; Nowak‐Göttl, Ulrike

doi:10.1016/j.bcmd.2020.102526

Cited by 16 publications

(12 citation statements)

References 32 publications

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“…Bleeding is a leading cause of morbidity and mortality in ECMO patients [ 5 , 9 ]. Acquired von Willebrand syndrome (aVWS) contributes to the bleeding tendency observed in patients on ECMO support [ 4 , 24 ]. In the current study, we recruited thirteen ECMO patients with ECMO-induced aVWS.…”

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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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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“…Panholzer et al found that bleeding symptoms in ECMO patients occurred in 23% in combination with aVWD. 11 Start of the ECMO therapy induces changes in the coagulation system including low platelets, platelet function disorders, consumption of coagulation factors, and aVWD. However, these laboratory changes do not lead to clinically overt bleeding symptoms in all patients.…”

Section: Discussionmentioning

confidence: 99%

“…The acquired vWD is common in ECMO patients. Panholzer et al found that bleeding symptoms in ECMO patients occurred in 23% in combination with acquired vWD [11]. Start of the ECMO therapy induces changes in the coagulation system including low platelets, platelet function disorders, consumption of coagulation factors, and aVWD.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Considering the limited evidence, pediatric patients seem to have a milder clinical course and better prognosis of bleeding complications than adults, 9 but sepsis-induced coagulopathy is also frequently observed in critical ill pediatric patients. 10 Acquired von Willebrand disease (aVWD) is frequently diagnosed in ECMO patients 2 11 and gastrointestinal (GI) bleeding events are common. 12 Most likely high-molecular-weight multimers (HMWM) of von Willebrand factor (VWF) are damaged due to mechanical stress inside the ECMO circuit.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Acquired von Willebrand Disease due to Extracorporeal Membrane Oxygenation in a Pediatric COVID-19 Patient with Vonicog Alfa: A Case Report and Literature Review

Heubner

Trautmann

Tiebel

et al. 2023

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Acquired von Willebrand syndrome (aVWD) is frequently observed in patients with the need for extracorporeal membrane oxygenation (ECMO). aVWD can be treated by plasma-derived concentrates containing FVIII and/or VWF and recombinant vWF concentrate as well as adjuvant therapies such as tranexamic acid and desmopressin. However, all of these therapeutic options possibly cause thromboembolism. Therefore, the optimal treatment remains uncertain. This report presents a case of a 16 year old patient suffering from severe acute respiratory distress syndrome due to COVID-19 with the need of ECMO support. Our patient developed aVWD under ECMO-therapy characterized by loss of high-molecular-weight multimers (HMWM) and severe bleeding symptoms following endoscopic papillotomy due to sclerosing cholangitis. At the same time standard laboratory parameters showed hypercoagulability with increased fibrinogen level and platelet count. The patient was successfully treated with recombinant vWF concentrate (rvWF; vonicog alfa; Veyvondi®) combined with topic tranexamic acid application and cortisone therapy. AvWD is characterized by ultra-large multimers and absence of FVIII. Patient could be successfully weaned from ECMO-support after 72 days. Multimer analysis one week after ECMO-decannulation showed an adequate reappearance of HMWM.

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“…We hypothesized that, with its origin in endothelial cells, the vWF may play a central role in coagulopathies in vascular anomalies. We showed in our previous work that vWF and platelet function are disturbed by abnormal blood flow as exemplified in patients with ventricular assist devices (VAD) or extracorporeal membrane oxygenation (ECMO) [ 6 , 7 , 8 , 9 , 10 ]. In these devices, the high molecular weight multimers of vWF are lost leading to a reduction in the vWF activity and ratio.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analyses of Coagulation Parameters in Patients with Vascular Anomalies

et al. 2022

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Background: Vascular anomalies comprise a diverse group of rare diseases with altered blood flow and are often associated with coagulation disorders. The most common example is a localized intravascular coagulopathy in venous malformations leading to elevated D-dimers. In severe cases, this may progress to a disseminated intravascular coagulopathy with subsequent consumption of fibrinogen and thrombocytes predisposing to serious bleeding. A separate coagulopathy is the Kasabach–Merritt phenomenon in kaposiform hemangioendothelioma characterized by platelet trapping leading to thrombocytopenia and eventually consumptive coagulopathy. Our previous work showed impaired von Willebrand factor and platelet aggregometry due to abnormal blood flow, i.e., in ventricular assist devices or extracorporeal membrane oxygenation. With altered blood flow also present in vascular anomalies, we hypothesized that, in particular, the von Willebrand factor parameters and the platelet function may be similarly impacted. Methods: We prospectively recruited 73 patients with different vascular anomaly entities and analyzed their coagulation parameters. Results: Acquired von Willebrand syndrome was observed in both of our patients with Kasabach–Merritt phenomenon. In six out of nine patients with complex lymphatic anomalies, both the vWF antigen and activity were upregulated. Platelet aggregometry was impaired in both patients with Kasabach–Merritt phenomenon and in seven out of eight patients with an arteriovenous malformation. Conclusions: The analysis of coagulation parameters in our patients with vascular anomalies advanced our understanding of the underlying pathophysiologies of the observed coagulopathies. This may lead to new treatment options for the, in part, life-threatening bleeding risks in these patients in the future.

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Acquired von Willebrand syndrome in ECMO patients: A 3-year cohort study

Cited by 16 publications

References 32 publications

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 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

Treatment of Acquired von Willebrand Disease due to Extracorporeal Membrane Oxygenation in a Pediatric COVID-19 Patient with Vonicog Alfa: A Case Report and Literature Review

Comprehensive Analyses of Coagulation Parameters in Patients with Vascular Anomalies

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