Shear-stress induced acquired von Willebrand syndrome in children with congenital heart disease

Loeffelbein, Florian; Funk, D C; Nakamura, Lea; Zieger, Barbara; Grohmann, Jochen; Siepe, Matthias; Kroll, Johannes; Stiller, Brigitte

doi:10.1093/icvts/ivu305

Cited by 23 publications

(25 citation statements)

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“…The clinical significance of AVWS remains controversial. Some authors have observed very low rates of bleeding in patients with AVWS secondary to CPD (Casonato et al , ; Loeffelbein et al , ). Conversely, some authors have reported increased rates of post‐operative and intracranial bleeding in the setting of congenital heart disease and/or use of ventricular assist devices (Onimoe et al , ; Jones et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…In children, AVWS is probably under‐diagnosed in patients with congenital heart defects as it is not looked for and additionally usually resolves with correction of the underlying congenital heart defect. Within congenital heart defects, AVWS has been described with ventricular septal defects, aortic stenosis, pulmonary stenosis, coarctation of the aorta and persistent ductus arteriosus (Gill et al , ; Rauch et al , ; Loeffelbein et al , ; Avila et al , ; Cochran et al , ). In the setting of congenital or acquired heart defects, AVWS is caused by high‐shear lesions that result in uncoiling of the VWF, which then increases its susceptibility to proteolytic cleavage by ADAMTS‐13 (Tsai et al , ).…”

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confidence: 99%

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Idiopathic pulmonary arterial hypertension – a unrecognized cause of high‐shear high‐flow haemostatic defects (otherwise referred to as acquired von Willebrand syndrome) in children

et al. 2018

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Acquired von Willebrand syndrome (AVWS) is reported in high-flow high-shear congenital cardiac disorders. We hypothesized that the narrowed pulmonary vasculature in idiopathic pulmonary arterial hypertension (IPAH) may induce AVWS. We conducted a cross-sectional evaluation of children with IPAH. Patients with bleeding symptoms and/or laboratory abnormalities (thrombocytopenia, anomalies in coagulation screening tests) were tested in-depth for haemostatic defects. Fourteen children were followed with IPAH of which 8 were eligible. Four children exhibited abnormal bleeding scores (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool: 3-5). All 8 patients showed very prolonged platelet function analyser (PFA)-100 closure times. Six children demonstrated either mild thrombocytopenia or low-normal von Willebrand factor (VWF) antigen (VWF:Ag) or VWF activity [mean (range), in iu/dl: VWF:Ag: 70 (61-91); VWF activity: 57 (34-70)]. Average VWF collagen binding capacity (VWF:CB) was 64 iu/dl (range: 53-123 iu/dl), with low-normal VWF activity/VWF:Ag or VWF:CB/VWF:Ag ratios occurring in five patients. All children had normal multimers distribution patterns. One patient underwent a lung transplantation, with normalization of haemostatic abnormalities post-surgery. Overall, 8 out of 14 children with IPAH had mild to moderate bleeding symptoms and/or laboratory abnormalities in keeping with AVWS. Normalization of the haemostatic defects following lung transplantation and lack of family history of bleeding attests to the acquired nature of their defects.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Idiopathic pulmonary arterial hypertension – a unrecognized cause of high‐shear high‐flow haemostatic defects (otherwise referred to as acquired von Willebrand syndrome) in children

et al. 2018

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“…Loeffelbein et al . showed some evidence of a positive correlation between the severity of stenosis and the severity of HMWM decrease . In the context of congenital heart disease (CHD) aVWS has previously been reported to be associated with shear stress caused by patent arterial ducts (PDA) , ventricular septal defects and aortic or pulmonary valve stenosis .…”

Section: Introductionmentioning

confidence: 96%

“…To the best of our knowledge, no data on the incidence of intraoperative aVWS in pediatric patients with complex CHD have been reported so far. The finding that patients with severe stenosis require significantly higher quantities of red packed blood cells units (RBC) and fibrinogen concentrate intraoperatively as compared to patients with mild stenosis indicates that aVWS might contribute to the development of intraoperative bleeding. In adults, lower perioperative von Willebrand factor antigen (VWF:Ag) and VWF collagen binding capacity (VWF:CB) correlated with higher postoperative blood loss , confirming the important role of von Willebrand factor (VWF) in the primary hemostasis following cardiopulmonary bypass (CPB).…”

Section: Introductionmentioning

confidence: 99%

Acquired von Willebrand syndrome in congenital heart disease surgery: results from an observational case‐series

Icheva

Nowak-Machen²,

Budde

et al. 2018

Journal of Thrombosis and Haemostasis

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Essentials Bleeding complications during congenital heart disease surgery in neonatal age are very common. We report the perioperative incidence of acquired von Willebrand syndrome (aVWS) in 12 infants. aVWS was detected in 8 out of 12 neonates and infants intraoperatively after cardiopulmonary bypass. Ten patients received von Willebrand factor concentrate intraoperatively and tolerated it well. SUMMARY: Background Cardiac surgery of the newborn and infant with complex congenital heart disease (CHD) is associated with a high rate of intraoperative bleeding complications. CHD-related anatomic features such as valve stenoses or patent arterial ducts can lead to enhanced shear stress in the blood stream and thus cause acquired von Willebrand syndrome (aVWS). Objective To evaluate the intraoperative incidence and impact of aVWS after cardiopulmonary bypass (CPB) in neonates and infants with complex CHD. Patients/Methods We conducted a survey of patients aged < 12 months undergoing complex cardiac surgery in our tertiary referral center. Twelve patients, whose blood samples were analyzed for aVWS before CPB and immediately after discontinuation of CPB on a routine basis, were eligible for the analysis. von Willebrand factor antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo), collagen binding activity (VWF:CB), VWF:multimers and factor VIII activity (FVIII:C) were determined. Results aVWS was diagnosed by VWF multimer analysis in 10 out of 12 patients (83%) prior to surgery and intraoperatively at the end of CPB in 8 out of 12 patients (66%). Ten patients received VWF/FVIII concentrate intraoperatively as individual treatment attempts during uncontrolled bleeding. They tolerated it well without intraoperative thrombotic events. One patient suffered a transient postoperative cerebral sinuous vein thrombosis. Conclusions aVWS is of underestimated incidence in complex CHD surgery. These data may offer a new approach to reduce the risk of severe bleedings and to achieve hemostasis during high-risk pediatric cardiac surgery by tailoring the substitution with von Willebrand factor concentrate.

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“…Maurer et al reported decreased aggregation when platelets were exposed to platelet agonists (15). Furthermore, Bailly et al found patients with systolic flow abnormalities to have abnormal platelet function (16), which could be explained by the fact that CHD patients may develop acquired von Willebrand disease, known to affect platelet aggregation testing (17). Finally, CHD associated with other genetic disorders may also present with platelet dysfunction.…”

Section: Differences In the Coagulation System Of Chd Patientsmentioning

confidence: 99%

Risk Factors, Prophylaxis, and Treatment of Venous Thromboembolism in Congenital Heart Disease Patients

Silvey

Brandão

2017

Front. Pediatr.

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Congenital heart disease (CHD) is a common condition in the pediatric population, affecting up to 1% of all live births (i.e., around 40,000 newborns/year in the United States). Although CHD does have a wide range of severity, by the age of 5 years approximately 80% of patients will require at least one surgical intervention to achieve a complete/palliative cardiac repair. Today, in light of their much-improved surgical survival, the care of these patients focuses on morbidity prevention and/or treatment. One such morbidity has been the increased frequency of thrombotic occlusions [e.g., cardioembolic arterial ischemic strokes; arterial, cardiac, and/or newly created shunt thrombosis; venous thromboembolism (VTE)]. Patients with CHD are at high risk of developing thrombosis due to the disruption of blood flow, CHD-related coagulopathy, inflammation, and/or platelet activation secondary to extracorporeal circulation support required during open-heart surgery or as a bridge to recovery, which can increase thrombus formation. In this article, we will discuss how the coagulation system is altered in patients with CHD in regard to the patient’s anatomy, procedures they undergo to correct their congenital heart defect, and other risk factors that may increase their thrombotic risk, focusing on VTE. We will also discuss the most recently published reports pertaining to guidelines on prophylaxis and treatment of VTE in this population. Finally, we will briefly address the long-term VTE outcomes for patients with CHD.

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Shear-stress induced acquired von Willebrand syndrome in children with congenital heart disease

Abstract: AVWS is detected in half of the children with high intra- or extracardiac stenoses and resolves completely after surgical or interventional repair. Even when undergoing surgery on cardiopulmonary bypass, excessive surgical site bleeding was not detected in our study patients.

Cited by 23 publications

References 23 publications

Idiopathic pulmonary arterial hypertension – a unrecognized cause of high‐shear high‐flow haemostatic defects (otherwise referred to as acquired von Willebrand syndrome) in children

Idiopathic pulmonary arterial hypertension – a unrecognized cause of high‐shear high‐flow haemostatic defects (otherwise referred to as acquired von Willebrand syndrome) in children

Acquired von Willebrand syndrome in congenital heart disease surgery: results from an observational case‐series

Risk Factors, Prophylaxis, and Treatment of Venous Thromboembolism in Congenital Heart Disease Patients

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