Misleading antigenic von Willebrand factor levels in acquired von Willebrand syndrome secondary to monoclonal gammopathy of undetermined significance.

In the diagnosis and treatment of acquired von Willebrand syndrome (AVWS), von Willebrand factor (VWF) antigen levels (VWF:Ag) are helpful for quantifying blood VWF-protein levels. Most clinical laboratories measure VWF:Ag by latex immunoassay (LIA), but underlying diseases of AVWS may influence LIA results. A 60 year-old AVWS patient with immunoglobulin G (IgG) kappa-type monoclonal gammopathy of undetermined significance (MGUS) showed reduced VWF activity but normal levels of VWF:Ag. His VWF multimers were broadly decreased, which represented a large discrepancy with VWF:Ag. To investigate the mechanism of this discrepancy, we measured the patient's plasma VWF:Ag by in-house enzyme-linked immunosorbent assay (ELISA) and LIA. We also purified the IgG fraction from the patient's serum and measured VWF:Ag in VWF-deficient plasma supplemented with this fraction. VWF:Ag measured by in-house ELISA (VWF:AgELISA) was much lower than that measured by LIA (VWF:AgLIA), which indicated reduced VWF-protein volume in blood. Indeed, VWF:Ag was detected by LIA in VWF-deficient plasma spiked with a patient-derived IgG fraction. These results suggest that LIA detected a non-specific immunoreaction and overestimated the patient's VWF:AgLIA. Clinicians should be aware that underlying diseases of AVWS could influence the LIA system, and interpret VWF:Ag cautiously.

Efficacy and safety of a recombinant von Willebrand factor treatment in acquired von Willebrand syndrome in case of bleeding and surgical procedures.

INTRODUCTION: Acquired von Willebrand syndrome (AVWS) is a rare haemorrhagic disorder. The prophylaxis and treatment of bleeding before surgery are complex. Since 2018, a new recombinant VWF (rVWF) concentrate that contains no factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France. AIM: To describe the real-world experience of using rVWF in non-surgical bleeding and surgical procedures in patients with AVWS. METHODS: Fifteen bleeding episodes in seven patients and 16 surgeries in 10 patients were retrospectively analysed in t French haemostasis centres. RESULTS: During bleeding, the median number of infusions was only 1 (range 1-27) with a median loading dose of 58 IU/kg (range 17-116) rVWF and a total median dose of 65 IU/kg (range 35-1488) rVWF. Bleeding control was rated markedly effective in 73% (11/15) of the cases and ineffective in 27% (4/15). During surgeries, the median number of infusions was 3 (range 1-8) with a preoperative loading dose of 60 IU/kg (range 23-118) rVWF and a total median dose of 123 IU/kg (range 31-542). The overall clinical efficacy was qualified as excellent, good and poor (ISTH criteria) in respectively 7 (43%), 6 (38%) and 3 (19%) procedures. There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events nor adverse events were reported. CONCLUSION: This French 'real-world' experience shows that rVWF could be of interest in the treatment and prophylaxis of bleeding in patients with AVWS, with no clinically significant safety concern.

Thrombocytopenia and Bleeding in Chronic Kidney Disease: A Case of Acquired Von Willebrand Syndrome.

Acquired von Willebrand disease is a rare condition with laboratory findings similar to the inherited type, which can be autosomal dominant or recessive. This case describes a rather rare clinical situation of a 65-year-old man with stage 4 chronic kidney disease who also had acquired von Willebrand syndrome (AvWS) with thrombocytopenia and bleeding. The patient had a complaint of easy fatigability, easy bruising, and prolonged bleeding from small cuts. The patient's initial laboratory workup included thrombocytopenia, which on further evaluation established the diagnosis of AvWS due to chronic kidney disease. More specific examination revealed reduced activity of the von Willebrand factor. The patient was managed with desmopressin and von Willebrand factor concentrates and there was a transient rise in platelet count and relief of symptoms of bleeding. This case underlines the importance of AvWS in any differential diagnosis of thrombocytopenia in patients with chronic kidney disease. This report aims to provide recommendations for early identification and management of AvWS to improve the outcome.

A rare case of acquired von Willebrand syndrome type 2B: diagnosis, treatment, and underlying pathophysiology.

Background: Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that usually mimics type 1 or 2A von Willebrand disease (VWD). Key Clinical Question: Can AVWS mimic the phenotype of type 2B VWD? Clinical Approach: A 64-year-old male patient presented with thrombocytopenia, normal routine hemostasis results, and normal VWF antigen and factor VIII levels but reduced von Willebrand factor (VWF) activity (31 IU/dL). The ristocetin-induced platelet aggregation test showed paradoxical aggregation at low doses of ristocetin, suggesting type 2B VWD, but no deleterious sequence variation was found in either the VWF or GP1BA genes, compatible with AVWS. Serum protein electrophoresis revealed a monoclonal immunoglobulin G antibody. Conclusion: This AVWS with a 2B phenotype VWD was probably related to a monoclonal immunoglobulin G antibody causing a VWF conformational change, resulting in increased affinity to platelet glycoprotein-Ib. In the event of surgery or bleeding, treatment with vonicog alfa seems to be the best option for this patient.

[Evaluation of a semi-automated test for quantification of von Willebrand multimers]. / Évaluation d'un test semi-automatisé de quantification des multimères du facteur von Willebrand.

The assessment of von Willebrand factor (VWF) multimer distribution, particularly following the implantation of circulatory support devices, is a crucial parameter in hemostasis. Our study aimed to evaluate the semi-automated quantification of VWF multimers using the Sebia Hydrasys analyzer. Our analysis focused on quantifying high molecular weight, intermediate weight, and low molecular weight VWF multimers. Electrophoretic migration was performed using the Hydrasys 2 scan, and interpretation was carried out using densitometric analysis with the Phoresis software. The Hydrasys scan 2 successfully separated all the expected VWF multimer profiles based on the type of von Willebrand disease. The analysis revealed that in patients with circulatory support devices, elevated levels of plasma VWF rendered multimer migration unanalyzable using the methodology recommended by the manufacturer. Therefore, adjustment to a 100 % VWF antigenic level improved gel precision. We also suggest using as a standardized control the Cryocheck™ plasma, and have established reference values. Overall, this semi-automated, standardized, and optimized VWF multimer analysis system allows for an effective assessment of the VWF multimeric profile.

Acquired von Willebrand syndrome during extracorporeal membrane oxygenation support: a comprehensive review of current evidence: communication from the ISTH SSC on perioperative and critical care thrombosis and hemostasis.

During extracorporeal membrane oxygenation (ECMO) support, the high shear stress in the ECMO circuit results in increased proteolysis of von Willebrand factor (VWF), loss of VWF high-molecular-weight multimers, and impaired ability to bind to platelets and collagen. These structural changes in VWF are consistent with acquired von Willebrand syndrome (AVWS) type 2A and may contribute to the bleeding diathesis frequently observed in ECMO patients. We performed a systematic review of all clinical studies evaluating the prevalence and associated outcomes of AVWS in ECMO patients. Our findings suggest that almost all ECMO patients develop partial or complete loss of VWF high-molecular-weight multimers within a few hours of device implantation. The AVWS persists as long as the patient is supported by ECMO. Weaning from ECMO rapidly and completely resolves the AVWS. Nevertheless, few studies have reported bleeding outcomes in ECMO patients with AVWS, and the extent to which AVWS contributes to the bleeding diathesis during ECMO support cannot be determined by current evidence. Data supporting the use of VWF concentrates to prevent bleeding complications in ECMO patients remain limited.

Acquired von Willebrand Syndrome in a 17-Year-Old With Essential Thrombocythemia: A Case Report With Literature Review.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that is often underdiagnosed. AVWS typically occurs in adults without a family history of bleeding disorders and with associated conditions such as lymphoproliferative, myeloproliferative, and cardiovascular disorders. Here, we present a case of AVWS in a young patient with essential thrombocythemia and a literature review on AVWS in the setting of essential thrombocythemia.

Acquired von Willebrand Syndrome Associated with a Smoldering Multiple Myeloma, Successfully Treated by Daratumumab, Lenalidomide, and Dexamethasone.

INTRODUCTION: Acquired von Willebrand syndrome (AvWS) is a rare entity with approximately 700 cases described in the literature. A number of etiologies are responsible for this condition, mainly lymphoproliferative, myeloproliferative syndromes and cardiac diseases. Management is aimed at preventing and treating bleeds, as well as treating the underlying pathology. In the case of a monoclonal gammopathy, there are limited evidence and high heterogeneity only based on old case reports, resulting in poor quality recommendations. It seems essential in 2023 to take into account and offer the new anti-myeloma treatments available. CASE PRESENTATION: We describe the case of a patient with an AvWS secondary to an IgG smoldering multiple myeloma, experiencing multiple bleeding, treated successfully with daratumumab, lenalidomide, and dexamethasone, after multiple treatment failure. CONCLUSION: Daratumumab, lenalidomide, and dexamethasone was demonstrated as a rapid and effective treatment for a patient with severe AvWS and multiple bleeding complications.

Acquired von Willebrand syndrome in a patient with monoclonal gammopathy of unknown significance: A case report.

Monoclonal gammopathy of uncertain significance associated acquired von Willebrand syndrome is a serious bleeding condition driven by immunological clearance of von Willebrand factor and has limited treatment options. We present a patient who achieved durable remission through eradication of the monoclonal paraprotein with clonal directed therapy with bortezomib.

Acquired von Willebrand syndrome and post-operative drainage: a comparison of patients with aortic stenosis versus coronary artery disease.

OBJECTIVE: Degenerative aortic stenosis and coronary artery disease are considered to be the most prevalent cardiovascular diseases in industrialized countries. This study aims to determine the change over time in von Willebrand factor antigen, von Willebrand factor activity, and factor VIII and where there is a correlation with total post-operative drainage. METHODS: The single-center retrospective study included 203 consecutive patients (64.5% male), undergoing coronary artery bypass surgery between March 1, 2019 and June 30, 2020 at the University Clinical Center of Serbia in the Clinic for Cardiac Surgery in Belgrade, Serbia. All patients 18 years or older who presented with isolated, hemodynamically significant aortic stenosis were included. The control group consisted of patients who presented with only coronary artery disease. RESULTS: Between patients with only coronary artery disease and patients with coronary artery diseases and aortic stenosis, there was a statistically significant difference between pre-op and 1-month post-op fibrinogen, factor VIII, von Willebrand factor antigen, and von Willebrand factor (p < 0.001), post-op drainage, with overall lower drainage in coronary artery disease patients, and consistent increase in von Willebrand factor antigen, von Willebrand factor activity, and Factor VIII post-operatively in patients with coronary artery diseases and aortic stenosis. CONCLUSION: This study has shown that there is a correlation between von Willebrand factor antigen, von Willebrand factor activity and total drainage to the level of statistical significance in aortic stenosis patients and in the overall study population.

Acquired von Willebrand's Syndrome in a Patient with Concomitant Chronic Lymphocytic Lymphoma and Smoldering Multiple Myeloma.

An African-American female in her sixties presented to the hospital with intermittent gum bleeding for the past two years along with severe anemia. This case details the differential and workup that lead to the diagnosis of acquired von Willebrand's syndrome (AvWS). A thorough investigation in the possible etiologies of AvWS revealed that the patient had concomitant chronic lymphocytic lymphoma (CLL) and smoldering multiple myeloma (SMM). Due to the concomitant diagnosis of CLL and SMM, there was a dilemma regarding whether CLL, SMM, or both was driving this patient's AvWS. Decision was made to treat the underlying CLL initially with rituximab and later on at recurrence with obinutuzumab/venetoclax with complete resolution of patient's bleeding and normalization of her factor VIII activity, von Willebrand factor antigen levels, and vWF:ristocetin cofactor levels. We believe this is first case in the literature of a patient with AvWS with concurrent CLL and SMM.

von Willebrand factor Ristocetin co-factor activity to von Willebrand factor antigen level ratio for diagnosis of acquired von Willebrand syndrome caused by aortic stenosis.

Background: Severe aortic stenosis (AS) causes acquired von Willebrand syndrome by the excessive shear stress-dependent cleavage of high molecular weight multimers of von Willebrand factor (VWF). While the current standard diagnostic method is so-called VWF multimer analysis that is western blotting under nonreducing conditions, it remains unclear whether a ratio of VWF Ristocetin co-factor activity (VWF:RCo) to VWF antigen levels (VWF:Ag) of <0.7, which can be measured with an automated coagulation analyzer in clinical laboratories and is used for the diagnosis of hereditary von Willebrand disease. Objectives: To evaluated whether the VWF:RCo/VWF:Ag is useful for the diagnosis of AS-induced acquired von Willebrand syndrome. Methods: VWF:RCo and VWF:Ag were evaluated with the VWF large multimer index as a reference, which represents the percentage of a patient's VWF high molecular weight multimer ratio to that of standard plasma in the VWF multimer analysis. Results: We analyzed 382 patients with AS having transaortic valve maximal pressure gradients of >30 mmHg, 27 patients with peripheral artery disease, and 46 control patients free of cardiovascular disease with osteoarthritis, diabetes, and so on. We assumed a large multimer index of <80% as loss of VWF large multimers since 59.0% of patients with severe AS had the indices of <80%, while no control patients or patients with peripheral artery disease, except for 2 patients, exhibited the indices of <80%. The VWF:RCo/VWF:Ag ratios, measured using an automated blood coagulation analyzer, were correlated with the indices (rs = 0.470, P < .001). When the ratio of <0.7 was used as a cut-off point, the sensitivity and specificity to VWF large multimer indices of <80% were 0.437 and 0.826, respectively. Conclusion: VWF:RCo/VWF:Ag ratios of <0.7 may indicate loss of VWF large multimers with high specificity, but low sensitivity. VWF:RCo/VWF:Ag ratios in patients with AS having a ratio of <0.7 may be useful for monitoring the loss of VWF large multimers during their clinical courses.

The left ventricular assist device: a literature review and guidelines for dental care.

About 6.2 million adults in the United States suffer from heart failure (HF). For patients with advanced HF refractory to medical therapy, an orthotopic heart transplant or a ventricular assist device (VAD) is the only long-term survival option. The most commonly used form of these devices is the left VAD (LVAD), implanted to support the left ventricle. As many as 2754 LVADs were implanted annually between 2006 and 2015, allowing recipients to maintain a relatively normal lifestyle, including both elective and emergency dental care in the ambulatory setting. As more LVADs are implanted, oral healthcare providers (OHCPs) are more likely to encounter these patients in an outpatient clinical setting. This study aims to educate OHCPs on the specific needs of these patients and to begin development of clinical guidelines for their dental management. A literature review using electronic resources was conducted to identify all literature relevant to the clinical topic. Appropriate literature was selected based on established inclusion and exclusion criteria, and 3 articles published between 2015 and 2020 were identified. None offered clinical practice guidelines for the care of patients with implanted LVADs. However, it is known that patients supported by an LVAD are at higher risk of thrombotic complications, which can lead to pump system failure and embolic stroke. To reduce the risk of complications, these patients are treated with anticoagulation therapy. Interruption of these drugs prior to dental treatment is not recommended. Due to the side effects of anticoagulation therapy and acquired coagulopathy, patients with an LVAD are also at increased risk of bleeding events. Thus, perioperative hemorrhagic risk during routine oral surgical procedures must be considered. While most dental care can be done in an outpatient setting, OHCPs should be aware of the special needs of these patients and provide appropriate care through close coordination with the LVAD/transplant team.

The Influence of Hypothyroid Metabolic Status on Blood Coagulation and the Acquired von Willebrand Syndrome.

The intent of this prospective study aimed to identify the influence of hypothyroid metabolic status on the coagulation and fibrinolytic system and association with the acquired von Willebrand syndrome (VWS-ac). We compared 54 patients without substitution therapy after radical thyroidectomy with 58 control subjects without pathological thyroid-stimulating-hormone (TSH)-values. Patients with TSH > 17.5 mU/L over a period of >4 weeks were included. The control-collective was selected based on age and sex to match the patient-collective. The data were collected using laboratory coagulation tests and patient questionnaires; a bleeding score was determined. There were significant differences in the measurement of activated-partial-thromboplastin-time (aPTT/p = 0.009), coagulation-factor VIII (p < 0.001) and von-Willebrand-activity (VWF-ac/p = 0.004) between the patient and control groups. The patient cohort showed an increased aPTT and decreased factor VIII and VWF-ac. 29.7% of the patient-collective compared to 17.2% of the control subjects met the definition of VWS-Ac (p = 0.12). The bleeding score showed significantly more bleeding symptoms in patients with a laboratory constellation of VWS-ac (no family history; p = 0.04). Our results suggest hypocoagulability in hypothyroid patients. Hypothyroidism appears to have a higher incidence of VWS-ac. The increased risk of bleeding complications in hypothyroid patients may be of relevant importance for the outcome, especially in the context of invasive interventions.

Development of an in-vitro model for extracorporeal blood pumps to study the effects of artificial pulsatility on human blood.

Introduction: The application of extracorporeal circulation (ECC) systems is known to be associated with several implications regarding hemolysis, inflammation, and coagulation. In the last years, systems with pulsatile blood flow are increasingly used with the intention to improve hemodynamics in reperfusion. However, their implications on the aforementioned aspects remain largely unknown. To investigate the effects of pulsatility, this ex-vivo study was initiated. Methods: Test circuits (primed with human whole blood) were set up in accordance with the recommendations of international standards for in-vitro evaluation of new components and systems of ECC. Diagonal pumps were either set up with non-pulsatile (n = 5, NPG) or pulsatile (n = 5, PG) pump settings and evaluated for 6 h. All analyses were conducted with human whole blood. Blood samples were repeatedly drawn from the test circuits and analyzed regarding free hemoglobin, interleukin 8 (IL-8), platelet aggregation and acquired von Willebrand syndrome (AVWS). Results: After 1 h of circulation, a significant coagulation impairment (impaired platelet function and AVWS) was observed in both groups. After 6 h of circulation, increased IL-8 concentrations were measured in both groups (NPG: 0.05 ± 0.03 pg./mL, PG: 0.03 ± 0.01 pg./mL, p = 0.48). Pulsatile pump flow resulted in significantly increased hemolysis after 6 h of circulation (NPG: 37.3 ± 12.4 mg/100 L; PG: 59.6 ± 14.5 mg/100 L; p < 0.05). Conclusion: Our results indicate that the coagulative impairment takes place in the early phase of ECC. Pulsatility did not affect the occurrence of AVWS ex-vivo. Prolonged durations of pulsatile pump flow led to increased hemolysis and therefore, its prolonged use should be employed cautiously in clinical practice with appropriate monitoring.

Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis.

AIMS: Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding. METHODS AND RESULTS: A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002). CONCLUSION: Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.

Beyond Acquired Von Willebrand Deficiency: Exploring Alternative Mechanisms of Heyde's Syndrome.

Heyde's syndrome (HS) is a complex condition characterized by the coexistence of severe aortic stenosis (AS) and gastrointestinal (GI) angiodysplasia. The prevailing belief has been that acquired von-Willebrand factor deficiency (AVWD) is the underlying cause of HS. However, the validity of this theory remains contentious, as there have been reports of bleeding angiodysplasia in the setting of AS despite normal von-Willebrand factor (vWF) activity. Here, we present a compelling case of HS with negative diagnostic testing for AVWD. A 61-year-old female with a history of end-stage renal disease on hemodialysis, AS, and a history of recurrent GI bleeding presented with dyspnea. Prior to arrival, she reported multiple episodes of melena and hematochezia and was found to have a hemoglobin of 6 g/dL. Notable exam findings included melenic stool on digital rectal exam and a grade three systolic crescendo-decrescendo murmur that radiated up to the carotids. A transthoracic echocardiogram demonstrated evidence of severe AS. Considering the recurrent GI bleeding and severe AS, HS was suspected. To investigate this further, a vWF disease panel was sent, revealing a normal multimeric pattern. Given hemodynamic stability, she was discharged but had multiple readmissions soon after with recurrent GI bleeding requiring endoscopic intervention. On her last visit, she underwent transcatheter aortic valve replacement (TAVR) with notable resolution in her GI bleeds thereafter. The prevailing theory regarding the etiology of HS is acquired vWF deficiency. However, the validity of this theory remains a topic of debate, as a growing body of evidence suggests that the absence of AVWD does not necessarily rule out the diagnosis. The absence of AVWD in our patient raises questions about its prevalence in HS and its status as a key feature and highlights the importance of considering HS events without AVWD, given the risk of recurrent life-threatening GI bleeds.

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

Extracorporeal membrane oxygenation (ECMO) is an increasingly acceptable life-saving mechanical assistance system that provides cardiac and/or respiratory support for several reversible or treatable diseases. Despite important advances in technology and clinical management, bleeding remains a significant and common complication associated with increased morbidity and mortality. Some studies suggest that acquired von Willebrand syndrome (AVWS) is one of the etiologies of bleeding. It is caused by shear-induced deficiency of von Willebrand factor (VWF). VWF is an important glycoprotein for hemostasis that acts as a linker at sites of vascular injury for platelet adhesion and aggregation under high shear stress. AVWS can usually be diagnosed within 24 h after initiation of ECMO and is always reversible after explantation. Nonetheless, the main mechanism for the defect in the VWF multimers under ECMO support and the association between AVWS and bleeding complications remains unknown. In this review, we specifically discuss the loss of VWF caused by shear induction in the context of ECMO support as well as the current diagnostic and management strategies for AVWS.

[Rare manifestations of monoclonal gammopathies: About two clinical cases and literature review]. / Manifestations rares des gammapathies monoclonales : à propos de 2 cas et revue de la littérature.

INTRODUCTION: Monoclonal gammopathies are common over the age of 50. Patients are usually asymptomatic. However, some patients present with secondary clinical manifestations, which are now grouped under the entity « Monoclonal Gammopathy of Clinical Significance ¼ (MGCS). CASE REPORT: Here, we report two rare cases of MGCS: an acquired von Willebrand syndrome (AvWS) and an acquired angioedema (AAE). CONCLUSION: The discovery of a decrease in von Willebrand activity (vWF:RCo) or angioedema in a patient over 50 years of age, in the absence of a family history, should prompt a search for a hemopathy and in particular, a monoclonal gammopathy.

Acquired von willebrand syndrome in patients with philadelphia-negative myeloproliferative neoplasm.

Background: Acquired von Willebrand syndrome (AVWS) has not been investigated in Korean patients with Philadelphia chromosome-negative myeloproliferative neoplasm. Methods: This study analyzed the prevalence at diagnosis and clinical features of AVWS in patients with essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic/early primary myelofibrosis (pre-PMF), or overt PMF (PMF) diagnosed between January 2019 and December 2021 at Chungam National University Hospital, Daejeon, Korea. AVWS was defined as below the lower reference limit (56%) of ristocetin cofactor activity (VWF:RCo). Results: Sixty-four consecutive patients (36 with ET, 17 with PV, 6 with pre-PMF, and 5 with PMF; 30 men and 34 women) with a median age of 67 years (range, 18‒87 yr) were followed for a median of 25.1 months (range, 2.6‒46.4 mo). AVWS was detected in 20 (31.3%) patients at diagnosis and was most frequent in ET patients (41.4%), followed by patients with pre-PMF (33.3%) and PV (17.6%) patients. VWF:RCo was negatively correlated with the platelet count (r=0.937; P=0.002). Only one episode of minor bleeding occurred in a patient with ET and AVWS. Younger age (<50 yr) [odds ratio (OR), 7.08; 95% confidence interval (CI), 1.27‒39.48; P=0.026] and thrombocytosis (>600×109/L) (OR, 13.70; 95% CI, 1.35‒138.17; P=0.026) were independent risk factors for developing AVWS. Conclusion: AVWS based on VWF:RCo was common in patients with ET and pre-PMF, but less common in patients with PV in the Korean population. Clinically significant bleeding is rare in these patients.