Platelet-Type Von Willebrand Disease: A Rare, Often Misdiagnosed and Underdiagnosed Bleeding Disorder

2011 ◽  
Vol 37 (05) ◽  
pp. 464-469 ◽  
Author(s):  
Maha Othman
Keyword(s):  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Von Willebrand

Coagulopathies

2020 ◽  
Author(s):  
Michael Levine
Keyword(s):  
Key Words ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Coagulation Cascade ◽  
Bleeding Disorders ◽  
Platelet Disorders ◽  
Von Willebrand

Coagulopathy can be caused by numerous hereditary or acquired etiologies. Although some of these conditions are known and the patient is aware of the bleeding disorder, other bleeding disorders are diagnosed only after the onset of excessive hemorrhage. This review discusses both hereditary and acquired disorders of coagulopathy. Platelet disorders are discussed elsewhere. This review contains 2 figures, 7 tables, and 72 references. Key words: Coagulopathies; Coagulopathy; Bleeding disorder; Hereditary bleeding disorder; Acquired bleeding disorder; von Willebrand disease; Hemophilia; Coagulation cascade; Hemorrhage; Anticoagulant-associated hemorrhage

Heavy Menstrual Bleeding in the Adolescent

2019 ◽  
Author(s):  
Kimberly Huhmann ◽  
Andrea Zuckerman
Keyword(s):  
Differential Diagnosis ◽  
Aminocaproic Acid ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Heavy Menstrual Bleeding ◽  
Menstrual Bleeding ◽  
Oral Contraceptive Pills ◽  
Sexually Transmitted ◽  
Contraceptive Pills ◽  
Von Willebrand

Heavy menstrual bleeding is a common presenting problem in the adolescent population. The average age of menarche is between 12 and 13 years. The most common reason for heavy menstrual bleeding soon after menarche is from an immature hypothalamic ovarian access, which spontaneously resolves once cycles become ovulatory. However, the broad differential diagnosis for heavy menses in adolescents includes coagulopathy, thyroid disease, sexually transmitted infections, specifically chlamydia, and chronic medical conditions. Von Willebrand disease is the most common bleeding disorder that can present with heavy menstrual bleeding at menarche or shortly after. A thorough history and physical exam with occasional labs needs to be completed and can assist in narrowing the differential diagnosis. Treatment of heavy menstrual bleeding consists of hormonal and nonhormonal options: combination oral contraceptive pills, patches, or rings taken continuously or cyclically; progesterone-only pills; progesterone implants; progesterone intrauterine devices; cyclic tranexamic acid; cyclic aminocaproic acid; and GnRH agonists with add-back therapy. This review contains 3 tables, and 28 references. Key Words: adolescent menses, anovulation, bleeding disorder, heavy menstrual bleeding, immature hypothalamic ovarian axis, menarche, treatment of heavy menses, Von Willebrand disease

The Power of a Standardized Bleeding Score in Diagnosing Pediatric Type 1 Von Willebrand Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1293-1293
Author(s):  
Paul D Marcus ◽  
Kidan G Nire ◽  
Linda Grooms ◽  
Jennifer Klima ◽  
Sarah O'Brien
Keyword(s):  
Platelet Function ◽  
Predictive Value ◽  
Care Setting ◽  
Tertiary Care ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
The Mean ◽  
Bleeding Score ◽  
Von Willebrand

Abstract Abstract 1293 Poster Board I-315 INTRODUCTION Type I von Willebrand disease (VWD) is the most common inherited bleeding disorder. Repetitive testing of von Willebrand factor (VWF) levels is necessary before the diagnosis can be safely ruled out, as VWF levels fluctuate in response to genetic and environmental factors. A predictive bleeding score (BS) could reveal individuals that may benefit from repetitive testing and those for whom repetitive testing is unlikely to be of benefit. While a standardized questionnaire (the Vicenza score) was developed to evaluate hemorrhagic symptoms, it was never prospectively validated for a pediatric population in a tertiary care setting. SUBJECTS The study targeted children, ages 0 to 17 years, referred to the Hemostasis and Thrombosis Center (HTC) of Nationwide Children's Hospital for a coagulation evaluation as a result of bleeding symptoms, family history of a bleeding disorder and/or abnormal coagulation labs found during pre-operative screening. Children were excluded if they had a previously diagnosed bleeding disorder, if their caregiver did not speak English or if the child did not undergo VWF:Ag and VWF:RCo testing. METHODS Prior to the diagnosis or exclusion of a bleeding disorder in the child, caregivers consented to answer the questionnaire over the telephone. Descriptions of the Vicenza score are available online (http://www.euvwd.group.shef.ac.uk/bleed_score.htm). LABORATORY TESTING A single VWF:Ag or VWF:RCo <30 IU/dL was classified as “Definite Type 1 VWD” while levels from 30-50 IU/dL were classified as “Low VWF” (http://www.nhlbi.nih.gov/guidelines/vwd). Platelet function analysis (PFA-100) screened for platelet function defects, with some patients undergoing follow-up platelet aggregation studies and/or platelet electron microscopy. Laboratory studies from other institutions were excluded from analysis. Patients' medical records were reviewed after hematologic evaluation, and the resultant data was analyzed with STATA 10.1 (Stata Corp., College Station, TX). RESULTS A total of 104 children (52 females and 52 males) with a mean age of 7.53 years (range 1 month to 17 years) were included. At least one hemorrhagic symptom was present in 99 of the 104 children (95%) with the mean number of symptoms being 2.87 (range 0 to 7). The mean Vicenza score was 3.24 (range -1 to 13). Of the 104 children, 8 met criteria for “Definite Type 1 VWD,” 23 met criteria for “Low VWF,” 14 were diagnosed with a “Platelet Function Defect,” and 2 children had bleeding secondary to Ehlers Danlos syndrome. Children with non-bleeding disorders (e.g. Factor XII deficiency) or no laboratory evidence of a bleeding disorder were classified as “No Bleeding Disorder.” In general, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive diagnostic likelihood ratio of the bleeding questionnaire demonstrated poor predictive value in our patient population with the exception of high specificity in ruling out “Definite Type 1 VWD” (Table). The NPV was comparably high with both qualitative (>2 bleeding symptoms) and quantitative (BS ≥2) criteria. CONCLUSIONS The Vicenza score, previously validated in adults and in a pediatric primary care setting, appears to have limited predictive value in a pediatric tertiary care setting when evaluating patients with platelet function defects or low VWF levels. While the Vicenza score has a high NPV to exclude “Definite Type 1 VWD,” the use of simpler qualitative criteria is similarly predictive. Disclosures No relevant conflicts of interest to declare.

Establishment Of a Reference Range For The Pbac-Score

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4772-4772 ◽  
Author(s):  
Susan Halimeh ◽  
Hannelore Rott ◽  
Guenther Kappert ◽  
Manuela Siebert
Keyword(s):  
Blood Loss ◽  
Blood Count ◽  
Reference Range ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Menstrual Blood ◽  
Control Group ◽  
Menstrual Blood Loss ◽  
The Mean ◽  
Von Willebrand

Introduction Heavy menstrual bleeding (HMB) is defined as bleeding that lasts for more than seven days or as the loss of more than 80mL of blood per mentrual cycle (1)The menstrual blood loss can be quantified by the use of a pictorial bleeding assessment chart (PBAC). The PBAC-Score was initially validated by Higham et al. (2) With the PBAC-Score the women can capture the number of pads or tampons and also state the intensity through the assessment of the drenching. The aim of this study was to establish a reference range for the PBAC-Score. Samples and Methods We analysed samples of 310 women with menorrhagia and 108 controls by conducting the following tests: Blood count, VWF:RCo, VWF:Ag, VWF:CB, VWF:multimers, Fibrinogen (Clauss), activities of FII, FV, FVII, FVIII (clotting and chromogenic), FIX, FX, FXI, FXII, FXIII. In all women the menstrual blood loss was quantified usind the PBAC-Score and the results were compared. Results In 202 of 310 women (65.1%) a bleeding disorder could be detected. In those with a bleeding disorder, the distribution was as followed: 64% of these women had a von Willebrand disease, 7.2% FVII-deficiency, 7.7% FXIII-deficiency and the remaining 21.1% other mild factor dificiencies. The mean PBAC-Score in women with menorrhagia was 262 (range 31 – 4212) in our control group the mean PBAC-Score was 60 (range 8 – 97). Discussion/Conclusion Attemps to measure the quantity of menstrual blood loss can be useful in clinical practice. In our opinion the best cut of for the PBAC-Score is 100 with a sensitifity of 90% and a specifity of 100%. We found a high correlation of a PBAC >100 and an inherited bleeding disorder, especially von Willebrand diesease. In 65.1% of our patients an abnormal coagulation was found. In 4 (3.7%) women of the control group slightly abnormal von Willebrand parameters could been dectected. We validated the reference range for the PBAC-Score as 0 - 100. Disclosures: Halimeh: Octapharma AG: Investigator Other, Research Funding.

scholarly journals Utility of Thromboelastography for the Diagnosis of Von Willebrand Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3788-3788
Author(s):  
Katherine Regling ◽  
Srikruthi Kakulavarapu ◽  
Ronald Thomas ◽  
Wendy Hollon ◽  
Meera B. Chitlur
Keyword(s):  
Platelet Count ◽  
Tissue Factor ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Diagnostic Methods ◽  
Blood Type ◽  
Clot Formation ◽  
Response To Treatment ◽  
P Value ◽  
Von Willebrand

Abstract Background: Von Willebrand Disease (VWD) is the most common bleeding disorder. Current gold standard diagnostic testing includes: VWF Activity (VWF:RCo), VWF Antigen (VWF:Ag) and Factor VIII Activity (FVIII). There are many difficulties associated with the current diagnostic methods. Thromboelastography (TEG) is a viscoelastic method of measuring coagulation function. The standard TEG assay has not been thought to be of use in VWD because of the lack of shear stress which is essential for the activation of VWF. Modified TEG using Ristocetin activation has been found to be useful in the diagnosis of VWD. The aims of this study were to evaluate the different parameters of Tissue factor (TF) initiated TEG in patients with VWD, to determine if this assay is sensitive to dysfunctional/low levels of VWF, as this does not require any significant change in procedure except for the use of TF as the activator instead of Kaolin. Methods: A retrospective chart review of patients who presented for a bleeding disorder workup that had TF initiated TEG analysis and Von Willebrand laboratory tests completed between January 2007 and December 2015 was performed. IRB approval was obtained, and current diagnostic tests for Von Willebrand Disease (CBC with platelet count, VWF:RCo and VWF:Ag, FVIII, ABO blood type; PT, PTT, Fibrinogen) and TF initiated TEG parameters, specifically K-Time and MRTG (Maximum rate of thrombin generation), were compared. To perform the TEG analysis, the citrated whole blood samples were activated using 20mL of 1:10,000 dilution of recombinant human tissue factor (Innovin, Dade Behring) and CaCl2. Results: A total sample size of 160 patients (ages ranging 2 weeks to 18 years) who had a workup for a bleeding disorder that included Von Willebrand studies and TEG were reviewed. Of these 160 patients, 75 patients had a VWF:RCo <50 IU/dL. These patients were categorized into two categories for the purposes of this study: Low VWF:RCo (30-50 IU/dL) and Abnormal VWF:RCo (<30 IU/dL). The clinical and lab characteristics of patients studied are presented in Table 1, including FVIII, platelet count, and fibrinogen levels. Fibrinogen levels on 15 patients with VWF:RCo <50 IU/dL were not reported, and are not included in the means as noted in Table 1. The TEG parameter, K-Time, (time for increase in amplitude from 2mm to 20mm representing the dynamics of clot formation, normal <2min) was determined abnormal for values greater than 2.2 (>10% above the normal). Of the patients with VWF:RCo <30 IU/dL, 23/30 (77%) had an abnormal K-Time of >2.2, with a p-value of ≤0.001 (Table 2); whereas patients with low VWF:RCo 30-50 IU/dL, only 13/45 (29%) had an abnormal K-Time of >2.2, which was not statistically significant. A ROC curve for patients with VWF:RCo <30 IU/dL and abnormal K-Time showed an area under the curve of 0.675, with a p-value of 0.003 (Fig 1). An analysis of the MRTG showed a mean of 9.45 in patients with VWF:RCo <30 IU/dL and a mean of 11.26 in patients with normal VWF:RCo, which was statistically significant (p=0.05). There was a moderate correlation (0.33) seen between patients with abnormal K-Time and FVIII, however, when analyzing regression data the correlation only accounts for 11% of the explained variance in abnormal K-Time values. Patients with abnormal K-Time and abnormal fibrinogen levels and platelet counts were also compared, and showed no significant correlation, indicating that these were not the determinants that influenced the K time. Conclusions: The TF activated TEG reflects impaired clot formation in patients with VWF <30% as reflected by the prolongation in the K-Time and the low MRTG. The TEG unlike VWF:RCo can be done in real time and results are available to the clinician within an hour. This will definitely be beneficial in acute situations like evaluation of and management of acute bleeding in patients with acquired deficiencies of VWF and may play an important role in the surgical management of patients with VWD. It will also help physicians monitor response to treatment, frequency of treatment, and the need for prophylactic dosing in patients with VWD. The next step will be to evaluate if this difference is also seen with Kaolin, which is the standard TEG assay. We anticipate that Kaolin being a stronger agonist may make the test less sensitive to VWF related changes. Disclosures Chitlur: Novo Nordisk: Consultancy; Bayer Pharmaceuticals: Honoraria; Baxalta: Honoraria; Biogen Idec: Honoraria; Pfizer: Honoraria.

Acquired von Willebrand syndrome in association with multiple myeloma: remission after stem cell transplant

2021 ◽  
Vol 14 (1) ◽  
pp. e239053
Author(s):  
Chintan P Shah ◽  
Jess Delaune ◽  
Molly W Mandernach
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Myeloproliferative Neoplasm ◽  
Significant Risk ◽  
Coagulation Factor ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Cell Transplant ◽  
Acquired Von Willebrand Syndrome ◽  
Von Willebrand

Acquired von Willebrand syndrome is a rare bleeding disorder characterised by a later age of onset without a personal or family history of bleeding diathesis. It is vital to discern acquired von Willebrand syndrome from inherited von Willebrand disease and other acquired bleeding disorders as management differs significantly. Acquired von Willebrand syndrome is usually secondary to an underlying disorder such as lymphoproliferative disorder, myeloproliferative neoplasm, solid tumour, cardiovascular disorder, autoimmune disorders or hypothyroidism. Diagnosis is often delayed with a significant risk of morbidity and even mortality. Here we present a case of a 74-year-old man with an acquired bleeding disorder and work up suggestive of acquired von Willebrand syndrome secondary to immunoglobulin G kappa multiple myeloma. He was treated successfully with intravenous immunoglobulin, von Willebrand Factor/Coagulation Factor VIII Complex (human), myeloma directed chemotherapy and autologous stem cell transplantation. We also discuss the management strategies that are largely based on retrospective studies and case reports.

Is a Standardized Preoperative Questionnaire a Good Tool To Detected Coagulation Disorders In Children

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4786-4786
Author(s):  
Susan Halimeh ◽  
Hannelore Rott ◽  
Guenther Kappert ◽  
Manuela Siebert
Keyword(s):  
Bleeding Time ◽  
Postoperative Bleeding ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Coagulation Disorders ◽  
Good Tool ◽  
Prolonged Bleeding Time ◽  
Prolonged Aptt ◽  
Von Willebrand ◽  
Preoperative Examination

Introduction In our study 144 children were send to our coagulation centre with a positive anamnesis (such as haematomas or nose bleeding’s) a positive family anamnesis (p.e. Mother with Menorrhagie) or a prolonged aPTT during a standardized preoperative examination. Samples and Methods We analyzed samples of 144 children by conduction the following tests: Blood count, VWF:RCo, VWF:Ag, VWF:CB, Fibrinogen (Clauss), activities of FII, FV, FVII, FVIII (clotting and chromogenic), FIX, FX, FXI, FXII, FXIII. Results In 107 of 144 children (74.3%) a bleeding disorder could be detected. In those with a bleeding disorder the distribution was as followed: 23.6% had a von Willebrand disease, 27.8% had a prolonged bleeding time and 5.6% a factor XIII-deficiency. The remaining 43% hat other bleeding. disorders (e.g. FVIII-deficiency, FVII-deficiency and other mild factor deficiencies). Discussion A standardized preoperative questionnaire can be useful in clinical practice. In our study 74.3% children with one or more positive evidence in the anamnesis suffer from a bleeding disorder. It is specifically noticeable that we found in 68% of the children which mother has a menorrhagia a bleeding disorder. In 31.8% of the children we found a von Willebrand disease. In our more coagulation disorders could be detected if a standardized preoperative questionnaire would be used and if we pay more attention to children with would a mothers with menorrhagia. Conclusions Children from mothers with menorrhagia suffer more frequently from a bleeding disorder. In our patients in 75% of the children with a mother with menorrhagia a bleeding disorder was found. To avoid an unexpected bleeding during a planned surgery or a postoperative bleeding a standardized preoperative questionnaire should be performed. Disclosures: Halimeh: Octapharma AG: Investigator Other, Research Funding.

Gastrointestinal angiodysplasia and bleeding in von Willebrand disease

2014 ◽  
Vol 112 (09) ◽  
pp. 427-431 ◽  
Author(s):  
Massimo Franchini ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Gastrointestinal Bleeding ◽  
Von Willebrand Factor ◽  
Severe Symptom ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Diagnosis And Treatment ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Mucocutaneous Bleeding

SummaryVon Willebrand disease (VWD), the most common genetic bleeding disorder, is characterised by a quantitative or qualitative defect of von Willebrand factor (VWF). Patients with VWD suffer from mucocutaneous bleeding, of severity usually proportional to the degree of VWF defect. In particular, gastrointestinal bleeding associated with angiodysplasia is often a severe symptom of difficult management. This review focuses on the pathophysiology, diagnosis and treatment of VWD-associated gastrointestinal angiodysplasia and related bleeding.

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