Characteristics of included studies
| First author . | Year . | Study design . | No. of patients . | Patient selection . | Index test . | Reference standard . |
|---|---|---|---|---|---|---|
| Bowman | 2008 | Cohort with DTA results for adults | 217 | Unrelated adults (age 20-88 y) recruited from primary care clinics investigated for VWD type 1 (35 male, 65 female) | MCMDM-1 VWD Bleeding Questionnaire. A bleeding score ≥4 was considered abnormal | Laboratory workup including ABO blood group, VWF:Ag, VWF:RCo, and FVIII:C |
| Deforest | 2015 | Cohort with DTA results for adults | 64 | Adult patients (age 18-73 y) referred for the first time to a hematologist because of a problem with bleeding or bruising (11 male, 53 female) | Self-BAT: ISTH-BAT was converted to a grade 4 reading level to produce the first version of the Self-BAT, which was then optimized to ensure agreement with the ISTH-BAT. A normal bleeding score was 0 to +5 for females and 0 to +3 for males | Laboratory workup including CBC, INR/PT/PTT, thrombin time, fibrinogen, ferritin, ABO blood group, VWF:Ag, VWF:RCo, FVIII:C, and VWF multimers |
| Philipp | 2008 | Cohort with DTA results for adults | 146 | Females (age 13-55 y) receiving a physician diagnosis of heavy menstrual bleed at the faculty gynecology practice of UMDNJ-Robert Wood Johnson Medical School or collaborating community gynecology and pediatric practices | 12-page questionnaire based on the bleeding symptoms found significant in women with WWD. A screening tool was positive if 1 of 4 criteria were met: severity of heavy menstrual period, history of treatment of anemia, excess bleeding after challenges including dental surgery, surgery and delivery, family history of bleeding disorder | Laboratory workup including VWF:Ag and VWF:RCo |
| Bidlingmaier | 2012 | Cohort with DTA results for children | 100 | Children (age 1-17 y), 44 with a positive bleeding history, 29 referred because of an isolated APTT prolongation, and 27 because of a positive family history of bleeding | Quantitative ISTH child bleeding score and the qualitative ITEM analysis. A bleeding score ≥2 was considered abnormal | Laboratory workup including VWF:RCo, VWF:Ag, FVIII:C, VWF multimers |
| Bowman | 2009 | Cohort with DTA results for children | 151 | Children (age <18 y) from the waiting room of the Childrens Outpatient Centre, the Hotel Dieu Hospital in Kingston, Ontario, investigated for VWD because of a personal history of hemorrhagic symptoms and/or a family history of VWD and/or for preoperative screening | PBQ: The MCMDM-1VWD Bleeding Questionnaire was modified by including pediatric-specific bleeding symptoms in the “other” category. A bleeding score ≥2 was considered abnormal | Laboratory workup including VWF:RCo, VWF:Ag, FVIII:C, VWF multimers, genetic testing |
| Malec | 2016 | Cohort with DTA results for children | 193 | Children (age <11 y) referred to an outpatient bleeding disorders clinic for evaluation of VWD and/or other bleeding disorders | Composite score that was considered positive when 2 of 4 criteria were positive: Tosetto bleeding score Z1; family history of VWD or bleeding; personal history of iron deficiency anemia; and positive James early bleeding score | Laboratory workup including VWF:RCo, VWF:Ag, FVIII:C, VWF multimers |
| Marcus | 2011 | Cohort with DTA results for children | 104 | Children (age <17 y) referred for evaluation of bleeding symptoms, family history of a bleeding disorder, and/or abnormal coagulation studies | Modified Vicenza score to include an “other” category with pediatric-specific bleeding questions. A bleeding score ≥2 was considered abnormal | Laboratory workup including VWF:RCo and VWF:Ag |
| Belen, B. | 2015 | Case control | 84 | Children (age <8 y) with VWD (46) and control group (32) with bleeding symptoms but had normal prothrombin time, APTT, PFA 100, VWF:Ag, VWF:RCo, and platelet function tests | PBQ administration. A bleeding score ≥2 was considered abnormal | Laboratory workup including VWF:Ag, VWF:RCo, and FVIII:C |
| Faiz | 2017 | Case control | 53 | Women (age 14-53 y): 41 previously untested family members of VWD patients, 26 previously diagnosed VWD patients, and 27 healthy controls | Modified screening tool considered positive if 1 of 3 criteria were met: severity of heavy menstrual period, history of treatment of anemia, excess bleeding after challenges including dental surgery, and surgery and delivery | Laboratory workup including CBC, ferritin, FVIII:C, VWF:Ag, and VWF:RCo |
| Mittal | 2015 | Case control | 1316 | Healthy children (age <18 y) without a diagnosis of a chronic medical condition presenting to a general pediatrician’s office for routine or sick visits, and 35 children (21 male, 14 female) with a known diagnosis of VWD | PBQ. Children with total bleeding questionnaire scores ≥3 were predicted to have VWD | Laboratory workup including VWF:Ag, VWF:RCo, and multimer analysis |
| Pathare | 2018 | Case control | 96 | 46 patients with type 1 VWD; 46 and 50 healthy subjects with no known history of bleeding or bruising (ages 7-49 y) | MCMDM-1 VWD questionnaire. Bleeding score >2 considered significantly abnormal | Laboratory workup including VWF:Ag, VWF:RCo, and FVIII:C |
| Bujnicki | 2011 | Case control | 160 | 80 children (age <11 y) with VWF:RCo <0.50 IU/mL, and 80 controls without VWD | Pediatric bleeding score modified for children based on the PBQ. A bleeding score ≥1 was predictive of VWD | Laboratory workup including VWF:Ag, VWF:RCo, and FVIII:C |
| Rodeghiero | 2005 | Case control | 341 | 42 adults that are obligatory carriers of VWD type I, 84 affected with VWD type 1, and 215 controls | A standardized questionnaire, using a bleeding score ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion) | Laboratory workup including VWF:Ag, VWF:RCo, FVIII:C, and APTT |
| First author . | Year . | Study design . | No. of patients . | Patient selection . | Index test . | Reference standard . |
|---|---|---|---|---|---|---|
| Bowman | 2008 | Cohort with DTA results for adults | 217 | Unrelated adults (age 20-88 y) recruited from primary care clinics investigated for VWD type 1 (35 male, 65 female) | MCMDM-1 VWD Bleeding Questionnaire. A bleeding score ≥4 was considered abnormal | Laboratory workup including ABO blood group, VWF:Ag, VWF:RCo, and FVIII:C |
| Deforest | 2015 | Cohort with DTA results for adults | 64 | Adult patients (age 18-73 y) referred for the first time to a hematologist because of a problem with bleeding or bruising (11 male, 53 female) | Self-BAT: ISTH-BAT was converted to a grade 4 reading level to produce the first version of the Self-BAT, which was then optimized to ensure agreement with the ISTH-BAT. A normal bleeding score was 0 to +5 for females and 0 to +3 for males | Laboratory workup including CBC, INR/PT/PTT, thrombin time, fibrinogen, ferritin, ABO blood group, VWF:Ag, VWF:RCo, FVIII:C, and VWF multimers |
| Philipp | 2008 | Cohort with DTA results for adults | 146 | Females (age 13-55 y) receiving a physician diagnosis of heavy menstrual bleed at the faculty gynecology practice of UMDNJ-Robert Wood Johnson Medical School or collaborating community gynecology and pediatric practices | 12-page questionnaire based on the bleeding symptoms found significant in women with WWD. A screening tool was positive if 1 of 4 criteria were met: severity of heavy menstrual period, history of treatment of anemia, excess bleeding after challenges including dental surgery, surgery and delivery, family history of bleeding disorder | Laboratory workup including VWF:Ag and VWF:RCo |
| Bidlingmaier | 2012 | Cohort with DTA results for children | 100 | Children (age 1-17 y), 44 with a positive bleeding history, 29 referred because of an isolated APTT prolongation, and 27 because of a positive family history of bleeding | Quantitative ISTH child bleeding score and the qualitative ITEM analysis. A bleeding score ≥2 was considered abnormal | Laboratory workup including VWF:RCo, VWF:Ag, FVIII:C, VWF multimers |
| Bowman | 2009 | Cohort with DTA results for children | 151 | Children (age <18 y) from the waiting room of the Childrens Outpatient Centre, the Hotel Dieu Hospital in Kingston, Ontario, investigated for VWD because of a personal history of hemorrhagic symptoms and/or a family history of VWD and/or for preoperative screening | PBQ: The MCMDM-1VWD Bleeding Questionnaire was modified by including pediatric-specific bleeding symptoms in the “other” category. A bleeding score ≥2 was considered abnormal | Laboratory workup including VWF:RCo, VWF:Ag, FVIII:C, VWF multimers, genetic testing |
| Malec | 2016 | Cohort with DTA results for children | 193 | Children (age <11 y) referred to an outpatient bleeding disorders clinic for evaluation of VWD and/or other bleeding disorders | Composite score that was considered positive when 2 of 4 criteria were positive: Tosetto bleeding score Z1; family history of VWD or bleeding; personal history of iron deficiency anemia; and positive James early bleeding score | Laboratory workup including VWF:RCo, VWF:Ag, FVIII:C, VWF multimers |
| Marcus | 2011 | Cohort with DTA results for children | 104 | Children (age <17 y) referred for evaluation of bleeding symptoms, family history of a bleeding disorder, and/or abnormal coagulation studies | Modified Vicenza score to include an “other” category with pediatric-specific bleeding questions. A bleeding score ≥2 was considered abnormal | Laboratory workup including VWF:RCo and VWF:Ag |
| Belen, B. | 2015 | Case control | 84 | Children (age <8 y) with VWD (46) and control group (32) with bleeding symptoms but had normal prothrombin time, APTT, PFA 100, VWF:Ag, VWF:RCo, and platelet function tests | PBQ administration. A bleeding score ≥2 was considered abnormal | Laboratory workup including VWF:Ag, VWF:RCo, and FVIII:C |
| Faiz | 2017 | Case control | 53 | Women (age 14-53 y): 41 previously untested family members of VWD patients, 26 previously diagnosed VWD patients, and 27 healthy controls | Modified screening tool considered positive if 1 of 3 criteria were met: severity of heavy menstrual period, history of treatment of anemia, excess bleeding after challenges including dental surgery, and surgery and delivery | Laboratory workup including CBC, ferritin, FVIII:C, VWF:Ag, and VWF:RCo |
| Mittal | 2015 | Case control | 1316 | Healthy children (age <18 y) without a diagnosis of a chronic medical condition presenting to a general pediatrician’s office for routine or sick visits, and 35 children (21 male, 14 female) with a known diagnosis of VWD | PBQ. Children with total bleeding questionnaire scores ≥3 were predicted to have VWD | Laboratory workup including VWF:Ag, VWF:RCo, and multimer analysis |
| Pathare | 2018 | Case control | 96 | 46 patients with type 1 VWD; 46 and 50 healthy subjects with no known history of bleeding or bruising (ages 7-49 y) | MCMDM-1 VWD questionnaire. Bleeding score >2 considered significantly abnormal | Laboratory workup including VWF:Ag, VWF:RCo, and FVIII:C |
| Bujnicki | 2011 | Case control | 160 | 80 children (age <11 y) with VWF:RCo <0.50 IU/mL, and 80 controls without VWD | Pediatric bleeding score modified for children based on the PBQ. A bleeding score ≥1 was predictive of VWD | Laboratory workup including VWF:Ag, VWF:RCo, and FVIII:C |
| Rodeghiero | 2005 | Case control | 341 | 42 adults that are obligatory carriers of VWD type I, 84 affected with VWD type 1, and 215 controls | A standardized questionnaire, using a bleeding score ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion) | Laboratory workup including VWF:Ag, VWF:RCo, FVIII:C, and APTT |
APTT, activated partial thromboplastin time; CBC, complete blood count; DTA, diagnostic test accuracy; INR, international normalized ratio; ITEM, Test Question Analysis; PBQ, Pediatric Bleeding Questionnaire; PFA 100, Platelet Function Assay; PT, prothrombin time; PTT, partial thromboplastin time; UMDNJ, University of Medicine and Dentistry of New Jersey.