Abstract

Type 1 Von Willebrand Disease (VWD) is the most common congenital bleeding disorder, affecting 1% of the population, and caused by a quantitative deficiency of Von Willebrand Factor (VWF). In addition to mucosal bleeding, VWD patients often suffer postoperative bleeding, leading to significant morbidity. Thus, a preoperative diagnosis could potentially reduce postoperative bleeding. Because symptoms correlate poorly with VWD assays, subject to extragenic effects and lab variability, diagnosis is difficult. The bleeding score (BS) is a simple quantitative tool recently developed to rate bleeding symptom severity, with 99% specificity for VWD. To determine the potential utility of BS in predicting postoperative bleeding in VWD, we evaluated preoperative BS by retrospective review of type 1 VWD patients who suffered postoperative bleeding prior to diagnosis. Preoperative clinical bleeding symptoms and VWD assays, including VWF:RCo, VWF:Ag, and FVIII:C, were obtained. The severity of clinical bleeding symptoms present prior to surgery was rated by the 4-point BS scale: 0 = no/trivial; 1 = present; 2 = intervention required; 3 = replacement therapy. Statistical analysis was by chi square analysis and Fisher’s exact test for categorical data, and by student t test for continuous data. Of 260 registered type 1 VWD patients, 71 (27.3 %) experienced surgical bleeding prior to a diagnosis of VWD. Of these 56 (78.9%) were female, 48 (67.6%) were adults (≥ 18 yr), and 61 (85.9%) had a family bleeding history. The surgeries included general, gynecologic, genitourinary, and otolaryngologic procedures. The median preop BS, 3 in females and 4 in adults, was significantly higher than in males and children, each median 1, p<0.01, respectively. A BS ≥ 3 would have identified only 59.1% patients before surgery, but as many as 90.1%, if combined with one abnormal VWD test; 94.4%, with family bleeding history; or 97.2% with both family history and one abnormal VWD test. The proportion of children identified by BS was significantly lower than in adults, 26.1% vs 75.0 % with BS > 3, p = 0.001. Yet this significantly improved by combining BS with family history, 91.3% vs 95.8%, not different from adults, p = 0.591. We conclude that obtaining a preoperative BS and family bleeding history may reduce postoperative bleeding and promote timely diagnosis among individuals with type 1 VWD patients, particularly children.

Preoperative Bleeding Score in Type 1 VWD Patients with Postoperative Bleeding

 Male Female Age < 18 Age ≥ 18 All 
 N = 15 N = 56 N = 23 N = 48 N = 71 
τp = .001, as compared with under 18 yr; σp = .007, as compared with males; ζ p > 0.5 as compared with age under 18 or males, respectively. 
BS≥1 10/15 (66.7%) 54/56 (96.4%) 18/23 (78.3%) 46/48 (95.8%) 64/71 (90.1%) 
BS≥3 4/15 (26.7%) 38/56 (67.8%)σ 6/23 (26.1%) 36/48 (75.0%)τ 42/71 (59.1%) 
BS≥5 2/15 (13.3%) 17/56 (30.3%) 2/23 (8.7%) 17/48 (35.4%) 19/71 (26.7%) 
Abnl VWF:RCo 8/15 (53.3%) 19/56 (33.9%) 6/23 (26.1%) 19/48 (39.6%) 27/71 (38.0%) 
Abnl VWD Test 11/15 (73.3%) 41/56 (73.2%) 16/23 (69.6%) 36/48 (75.0%) 52/71 (73.2%) 
Fam Bld History 15/15 (100%) 47/56 (83.9%) 21/23 (91.3%) 40/48 (83.3%) 61/71 (85.9%) 
BS≥3 ± Abnl VWD Test 13/15 (86.7%) 51/56 (91.1%) 18/23 (78.3%) 46/48 (95.8%) 64/71 (90.1%) 
BS≥3 ± Fam Hx 15/15 (100.0%) 52/56 (92.8%)ζ 21/23 (91.3%) 46/48 (95.8%)ζ 67/71 (94.4%) 
BS≥3 ± Fam Hx ± Abnl VWD Test 15/15 (100.0%) 54/56 (96.4%) 22/23 (95.6%) 47/48 (97.9%) 69/71 (97.2%) 
 Male Female Age < 18 Age ≥ 18 All 
 N = 15 N = 56 N = 23 N = 48 N = 71 
τp = .001, as compared with under 18 yr; σp = .007, as compared with males; ζ p > 0.5 as compared with age under 18 or males, respectively. 
BS≥1 10/15 (66.7%) 54/56 (96.4%) 18/23 (78.3%) 46/48 (95.8%) 64/71 (90.1%) 
BS≥3 4/15 (26.7%) 38/56 (67.8%)σ 6/23 (26.1%) 36/48 (75.0%)τ 42/71 (59.1%) 
BS≥5 2/15 (13.3%) 17/56 (30.3%) 2/23 (8.7%) 17/48 (35.4%) 19/71 (26.7%) 
Abnl VWF:RCo 8/15 (53.3%) 19/56 (33.9%) 6/23 (26.1%) 19/48 (39.6%) 27/71 (38.0%) 
Abnl VWD Test 11/15 (73.3%) 41/56 (73.2%) 16/23 (69.6%) 36/48 (75.0%) 52/71 (73.2%) 
Fam Bld History 15/15 (100%) 47/56 (83.9%) 21/23 (91.3%) 40/48 (83.3%) 61/71 (85.9%) 
BS≥3 ± Abnl VWD Test 13/15 (86.7%) 51/56 (91.1%) 18/23 (78.3%) 46/48 (95.8%) 64/71 (90.1%) 
BS≥3 ± Fam Hx 15/15 (100.0%) 52/56 (92.8%)ζ 21/23 (91.3%) 46/48 (95.8%)ζ 67/71 (94.4%) 
BS≥3 ± Fam Hx ± Abnl VWD Test 15/15 (100.0%) 54/56 (96.4%) 22/23 (95.6%) 47/48 (97.9%) 69/71 (97.2%) 

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