Postpartum Hemorrhage in Patients with Type 1 von Willebrand Disease: A Systematic Review

2021 ◽  
Author(s):  
Rebecca A.M. Pierce-Williams ◽  
Mona M. Makhamreh ◽  
Sophia Blakey-Cheung ◽  
Zimeng Gao ◽  
Huda B. Al-Kouatly
Keyword(s):  
Systematic Review ◽  
Blood Loss ◽  
Postpartum Hemorrhage ◽  
Primary Outcome ◽  
Signs And Symptoms ◽  
Von Willebrand Disease ◽  
Inclusion Criteria ◽  
Increased Risk ◽  
Von Willebrand

AbstractType 1 von Willebrand disease (VWD) is the most common subtype of VWD, comprising 75% of VWD patients. We provide a systematic review of type 1 VWD in pregnancy. Our objective was to evaluate the rate of postpartum hemorrhage (PPH) in patients with known type 1 VWD. The primary outcome was rate of PPH. Primary PPH was defined as a cumulative blood loss ≥1,000 mL, or blood loss accompanied by signs and symptoms of hypovolemia within 24 hours postpartum or requiring blood products. Secondary PPH was defined as significant bleeding 24 hours to 12 weeks postpartum. Relevant articles published in English pertaining to VWD and pregnancy were identified without any time or study limitations. Seven articles (n = 144 pregnancies) met inclusion criteria. The rate of primary PPH was 4/144 (2.8%). The secondary PPH rate was reported in four studies, and occurred in 7/48 pregnancies (14.6%), ranging from 2 to 19 days postpartum. In conclusion, according to this systematic review, the frequency of primary PPH in pregnancies with known type 1 VWD is 2.8%. This is similar to the overall PPH rates of 3% reported in the literature. Although the sample size was small, secondary PPH occurred in almost 15% of pregnancies, while in the overall obstetrical population this occurs in approximately 1% of cases. Patients with known type 1 VWD may not be at increased risk of primary PPH, though they appear to bear increased risk of secondary PPH.

Experience with Epidural Anesthesia in Pregnant Women with Von Willebrand Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1026-1026
Author(s):  
Jay Varughese ◽  
Alice J. Cohen
Keyword(s):  
Pregnant Women ◽  
Von Willebrand Factor ◽  
Epidural Anesthesia ◽  
Postpartum Hemorrhage ◽  
Postoperative Bleeding ◽  
Von Willebrand Disease ◽  
Bleeding Complications ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Von Willebrand Disease (vWD) is an autosomal dominant inherited bleeding disorder that is characterized by epistaxis, mucosal and postoperative bleeding, menorrhagia and postpartum hemorrhage. In particular, there is a paucity of safety data for, and thus a reluctance to use, epidural anesthesia (EA) for delivery. We thus conducted a review of all women followed with vWD in a referral hemophilia clinic who had ≥ 1 pregnancy. Thirty-three subjects were screened; 31/33 (94%) had type 1 and 2/33 (6%) had type 2A vWD. There were 59 term pregnancies (range 1–3 per patient), and 5 fetal losses (in 4 patients). Of the term pregnancies, 16/59 (27%) were delivered by Caesarian Section (C-Section), complicated by postpartum hemorrhage in 3 (19%); 43/59 (73%) were delivered by normal spontaneous vaginal delivery (NSVD), complicated by hemorrhage in 21 (49%) (p=0.05). EA was administered during 14 (13 with type 1 vWD) of 59 (24%) of the deliveries, all without DDAVP, plama-derived factor VIII-von Willebrand factor containing concentrates or blood products, and in no patient were bleeding complications encountered at the site of EA nor were there any neurologic complications. Conclusion: Postpartum hemorrhage was a common complication in patients with vWD, more after NSVD than C-Section. In a selected subset, EA was safely administered without bleeding complications, possibly due to pregnancy induced increase in factor VIII:C and von Willebrand factor activity counteracting the tendency to bleed. Larger series and prospective studies should be performed to confirm the safety of EA and the relationship to coagulation factor levels in pregnant women with vWD.

Women with Moderate and Severe Von Willebrand Disease Have a High Morbidity of Gynecological and Obstetric Bleeding

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 542-542
Author(s):  
Eva de Wee ◽  
Marieke Knol ◽  
Eveline Mauser-Bunschoten ◽  
Anske van der Bom ◽  
Manon Degenaar-Dujardin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Oral Contraceptives ◽  
Postpartum Hemorrhage ◽  
Von Willebrand Disease ◽  
Menstrual Bleeding ◽  
Advisory Committees ◽  
Bleeding Score ◽  
Type 3 ◽  
Von Willebrand

Abstract Abstract 542 Introduction Von Willebrand Disease (VWD) is the most common inherited bleeding disorder worldwide. Men and women are equally likely to be affected, but in women VWD is more often clinically manifest because of bleeding associated with menstruation and childbirth. Most studies investigating the prevalence of gynaecological bleeding problems in women with VWD are small case series of women with mainly type 1 or mild VWD. These studies may be hampered by selection bias given the fact that patients seeking medical attention for bleeding and menorrhagia have predominantly been included. Objective The aim of our study was to assess gynaecological and obstetrical symptoms in a large unselected cohort of women with moderate and severe VWD, and to investigate whether gynaecological bleeding problems affect quality of life (QoL). Design National cross-sectional study with patients recruited from all 13 Haemophilia Treatment Centers covering the Netherlands (the Willebrand in the Netherlands, WiN Study). Setting and Participants For this analysis, all 423 women aged 16 years or above from the WiN cohort were included. Methods Participants completed a detailed questionnaire, including the SF-36 for QoL and Tosetto Bleeding Score for bleeding severity. Menorrhagia was defined as the occurrence of ≥2 of the following symptoms: subjective excessive menstrual bleeding, loss of blood clots during menstrual bleeding, requirement of iron or blood transfusion, heavy menstrual flow that interferes with daily life, menstrual period that lasts longer than 7 days. Results 274 out of 423 (65%) women had type 1 VWD, 135 (32%) type 2 VWD, 10 (2%) type 3 VWD, and in 4 (1%) type was not specified. Menorrhagia was reported by 79% of the women. The two most frequent symptoms were excessive menstrual bleeding (82%) and loss of blood clots (80%). Women with type 3 VWD compared to women with type 1 and 2 VWD had more days with heavy menstrual bleeding (5 days versus 4 and 3 days respectively, p=0.03) and needed iron suppletion or blood transfusion more frequently (70% versus 43% and 36% respectively, p=0.08). Compared to women without menorrhagia, women with menorrhagia had significantly lower VWF antigen levels (29 vs 34 U/dL, p=0.022) and VWF ristocetin-cofactor levels (17 vs 23 U/dL, p=0.005). Treatment for menorrhagia consisted mainly of oral contraceptives (68%) and/or tranexamic acid (31%). QoL scores of women with menorrhagia were similar to those of women without menorrhagia. However, the subgroup of women with severe menorrhagia (Tosetto Bleeding Score on the menorrhagia item 4), had significantly lower QoL scores compared to women with no menorrhagia (BSmenorrhagia 0) for all four physical domains, the vitality domain, the social functioning domain and the physical component summary. Two domains: bodily pain (difference -17 [CI -25,-8]) and general health perceptions (difference -11 [CI -18,-4]), were clinically relevant with effect sizes ≥ 0.5. For all affected QoL domains, women with menorrhagia who used oral contraceptives or antifibrinolytics had higher scores, reflecting better QoL, than those who were not treated. Of all VWD women, 20% underwent a hysterectomy. In the group of women >40 years even 28% underwent a hysterectomy. The occurrence of postpartum hemorrhage was strongly increased compared to the general Dutch population: 24% vs 4% for primary postpartum hemorrhage, and 4% vs 2% for secondary postpartum hemorrhage. In 52% of the women with VWD who reported pregnancy losses (elective abortions, spontaneous miscarriages and fetal deaths), additional curettage was needed because of bleeding. Conclusion Women with moderate and severe VWD frequently have menorrhagia and bleeding complications during childbirth or after pregnancy loss. These gynecological complaints are associated with a lower QoL. Treatment of menorrhagia with oral contraceptives and tranexamic acid may improve QoL. Disclosures: Mauser-Bunschoten: CSL Behring: Membership on an entity's Board of Directors or advisory committees. Meijer:CSL Behring: Membership on an entity's Board of Directors or advisory committees. Leebeek:CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Research Funding, round table meetings; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Von Willebrand Factor Levels in The Diagnosis of Von Willebrand Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Mohamad A. Kalot ◽  
Nedaa Husainat ◽  
Abdallah El Alayli ◽  
Omar Abughanimeh ◽  
Osama Diab ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Health Benefit ◽  
Von Willebrand Disease ◽  
Test Accuracy ◽  
Sequence Variants ◽  
Continuous Variables ◽  
Von Willebrand

Von Willebrand Disease (VWD) is associated with significant morbidity as a result of excessive mucocutaneous bleeding symptoms. Patients with VWD can experience easy bruising, epistaxis, gastrointestinal and oral cavity bleeding, as well as heavy menstrual bleeding and bleeding after dental work, surgical procedures, and childbirth. Early diagnosis and treatment is important to prevent and treat these symptoms. We systematically reviewed the accuracy of diagnostic tests using different cut-off values of VWF:Ag and platelet-dependent VWF activity assays in the diagnosis of VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. Two investigators screened and abstracted data. Risk of bias was assessed using QUADAS-2 and certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity and reported patient important outcomes when relevant. This review included 21 studies that evaluated VWD diagnosis, including the approach to patients with VWF levels that have normalized with age (6 studies), VWF cut-off levels for the diagnosis of Type 1 VWD (9 studies), and platelet-dependent VWF activity/VWF:Ag ratio cut-off levels for the diagnosis of Type 2 VWD (6 studies). The results showed low certainty in the evidence for a net health benefit from reconsidering the diagnosis of VWD versus simply removing the disease in patients with VWF levels that have normalized with age. For the diagnosis of Type 1 VWD, in patients with VWF:Ag <0.30 IU/mL, VWF sequence variants were detected in 75-82% of patients in 2 studies, and for VWF:Ag between 0.30-0.50 IU/mL, VWF sequence variants were detected in 44-60% of patients in 3 studies. A sensitivity of 0.90 (95% CI: 0.83 to 0.94), and a specificity of 0.91 (95% CI: 0.76 to 0.97) were observed for a platelet-dependent VWF activity /VWF:Ag ratio of <0.7 in detecting type 2 VWD (moderate certainty in the test accuracy results). VWF antigen and platelet-dependent activity are continuous variables with an increase in bleeding risk with decreasing levels. This systematic review shows that using a VWF activity/VWF:Ag ratio of <0.7 versus lower cutoff levels in patients with an abnormal initial VWD screen is more accurate for the diagnosis of type 2 VWD.

scholarly journals Traumatic Hyphema in a Type 1 Von Willebrand Patient: Clinical Case and Management

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-30
Author(s):  
Jason Lewis ◽  
Jatinder Dhami ◽  
Michael Langue ◽  
Gayle Smink
Keyword(s):  
Intraocular Pressure ◽  
Board Of Directors ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Advisory Committees ◽  
Increased Risk ◽  
Elevated Intraocular Pressure ◽  
Von Willebrand ◽  
Willebrand Factor

Von Willebrand disease (vWD) is the most common inherited congenital bleeding disorder. Type 1 is a deficiency, but not absence, of von Willebrand factor (vWF) and is the most common type. Bleeding episodes in patients with type 1 vWD vary and are related to the relative amount of von Willebrand factor produced. We report a case of a 15-year-old male with mild von Willebrand disease type 1 (vWF: 35%) who presented with a right eye grade lll hyphema and elevated intraocular pressure (IOP) following a traumatic injury. Despite medical management with Diamox, ophthalmic steroids, vWF replacement with Humate-P, the patient had a repeat bleeding event and worsening of his elevated intraocular pressure. Due to concern for corneal blood staining, the patient required surgical intervention with an anterior chamber washout. Von Willebrand factor replacement was given on presentation and prior to the procedure with goal von Willebrand factor (vWF) activity and Factor Vlll (FVlll) levels of 80-100 IU/dL. Factor replacement for a traumatic hyphema is necessary to reduce bleeding, but could lead to increased risk of thrombosis formation and increase risk of corneal staining. Balance between bleeding and thrombosis can lead to treatment challenges in patients with bleeding disorders including vWD. Disclosures Smink: Forma Therapeutics:Membership on an entity's Board of Directors or advisory committees;Highmark Insurance:Membership on an entity's Board of Directors or advisory committees.

Pregnancy In Type 1 Von Willebrand Disease: A Prospective Study of VWF Levels and Risk Factors for Bleeding

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1410-1410
Author(s):  
Suman L. Sood ◽  
Andra H. James ◽  
Doug Bolgiano ◽  
Margaret V. Ragni ◽  
Amy D. Shapiro ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Loss ◽  
Exponential Growth ◽  
Research Funding ◽  
Von Willebrand Disease ◽  
Blood Type ◽  
Decay Model ◽  
Von Willebrand ◽  
Best Fit

Abstract Abstract 1410 Women with Type 1 von Willebrand disease (VWD) experience menorrhagia and postpartum hemorrhage (PPH) more than twice as often as women without VWD. VWF levels in women without VWD increase during pregnancy in an exponential manner, and fall postpartum. In type 1 VWD, limited data exist. The goal of this study is to model changes in VWF levels during and after pregnancy in women with Type 1 VWD, and correlate findings with blood loss. Women with Type 1 VWD, defined as at least 1 value of VWF:Antigen (Ag) or VWF:Ristocetin Cofactor (RCo) < 50%, VWF Ag/RCo > 0.7, and compatible history of mucosal bleeding pre-pregnancy, were recruited prior to 36 weeks gestation. Twin gestation, additional bleeding disorder, and anti-coagulant or -platelet therapy were excluded. Baseline demographic and bleeding scores were recorded. FVIII, VWF:Ag, and VWF:RCo were obtained monthly after enrollment, at labor, and postpartum (PP; 12, 24, 48 hours and 1, 2, and 6 weeks) and assayed centrally. Change in VWF:Ag levels during gestation and postpartum were modeled using longitudinal regression analysis. Twelve women were recruited from 4 HTCs with median (range) age 31.3 years (19-43), BMI 24.3 kg/m2 (18.1-40.5). All were Caucasian and of non-Hispanic ethnicity. One patient dropped out at 21 weeks gestation. 67% were blood type O; 25% A; 8% B; and 5/12 (42%) were primigravidae. Four patients reported prior PPH. Mean (SD) baseline bleeding score was 8 (7). Mean weeks gestation at delivery was 39 (1), with 2 Cesarean sections (18%). Seven women (64%) used epidural anesthesia, and 1 woman each used spinal, general, local, or no anesthesia. Seven women (64%) suffered genital laceration. Estimated blood loss (EBL) was mean 643 cc (309). One woman experienced immediate PPH, likely due to uterine atony, requiring 2 U PRBC. Three women experienced bleeding at 24–48h PP, and 1 at 1–2 weeks PP. One woman received DDAVP; 3 treated with VWF concentrate peri- and postpartum. Mean length of stay was 2 days (1). None required readmission, ICU stay, or procedures to stop bleeding. Mean (SD) VWF:Ag, VWF:RCo, and FVIII levels (%), respectively, at baseline were (n=11, 41.1 (7.1), 34.4 (8.4), 76.4 (70.8)), labor (n=11, 136.4 (50.8), 128.9 (47.8), 134.2 (42.7)), and 6 weeks PP (n=10, 57.8 (22.8), 52.1 (25.4), 80.9 (32.2)). VWF:Ag and VWF:RCo levels correlated well throughout for each woman (r 0.91–1, p <0.01). The rate of change of VWF levels was heterogeneous and varied individually, with differences between VWF:Ag value at baseline vs. labor ranging from 43–164% and from labor vs. 6 weeks PP 21–128%. During the gestational period, an exponential growth model best fit the rise in VWF:Ag level at labor relative to pre-pregnancy, VWF:Ag=exp(0.029 × gestational age in weeks), SD 0.0077. VWF:Ag is predicted to double from 17 weeks upwards. Postpartum, an exponential decay model predicted VWF:Ag levels should return to baseline by mean 3.6 weeks (SD 1.9) PP. 59 data points were available for the gestational, and 61 for the PP analyses. Variables associated with increased EBL include higher BMI (r, p; 0.88, 0.01), C-section (0.79, 0.03), genital laceration (0.79, 0.01), and manual placenta delivery (0.79, 0.01). Variables correlating with increased hemoglobin loss from 36 weeks to 24 h PP include episiotomy (0.75, 0.03) and degree of tear (0.99, 0.01). Cord blood obtained on 9 infants revealed a mean (SD) VWF:Ag, VWF:RCo, and FVIII level (%) 97.9 (35.8), 96.2 (34.8), 67.7 (22.6) at birth. None of 3 infants bled with procedures (1 circumcision, 2 blood draws). Infant VWD levels did not significantly correlate with respective maternal VWD levels at either baseline or labor. In conclusion, subjects with Type 1 VWD appear to have highly individual and heterogeneous rates of rise and decline of VWF levels during gestation and postpartum. Only one of 12 women in this study experienced PPH, attributed to atonic uterus. An exponential growth and decay model best fit the VWF:Ag peripartum levels. Variables correlating with blood loss include higher BMI, C-section, genital laceration, episiotomy, and degree tear. Although this study is small and the population homogenous, it demonstrates the importance of monitoring factor levels in women with Type 1 VWD, as the rise and fall in VWF levels are variable. Mutation analysis may help further explain the heterogeneity of individual responses. Additional studies are needed to better define risk factors associated with PPH in this population. Disclosures: James: CSL Behring: Consultancy, Research Funding. Shapiro:Baxter BioScience: Consultancy. Konkle:CSL Behring: Consultancy, Research Funding.

Characterisation of Type 2N von Willebrand Disease Using Phenotypic and Molecular Techniques

1996 ◽  
Vol 75 (06) ◽  
pp. 959-964 ◽  
Author(s):  
I M Nesbitt ◽  
A C Goodeve ◽  
A M Guilliatt ◽  
M Makris ◽  
F E Preston ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Von Willebrand Disease ◽  
Molecular Techniques ◽  
Haemophilia A ◽  
Binding Region ◽  
Gene Encoding ◽  
Covalently Linked ◽  
Von Willebrand ◽  
Willebrand Factor

Summaryvon Willebrand factor (vWF) is a multimeric glycoprotein found in plasma non covalently linked to factor VIII (FVIII). Type 2N von Willebrand disease (vWD) is caused by a mutation in the vWF gene that results in vWF with a normal multimeric pattern, but with reduced binding to FVIII.We have utilised methods for the phenotypic and genotypic detection of type 2N vWD. The binding of FVIII to vWF in 69 patients, 36 with type 1 vWD, 32 with mild haemophilia A and one possible haemophilia A carrier with low FVIII levels was studied. Of these, six were found to have reduced binding (five type 1 vWD, one possible haemophilia A carrier), DNA was extracted from these patients and exons 18-23 of the vWF gene encoding the FVIII binding region of vWF were analysed. After direct sequencing and chemical cleavage mismatch detection, a Thr28Met mutation was detected in two unrelated individuals, one of whom appears to be a compound heterozygote for the mutation and a null allele. No mutations were found in the region of the vWF gene encoding the FVIII binding region of vWF in the other four patients

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

2021 ◽  
Vol 47 (02) ◽  
pp. 192-200
Author(s):  
James S. O'Donnell
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Personalized Treatment ◽  
Treatment Plans ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

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