Acute Hemorrhagic Manifestations in a Pregnant Patient With Type 1 von Willebrand Disease: Challenges in Management of Bleeding Disorders During Gestation

ABSTRACT

This case reports a primigravida with Type 1 von Willebrand disease experiencing hematuria and gingival bleeding despite prophylaxis. Although pregnancy raises factor levels, her response was insufficient. Desmopressin successfully controlled mucosal hemorrhage, avoiding antifibrinolytics due to obstructive risk. Management requires multidisciplinary surveillance to tailor peripartum hemostatic interventions.

Key Clinical Message

Managing Type 1 von Willebrand disease in pregnancy requires multidisciplinary surveillance, as physiological factor increases may not prevent bleeding. While desmopressin effectively controls mucosal hemorrhage, antifibrinolytics should be avoided if hematuria presents an obstructive risk. Tailored hemostatic interventions are essential for safe peripartum care.

1. Introduction

Von Willebrand disease (VWD) is recognized as the most prevalent inherited bleeding disorder, affecting approximately 0.1%–1.3% of the general population [1]. It arises from either quantitative deficiencies or qualitative defects in von Willebrand factor (VWF), a large multimeric glycoprotein essential for hemostasis [2]. VWF performs two critical functions: mediating platelet adhesion to the vascular subendothelium at sites of injury and acting as a protective carrier for coagulation factor VIII (FVIII), preventing its premature degradation in circulation [2]. VWD is categorized into three primary types, with Type 1 representing approximately 75%–80% of cases, characterized by a partial quantitative deficiency of functionally normal VWF [3].

Pregnancy typically induces a profound prothrombotic shift, characterized by a progressive increase in several procoagulant factors, most notably VWF and FVIII, which can rise to 200% to 300% of pre‐pregnancy baselines in healthy individuals [3]. While many patients with Type 1 VWD experience a physiological normalization of these factors by the third trimester, this rise is inconsistent and highly dependent on the underlying molecular subtype and baseline factor levels [2]. Consequently, despite the protective effect of pregnancy, individuals with VWD remain at an elevated risk for both antepartum and postpartum hemorrhagic complications [3].

Clinical manifestations usually involve mucocutaneous bleeding, such as epistaxis, gingival bleeding, and easy bruising, though more severe presentations like hematuria can occur [2]. Management requires a highly coordinated, multidisciplinary approach to navigate the risks of hemorrhage during the gestational and peripartum periods [3]. Severe complications due to bleeding manifestations may compromise maternal and child health and often represent a challenge for obstetricians. We present a case of a 27‐year‐old primigravida patient with a history of VWD who has been managed with a monthly dose of factor VIII, and who presented to the emergency department with hyperemesis gravidarum and bleeding manifestations. The patient was successfully managed with the administration of desmopressin (DDAVP) with a favorable outcome.

2. Case History/Examination

A 27‐year‐old female patient, primigravida (G1L0), with a 6‐week pregnancy and a prior diagnosis of Type 1 VWD, was admitted to the emergency department with a 5‐day history of recurrent vomiting, holocranial headache, hematuria, dysuria, and gingival bleeding. Due to her previous diagnosis of VWD, she has been managed on an outpatient basis with monthly administration of plasma‐derived factor VIII/von Willebrand factor (FVIII/VWF) concentrate at a dose of 30 IU/kg, in accordance with national protocols for VWD. However, it should be noted that the patient reported not receiving her concentrate for the past 2 months due to administrative barriers.

3. Differential Diagnosis, Investigations, and Treatment

Upon admission, the physical exam showed slight signs of dehydration, hypogastrium tenderness, and bleeding stigma in the urethra. Vaginal examination showed no cervical changes, and a quick transvaginal ultrasound scan showed an intrauterine gestational sac with a positive normal embryocardia. Laboratory tests revealed a complete blood count with a hemoglobin level of 13.9 g/dL, without leukocytosis or neutrophilia, a normal platelet count, and a completely normal coagulation profile. Urine analysis showed macroscopic hematuria with a red blood cell count of 100 RBC/hpf and +++ bacteria. Serum electrolytes showed mild hyponatremia and hypokalemia.

Management with intravenous fluids and antiemetics was initiated with the diagnosis of hyperemesis gravidarum, with a favorable clinical response. Urine culture results showed Escherichia coli with the usual sensitivity pattern, so a 7‐day course of cefazolin was also initiated to treat the lower urinary tract infection. However, the patient persisted with clinical bleeding manifestations (gingival bleeding and hematuria), with a decrease in hemoglobin to 8.4 g/dL. The internal medicine team recommended transfusion of 1 unit of PRBC, with adequate rise in hemoglobin levels.

4. Conclusion and Results

Since there was no availability of factor VIII in the institution, it was decided to administer desmopressin at a dose of 15 mcg subcutaneously daily for 3 days. The patient showed a favorable clinical course, with resolution of the vomiting episodes, control of the bleeding sites, allowing for hospital discharge without further complications. Specific plasma hemostatic assays—including von Willebrand factor antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII activity (FVIII:C)—were unavailable in our emergency setting for urgent pre‐ and post‐treatment monitoring. Consequently, therapeutic management was guided by clinical evaluation and standard complete blood counts.

5. Discussion

The presentation of this primigravida with Type 1 VWD exhibiting hematuria and gingival bleeding highlights the complexity of managing inherited bleeding disorders during pregnancy. Although Type 1 VWD is often considered a milder form of the disease, the severity of bleeding symptoms is variable and correlates with the degree of VWF and FVIII reduction [4]. In this case, the patient was previously managed with monthly applications of Factor VIII, a strategy typically reserved for more severe phenotypes or those with significant bleeding histories to maintain adequate hemostatic coverage [5].

The physiological dynamics of VWF during pregnancy are largely driven by rising estrogen levels, which stimulate the synthesis and secretion of VWF from endothelial cells [5]. In most Type 1 VWD patients, VWF and FVIII levels rise progressively, often reaching hemostatically safe thresholds (above 0.50 IU/mL) by delivery time [6]. However, patients with specific genetic variants, such as those associated with Type 1C (increased clearance), may fail to achieve these protective levels despite increased synthesis [6]. The occurrence of hematuria and gingival bleeding in this patient suggests that her endogenous factor rise was insufficient to prevent mucosal and renal tract hemorrhage, necessitating acute intervention.

Desmopressin (DDAVP), a synthetic analog of vasopressin, remains the treatment of choice for most of the Type 1 VWD patients who have demonstrated responsiveness in pre‐pregnancy trials [7]. DDAVP acts by triggering the release of endogenous VWF and FVIII from Weibel‐Palade bodies in endothelial cells, typically providing a three‐ to five‐fold increase in plasma activity [7]. Its use in this case successfully managed the acute bleeding manifestations. However, the administration of DDAVP during pregnancy requires caution; its antidiuretic properties necessitate strict fluid restriction and monitoring of serum sodium to prevent severe hyponatremia, particularly when administered concurrently with intravenous fluids or oxytocics during labor [4]. The management of hematuria in VWD presents a unique therapeutic challenge.

A critical limitation in repeated DDAVP administration is the development of tachyphylaxis. DDAVP acts by stimulating the exocytosis of stored VWF and FVIII from endothelial Weibel‐Palade bodies; repeated daily dosing over 24–48 h leads to progressive depletion of these intracellular pools, resulting in diminished hemostatic response by the third day [5]. While daily DDAVP for 3 days successfully controlled mucosal hemorrhage in this emergency presentation, extended or repeated dosing carries a high risk of loss of efficacy. In scenarios requiring sustained hemostatic support beyond 24–48 h, transitioning to plasma‐derived VWF/FVIII concentrate is required.

While antifibrinolytic agents like tranexamic acid (TXA) are standard adjunctive therapies for mucosal bleeding in VWD, they are relatively contraindicated in the presence of gross hematuria [5]. This is due to the risk of forming non‐lysable clots within the ureters or bladder, potentially leading to urinary tract obstruction and subsequent renal complications [5]. Therefore, reliance on DDAVP or VWF/FVIII concentrates is preferred in such scenarios to achieve hemostasis without compromising renal drainage [4].

Literature emphasizes that the goal of peripartum management is maintaining VWF activity and FVIII levels at a minimum of 0.50 IU/mL for delivery and the immediate postpartum period [5]. For patients whose levels do not correct to this threshold, exogenous replacement with plasma‐derived VWF/FVIII concentrates or DDAVP is mandatory [7]. Furthermore, because factor levels decline precipitously following the delivery of the placenta—returning to baseline within 7–21 days—there is a significant risk for secondary (late) postpartum hemorrhage. Extended prophylaxis with antifibrinolytics or factor support for 1–2 weeks postpartum is often recommended to bridge this period of physiological decline [7].

Finally, the care of the VWD patient must account for neonatal risks. Most forms of VWD are inherited in an autosomal dominant manner, meaning the fetus has a 50% chance of being affected [1]. To protect a potentially affected neonate, current guidelines recommend the avoidance of traumatic delivery techniques, such as vacuum extraction or high‐cavity forceps, which significantly increase the risk of neonatal intracranial hemorrhage [1]. The successful management of Type 1 VWD in pregnancy requires an integrated management paradigm that balances the physiological changes of gestation with the patient's specific hemorrhagic risks.

While many women experience a natural improvement in factor levels, this case demonstrates that clinically significant bleeding, such as hematuria and gingival hemorrhage, can still occur and requires prompt treatment. Desmopressin remains a highly effective targeted therapy for Type 1 VWD responders, though its use must be carefully balanced with fluid management to avoid hyponatremia. A multidisciplinary framework involving hematology, obstetrics, and anesthesia is essential to ensure a safe delivery and to minimize the heightened risk of both primary and secondary postpartum hemorrhage in this vulnerable population.

Author Contributions

Jose Luis Rojas‐Oviedo: conceptualization, writing – original draft, methodology, investigation. María Fernanda Leal Walteros: writing – original draft, visualization, formal analysis. Dauris Lineth Mejía Pérez: conceptualization, supervision, writing – review and editing. Jorge Eliecer Castellanos Corredor: investigation, project administration, writing – review and editing. Danna Geraldinne Amaya Sánchez: formal analysis, data curation, methodology. Ana Sofía Lancheros Ramírez: methodology, validation.

Funding

The authors have nothing to report.

Ethics Statement

Ethical compliance with the Helsinki Declaration, current legislation on research Res. 008430‐1993 and Res. 2378–2008 (Colombia), and the International Committee of Medical Journal Editors (ICMJE) were ensured under our Ethics and Research Institutional Committee (IRB) approval, prior signing of informed consent by the patient. The protocol for this article was previously approved by the Ethics Committee of our institution (Subred Integrada de Servicios de Salud Sur).

Consent

The patient subject of this report previously signed the written informed consent form in the presence of two witnesses, authorizing the anonymous use of all the information from her medical history and corresponding images in any publications with scientific or academic interest.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data used in the present study are available upon request to the corresponding author.