A 12-year-old Hispanic girl presented to the emergency department reporting blood in her stool for the past 3–4 months. She noted her stool became more strand-like and occasionally loose. Patient denied abdominal pain, constipation, dizziness, or tiredness. Family history included polycystic kidney in the father and Inflammatory bowel disease (IBD) and thyroiditis in the mother. The ED considered various differentials such as infectious colitis, IBD, and Meckel's diverticulum. CBC, CMP, CRP, ESR, Lipase, PT, PTT, urine dipstick, and urine pregnancy were tested and were all within normal range. An outpatient colonoscopy revealed diffuse areas of moderately congested erythematous, inflamed, and ulcerated mucosa in rectum, sigmoid colon, and descending colon (Figure 1). The transverse and ascending colon and cecum were normal. She was diagnosed with uncomplicated ulcerative rectosigmoiditis and prescribed sulfasalazine, prednisone, lansoprazole, and folic acid by pediatric GI. Cultures for Salmonella, Shigella, Campylobacter, Escherichia coli, and Clostridioides difficile were negative. The upper endoscopy done a week later showed acute on chronic gastritis with contiguous colitis from splenic flexure to the rectum. Her diagnosis was changed to indeterminate colitis due to concurrent gastric inflammation. Her Pediatric Ulcerative Colitis Activity Index (PUCAI) was 55–60 and she was deemed to have moderate disease activity. Subsequently, her IBD disease activity as well as anxiety levels waxed and waned, and she required occasional inpatient psychiatric care due to suicidal thoughts. Over the next few years, she had intermittent hematochezia and microcytic anemia, and she received several blood transfusions and iron infusions. Due to suboptimal response to therapy, she was transitioned to adalimumab, after which she developed thrombocytopenia. Her thrombocytopenia was treated with intravenous immunoglobulins and eltrombopag. She had her first intestinal resection surgery (laparoscopic total abdominal colectomy with end ileostomy) about a year into her diagnosis, and it was “complicated by excessive blood loss/oozing that required several units of blood and platelets.” Because of continued symptoms, she underwent a second surgery (proctectomy) 1 year later. Over the past 1 year, her platelet count stayed around 100,000 per µL, and her GI symptoms were moderately controlled on ustekinumab. Subsequently, the family relocated and established care with local pediatric specialists. When we first saw the patient, she had been treated for over 5 years and reported ongoing intermittent rectal bleeding and blood-stained mucus discharge. Lab testing showed von Willebrand factor (vWF) antigen level of 61% and vWF activity of 20%. This disparity was confirmed on several tests over the next 6 months (Figure 2). The VW multimers and vWF GPIbM activity were in normal range, but vWF collagen binding activity was low. Genetic testing showed a heterozygous mutation c.8366C>G (p.Thr2789Ser) in the vWF gene. Coincidentally, this specific genetic mutation was also described in the Spanish Von Willebrand disease (VWD) registry in a 45-year-old symptomatic female by Borràs et al. 1. Our patient was prescribed on-demand and prophylactic vWF replacement after which her rectal bleeding resolved. Coexistence of VWD and IBD presents a rare but clinically significant diagnostic and management challenge. Both conditions, though distinct in etiology—one being a congenital bleeding disorder and the other an immune-mediated gastrointestinal inflammatory disease—share overlapping clinical manifestations, especially gastrointestinal bleeding. This review explores the diagnostic and clinical challenges of coexisting VWD and IBD. The clinical overlap between VWD and IBD centers on mucosal bleeding, fatigue, and iron deficiency anemia—symptoms that are common to both conditions. Those with VWD, especially Types 2 and 3, often have gastrointestinal bleeding from angiodysplasia or mucosal fragility. Concurrently, IBD—especially ulcerative colitis—often presents with hematochezia, cramping, and diarrhea, which may mask or mimic bleeding related to coagulopathies. This symptom overlap complicates diagnosis and delays care. In a case report by Olivier et al., a patient with hemophilia A and ulcerative colitis presented with significant rectal bleeding, initially attributed to the bleeding disorder but later confirmed to be exacerbated by mucosal inflammation secondary to IBD 2. This case exemplifies the diagnostic uncertainty that arises when a known bleeding disorder coexists with gastrointestinal pathology. The challenge gets magnified manyfold when the patient does not have a previously confirmed diagnosis of bleeding disorder, as happened in our patient. Typically, acute and chronic inflammation trigger an increase in circulating vWF levels, reflecting inflammation. Meucci et al. demonstrated that serum vWF levels correlate with disease activity and systemic inflammation in IBD, suggesting vWF as a marker of disease severity 3. Similarly, Zezos et al. noted elevated plasma vWF levels in those with active ulcerative colitis, linking this rise to endothelial perturbation and systemic inflammatory stress 4. However, in our case, the patient's laboratory profile revealed decreased vWF activity during active IBD, deviating from the expected inflammatory response. This finding may reflect an underlying congenital VWD whose phenotypic expression is not masked—even in the setting of inflammation. Alternatively, it could suggest a consumptive process where vWF is rapidly degraded or cleared, potentially from enhanced proteolysis or endothelial dysfunction exacerbated by mucosal inflammation. Lagrange et al. expanded on this by showing that vWF's role in IBD extends beyond bleeding and thrombosis. They proposed that vWF may modulate immune cell trafficking and tissue repair, linking it to pathogenesis and regulation of mucosal inflammation 5. Thus, variations in vWF levels in IBD may not solely reflect hemostatic status but also underlying immune dysregulation. The interplay between platelets, vWF, and the procoagulant phenotype of IBD further complicates clinical assessment. Schellenberg et al. described a paradoxical prothrombotic state in IBD, with high platelet counts and activation, partly mediated by increased vWF and its interaction with platelet glycoprotein Ib receptors 6. In such a milieu, coexisting VWD might alter the thrombotic balance, possibly mitigating some risks while exacerbating bleeding tendencies. These hemostatic shifts suggest that VWD may, paradoxically, influence IBD activity and progression. Thompson et al. investigated whether inherited coagulopathies confer protection against IBD and found a reduced prevalence of IBD in individuals with bleeding disorders, including VWD 7. They hypothesized that hypocoagulability might dampen the thromboinflammatory feedback loop that sustains mucosal damage in IBD. This may explain the atypical disease course or severity observed in those with both VWD and IBD. Nonetheless, protective effects are not universally observed and do not eliminate the challenge of managing bleeding and flares. Diagnosing either condition with the other requires careful consideration and a comprehensive diagnostic workup. In cases of unexplained or disproportionate gastrointestinal bleeding, coagulation studies including vWF antigen, ristocetin cofactor and GP1bM activity, Factor VIII levels, and multimer analysis should be pursued alongside standard endoscopic and inflammatory assessments. Our case illustrates a dilemma: a patient with active ulcerative colitis, without varices or angiodysplasia, had gastrointestinal bleeding with disproportionately low vWF activity. Here, relying on inflammation-induced vWF elevation as a diagnostic clue may be misleading. Instead, a nuanced interpretation of vWF assays, ideally repeated over time and in correlation with markers like C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), becomes essential. Further complicating diagnosis is the potential for acquired von Willebrand syndrome (AvWS), especially in those with autoimmune diseases, malignancies, or cardiac conditions. While rare, AvWS should be considered when vWF activity is unexpectedly low, especially without a known family history of bleeding disorders. The dual presence of VWD and IBD necessitates Individualized care. Bleeding control in VWD typically requires desmopressin (DDAVP), vWF-containing concentrates, and antifibrinolytics. However, DDAVP may have limited utility in Type 2B and Type 3 VWD or when the response is unpredictable during systemic inflammation. In parallel, IBD management with corticosteroids, immunomodulators, or biologics (e.g., anti-TNF agents) must consider the patient's hemostatic profile. For example, biologic agents may increase infection risk and, in some cases, affect coagulation. Furthermore, mesalamine, a common first-line agent in ulcerative colitis, may cause platelet dysfunction, potentially compounding bleeding risks in VWD patients. Prophylactic vWF replacement therapy may be warranted before invasive procedures. Interdisciplinary collaboration between gastroenterologists, hematologists, and surgeons is critical in minimizing iatrogenic complications. Thromboprophylaxis poses another therapeutic conundrum. Despite the bleeding tendency in VWD, those with IBD, especially during flares or hospitalization—are at increased risk of venous thromboembolism (VTE). The use of low molecular weight heparin or other anticoagulants must be judicious, balancing VTE prevention with the risk of gastrointestinal hemorrhage. Coexisting VWD and IBD are rare but diagnostically and therapeutically complex. The overlapping clinical presentations, contradictory laboratory trends—such as decreased vWF activity despite active inflammation—and the dual demands of managing bleeding and inflammation underscore the need for vigilant clinical assessment and personalized care. Emerging literature suggests that vWF plays multifaceted roles in both bleeding and inflammatory processes. While systemic inflammation typically elevates vWF levels, congenital deficiencies may manifest atypically, during inflammation. Although DNA testing is not required to establish a diagnosis of VWD in most instances, this case shows a useful role for DNA testing when comorbid disease processes alter more typical protein interactions. Future research should focus on developing diagnostic algorithms and treatment guidelines tailored to patients with overlapping hematologic and gastrointestinal conditions. Until then, a collaborative, evidence-informed approach remains essential. S.P. conceptualized and wrote the original draft. All authors contributed to review & editing, formal analysis, and validation of the manuscript. We are grateful to the nurses and staff of Cure 4 The Kids Foundation for their commitment, care, and support towards pediatric hematology and oncology patients. The authors have nothing to report. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. The authors have nothing to report.
Pratap et al. (Fri,) studied this question.