A Perfect Storm for Bleeding: Concurrent Deficiencies of Vitamin C, Selenium, and Zinc in a Young Adult

We describe, to our knowledge, the first reported case of concurrent vitamin C, selenium, and zinc deficiencies manifesting as spontaneous calf hematoma and profound anemia in a young adult with extreme dietary selectivity. This case underscores the importance of considering micronutrient deficiencies in the differential diagnosis of unexplained bleeding and anemia, particularly in patients with restrictive eating patterns and unremarkable coagulation studies.

A 21-year-old male with a history of anxiety on stable fluoxetine presented with 1 week of spontaneous left calf bruising, swelling, and progressive leg pain causing difficulty with ambulation. This was associated with gingival bleeding for the same duration. He also reported a year-long history of petechiae on his arms and legs. He denied any history of trauma, gastrointestinal bleeding, or a personal or family history of bleeding disorders. Over the past year, his diet had been highly restrictive, limited to one meal per day and occasional snacks of crackers and pretzels, with a complete exclusion of leafy greens, red meat, and minimal intake of fruits. He denied alcohol use or a history of eating disorders but described himself as a picky eater. On presentation, he was hemodynamically stable but underweight, with a body mass index (BMI) of 18.12 kg/m². Physical examination revealed a swollen left calf with extensive ecchymosis extending above the knee and perifollicular hemorrhages on his limbs (Figure 1).

Laboratory studies demonstrated hemoglobin (Hb) of 7.8 g/dL (reference range [RR]: 13.0–18.0 g/dL), mean corpuscular volume (MCV) of 80 fL (RR: 80–100 fL), with normal white blood cell and platelet counts. Last complete blood count done 5 years ago showed Hb of 15.1 g/dL with MCV of 81.5 fL. Coagulation studies showed a borderline elevated international normalized ratio (INR) of 1.2 (RR: 0.9–1.1) and a normal activated partial thromboplastin time (aPTT). Initial laboratory evaluation showed mild elevations in total bilirubin (3.9 mg/dL; RR: 0.3–1.2 mg/dL) and indirect bilirubin (2.8 mg/dL; RR: 0.1–1 mg/dL), normal albumin level and an elevated reticulocyte count (152 × 10³/μL; RR: 28–139 × 10³/μL). Peripheral blood smear review was unremarkable. Hematologic workup for hemolysis was unremarkable, with a normal disseminated intravascular coagulation (DIC) panel, lactate dehydrogenase (LDH), haptoglobin, and a negative direct Coombs test.

Imaging, including an x-ray of the left knee and Doppler ultrasound, revealed no acute osseous abnormalities or deep vein thrombosis. Computed tomography (CT) angiogram of the left lower extremity demonstrated soft tissue swelling of the posterior compartment musculature of the left leg involving gastrocnemius and soleus muscles concerning for intramuscular hematoma without evidence of active extravasation.

Evaluation for inherited and acquired bleeding disorders was unremarkable except for mildly decreased Factor VII (FVII). Given the patient's highly selective diet, nutritional testing was pursued, revealing severe vitamin C deficiency, with concurrent low selenium, zinc, and iron levels. Full laboratory data are summarized in Table 1.

He was diagnosed with scurvy, along with concomitant selenium and zinc deficiencies. He was started on intravenous vitamin C, intravenous iron, and oral selenium and zinc supplementation. During his hospitalization, the calf hematoma and anemia improved. He was discharged with oral nutritional supplementation and arranged for close outpatient follow-up with hematology and adolescent eating disorder clinic. On outpatient follow-up, his hematoma had completely resolved, and his blood work about 2 months later showed significant improvement, with correction of anemia (Hb 15.9 g/dL, MCV 83.7 fL) and nutritional deficiencies (Table 1).

Scurvy is a nutritional disorder caused by a deficiency of vitamin C (ascorbic acid). Insufficient dietary intake of vitamin C is the most common cause of scurvy in children and young adults. In our patient, a nutritionally inadequate diet, with no consumption of fruits and vegetables, resulted in scurvy. Vitamin C is crucial for the hydroxylation of proline and lysine residues in collagen, a process catalyzed by the enzymes prolyl hydroxylase and lysyl hydroxylase, respectively, to produce hydroxyproline and hydroxylysine. Inadequate hydroxylation impairs collagen synthesis, leading to increased vessel wall and skin fragility, and delayed wound healing [1]. Symptoms of scurvy typically emerge after 4–12 weeks of inadequate vitamin C intake when serum ascorbic acid levels fall below 0.2 mg/dL [1]. In our patient, the vitamin C level was severely low at less than 0.1 mg/dL. Common dermatological manifestations include dry skin, petechiae, ecchymoses, and follicular hyperkeratosis. Musculoskeletal symptoms (joint bleeding and muscle hematomas) and bleeding gums result from impaired collagen formation in vascular walls.

Alongside vitamin C deficiency, our patient had deficiencies in selenium and zinc, both of which play essential roles in maintaining tissue integrity and hemostasis. Selenium, found primarily in the form of selenoproteins like glutathione peroxidase (G-Px), is critical for antioxidant protection, helping to shield cells from oxidative damage. Selenium is naturally found in soil, leading to its presence in plants, as well as in animals that consume selenium-containing plants [2]. In the United States, the recommended dietary allowance for selenium is typically met through a mixed diet, with deficiency in other countries usually resulting from insufficient intake due to regional scarcity [3]. Selenium deficiency, particularly in regions with low soil selenium or in individuals receiving parenteral or enteral nutrition, or those with malabsorption disorders, can lead to a spectrum of musculoskeletal complications, including muscle pain, weakness, and fatigue. Chronic selenium deficiency impairs the function of selenoenzymes, which protect muscle tissue from oxidative damage. Although selenium deficiency has been associated with muscle disorders, direct evidence linking it to an increased bleeding tendency is sparse [4].

Zinc is another vital trace element that plays a pivotal role in coagulation and wound healing. It contributes to platelet function by promoting activation and aggregation, partly through reactive oxygen species generation [5]. Zinc also supports coagulation by influencing plasma clotting factors and facilitating interactions between platelets and the vascular endothelium. Serum zinc levels below 50 μg/dL impair platelet function, while levels below 60 μg/dL affect coagulation, increasing bleeding risk. In our patient, zinc level was low at 52 μg/dL. Additionally, zinc is essential for wound healing, promoting epithelial regeneration, angiogenesis, and extracellular matrix remodeling [5]. Deficiency impairs these processes, leading to bleeding and delayed wound repair.

Our patient also had a mildly reduced FVII level despite a normal Vitamin K level. Given that bleeding events are uncommon when FVII activity exceeds 10%, the slight decrease in FVII is unlikely to have contributed significantly to his presentation [6]. The reason for the mildly low FVII level in the setting of normal Vitamin K remains unclear. The FVII level self-corrected on repeat testing, suggesting that the mildly low FVII at presentation was likely due to factor consumption from the extensive calf hematoma.

Our patient also had anemia with low-normal MCV. Iron studies showed low serum iron, low-normal TIBC, low iron saturation, and low-normal ferritin, consistent with a mixed picture of anemia of inflammation with probable iron deficiency. Vitamin C is necessary for GI absorption of iron, integrating iron into heme and maintaining RBC cytoskeletal integrity [7]. Low selenium levels are linked to anemia because selenium's antioxidant function protects red blood cells from oxidative stress, preventing increased fragility. Due to the antioxidant role of selenium, it is thought that selenium deficiency can lead to increased RBC fragility through increased oxidative stress. Given low-normal MCV and ferritin, poor iron intake with inadequate iron absorption from the gut due to scurvy was the most likely contributory factor in our patient. Calf intramuscular hematoma contributed to anemia. Normal LDH in our patient suggests a lack of significant intravascular hemolysis. The lower extremity ecchymosis and its resorption likely caused an increase in indirect bilirubin due to extravascular breakdown of RBCs at the sites of bruising. Although not relevant to our case, patients with a history of gastrointestinal issues or bariatric surgery are at increased risk for micronutrient deficiencies and should be considered for comprehensive micronutrient testing as part of the anemia workup.

In this case, the patient's multifactorial bleeding diathesis was probably a result of severe deficiencies in vitamin C, selenium, and zinc, each contributing to the observed bleeding manifestations leading to a “perfect storm” to bleed. We hypothesize that the bleed resulted from the combined effects of vitamin C deficiency-induced impaired collagen synthesis and selenium deficiency-related muscle fragility. Vitamin C deficiency contributed to the patient's gingival bleeding through compromised vascular integrity and defective connective tissue support. Meanwhile, zinc deficiency likely exacerbated the bleeding tendency by impairing platelet function and disrupting normal hemostasis. This is the first case reporting a combination of scurvy, with selenium and zinc deficiencies, presenting as spontaneous calf hematoma and significant anemia. There is one other case in the literature reporting a 7-year-old boy with autism spectrum disorder and highly selective diet who presented with anemia, gingival bleeding, and perioral lesions and was found to have concomitant scurvy and selenium deficiency [8].

A number of teaching points can be gleaned from this case. First, even in developed countries, scurvy can occur, especially in patients with restrictive diets. Second, this case underscores the importance of considering micronutrient deficiencies in the differential diagnosis of unexplained bleeding, especially when initial coagulation labs are normal. Thirdly, scurvy and trace mineral deficiency should also be considered as a differential diagnosis for unexplained anemia and/or easy bruising, particularly, if the patient has risk factors for nutritional deficiency.

Z.K. and R.V. involved in conception and design, collected the data, drafted the manuscript, and finally approved the version to be published. P.K. revised the manuscript, and finally approved the version to be published.

This case report was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. Informed consent was obtained from the patient for the publication of this report, including relevant clinical details and any accompanying images. All efforts have been made to maintain patient anonymity, and no identifiable information has been disclosed. The authors declare no conflicts of interest related to this case.

Written informed consent was obtained from the patient.

The authors declare no conflicts of interest.