A 48-year-old Caucasian man from Wisconsin, USA, was referred to our hospital for further evaluation of iron deficiency anemia, palpitations, dizziness, and right calf discomfort. His symptoms progressively developed over a period of two weeks before presentation. Apart from a history of intermittent heartburn relieved by calcium carbonate, he had no other major medical problems and was not on any prescription medications. He was not a smoker and did not drink alcohol or use any illicit drugs. He denied a previous history of malignancy or venous thromboembolism. His parents and siblings were healthy and there was no history of VTE in any first-degree relatives. He was complaining of mild dizziness and intermittent mild shortness of breath that started on the day of presentation. He denied any chest pain, syncope, bloody stools, or fevers.
Physical exam revealed a well appearing male in no distress. He was afebrile, normotensive, and tachycardic with a heart rate of 103 beats per minute. Laboratory studies showed severe iron deficiency anemia (Hgb: 91 g/dL, MCV: 60 fL, iron: 14 mcg/dL, iron saturation: 4%, TIBC: 369 mcg/dL, and ferritin: 7 mcg/dL). Other laboratory studies included WBC: 5.8, Plt: 269, and INR: 1.1. Fecal occult blood testing was negative. He had no microscopic hematuria and liver function tests were normal. Troponin I was undetectable.
Doppler of the right lower extremity showed extensive DVT, occlusive in the calf veins, popliteal and lower segments of right femoral vein and nonocclusive thrombosis in the mid and upper segments of the femoral vein. CT scan of the chest with IV contrast showed bilateral pulmonary emboli, greater on the right, most prominently seen within the distal right main pulmonary artery and to a lesser degree on the left within segmental and subsegmental branches (Figure 1). There was some flattening of the interventricular septum suggesting right heart strain. Echocardiogram was subsequently performed and demonstrated normal left ventricular ejection function, mild decrease in right ventricular ejection function, and no wall motion abnormalities. He received IV heparin initially and was transitioned to apixaban for long term anticoagulation. Extensive work-up for hypercoagulability revealed no abnormalities. It included Factor V Leiden, protein C and S levels, prothrombin mutation, antithrombin deficiency, antiphospholipid antibodies, and homocysteine levels. CT scan of abdomen and pelvis with and without IV contrast showed no masses suspicious for malignancy.
Serologic studies for celiac disease revealed positive and significantly elevated antibodies: anti-gliadin IgA (>150 units, normal range < 20 units), anti-gliadin IgG (81.5 units, normal range < 20 units), anti-tissue transglutaminase IgA (127.3 units, normal range < 15 units), anti-tissue transglutaminase IgG (60.1, normal range < 15 units), and positive IgA endomysial antibodies (1 : 80 titer). Celiac associated HLA-DQ typing revealed a permissive genotype with positive HLA-DQ2 and HLA-DQ8. Esophagogastroduodenoscopy (EGD) showed nearly complete absence of duodenal folds along with flattened duodenal mucosa. Biopsies were taken and histology showed partial villous atrophy (villous : crypt ratio 1 : 3) with crypt hyperplasia and a marked increase in intraepithelial lymphocytes (80 lymphocytes per 100 epithelial cells) consistent with celiac sprue, Marsh classification 3B (Figures 2 and 3). Colonoscopy showed normal mucosa throughout the colon. He was started on a gluten-free diet and was prescribed iron supplements for 3 months. For his pulmonary embolism, he has been placed on long term anticoagulation using apixaban. Three months following the diagnosis, his hemoglobin, iron, and ferritin levels have normalized. He continues to follow a gluten-free diet and has experienced no adverse effects from anticoagulation.