Discussion
To our best knowledge, this is the first report of endoscopic findings of gastric lesions likely caused by PNH-related thrombosis; patchy areas of gastric redness were the distinctive features. We hope this report will help clinicians recognize and manage the rare but potentially serious gastrointestinal complications of PNH.
Making the diagnosis of PNH-related thrombosis can be challenging, mainly because of unfamiliarity with this rare complication. In our patient, the cause of the gastroduodenal lesions in our patient was initially unexplained: H. pylori had been eradicated; she used non-steroidal anti-inflammatory drugs only occasionally; she did not take antithrombotic drugs; and she had no abnormal laboratory tests or past history or family history suggesting other gastrointestinal diseases, e.g., inflammatory bowel diseases, autoimmune vasculitis, or viral infection. In addition, endoscopic biopsy did not show any disease-specific findings.
PNH-related thrombosis is rarely encountered in Japan. The prevalence of PNH is 6.93 per million population,7 and PNH-related thrombosis is reported in only 4.3% of PNH patients in Japan.8 On the other hand, about half of PNH patients in Western countries die from thrombotic complications9; this regional difference is unexplained. Nonetheless, thromboembolic complications are a significant cause of death in PNH. Hemolysis and elevation of D-dimer levels, noted in our patient, are known as the signs of thrombotic complications.4, 10 In addition, in PNH-related thrombosis, intraabdominal veins are most often involved.11 Thus, thrombotic gastrointestinal injury should be suspected in patients with PNH presenting with such laboratory findings and gastrointestinal symptoms.
Clinical manifestations and endoscopic findings of PNH-related upper gastrointestinal lesions are not well known. As far as we know, only six case reports have been published5, 12–16; their salient findings are summarized in Table 2. According to those reports, any portion of the duodenum was affected, the small bowel was frequently involved simultaneously, and surgical treatment was sometimes required. Pathologically, intravenous thrombosis, vascular proliferation, and papillary endothelial hyperplasia within the duodenal submucosa have been reported12–15; a characteristic CT finding is edematous thickening of the duodenal wall.5, 13–15Among EGD findings, various degrees of erosion and/or ulceration with clear demarcation have been described.5, 12–15 The patchy areas of gastric redness present in our patient have not been reported so far.
Treatment with corticosteroids, proton pump inhibitors, and diet control was successful in our patient. Various treatments have been reported for PNH-related thrombosis.2 In cases of bowel obstruction or perforation, surgical treatment has been needed15, 16; in cases without such complication, nonoperative therapy was appropriate.17 In patients with life-threatening thrombosis, anticoagulation therapy is necessary. In Japan, however, PNH patients die from bleeding events more often than from thrombotic complication.8 Thus, we avoided anticoagulation therapy. Eculizumab is another treatment option2, 18; however, at least two weeks after vaccination against Neisseria meningitides are required before initiation of eculizumab. We used corticosteroids, expecting a rapid suppression of hemolysis,19 but its effect on thrombosis was unclear. Fortunately, corticosteroid therapy together with proton pump inhibitor and diet control were adequate in our case. In the absence of definitive treatment, early and accurate diagnosis of thrombotic complications seems important so the thrombotic manifestations can be treated and surgical intervention avoided.
In conclusion, in patients with PNH who have abdominal symptoms, gastrointestinal injury caused by PNH-related thrombosis should be suspected. In addition to laboratory data suggesting thrombosis, recognition of gastric patchy redness at EGD may help reach the diagnosis of this potentially serious complication of PNH.