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.