Disseminated intravascular coagulation as an unusual feature of hypereosinophilic syndrome

To the Editor: A 66-year-old man complaining abdominal pain and bloating for 1 month was admitted to the Department of General Surgery of Xuanwu Hospital, Beijing, China. The patient had a normal body temperature and did not have symptoms such as nausea, diarrhea, or bone/joint pain. He had no history of allergies, no particular past medical or family history. He had taken no medications that could cause eosinophilia. No parasites were found in the stool. Abdominal computerized tomography (CT) scan showed thickening of the stomach wall and peristaltic stiffness with the swelling of the surrounding lymph nodes, indicating possibility of gastric cancer [Figure 1A]. Biopsy from gastroscopy showed a massive eosinophil infiltration of the stomach wall [Figure 1B]. Meanwhile, blood test showed white blood cell (WBC) count was elevated to 11.09 × 10⁹/L, eosinophils were elevated to 2.53 × 10⁹/L, hemoglobin 160 g/L, and platelet 269 × 10⁹/L. A bone marrow biopsy showed normal cellularity with increased eosinophils. breakpoint cluster region/c-abl oncogene 1, non-receptor tyrosine kinase and Fip1-like1 and platelet-derived growth factor receptor alpha fusion genes were not detected. He was diagnosed as hypereosinophilic syndrome (HES) and treated with corticosteroids (prednisone 20 mg, oral, twice per day). The patient's abdominal pain and bloating symptoms gradually reduced, and the total number of eosinophils was back to normal in 2 weeks. The follow-up gastroscopy performed at 3 and 6 months after treatment showed normal stomach wall [Figure 1C and 1D]. The corticosteroid was tapered and stopped after 8 months treatment.

Figure 1.

The imaging and biopsy results of this patient. (A) Abdominal enhanced CT showed a marked thickening of the small curved side of the stomach, accompanied by enlargement of the ipsilateral mesenteric lymph node (red arrow). (B) A marked infiltration of eosinophilic granulocytes was seen in the biopsy of the gastric wall using hematoxylin and eosin staining (original magnification ×200); (C and D) Abdominal CT was performed after 3 and 6 months, respectively, and showed the stomach wall tends to become normal. (E, F, G) Pelvic CT showed significant thickening of the bladder wall from different sections (red arrows). (H) Pelvic MRI was performed 1 year later, showing the bladder wall (red arrow) returned to normal. CT: Computerized tomography; MRI: Magnetic resonance imaging.

One year later, the patient was admitted to our hospital again because of hematuria for one day accompanied with difficulty to urinate and pain during urination. There were no changes in urinary frequency and urgency. The patient was conscious and had no fever, anemia, abdominal pain, or bloating. Multiple fresh areas of purpura were found on the skin of the extremities. No surface lymph nodes were palpable. There was no tenderness on the sternum, no unheard and dryness sound in the lungs. Heart rate was 80 beats per minute with regular rhythm. The patient's abdomen was soft and flat without hepatosplenomegaly. No mass was palpable, kidney area pain was negative, ureteral tenderness was negative. His right leg was slightly edematous. Laboratory tests showed an elevated WBC count (13.5 × 10⁹/L), eosinophil (1.6 × 10⁹/L), thrombocytopenia with platelet (23.0 × 10⁹/L), and a hemoglobin level at 13.3 g/dL. Laboratory tests also showed abnormal blood coagulation, including prothrombin time at 17.3 s (normal range: 11.0–15.0 s), an activated partial thromboplastin time at 44.3 s (normal range: 25.0–37.0 s), a fibrinogen level at 107 mg/ dL (normal range: >220 mg/dL), and a D-dimer ≥20.0 μg/mL (normal range: 0.01–0.50 μg/mL). These laboratory results along with the clinical manifestations described above suggested disseminated intravascular coagulation (DIC). All tumor markers tested were negative. Stool was tested negative for parasites. The possibility of a major parasitic infection or allergic diseases was ruled out. A bone marrow examination of the posterior superior iliac showed normal but elevated proportion of eosinophils. Abdominal ultrasound sonography and abdominal-pelvic CT showed significant thickening of the bladder wall [Figure 1E–G], while stomach wall was normal. Concerning the serious DIC, the biopsy of bladder wall was not performed. After admission, urgent care was immediately instituted, including placement of indwelling catheter, bladder irrigation, administration of antibiotics, and daily infusion of fresh frozen plasma and platelets. The patient felt pain during urination was relieved and hematuria was slightly reduced, but the coagulation index continued to deteriorate with fibrinogen reduction (lowest to 46 mg/dL). There was bleeding at the bone marrow puncture site for 2 days before. The patient developed swelling and pained in the left lower limb. Ultrasound confirmed venous thrombosis at lower extremity. Conditions that may cause thrombosis and bleeding, such as infection or autoimmune diseases, were ruled out. Given the imaging features of the bladder described above, exfoliated cells in the urine were examined and no cancerous cells were seen. The patient was diagnosed as HES. Considering that the eosinophilia could be the major cause of this serious clinical condition, and corticosteroids was not a contraindication at that time, methylprednisolone (80 mg per day, intravenously) was administered. Eosinophil counts of peripheral blood displayed a downward trend, but the patient's bleeding symptoms and the coagulation parameters did not improve. Considering bleeding and thrombosis existed at the same time, anti-coagulant therapy with a half dose of low molecular weight heparin was cautiously prescribed. One day later, the bleeding stopped, and the urine color became lighter. Consistent with the clinical manifestations, the blood tests showed that the platelet count was stable around 30.0 × 10⁹/L with no transfusion, the fibrinogen was stable around 100 mg/dL. The blood routine and blood coagulation index were significantly improved and returned to normal levels in 1 week. Considering the patient's previous experience, measurements were taken by regular monitoring the absolute number of eosinophils, regular examining the bladder by ultrasound, and by slowly tapering corticosteroids for a total of 1 year. As the venous thrombosis of the lower extremities disappeared, the anti-coagulant medications were stopped after 3 months of anti-coagulant therapy. The pelvic magnetic resonance imaging was performed 1 year later and the thickness of the bladder wall returned to normal [Figure 1H]. To date, methylprednisolone has been stopped for 2 years and the patient has no symptoms.

HES can have a variety of clinical manifestations, especially in the presence of malignant tumors.^[1] It has been rarely reported that DIC is caused solely by HES.^[2,3]

From this case, we have gained a very important experience for managing patients with HES. First of all, damage of tissues and organs can be the first manifestation of HES. In this case, peripheral eosinophil counts were normalized immediately after corticosteroid administration, but the consumptive coagulopathy was not corrected quickly. This result is consistent with the findings that peripheral eosinophil count is not always paralleled with tissue damage.^[2] Therefore, the number of eosinophils in peripheral blood cannot be used as the only indicator for adjusting the dosage of corticosteroid. In addition, the time of taking corticosteroid should be long enough to prevent disease recurrence. Second, in the case of coagulation of hemorrhage and thrombus, simple hemostasis therapy cannot improve the bleeding. Upon initiating the treatment of the primary disease, the use of anti-coagulant should be started as soon as possible to interrupt the initiation of DIC.

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Conflicts of interest

None.