J Clin Gynecol Obstet
Journal of Clinical Gynecology and Obstetrics, ISSN 1927-1271 print, 1927-128X online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Gynecol Obstet and Elmer Press Inc
Journal website http://www.jcgo.org

Case Report

Volume 7, Number 3-4, November 2018, pages 81-83

Beyond HELLP: Peripartum Catastrophic Thromboembolism due to Hereditary Diffuse Gastric Cancer

Zara Bashira, Omar Rahmanb, e, Rajat Kapoorb, Udit Dhalc, Emily Gundertd

aAga Khan University, Karachi, Pakistan
bDepartment of Pulmonary & Critical Care, Indiana University School of Medicine, Indianapolis, IN, USA
cDepartment of Internal Medicine, Cleveland Clinic Akron General, Akron, OH, USA
dDepartment of Emergency Medicine/Anesthesiology and Pain Medicine, UT Southwestern Medical Center, Dallas, TX, USA
eCorresponding Author: Omar Rahman, Department of Pulmonary & Critical Care, Indiana University of Medicine, 340 West 10th Street #6200, Indianapolis, IN 46202, USA

Manuscript submitted September 7, 2018, accepted September 17, 2018
Short title: Peripartum Thromboembolism due to Gastric CA
doi: https://doi.org/10.14740/jcgo512w


Peripartum thrombocytopenia and thrombotic events are usually attributable to diseases like Hemolysis Elevated Liver Enzymes Low Platelets (HELLP) and thrombotic thrombocytopenic purpura (TTP). Malignancy is a rare cause and gastric cancer even more unusual. We report the case of a 28-year-old female with undiagnosed hereditary diffuse gastric cancer (HDGC) in the peripartum period initially presenting with nausea and blurry vision at 35 weeks’ gestation. Following cesarean section 1 week later, she developed thrombocytopenia and elevated blood pressure; HELLP was diagnosed. Development of acute kidney injury, decreasing platelet count and anemia lead to consideration of TTP. Despite plasmapheresis she had no improvement, developed respiratory failure and had acute large vessel arterial and venous thrombosis with multiple cerebral, renal, splenic and lower extremity arterial infarctions. Deep venous thrombosis of lower limbs was also seen. She was placed on corticosteroids and anticoagulation. Following extensive workup, vegetations on mitral valve were seen on echocardiography and she was started on antibiotics for endocarditis. She deteriorated into refractory shock, multiple organ failure and died on postpartum day 8. Autopsy done revealed diffuse submucosal gastric adenocarcinoma (linitus plastica). Metastases were present on small bowel, fallopian tubes, ovary and the placenta. Mitral valve had marantic vegetations. Tumor cells showed CDH1 gene mutation. Such a diagnosis in pregnancy is very challenging due to overlapping symptoms leading to misdiagnosis. Here, thromboembolism was malignancy-related and rapid spread probably hormone-associated. The purpose of this report is to highlight the need to warrant investigation for cancer, among workup for other common conditions, for atypical thromboembolism in pregnancy.

Keywords: Peripartum; Thromboembolism; Gastric cancer


Pregnancy-associated gastric carcinoma is a rare occurrence, accounting for 0.025-0.1% of all pregnancies [1]. The diagnosis is often delayed due to several contributing factors particularly the non-specific symptoms which may be misinterpreted as pregnancy-related, a lack of suspicion and the hesitancy associated with performing invasive procedures in pregnant patients [2]. Therefore, most, if any, are identified at a very advanced stage with poor prognosis and of those, only 45-56% undergo surgical resection [1]. Hereditary diffuse gastric cancer (HDGC), a subtype of gastric carcinomas, follows a germline mutation in the type 1 E-cadherin (epithelial) gene (CDH1) with 70% of individuals with said mutation at a life-time risk for developing diffuse gastric cancer [3]. It is suggested that in addition to environmental and genetic factors, pregnancy itself may prove to be a risk factor [4]. There exists minimal subject matter on HDGC and pregnancy. Consequently, we report the case of a 28-year-old woman with undiagnosed HDGC presenting in her third trimester with symptoms eliciting emergent C-section following which her condition rapidly deteriorated resulting in death. Diagnosis was made on autopsy.

Case Report▴Top 

A 28-year-old Hispanic lady, gravida-2 para-1, presented to the obstetrics department with symptoms of nausea, vomiting and fatigue. She was in her third trimester at 35 weeks’ gestation. Her previous pregnancy was uneventful with no significant past medical and family history. She had no prior history of smoking, alcohol or recreational drug use and was HIV-negative. Her current pregnancy was going well until the 35th week. She did not report any fever or weight loss. Further investigation showed low platelets on CBC following which she was diagnosed with a query of either Idiopathic Thrombocytopenic Purpura (ITP), Thrombotic Thrombocytopenic Purpura (TTP) or Hemolysis Elevated Liver Enzymes Low Platelets (HELLP), all of which require steroid therapy. She was therefore started on methylprednisolone, transfused with packed red blood cells and discharged home.

One week after discharge, she again presented to the hospital with confusion, nausea and anemia. On subsequent evaluation, she was found to have acute kidney injury (AKI), thrombocytopenia and hypofibrogenemia for which she was taken in for emergent caesarian section for possible HELLP syndrome (hemolysis, elevated liver enzymes and low platelets). However, following the procedure, her symptoms persisted with an additional blurring of vision. She had no abdominal pain, headache or fever. A repeat CBC was consistent with thrombocytopenia (23,000), anemia (hemoglobin of 7.9), AKI with creatinine of 1.9, fibrinogen of 150 and liver function tests (LFTs) mildly elevated (100s). An MRI was done demonstrating an occipital cerebrovascular event in the posterior cerebral artery distribution accounting for the blurry vision. Neurology was brought on board and the decision to start plasmapheresis for presumed TTP was made due to the AKI and worsening hematological tests. She was transferred to our department for further investigation and management.

Despite plasmapheresis she did not show improvement. Over the course of 24 h, she developed respiratory failure with new lung infiltrates and hypoxemia requiring intubation. Subsequently, she became hypotensive, was unresponsive to fluid challenge and was started on vasopressors for refractory shock. Hematology/oncology was consulted due to the presence of schistocytes on blood smear and an abdominal CT was done which was suggestive of lymphadenopathy. Clinically, she developed cyanosis of her lower extremity as well as further decline in mental status. Further investigation identified tibial artery occlusion and multiple new cerebral infarcts on head CT. She was tested for antiphospholipid antibody syndrome, placed on corticosteroids and anticoagulation. Blood cultures were positive for pneumococcus and echocardiography revealed mitral valve vegetations. She was, therefore, started on antibiotics for endocarditis. Her condition continued to decline rapidly. She started bleeding vaginally requiring IR embolization. She ultimately developed multiple organ failure with bradycardia despite efforts which progressed to asystolic arrest on post-partem day 8. Following her death, an autopsy was performed which revealed diffuse submucosal gastric adenocarcinoma (linitis platica) with extensive transperitoneal metastases on the diaphragm, small bowel, fallopian tubes, ovaries and the placenta. Multiple cerebral, renal, splenic and lower extremity infarcts were seen. Mitral valve had marantic vegetations and there was necrosis of the liver. Tumor cells shower CDH1 mutation indicative of HDGC.


Although there has been a reported declining trend in the occurrence of gastric cancers [5], it continues to remain a leading cause of cancer-related mortality, more so in Asian countries [6]. It is a disease primarily in patients aged over 50 years [2]; however, approximately 10% occurs in those less than 45 years of age [7] with a female predominance [8]. Pregnancy-associated gastric carcinoma is an uncommon occurrence, accounting for up to 0.1% [2, 9] with HDGC being even rarer with a mutation in CDH1 gene affecting E-cadherin expression [3].

There exist common presenting signs and symptoms in patients which elicit a suspicion of gastric carcinoma inclusive of nausea, vomiting, dysphagia, dyspepsia, early satiety, epigastric pain, weight loss and melena [2]. However, most of these are commonly seen at some point in pregnancy and are therefore misinterpreted and attribute to the delay in diagnostic workup. Alternatively, in the early stages, it has been shown that up to 80% of patients are asymptomatic, further delaying diagnosis [10]. A study was done by Maconi et al which resulted in a mean delay of 29.3 ± 39.9 weeks in the diagnosis of gastric cancer in young patients with no alarm symptoms [11]. Pregnancy-related hormones have also been suggested as contributing factors towards the growth and pathogenesis of gastric cancers [12, 13].

Our patient developed thromboembolism which was secondary to malignancy and showed a rapid spread which may have been due to the hypercoagulable state induced by pregnancy hormones. A study done showed thromboembolism in malignancy, commonly known as Trousseau’s syndrome, having the second highest incidence in relation to metastatic gastric cancer (10.7 events per 100 patient-years) following pancreatic cancer (20) [14]. The exact etiology is unknown, but the expression of tissue factor on tumor cells has shown to be an important factor as seen in gastric, colon, pancreatic, lung and breast carcinomas [15]. Another study done on Asian gastric cancer patients resulted in a 2-year cumulative incidence of venous thromboembolism (VTE) of 0.5% in stage I disease, 3.5% in stage II-IV(M0) and 24.4% in stage IV(M1) with most common being 62% intra-abdominal VTEs [16].

Previous studies done have shown that among pregnant women, the highest risk for thromboembolism lies in the postpartum period [17] with the most recognized risk factors being age, race, thrombophilia, lupus, heart disease, sickle cell disease, obesity, electrolyte imbalance, infection and transfusion [18]. However, very limited subject matter is available for the incidence of pregnancy-related gastric cancer and thromboembolism. Consequently, atypical thromboembolism in pregnancy should warrant investigation for cancer among workup for other common conditions.

  1. Sakamoto K, Kanda T, Ohashi M, Kurabayashi T, Serikawa T, Matsunaga M, Hatakeyama K. Management of patients with pregnancy-associated gastric cancer in Japan: a mini-review. Int J Clin Oncol. 2009;14(5):392-396.
    doi pubmed
  2. Fill S, Taran A, Schulz HU, Kahl S, Kalinski T, Smith B, Costa SD. Sister Mary Joseph's nodule as the first sign of pregnancy-associated gastric cancer: a case report. World J Gastroenterol. 2008;14(6):951-953.
    doi pubmed
  3. Lynch HT, Kaurah P, Wirtzfeld D, Rubinstein WS, Weissman S, Lynch JF, Grady W, et al. Hereditary diffuse gastric cancer: diagnosis, genetic counseling, and prophylactic total gastrectomy. Cancer. 2008;112(12):2655-2663.
    doi pubmed
  4. Chong VH, Lim CC. Advanced disseminated gastric carcinoma in pregnancy. Singapore Med J. 2003;44(9):471-472.
  5. Neugut AI, Hayek M, Howe G. Epidemiology of gastric cancer. Semin Oncol. 1996;23(3):281-291.
  6. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA Cancer J Clin. 2006;56(2):106-130.
    doi pubmed
  7. Al-Refaie WB, Hu CY, Pisters PW, Chang GJ. Gastric adenocarcinoma in young patients: a population-based appraisal. Ann Surg Oncol. 2011;18(10):2800-2807.
    doi pubmed
  8. Lai IR, Lee WJ, Chen CN, Lee PH, Chang KJ, Chang-Yu S, Chen KM. Gastric cancer in the young. Hepatogastroenterology. 1997;44(18):1641-1645.
  9. Khatib F, Shaya M, Samueloff A. Gastric carcinoma with metastasis to the placenta and amniotic fluid: case report and review of the literature. Eur J Obstet Gynecol Reprod Biol. 2003;107(2):208-209.
  10. Koh T, Wang T. Tumors of the stomach. Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 7th ed. Philadelphia: Saunders. 2002:829-844.
  11. Maconi G, Kurihara H, Panizzo V, Russo A, Cristaldi M, Marrelli D, Roviello F, et al. Gastric cancer in young patients with no alarm symptoms: focus on delay in diagnosis, stage of neoplasm and survival. Scand J Gastroenterol. 2003;38(12):1249-1255.
    doi pubmed
  12. Furukawa H, Iwanaga T, Hiratsuka M, Imaoka S, Ishikawa O, Kabuto T, Sasaki Y, et al. Gastric cancer in young adults: growth accelerating effect of pregnancy and delivery. J Surg Oncol. 1994;55(1):3-6.
    doi pubmed
  13. Maeta M, Yamashiro H, Oka A, Tsujitani S, Ikeguchi M, Kaibara N. Gastric cancer in the young, with special reference to 14 pregnancy-associated cases: analysis based on 2,325 consecutive cases of gastric cancer. J Surg Oncol. 1995;58(3):191-195.
    doi pubmed
  14. Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006;166(4):458-464.
    doi pubmed
  15. Callander NS, Varki N, Rao LV. Immunohistochemical identification of tissue factor in solid tumors. Cancer. 1992;70(5):1194-1201.
  16. Lee KW, Bang SM, Kim S, Lee HJ, Shin DY, Koh Y, Lee YG, et al. The incidence, risk factors and prognostic implications of venous thromboembolism in patients with gastric cancer. J Thromb Haemost. 2010;8(3):540-547.
    doi pubmed
  17. Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ, 3rd. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med. 2005;143(10):697-706.
    doi pubmed
  18. James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol. 2006;194(5):1311-1315.
    doi pubmed

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal of Clinical Gynecology and Obstetrics is published by Elmer Press Inc.


Browse  Journals  


Journal of Clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

Journal of Neurology Research

International Journal of Clinical Pediatrics






Journal of Clinical Gynecology & Obstetrics, quarterly, ISSN 1927-1271 (print), 1927-128X (online), published by Elmer Press Inc.                     
The content of this site is intended for health care professionals.
This is an open-access journal, the authors retain the copyright, the journal is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International
License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)

This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.jcgo.org   editorial contact: editor@jcgo.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.

Disclaimer: The views and opinions expressed in the published articles are those of the authors and do not necessarily reflect the views or opinions of the editors and Elmer Press Inc. This website is provided for medical research and informational purposes only and does not constitute any medical advice or professional services. The information provided in this journal should not be used for diagnosis and treatment, those seeking medical advice should always consult with a licensed physician.