Atraumatic idiopathic splenic rupture induced by granulocyte-colony stimulating factor (G-CSF) for the treatment of pancytopenia, managed successfully by laparoscopic splenectomy
- Ugochukwu Chinyere Chinaka ,
- Joshua Fultang ,
- Jelizaveta Pereca and
- Abdulmajid Ali
- General Surgery, University Hospital Ayr, Ayr, UK
- Correspondence to Professor Abdulmajid Ali; abdulmajidali@hotmail.com
Abstract
Splenic rupture is a potentially life-threatening condition and an uncommon short-term complication of granulocyte-colony stimulating factor (G-CSF) administration. It may present as acute abdominal pain or suddenly precipitously worsening anaemia with haemodynamic instability that requires urgent operative intervention for survival. We present a case of an atraumatic idiopathic splenic rupture in University Hospital, Ayr in a patient who received G-CSF treatment for chemotherapy-induced (methotrexate) pancytopenia and was successfully managed by laparoscopic splenectomy.
Background
Granulocyte-colony stimulating factor (G-CSF) administration induces splenic enlargement and could uncommonly cause a potentially life-threatening splenic rupture. For this rare complication to be adequately managed with a good outcome, a high index of suspicion and prompt intervention are required.
Case presentation
A 48-year-old woman was referred by her general practitioner to the medical team due to pancytopenia in the background of a recent chest infection. The chest infection was treated in the community with oral amoxicillin. Our patient’s most recent blood tests before the admission showed haemoglobin (Hb) 107 g/L, white cell count (WCC) 5.5×109/L and platelet count of 200×109/L.
She has a history of rheumatoid arthritis, diagnosed in 2002 (managed with methotrexate and etanercept) and focal segmental glomerulosclerosis, diagnosed in 2013. Her renal function deteriorated over the course of the last 4 months, with estimated glomerular filtration rate decreasing from 48–53 mL/min/1.73 m2 to 25 mL/min/1.73 m2. The renal team subsequently reduced methotrexate dose from 25 mg/day to 15 mg/day 1 month before this admission.
On physical examination, there was reduced air entry over the left lung base, the abdomen was soft and non-tender with no hepatosplenomegaly. Her chest X-ray showed consolidation in the left lower lobe and a right pleural effusion. Laboratory investigations revealed pancytopenia with Hb of 61 g/L, WCC of 2.4×109/L (with neutropenia 0.2×109/L), a platelet count of 27×109/L and C reactive protein (CRP) of 20 mg/L. She was started taking piperacillin/tazobactam and clarithromycin for ongoing pneumonia and subcutaneous Filgrastrim PFS 300 μg in 0.5 mL injection once daily for 5 days for pancytopenia.
Subsequently, her Hb and platelet levels were noted to be dropping and she was transfused accordingly.
On the seventh day of admission, she complained of upper abdominal pain mostly on the left upper quadrant (LUQ) after a coughing fit, light headedness and bloating. Further examination revealed epigastric and LUQ tenderness. A repeat blood test showed a drop in her Hb to 34 g/L.
Investigations
An emergency CT of her abdomen demonstrated a splenic laceration with free intra-abdominal fluid (figure 1).
Non-contrast CT showing splenic laceration. Axial view of a non-contrast CT (due to renal impairment) above showing a bulky spleen, lamellated appearance laterally and evidence of a laceration.
Treatment
Consequently, the patient underwent an emergency laparoscopic splenectomy.
The operation was performed by a standard laparoscopic approach. Intraoperatively, a large amount of haemoperitoneum was evacuated from a grade IV splenic laceration. The hilum was divided and stapled safely from the pancreatic tail, and morcellated fragments of the spleen were removed. Small splenic fragments were implanted in the omentum.
Outcome and follow-up
Pathology of the specimen showed a fragmented ruptured spleen, weighing 390 g and measuring 150×140×50 mm. Microscopically, it showed the expansion of the red pulp, with no malignancy seen.
Postoperative period was uneventful. Methotrexate was stopped before the operation. Her Hb level and observations remained stable and she was discharged after ensuring vaccination against encapsulated organisms. She was started taking prophylactic oral phenoxymethylpenicillin as per local antimicrobial policy.
One year after surgery, her blood test shows Hb of 91 g/L, WCC of 5.7×109/L and platelet count of 187×109/L. She is getting routine dialysis for her renal condition and has been planned for a renal transplant.
Discussion
Splenic rupture is a potentially life-threatening condition and the majority of cases occur as a result of trauma.1
Rupture of the spleen without trauma, which is very rare (constitutes 1% of all splenic ruptures), has been described in various terms such as ‘atraumatic’, ‘spontaneous’, ‘pathological’, ‘idiopathic’, ‘true spontaneous’ and ‘occult’.2 3 The more frequently used term, the spontaneous splenic rupture was first introduced by Rokitansky (1861) and Atkinso (1874).1
In a bid to further clarify the diagnosis of spontaneous rupture, Orloff and Peskin in 1958 came up with four-point criteria viz: no history of trauma, no perisplenic adhesions indicating previous trauma, no disease process involving the spleen, presence of microscopic and macroscopic normal spleen. The fifth criteria by Crate and Payne in 1991 included a history of pertinent viral infection and absence of viral antibody titers.2
However, the term ‘atraumatic’ appears more accurate and can be classified as ‘atraumatic pathological splenic rupture’ and ‘atraumatic–idiopathic splenic rupture’ clarifying etiological and pathological changes in the spleen.3 Atraumatic idiopathic splenic rupture accounts for about 7% of the cases while the pathological type makes up 93% of the remainder.4
Splenic rupture has been witnessed as a possible complication of the use of myeloid growth factors for all indications, including stem cell mobilisation, chronic severe neutropenia or after administration of myelosuppressive anticancer drugs.5
There have been reports of splenic enlargement and rupture in association with G-CSF administration for stem cell harvest and with the use of granulocyte-macrophage CSF.6–9
G-CSF has been used to improve granulocyte count in chronic neutropenia and myelodysplasia, to minimise the incidence and duration of neutropenia during conventional chemotherapy and to mobilise peripheral blood stem cells before leukapheresis for use in autologous and allogeneic marrow transplantation.9
Even among healthy peripheral blood progenitor cell donors, G-CSF has been noted to cause a slight spleen enlargement in the majority of healthy donors which normally resolves within a few weeks.10 11 The magnitude of splenomegaly might be related to the daily dose and duration of G-CSF treatment.12
There are cases of splenic rupture in healthy donors after G-CSF application reported in the literature.9 13 In these donors, the daily G-CSF dosage was between 10 and 20 µg/kg, in three cases mobilisation was continued until day 6.12
Although the cause of splenic rupture does not appear to be associated with any specific condition, physicians should be alerted to the possibility of this potentially fatal complication in individuals receiving G-CSF therapy.14
It becomes therefore important to assemble cases of splenic rupture after growth factor administration to identify potential risk factors for this rare but life-threatening complication.5
Atraumatic idiopathic splenic rupture when it occurs could be missed as a possible cause of an abdominal emergency, a situation that has catastrophic consequences. Therefore, a high index of suspicion is required especially in patients receiving G-CSF, because immediate diagnosis and prompt surgical intervention ensures good outcome.15
Conservative approach to atraumatic splenic rupture has been unimpressive with a reported 22% mortality at 30 days compared with the well-established approach in trauma.2 Operative intervention therefore not only ensures better outcome but also affords the opportunity of pathological diagnosis.
Laparoscopic splenectomy was initially reserved for delayed intervention in splenic trauma and elective splenectomy. Recently, it has been safely accomplished immediately after trauma.2 Drawing from the expertise in trauma and elective procedures, laparoscopic splenectomy is increasingly being deployed for management of atraumatic idiopathic splenic rupture.
Though a technically demanding procedure that requires experience, laparoscopic splenectomy for atraumatic idiopathic splenic rupture as reported here, is a safe procedure and carries with it the known advantages over open splenectomy.
Learning points
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Granulocyte-colony stimulating factor (G-CSF) can potentially cause a splenic rupture.
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While administering G-CSF to a patient/donor, maintain a high index of suspicion for warning signs of haemodynamic instability.
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Prompt recognition of splenic rupture and intervention will avoid fatal consequences.
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Minimally invasive approach is possible and safe in experienced hands.
Footnotes
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UCC and JF are joint first authors.
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Contributors UCC and JF co-authored the case report. They both conceived the topic and were involved in the research and write-up. JP was involved in the research. AA performed the surgery and reviewed the paper.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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