Inferior mesenteric vein thrombosis in the setting of testosterone therapy
- Ngoda Manongi ,
- Kory Byrns ,
- Malvina Fulman and
- Amir Jaffer
- Internal Medicine, NewYork-Presbyterian Queens, Flushing, New York, USA
- Correspondence to Dr Ngoda Manongi; nmanongi@gmail.com
Abstract
Inferior mesenteric vein thrombosis (IMVT) is a rare and potentially lethal complication that can progress to mesenteric ischaemia if left untreated. We report a case of a man in his 70s with a history of polycythaemia vera (PV) with a known negative Janus kinase-2 mutation (JAK2V617) who was started on testosterone therapy 2 months before presenting with left lower quadrant abdominal and flank pain. Evaluation revealed thrombocytosis and IMVT on CT scan. A non-operative approach was deferred for anticoagulation therapy. Within 24 hours, the patient demonstrated significant clinical improvement, and he subsequently made a full recovery. The patient underwent 6 months of anticoagulation therapy with Apixaban. This case documents the first case of IMVT in the setting of PV and testosterone therapy in the literature.
Background
Mesenteric vein thrombosis (MVT) is a rare condition that carries high mortality. Patients generally present with severe abdominal pain, nausea, vomiting and/or melena. Most reported cases of MVT involves the superior mesenteric and portal veins. Inferior MVT (IMVT) is extremely rare and constitutes about 5% of cases of acute MVT.1 Although there are not randomised controlled trials to date to guide effective therapy, immediate anticoagulation therapy is imperative and effective. CT scan provides definitive diagnostic because it can divulge the presence of thrombosis within the mesenteric veins. Our case is the first case described in literature of MVT in the setting of testosterone therapy in a patient with negative JAK2V617 polycythaemia vera (PV). Our case highlights two key issues including the importance of reviewing medications as it may have a direct impact on the patient’s diagnosis, and adding the diagnosis of IMVT to the differential in patients presenting with abdominal pain in setting of known history of prothrombotic state.
Case presentation
A man in his 70s presented to the emergency department for evaluation of left lower quadrant (LLQ) and left flank pain. The patient stated that the pain began suddenly in the morning. The pain was sharp, constant, non-radiating and rated 10/10 on a subjective scale. The pain was exacerbated by eating and he denied any alleviating factors. His medical history is notable for history of PV diagnosed 15 years prior using the WHO criteria when his blood work showed haemoglobin (Hg) of 180 g/L and low serum erythropoietin with bone marrow biopsy revealing substantial hypercellularity with panmyelosis. Genetic workup for PV mutation including JAK2V617, MPL and CALR mutation analysis was found to be negative. The patient was managed with therapeutic phlebotomy and low-dose aspirin. Patient denied any history of thrombotic events. On this admission, the patient endorsed chills and nausea. Interestingly, he reported that 2 months prior he was started on testosterone therapy to remedy complaints of low libido and fatigue. On physical examination, the patient was febrile to 39.2°C, his vital signs were otherwise within normal limits. His abdominal examination revealed intact bowel sounds, with a soft; non-distended abdomen with LLQ tenderness on palpation with no guarding, rebound or costovertebral angle tenderness. His physical exam was otherwise without abnormality. Laboratory studies revealed a normal basic metabolic panel, white cell count (WCC) 13× 10∧9/L, Hg 160.0 g/L and haematocrit (Hct) 50.1%, platelet count of 244× 10∧9L, and an unremarkable urinalysis. CT scan of the abdomen and pelvis was significant for thrombosis of the IMV with an approximately 1.7 cm linear thrombus extending into the contiguous splenic vein with oedema and adenopathy surrounding the IMV concerning for thrombophlebitis (figures 1 and 2). There was no bowel wall thickening identified other than colonic diverticulosis without evidence of acute diverticulitis. Review of outpatient laboratory workup right before testosterone therapy showed WCC 8000 per mm3, Hg 14 g/dL, Hct 47% and a platelet count of 187 K/uL.
(A) Axial contrast-enhanced CT at the level of the lower abdomen demonstrates occlusion of the inferior mesenteric vein (white arrowhead) and an adjacent IMV tributary (black arrowhead). There is surrounding mesenteric oedema and adenopathy (black arrow), consistent with thrombophlebitis. (B) A more superior image from the same study demonstrates thrombus extending into the splenic vein (white arrow). IMV, inferior mesenteric vein.
(A–C) Sequential coronal reformations from the same CT examination demonstrate occlusion of the entire course of the IMV (white arrowheads) as well as contiguous thrombus extending into the splenic vein (white arrow). IMV, inferior mesenteric vein.
Treatment
The treatment for MVT usually involves the discontinuation of potential offending agents and anticoagulation. The recommended treatment involves anticoagulation for 3–6 months in patients with acute MVT. In our case, testosterone was discontinued and the patient was anticoagulated with IV heparin drip until symptoms subsided 24 hours later. The patient was then switched from intravenous heparin to apixaban for which he continued to take for a total of 6 months. Although direct acting oral anticoagulants such as apixaban have not been studied extensively for MVT, several studies have shown that they are safe and efficacious alternatives to traditional anticoagulation with low molecular weight heparin and vitamin K antagonists in the treatment of acute venous thrombosis.2 3 In addition, we wanted to provide the patient with a drug that was efficacious that did not require regular laboratory monitoring and not affected by food.
Outcome and follow-up
Within 24 hours of starting anticoagulation, the symptoms of LLQ pain, nausea and vomiting subsided. The patient was able to tolerate a normal diet. In addition, blood tests had normalised. At a 6-month assessment, the patient remained well and no further episodes of thrombosis. Further outpatient hypercoagulable workup including protein C and S deficiency, antithrombin III deficiency, factor V Leiden mutation, plasminogen activator inhibitor, prothrombin 20 210 mutation and flow cytometry for paroxysmal nocturnal haemoglobinuria were all negative. Subsequent CT scan 2 months later revealed resolution of previously identified filling defect within the IMV/splenic vein. The patient continued to follow up with haematologist and genitourinary oncologist.
Discussion
MVT accounts for one-in-five cases of AMI. The majority of MVT occurs in the superior mesenteric and portal veins. Superior mesenteric venous thrombosis accounts for up to 95% of acute MVT, and with a mortality rate reaching as high as 33% in recurrent cases.4 IMVT is extremely rare and constitutes close to 5% of cases of acute MVT but carries up to 20% risk of mortality.4 The risk factors for MVT include local inflammation processes and prothrombotic states (figure 3). The exact pathological mechanism underpinning why thrombosis is less frequent in the IMV compared with the SMV is not yet understood. There has been suggestions that anatomically, the extensive collateral circulation of the venous drainage from the pelvic area into the portal vein via the left renal vein, splenic vein and hemiazygos veins is a plausible explanation. For example, normally the IMV drains into the splenic vein in over 40% of patients, however, it has been documented that the IMV also drain directly into the portal vein (30%) and into the SMV (20%).5 6 In addition, it has been reported that MVT of larger distal portions such as portal veins is mediated by local factors, such as malignancy, inflammation and infection while isolated MVT thrombosis is most commonly related to a prothrombotic state that originate from the vena rectae.6–8 There are very few case reports on IMVT, which have revealed associations with diverticulitis, antiphospholipid syndrome, postoperative and SARS-CoV-2 infection without definitive description of pathophysiology.9–13
Conditions predisposing to mesenteric vein thrombosis.
Our patient had extensive outpatient workup for thrombophilia, which was negative. Also, bone marrow biopsy 15 years ago, showed substantive hypercellularity with panmyelosis. Given the absence of a clear cause and on background of recent initiation of testosterone therapy, we explored a link between his recent testosterone therapy and the thrombosis. Our hypothesis could not be supported by patient’s bioavailable testosterone levels because the patient decline testosterone levels inpatient. However, it is well documented that drugs play a key role in development of venous thrombosis either through direct endothelial damage or by augmenting the secretion of procoagulation and anticoagulation mediators. Some drugs, specifically testosterone, augment the action of erythropoietin causing the elevation of Hg and haematocrit and increasing the risk for venous thromboembolism (VTE).14 15 It has been reported that testosterone can increase Hg by as much as 5%–7% and can lead to polycythaemia in over 20% of men.16 However, in majority of case reports and some large cohort studies of VTE associated with testosterone use, erythrocytosis was either not present, not reported or differing conclusions.17–24 Only one case report has been published about a patient taking testosterone with an otherwise unprovoked MVT in the setting of erythrocytosis.25 However, a recent large observational study done in men on such therapy showed a significant increase in the VTE risk shortly after the initiation of testosterone.26
A closer examination of our patient’s biochemical analysis appears to show that his recent testosterone therapy may have contributed to the rise in Hg and possibly to the thrombosis, however, it is difficult to draw any definitive conclusion. While the association remains uncertain, venous thrombotic events have been reported in patients on testosterone therapy as described in the previous paragraph. Therefore, this should prompt clinicians to seek out prescription and over-the-counter androgen supplementation in cases of unusual site thrombosis in the absence of other evident etiologies.When left untreated, MVT can progress to bowel ischaemia and infarction. As described above, our case demonstrates that good outcomes can be achieved following intensive medical management with immediate anticoagulation. As noted above, subsequent CT scan 2 months after his diagnosis of IMVT revealed resolution of previously identified filling defect within the IMV/splenic vein with complete symptoms resolution. Therefore, there was no need for IMV recanalisation.
This is the first case described in the literature of IMVT caused by secondary polycythaemia from a testosterone implant in the setting of PV. This case highlights the importance of adding this diagnosis to the differential in patients presenting in the appropriate clinical context and the importance of reviewing a patient’s medication, and potential interaction with his or her known diagnoses.
Learning points
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Inferior mesenteric vein thrombosis (IMVT) is extremely rare and potentially a lethal complication that can progress to bowel ischaemia if left untreated. Thus, early recognition of patients with IMVT is crucial in successful treatment with prompt anticoagulation.
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Secondary polycythaemia is a known side effect of testosterone, thus, when someone taking testosterone presents with abdominal pain and thrombocytosis, IMVT must be on one’s differential diagnoses.
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It is important to review a patient’s medication and reconcile with patient’s medical history to help prevent adverse reactions.
Ethics statements
Patient consent for publication
Footnotes
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Contributors Description of author roles in manuscript creation. Conceptualisation: NM and MF. Data curation: NM and MF. Validation: NM, MF and AJ. Visualisation: NM, AJ and KB. Writing—original draft: NM and MF. Writing—review and editing: NM, KB and AJ. The article guarantor: NM.
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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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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
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