Anticoagulation-induced unilateral adrenal haemorrhage and pseudoaneurysm

Abstract

Spontaneous unilateral adrenal haemorrhage (AH) is extremely rare. Its presentation is usually non-specific and requires a high degree of suspicion as it is associated with high morbidity and mortality if diagnosis is delayed. Hereby, we present a case of 67-year-old man with significant cardiac history presented with right-sided chest pain and non-specific abdominal pain. He was previously treated for non-ST elevation myocardial infarction 5 days ago prior to the current presentation. CT scan of abdomen and pelvis demonstrated a right-sided active AH. The patient subsequently underwent digital subtraction angiography. Angio-embolisation was attempted for the pseudoaneurysm but failed due to spasm of the vessel. He was managed conservatively and discharged after clinical improvement. Clinic review 6 months later showed significant size reduction of the pseudoaneurysm.

Background

Adrenal haemorrhage (AH) is a rare condition with high fatality rate. Based on the aetiology of AH, it is categorised into traumatic and non-traumatic. In particular, non-traumatic AH with pseudoanuerysm is rare. It is clinically difficult to differentiate AH from other pathologies and the clinical concern is that this could potentially be overlooked and lead to acute adrenal insufficiency which can be fatal.

Case presentation

A 67-year-old morbidly obese man initially presented with right-sided chest pain and non-specific right-sided abdominal pain. Given his significant medical history of ischaemic heart disease, atrial fibrillation on rivaroxaban, he was managed as non-ST segment elevation myocardial infarction (NSTEMI). He received loading doses of 300 mg aspirin and 180 mg of ticagrelor. After subsequent review by cardiologist, ticagrelor was ceased as his chest pain was thought to be secondary to lower respiratory tract infection. He represented 5 days later with right lower quadrant abdominal pain which was constant and dull in nature, with intermittent radiation to lower back. He had no diarrhoea or urinary symptoms.

His medical history includes localised perforation of sigmoid diverticulitis 12 months ago that was managed non-operatively. There was no family history of haematological disorder.

On presentation, he was afebrile and haemodynamically stable. His examination showed temperature of 36.4°C, pulse of 83 beats/min and regular, blood pressure 152/83 mm Hg and respiratory rate 16/min. On examination, there was localised tenderness on his right lower abdomen with no guarding.

Investigations

The initial laboratory investigations revealed a haemoglobin level of 142 (130–180 g/L), white cell count of 15.0 (4.5–6.5×10¹²/L) and platelet of 192 (150–400/L), creatinine 90 (55–115 μmol/L) and C-reactive protein 150.1 (<3 mg/L). His coagulation profile was abnormal: international normalised ratio (INR) 2.0 (0.9–1.3), activated partial thromboplastin time (APTT) 54 (24–36 s), prothrombin 26 (11–19 s) and raised fibrinogen of 7.9 (2.0–4.0 g/L). Other biochemistry tests were within the normal limits.

Given his previous history of diverticulitis, a CT scan of the abdomen and pelvis was organised. For comparison, CT scan from 12 months prior did not show any evidence of an underlying adrenal mass (figure 1). The initial portal venous phase CT showed no evidence of diverticulitis but a right adrenal haematoma measuring 4.8×3.2 cm right adrenal mass with associated adrenal and peri-adrenal stranding, consistent with adrenal haematoma (figure 2). Further triphasic CT scan revealed a blush of contrast enhancement at the posterior aspect of the right adrenal haematoma (figure 3).

Figure 1.

(A and B) Axial and coronal views of CT abdomen performed 1 year prior to current presentation for localised perforated sigmoid diverticulitis. The arrows showed normal appearance of right adrenal gland with no evidence of underlying mass (arrows).

Figure 2.

(A and B) Axial and coronal views of CT abdomen (portal venous phase) showing a 4.8×3.2 cm right adrenal mass with associated adrenal and peri-adrenal haemorrhage (thick arrows), consistent with adrenal haemotama. (C) Axial views of CT abdomen showing the significant right periadrenal stranding (thin arrow).

Figure 3.

(A and B) Axial and coronal views of CT scan (arterial phase) performed showing a blush (arrows) indicating active right adrenal haemorrhage.

Differential diagnosis

Given his previous history of diverticulitis with raised inflammatory markers, it was thought that a recurrence of diverticulitis was most likely. Other differential diagnoses included severe pneumonia where he first presented with.

Outcome and follow-up

He was transferred to a tertiary hospital as there was suggestion of active bleeding on the triphasic CT scan and his history of anticoagulation and antiplatelet use. Prior to the transfer, he was given oral vitamin K and prothrombinex to reverse the effect of coagulopathy on the advice of the haematology team. On discussion with the interventional radiologist, the initial CT scan which showed the contrast blush was likely indicative of a pseudoaneurysm (figure 3).

A repeat CT 2 days later again demonstrated the pseudoaneurysm of right adrenal artery that remained unchanged in size. A fasting plasma metanephrines was done and was normal. The interventional radiologist attempted to coil the pseudoaneurysm and was unsuccessful due to the tortuosity and spasm of the right adrenal artery (figure 4).

Figure 4.

(A) Angiogram of the right renal artery showed a tortous right adrenal artery with a pseudoaneurysm. (B) Subsequent angiogram showing complete occlusion of the adrenal artery after attempts to pass a microwire.

He was discharged well on day 5. A repeat outpatient CT angiogram at 1 month showed stable appearance of the pseudoaneurysm (figure 5).

Figure 5.

Coronal view of CT abdomen (arterial phase) on follow-up 1 month after angiogram showing a stable appearance of the a 6-mm hyperdense focus (arrow) and right adrenal haemorrhage.

On his subsequent imaging 6 months later, CT scan showed a significant reduction in size of the right adrenal pseudoaneurysm.

Discussion

AH is a rare medical emergency with reported incidence of 0.14%–1.1% on postmortem studies.^{1 2} Specifically, non-traumatic AH has been associated with underlying physiological stress, such as sepsis, pregnancy, post-abdominal surgery, anti-phospholipid syndrome and rarely anticoagulation.^3–7 In the setting of sepsis, Waterhouse-Friderichsen syndrome is classically associated with AH and clinical adrenal insufficiency, it has high mortality due to the nonspecific clinical manifestations masked by concurrent sepsis.⁸ Haemorrhagic adrenal gland can also arise in the setting of pre-existing adrenal neoplasms, such as pheochromocytoma, myelolipoma, melanoma, neuroblastoma, adrenocortical carcinoma, hepatocellular carcinoma and lung cancer metastases.⁹ Box 1 has summarised a list of differential diagnosis of an unilateral adrenal mass. Iatrogenic complication of adrenal vein sampling has been reported causing AH.^{10 11} Table 1 has outlined several case reports on different aetiologies of unilateral AH.

Box 1. The differential diagnosis of unilateral adrenal mass.

• Adrenal adenoma (non-functioning).

• Functioning adrenal tumours:

  • Cortisol secreting adenoma.

  • Pheochromocytomas.

  • Aldosteronoma.

• Adrenal carcinomas.

• Metastases:

  • Breast, lung, lymphoma, leukaemia.

• Other:

  • Adrenal haemorrhage (AH).

  • Myelolipoma.

  • Neurofibromas.

  • Hamartomas.

  • Teratoma.

  • Cyst.

  • Granulomatosis.

  • AH/haematoma.

• Pseudoadrenal:

  • Renal, pancreas, spleen.

Table 1.

Case reports on different aetiologies of unilateral adrenal haemorrhage

Citations	Patient’s demographics	Predisposing factors	Urgent intervention	Functionality	Follow-up/management	Final diagnosis/outcome
Jayaweera et al19	24, M	Immunotherapy for multiple sclerosis and EBV infection	No	No	Not reported	Not reported
Lawson et al20	31, F G1P0	Pregnancy (third trimester)	No	No	Repeat ultrasound throughout pregnancy	Reduced in size
Chronopoulos et al21	73, M	Hypertension, prophylactic anticoagulation	No	No	Not reported	Discharged postoperative day 16
Ito et al22	67, F	Glomerulonephritis and alveolar haemorrhage	No	Yes	–	Died of disseminated intravascular coagulation
Khare et al23	35, F	Antiphospholipid antibody syndrome	No	No	Repeat MRI 1 and 4 months	Resolved right adrenal haemorrhage
Burnet et al24	68, F	Essential thrombocythaemia	No	No	Commenced on hydroxyurea and aspirin	Discharged
Carter et al25	33, F	G1P0, gestational trophoblastic neoplasia	No	No	Weekly methotrexate	Discharged

EBV, Epstein-Barr Virus.

To our knowledge, CT findings of non-traumatic unilateral adrenal pseudoaneurysm from rivaroxaban have never been described before in literature. Many case reviews have discussed bilateral AH secondary to heparin-induced thrombocytopaenia.¹²

The pathogenesis of spontaneous AH remains unclear. Increased adrenocorticotropic hormone in the setting of stress has been hypothesised to increase adrenal blood flow.^11–13 The vascular architecture of adrenal gland has also predisposed itself to AH given the abrupt transition from arterial system to capillary plexus around the zone reticularis, commonly known as the ‘vascular dam’.¹³ AH occurs very rarely in patients who are anticoagulated; when it does, it is usually within the first 2–12 days of therapy. A case-control study reported that thrombocytopenia, heparin use and sepsis were the variables that were most strongly and independently associated with AH risk.^{12 13}

Clinically, most patients present with non-specific signs and require a high degree of suspicion. Similarly, the clinical examination usually yields non-specific findings such as fever, tachycardia and non-specific abdominal tenderness.¹⁴ Orthostatic hypotension is present in one-fifth of patients with extensive bilateral AH. This is an early sign which could potentially lead to shock. Rarely, hypertension has been reported in patients with unilateral AH. Biochemistry investigations may depict a sudden fall in haemoglobin, progressive hyperkalaemia and hyponatraemia in the setting of bilateral AH.

CT scan is the choice of imaging modality and is usually performed for the suspicion of other diagnoses. If the initial portal venous phase of CT shows evidence of AH, it should be followed by an arterial phase to evaluate if there is active bleeding. During the acute phase, it is difficult to identify if there is any underlying adrenal mass. Therefore, a repeat CT scan should be performed once the AH has resolved.

The management of AH depends largely on (1) whether there is evidence of active bleeding and (2) unilateral versus bilateral involvement of the adrenal gland(s). In patients presenting with signs of shock, fluid resuscitation should be initiated. Any coagulopathy should also be corrected. Once stabilised, a CT scan can be organised to investigate further. In the emergency setting where there is evidence of active bleeding on the arterial phase of CT scan, embolisation should be attempted. Given the complexity of vascular supply of adrenal, it is crucial to be highly selective to prevent further ipsilateral adrenal gland infarction. Cases of superselective embolisation of adrenal glands have been reported in literature with good prognosis.¹⁵

In cases with bilateral AH, it is often life-threatening due to the development of adrenal insufficiency as a sequela. Due to inadequate response to stress with low basal and stress levels of plasma cortisol, it can lead to cardiovascular collapse and death. Appropriate hydrocortisone replacement therapy should be commenced.

Pseudoaneurysm is defined as a pulsating, encapsulated haematoma in communication with the lumen of a rupture vessel.¹⁶ It is usually caused by penetrating trauma. A few cases of adrenal pseudoaneurysm secondary to blunt trauma have been reported in the literature and both were successfully managed with embolisation of the adrenal artery.^16–18 To the best of our knowledge, there are no cases of adrenal pseudoaneurysm associated with anticoagulation reported. For cases of AH with associated pseudoaneurysm, it is vital to rule out a potential functional pheochromocytoma with biochemistry prior to any intervention attempt to prevent adrenergic crisis.

Learning points.

• Adrenal haemorrhage (AH) occurs very rarely in patients who are anticoagulated; when it does, it is usually within the first 2–12 days of therapy.

• Early use of cross-sectional imaging and clinical suspicion will help to recognise the AH and will allow physicians to treat patient expeditiously.

• Unilateral haemorrhage can usually be managed conservatively, whereas bilateral AH is often life-threatening.