1

Introduction

Spontaneous, non-traumatic bleeding into the subcapsular and perirenal space is a rare and potentially fatal condition known as Wunderlich syndrome (WS). Patients may present with Lenk’s triad which is characterized by acute flank pain, flank mass, and hypovolemic shock. Majority of WS cases are attributed to be caused by renal tumors and vascular diseases, less common causes include infections and anticoagulation therapy.

Warfarin is a commonly used anticoagulant for various conditions. It works by the inactivation of vitamin K synthesis in the liver. However, therapeutic levels can exceed the desired level due to interactions with other drugs. For example, Ciprofloxacin is a broad-spectrum antibiotic that belongs to fluroquinolones and covers broad spectrum of bacteria which made it popular to use among physicians. however, it may have the ability to interact with warfarin leading to several serious complications

In this paper, we report a case of a 47 year old female on warfarin who developed subcapsular hematoma and retroperitoneal hematoma after the completion of ciprofloxacin treatment course.

2

Case presentation

47 years old female K/C of Primary Anti Phospholipid Syndrome on Hydroxychloroquine, Previous unprovoked right Arm DVT on 6 mg Warfarin daily for 10 year, HTN on 5 mg amlodipine daily, and status post hysterectomy many years back due to menorrhagia. The patient presented to the ER complaining of abdominal pain for 1 day mainly in left flank and supra pubic area. Dull aching, non-radiating, not related to position and the severity is 9/10. It was associated with nausea and vomiting for the previous 3 days. She was in Europe one week before her presentation, where she had a simple UTI that was managed with Ciprofloxacin for one week. Last dose was received one night prior to her presentation.

No history of trauma. No history of neurological, respiratory or gastrointestinal symptoms.

No previous urological history.

Upon examination, she was a middle-aged lady, lying on the bed, looked in pain and distress. She was febrile and temperature was reaching 38.2 °C, her heart rate was 100–110 beats per minute, and she was noted to be tachypneic. Blood pressure was maintained within the normal range. Abdominal examination revealed suprapubic and left flank tenderness. Chest and cardiovascular system examination were unremarkable as well as pelvic and genitalia examination.

Laboratory investigations done, which showed a normal white blood cell and platelet count, and a hemoglobin level of 10.6 g/dl. Her prothrombin time was 101 seconds (reference range, 10–13 seconds), international normalized ratio was 7.21 seconds. Her blood urea nitrogen concentration as well as her creatinine level were in the normal range.

Computed tomography scan for the abdomen and pelvis revealed It showed a well-demarcated subcapsular fluid collection measuring around 13Χ8Χ2 cm on the anterior aspect with a compression effect over the left kidney ( Fig. 1 ). There was also a large hypodense area in the left peritoneal space. The Hounsfield unit was around 60, which is indicative for the presence of hematoma. the urinary bladder and the ureters were normal bilaterally. These findings were suggestive for the presence of left subcapsular renal hematoma complicated by retroperitoneal hematoma.

Axial view of computed tomography scan of the abdomen at presentation which showed left subcapsular renal hematoma measuring 13x8x2 cm with a compression effect over the left kidney.

Right after the admission, The patient became drowsy, her blood pressure dropped to 75/40 mmHg. Hb dropped to 6.7 g/dl then to 5.9 g/dl, and Creatinine jumped from 1.06 to 1.7 mg/dl.

The patient was resuscitated with IV fluids and blood transfusion, two units of packed red blood cells and four units of fresh frozen plasma transfused. coagulation profile has been corrected in which prothrombin time and international normalized ratio decreased to 20 and 1.4, respectively. Hemoglobin level increased to 7.0 g/dl, and INR was corrected with IV Vitamin K. After patient stabilization, she was referred to interventional radiology for angioembolization. The patient improved clinically, the pain improved, and her abdomen became soft and lax. Hemoglobin and creatinine levels were normalized. and she was discharged home with good condition after two weeks.

3

Discussion

The clinical picture of subcapsular renal hematoma (SRH) is not always represented by the classical symptoms of link’s triad. In one published series that included 13 cases, only 2 patients presented with all the three symptoms of the triad. Zhang et al. published a meta-analysis of 165 WS cases from 47 studies. Flank pain was observed in 83 % of the patients, 19 % patients presented with hematuria, and 11 % presented with signs and symptoms of hypovolemic shock.

There are multiple causes of SRH. A literature review conducted in 1974 by McDougal et al. revealed that 58 % of the cases were due to renal tumors. Clear cell carcinoma and angiomyolipoma were the most common malignant and benign tumors, respectively. Vasculopathies comes next representing 17.9 % of the cases. Infection, nephritis, and blood dyscrasias were less common with the latter representing only 5.1 % of the cases. Recently, the number of SRH cases caused by coagulation abnormalities has increased. Moreover, a retrospective study done in 2016 showed that 29.6 % of the cases were due to renal tumors and 27.1 % were due to coagulation abnormalities. The reason behind that might resides in the fact that warfarin is one of the most commonly prescribed anticoagulants due to its wide-spread uses.

Many drugs have been reported to increase the effect of warfarin including antibiotics, like erythromycin, fluconazole, ketoconazole, metronidazole, sulfonamides and ciprofloxacin. In our case the patient was on warfarin and got diagnosed with SRH right after the completion of ciprofloxacin course, which leaves the interaction between warfarin and ciprofloxacin the culprit in this case. The interaction between warfarin and ciprofloxacin has been a matter of controversy as there is a contradiction between the available information from case reports and clinical studies, as the latter hasn’t shown that ciprofloxacin augment the effect of warfarin. ^, To our best knowledge, this is the first reported case about SRH induced by ciprofloxacin and warfarin interaction.

Ultrasound can be used as an initial test for diagnosing a patient with spontaneous SRH. It’s a rapid and non-invasive method that give information about the size and location of the hematoma. Yet, it’s unnecessary as the patient will eventually need computed tomography (CT) scan to detect the underlying cause. However, large hematomas on initial CT scan can hide the presence of any tumors or masses. Also, vascular abnormalities will not be apparent without contrast. In a series published in 2020. 42 patients were included, and CT combined with magnetic resonant imaging (MRI) were used in the acute stage. Both modalities failed in identifying the cause of bleeding in 10 patients. Thus, a follow up CT is required after a short period to reveal any obscured masses that haven’t been shown in the initial image.

Dealing with a case of spontaneous SRH in a patient on anticoagulation can be challenging. The dilemma lies in the difficulty of finding the etiology of the bleeding, and in choosing the proper way of management based on it. The management depends mainly on the patient’s hemodynamic stability, the presence of active bleeding, and the underlying etiology. Conservative management includes resuscitating the patient with Intravenous fluids with or without blood products, using anticoagulation reversals and treating sepsis or obstruction if present. Different other treatment methods have been reported in the literature. Kendall AR et al. have proposed nephrectomy when there’s no etiology can be identified. Shen Z et al. have proposed a novel method where percutaneous drainage is done followed by intracavitary urokinase injection. With the advancement of interventional radiology, trans-arterial embolization has become the treatment of choice as it has shown to be safe and effective, while open surgery is rarely required now and it’s reserved for cases of tumors or refractory bleeding. In our case, the patient was managed by trans-arterial embolization as malignancy and other causes have been ruled out, and warfarin seems to be the reason behind the bleeding especially with the abnormal coagulation profile.

4

Conclusion

Spontaneous subcapsular hematoma is a rare entity that can present with various clinical pictures. However, physicians should have a high index of clinical suspicion specially in patients on anticoagulation. There are various etiologies of Spontaneous SRH including tumors, vascular diseases, and coagulation abnormalities. Whenever a renal hematoma is suspected, CT scan is the preferred modality for diagnosis. We believe that conservative management and trans-arterial embolization are the treatments of choice in managing spontaneous SRH when malignancy has been ruled out.

CRediT authorship contribution statement

Masoud Basheer Alshammari: Writing – review & editing, Writing – original draft. Zainab Ali Alhassar: Writing – review & editing, Writing – original draft. Abdulla Abduljaleel Alkhalifa: Writing – review & editing, Writing – original draft. Abdulmalik Abdulaziz Alkhamis: Writing – review & editing, Writing – original draft. Hatem Hamed Al-Thubiany: Writing – review & editing, Writing – original draft.