Postpartum ovarian vein thrombosis with left renal venous infarction after vaginal delivery

Abstract

A primipara in her late 20s presented with abdominal pain and pain in the left flank 14 days after a ventouse delivery. She was treated with antibiotics, antiemetics and analgesics with the initial differential diagnosis of cystitis, pyelonephritis or nephrolithiasis. Despite the treatment, the patient experienced increased colic pain and nausea. An ultrasound showed an enlarged left kidney, suggesting pyelonephritis, and thereby, the antibiotic treatment was adjusted accordingly. Despite additional pain medication, pain relief could not be achieved. The diagnosis of ovarian venous thrombosis was considered, and an abdominal CT scan confirmed the diagnosis. The patient was treated with anticoagulant therapy. Hypercoagulability work-up revealed a heterozygous mutation of the Factor V Leiden. Our patient awaits a haematologic follow-up.

Background

During pregnancy, many physiological changes occur. Besides increased oestrogen levels contributing to hypercoagulability, coagulation factors, platelet-activating factors and von Willebrand factor are also increased.^1–4 Meanwhile, factors that inhibit blood clotting, such as protein S and antithrombin III, decrease during pregnancy.^{5 6} Endothelial damage is believed to be easily caused by uterine infection during the postpartum period, increasing the risk of venous thrombosis compared with non-pregnant healthy women.⁷ Therefore, extra attention is given to the risk assessment, prevention, clinical awareness of the possible occurrence, early detection and management of deep venous thrombosis and pulmonary embolism during pregnancy and the postpartum period.⁸

Postpartum ovarian venous thrombosis (POVT) is a rare condition occurring mostly in the postpartum period. 90% of POVT presents within 10 days postpartum.⁹ The diagnosis is made in 0.05–0.18% after vaginal birth and in 2% after caesarean sections.^{10 11} 80–90% of the cases involve the right ovarian vein. It is hypothesised that the compression of the right ovarian vein due to the dextroflexion of the uterus during pregnancy, causing venous stasis, contributes to the more frequent involvement of the right ovarian vein in POVT.⁹ Additional factors are the higher amount of incompetent valves on the right side, making it more prone to thrombosis. The antegrade blood flow in the right ovarian vein has been postulated to favour ascension of bacterial uterine contaminants that can cause endothelial injury in the right ovarian vein, which is believed to be another key step to thrombus formation in the pathophysiology of POVT.^{9 12} Munsick et al proved that blood flow in the left ovarian vein is reversed, which has been hypothesised to decrease the chance of vascular damage by bacteria in the left ovarian vein.¹³

This report describes a rare case of POVT involving the left ovarian vein 2 weeks after an assisted vaginal birth through ventouse delivery.

Case presentation

A woman in her late 20s, gravida 1 para 1, with a medical history of hypothyroidism, presented with pain in the lower abdomen and in the lower back 13 days after an uncomplicated assisted vaginal birth through ventouse delivery. She showed no symptoms other than fatigue.

The antepartum period was uncomplicated and was routinely managed by the midwifery practice. She used no medication throughout her pregnancy. She was admitted to the hospital due to meconium-stained amniotic fluid. Ventouse delivery including mediolateral episiotomy was performed at station+2 because of an abnormal foetal heart trace. A healthy son was born. The third stage of labour was uncomplicated, and she was discharged 1 day after delivery.

On the day of the presentation, physical examination showed pain on palpation in the left flank and left lower back. Vital signs were as follows: blood pressure, 110/60 mm Hg; heart rate, 74 beats per minute; oxygen saturation, 99% on room air; temperature, 37.1°C; and respiratory rate, 12 breaths per minute (Early Warning Score of 0). Laboratory results showed a C-reactive protein (CRP) level of 40 mg/L (reference range: 0–8.2 mg/L) and leucocytosis of 21×10⁹/L (reference range: 4–10×10⁹/L). Urine sampling showed erythrocytes of 160, leucocytes of >800×10⁹/L and bacteriuria. The differential diagnosis included cystitis and incipient pyelonephritis or nephrolithiasis. A urine culture was performed. Our patient was first treated with oral antibiotic treatment (amoxicillin and clavulanate potassium 625 mg three times daily), antiemetic (ondansetron), painkillers (paracetamol 1000 mg four times daily and diclofenac 75 mg three times daily) and hyoscine butylbromide (10 mg suppository).

One day later, she was readmitted with increased pain despite pain medication, nausea, vomiting and colic pain. Vital parameters showed a blood pressure of 146/96 mm Hg, heart rate of 71 beats per minute, oxygen saturation of 98%, respiratory rate of 12 breaths per minute and temperature of 37.0°C. Laboratory results showed an increased CRP level of 164 mg/L, leucocytosis of 23.8×10⁹/L, estimated glomerular filtration rate (eGFR) of 49 mL/min (reference range: >90 mL/min/1.73 m²), creatinine level of 128 µmol/L (reference range: 45–80 µmol/L) and urea of 6.6 mmol/L (reference range: 2.5–7.5 mmol/L).

Investigations

As described above, we started with vital signs, laboratory examination and urine sampling. Since the pain increased, we performed an abdominal ultrasound by the radiology department. Ultrasound imaging of the abdomen showed an enlarged and hyperechogenic left kidney, which fitted the diagnosis of pyelonephritis. Our patient was admitted to the maternity ward, and antibiotic treatment was switched to intravenous administration and adjusted to treat pyelonephritis (cefuroxime 1500 mg three times daily) with the results of a final urine culture pending. As an additional pain medication, the patient received a patient-controlled analgesia pump with hyoscine butylbromide of 80 mg/day and intramuscular piritramide (opioid) of 15 mg 4 to 6 times daily.

Blood tests the next day showed an increased CRP level of 380 mg/L. Despite additional pain medication with intramuscular and transdermal treatment with opioids, our patient experienced increasingly severe pain in the left flank. Urine culture revealed growth of Enterococcus faecalis, after which we switched to amoxicillin and clavulanate potassium (1200 mg intravenous 4 times daily) based on the antibiogram.

Differential diagnosis

The differential diagnosis included pyelonephritis, another source of infection or an ovarian venous thrombosis due to the lack of fever and persistent severe pain. Since the analgesics and change of antibiotics did not improve the patient’s pain, we decided to extend additional imaging of the upper abdomen. Ultimately, an abdominal CT scan (figure 1) with contrast was performed and showed left ovarian venous and left renal venous thromboses extending to the inferior vena cava with infarction of the left kidney, which was deemed afunctional.

Figure 1.

Abdominal CT scan (coronal view) with contrast shows an enlarged left kidney with complete venous thrombosis of the left renal vein, originating from a left ovarian venous thrombosis, with signs of venous infarction of the left kidney. There is perirenal oedema, and radiologically, the left kidney is deemed afunctional.

Treatment

A therapeutically dosed low-molecular-weight heparin (0.8 mL) and acenocoumarol (1 mg) daily was started. Anticoagulant therapy needed to be continued for at least 3 months after the event. We continued antibiotic treatment orally. She received morphine intravenously or transdermally as additional pain medication during hospitalisation. The patient was discharged home after 13 days of hospitalisation.

POVT can resolve spontaneously, but due to several complications that can occur including pulmonary embolism, it is advised to treat the patient with anticoagulants. Standard guidelines and uniform consensus are lacking in the treatment of POVT. Although not supported by prospective randomised trial data, the mainstays of treatment of POVT consist of anticoagulants and antibiotics.

Most commonly, anticoagulation therapy consists of low-molecular-weight heparin initially to resolve the thrombus, followed by a vitamin K antagonist. Direct oral anticoagulants are discouraged in lactating mothers. It is yet debatable what the optimal duration is for the treatment.^{7 14} Multiple studies have described that treatment of 3 to 6 months seemed sufficient.^{9 14 15} The recurrence risk of a venous thromboembolic event in women with ovarian venous thrombosis was found to be comparable to that of patients with lower extremity deep venous thrombosis.^{15 16} However, regarding a subsequent pregnancy, it is recommended to give antenatal anticoagulant prophylaxis until 6 weeks postpartum for patients with a history of POVT.^{7 17 18}

Antibiotic treatment has been recommended for the treatment of POVT in case of fever and leucocytosis to prevent the extension of the thrombus and probably to treat an underlying cause.¹⁹ There is no consensus, however, about the class, dosage or duration of the antibiotic treatment.²⁰ Although there is no conclusive evidence of its efficacy, antibiotics are typically prescribed for 1 week.²¹ However, in other comparable case reports, the authors refrained from antibiotic treatment in the case of an afebrile patient and therefore treated with anticoagulation only.²² Our patient received antibiotic treatment because the initial differential diagnoses consisted of mainly infectious conditions and her urine culture was positive.

POVT can also be treated surgically with ovarian venous ligation, excision and caval thrombectomy.^{2 23} This method is mainly reserved for specific cases only, such as a contraindication for anticoagulation therapy, recurrent pulmonary embolism despite medical treatment and free-floating thrombosis.^{23 24}

Outcome and follow-up

Hypercoagulability work-up revealed a heterozygous mutation of the factor V Leiden gene. Her eGFR was improved (72 mL/min/1.73 m²) at follow-up, with a slightly elevated creatinine level of 93 µmol/L. On a follow-up CT scan, the left kidney was atrophic after venous infarction with decreased blood flow, and the left renal vein was completely collapsed. The right kidney showed no abnormalities. She received a levonorgestrel-intrauterine device (LNG-IUD) as postpartum contraception, which is a safe option for patients with a factor V Leiden mutation and patients after a venous thromboembolic event.²⁵

It is generally not advisable to repeat imaging because it does not contribute to determining the appropriate type or length of treatment and can entail additional risks and challenges in interpretation.²³

At a 1-year follow-up, our patient still experiences pain in her left flank. She has been diagnosed with a mild chronic kidney disease stage: her eGFR is 84 mL/min/1.73 m² (antepartum >90 mL/min/1.73 m²) and creatinine is 81 µmol/L. Our patient is undergoing psychological support to process her experiences.

Discussion

POVT is described to mostly occur on the right side, to appear more often after a caesarean section compared with vaginal birth and to present within 10 days postpartum. This case describes the rare occurrence of POVT in the left ovarian vein 14 days after vaginal birth.

The pathophysiology of POVT can be described with the triad of Virchow: hypercoagulability, venous stasis and endothelial damage.²⁶ Hypercoagulability is a physiological state during pregnancy as the body prepares for childbirth, preventing blood loss during delivery. Additionally, our patient had a heterozygous mutation of the factor V Leiden gene, which leads to a higher risk of thrombus formation. However, this was not diagnosed before our patient was admitted to our hospital. Venous stasis could have happened due to immobilisation after delivery, which is more often seen after a caesarean section. Our patient had no known difficulties in mobilising after vaginal birth. Our patient had cystitis or pyelonephritis, which could have caused endothelial damage in the ovarian vein.

Previous studies reported that most patients with POVT present with fever (80% of all cases) and lower abdominal pain usually on the side of the thrombosed vein, radiating to the flank, upper abdomen or groin. Non-specific symptoms are malaise, diffuse abdominal pain or breathing difficulties.²⁴ Additional suspicion for the diagnosis of POVT should arise when a woman’s fever is non-responsive to antibiotics. Patients may also show a mass at the location of the thrombosis during deep palpation of the physical examination in approximately 50% of all cases.^{13 24} A non-symptomatic POVT has also been described in the literature, which is sometimes diagnosed as an incidental finding or when complicated by a pulmonary embolism.²⁷

The differential diagnosis for POVT is very broad as the presentation of symptoms overlaps with other conditions. The differential diagnosis consists of acute appendicitis, endo(myo)metritis, pyelonephritis, infected haematoma, adnexal torsion, peritonitis and tubo-ovarian abscess, ectopic pregnancy and septic pelvic thrombo-phlebitis.²⁷

Diagnosis of POVT based on clinical presentation alone is not possible due to varied signs and symptoms. Diagnosis of POVT is confirmed using different imaging techniques. MRI has a high specificity (100%) and sensitivity (92%) but is not directly available in all hospitals. Ultrasound imaging shows the thrombosed ovarian vein as an anechoic to hyperechoic tubular structure that extends to the great vessels in the retroperitoneum, with a lack of colour-flow filling and the absent of spectral waveform when using a Doppler ultrasound. It has a specificity of 99%, but it is not recommended for differentiating POVT from other diagnoses, as it has a low sensitivity (50–56%).^{28 29} Additionally, it requires experience to visualise the ovarian vein with the ultrasound as several structures, such as bowels and body habitus, can obstruct the view.²⁷ The CT scan with contrast is the most preferred method to confirm the diagnosis of POVT, which presents itself as a tubular grey structure next to the ovary.¹² It has high accuracy (specificity, 99% and sensitivity, 100%) and is easily accessible.^{19 28 29}

POVT comes with increased morbidity and mortality, and therefore, swift diagnosis and subsequent treatment are necessary. Mortality is mainly caused by pulmonary embolism (5% mortality rate), which occurs in 25% after POVT.⁹ Other complications are ovarian abscess, ovarian infarction, sepsis, ureteral obstruction, hydronephrosis and renal failure with dialysis.²³

Patient’s perspective.

The first few days after my delivery, my focus was mainly on my recovery and breastfeeding. We took it easy and savoured our time as a brand new family of three.

On the 13th day after my delivery, I suddenly experienced an excruciating amount of pain, a pain I did not recognise at all. At first, I could not quite pinpoint what the source of the pain was, because the pain was so intense. Since I had to vomit repeatedly and experienced an urge to move, I knew something was seriously wrong.

Unfortunately, the first few medical examinations did not immediately reveal what was happening with my body. This left me feeling uncertain. I did not feel understood.

When I finally received my diagnosis, I felt a tremendous amount of relief but also insecurity. Relief because I could finally get the right care to treat the excruciating pain I was experiencing. Insecurity because I was not entirely sure what was truly wrong with my body, what is going to happen next and what would it mean for my health? I was also unsure if I could I be there for my newborn baby.

It’s been a year now and I am still struggling with physical and mental issues, along with a heavy sense of guilt toward my child, because I was feeling so sick and I couldn’t be there for them as much as I wanted to.

The patient’s perspective has been translated into English by the first author (WC).

Learning points.

• Ovarian venous thrombosis is a rare condition occurring mostly in the postpartum period. In case of persistent pain in the lower abdomen or flank and fever after delivery, postpartum ovarian venous thrombosis (POVT) should be considered within the differential diagnosis.

• POVT occurs mostly on the right side, after a caesarean section and within 10 days after delivery. However, the diagnosis of POVT should still be considered after vaginal delivery more than 10 days postpartum.

• A CT scan with intravenous contrast of the abdomen is recommended to diagnose POVT.

• POVT might, in specific cases, lead to renal infarction and result in (mild) chronic kidney disease.

• Due to potentially fatal complications such as pulmonary embolism and systemic sepsis, physicians are recommended to treat patients with POVT with anticoagulants (low-molecular heparin and vitamin K antagonists). Additional treatment with broad-spectrum antibiotics is recommended in cases with symptoms of a suspected infection, such as fever or leucocytosis.

Ethics statements

Patient consent for publication

Consent obtained directly from the patient.