








key: cord-281733-bsq0ewac
authors: Veyseh, Maedeh; Pophali, Prateek; Jayarangaiah, Apoorva; Kumar, Abhishek
title: Left gonadal vein thrombosis in a patient with COVID-19-associated coagulopathy
date: 2020-09-07
journal: BMJ Case Rep
DOI: 10.1136/bcr-2020-236786
sha: 
doc_id: 281733
cord_uid: bsq0ewac

COVID-19 disease is a viral illness that predominantly causes pneumonia and severe acute respiratory distress syndrome. The endothelial injury and hypercoagulability secondary to the inflammatory response predisposes severely ill patients to venous thromboembolism. The exact mechanism of hypercoagulability is still under investigation, but it is known to be associated with poor prognosis. The most common thrombotic complication reported among these patients is pulmonary embolism. To our knowledge, gonadal vein thrombosis is an uncommon phenomenon that has not been reported in the setting of COVID-19-associated coagulopathy. We report an unusual case of ovarian vein thrombosis and pulmonary embolism associated with COVID-19 presenting with abdominal pain. To our knowledge, this is the first reported case of COVID-19 with absent respiratory symptoms and presentation with venous thrombosis in an unusual location.

SUMMARY COVID-19 disease is a viral illness that predominantly causes pneumonia and severe acute respiratory distress syndrome. The endothelial injury and hypercoagulability secondary to the inflammatory response predisposes severely ill patients to venous thromboembolism. The exact mechanism of hypercoagulability is still under investigation, but it is known to be associated with poor prognosis. The most common thrombotic complication reported among these patients is pulmonary embolism. To our knowledge, gonadal vein thrombosis is an uncommon phenomenon that has not been reported in the setting of COVID-19-associated coagulopathy. We report an unusual case of ovarian vein thrombosis and pulmonary embolism associated with COVID-19 presenting with abdominal pain. To our knowledge, this is the first reported case of COVID-19 with absent respiratory symptoms and presentation with venous thrombosis in an unusual location.

Since the emergence of SARS-CoV-2 in December 2019, the world has faced an unprecedented public health crisis due to its high rate of transmission and the broad spectrum of the disease severity. The manifestation of the disease ranges from asymptomatic carriers to severe acute respiratory distress syndrome requiring mechanical ventilation and intensive care unit (ICU) admission. The severe cases are more prone to arterial and venous thrombosis. These thrombotic events have been related to poor prognosis and linked to unexpected cardiac deaths. 1 The pathophysiology of thrombosis in COVID-19 is hypothesised to be due to a hypercoagulable state from excessive inflammation, hypoxia, immobilisation and in severe cases of disseminated intravascular coagulation. 2 The most common location of thrombosis is pulmonary arteries. Other reported venous thromboembolisms (VTEs) include lower extremity thrombosis and catheter-associated thrombi. 3 Ovarian vein thrombosis (OVT) is a rare and potentially fatal condition of postpartum period, which can act as a source of pulmonary embolism. 4 5 Gonadal vein thrombosis has never been reported during this pandemic as a result of COVID-19. We present a unique case which demonstrates left gonadal vein thrombosis secondary to COVID-19 as the first presenting sign.

A 52-year-old postmenopausal woman, with no known medical history, presented to our hospital with sudden onset of severe sharp right upper quadrant abdominal pain for 2 days. She described the pain to be unrelated to food and not associated with any other gastrointestinal (GI)-related symptoms.

She denied recent fevers, cough or upper respiratory tract infection symptoms. She was afebrile (temp 97.7°F), pulse rate 93 beats/min, respiratory rate 22/min and oxygen saturation was 94% on room air, body mass index 29 kg/m 2 . Her physical examination on admission was notable for shallow breathing, clear lungs and non-tender abdomen.

The labs were significant for increased inflammatory markers, including ferritin (883 µg/L), C reactive protein (217 mg/L) and D-dimer was markedly elevated to 3813 ng/mL (table 1) .

Chest X-ray showed patchy peripheral densities seen in the upper lobe on the frontal view. On the lateral view there were patchy infiltrates posteriorly in the lower lobes suggestive of COVID-19.

CT of the abdomen/pelvis with contrast showed left OVT, which extended partially to the renal vein (figures 1 and 2). Additionally, there was a finding of pulmonary embolism in the posterior branch of pulmonary artery in the right lower lobe (RLL). Pulmonary windows of the CT confirmed presence of bilateral lower lobe consolidations, ground-glass opacities in the right middle lobe and foci of consolidation in the lingula suggestive of COVID-19 pneumonia. Subsequent chest CT angiography confirmed the presence of an acute RLL pulmonary artery thrombosis (figure 3). Deep vein thrombosis (DVT) studies were negative for lower extremity venous clots.

Nasopharyngeal swab confirmed the diagnosis of COVID-19. Echocardiography showed normal biventricular systolic function in the absence of right heart strain.

To further investigate secondary causes of hypercoagulability, rheumatologic panel including antinuclear antibody-extractable nuclear antigen panel, lupus anticoagulant, protein C, protein S and antithrombin III were tested and resulted negative. Tumour markers, including carcinoembryonic antigen, carbohydrate antigen 9/19 and cancer antigen-125 were negative and the initial CT scan Unusual presentation of more common disease/injury of chest/abdomen/pelvis was without any evidence of malignancy. COVID-19 was deemed to be the provoking cause of the thrombosis.

The patient was started on therapeutic low molecular weight heparin (enoxaparin) 1 mg/kg two times per day, which resulted in significant improvement of the abdominal pain few hours after the first dose. She remained afebrile, denied any cough or shortness of breath, and oxygen saturation remained stable on room air. She was discharged after 3 days of hospitalisation on apixaban 10 mg two times per day for a week, followed by 5 mg two times per day for 3 months.

During follow-up after a month, the patient reported mild abdominal pain, but remained afebrile and without any respiratory symptoms. She denied any bleeding complication. A repeat CT of the abdomen and pelvis showed resolution of thrombosis. D-dimer at the follow-up visit was 234 ng/mL.

The COVID-19 pandemic caused by the SARS-CoV-2 has affected millions of people worldwide. While a majority of the people affected by the virus remain asymptomatic, most patients admitted to the hospital present with severe respiratory illness. The most extensive published case series from China and New York report that the majority of patients present with fever, cough, fatigue and GI symptoms. 6 7 Nearly 20% of these patients present with severe coagulation abnormalities. But rarely, VTE may be the initial presenting feature in patients with SARS-CoV-2 infection. 8 Concomitant VTE, a potential cause of unexplained deaths, has been frequently reported in COVID-19 cases. 8 9 Our patient was distinctive in terms of presentation as she lacked the common respiratory symptoms, rather acute venous thrombosis in an unusual location prompted the diagnosis of COVID-19.

Virchow's triad defined as blood stasis, endothelial injury and a hypercoagulable state leads to the pathogenesis of thrombosis. 10 Patients with COVID-19 usually present with dehydration and prolonged bed rest, which are risk factors for blood stasis. 11 SARS-CoV-2 infects ACE 2 receptors, which is present on multiple organs, including the endothelial cells. In a recent study on postmortem autopsies, there was evidence of endothelitis caused by either direct viral invasion of the endothelial cells or endothelial injury derived from the inflammatory response. This possibly explains why patients with endothelial dysfunction due to pre-existing conditions are more prone to organ failure secondary to microthrombi and present with a more severe form of the illness. 12 Also, the COVID-19 infection can cause a severe inflammatory response, which results in the release of cytokines such as interleukin 6, tumour necrosis factor-alpha. 13 These cytokines stimulate the activation of the coagulation cascade and increase the risk of VTE. 14 Other proposed pathophysiology behind an increased propensity to thrombosis is the finding of antiphospholipid antibodies, which can transiently arise in patients with critical illness and various infections and potentially contribute to a hypercoagulable state. 15 16 Based on the available literature, most thrombotic events in COVID-19, including pulmonary embolism or DVTs, develop in critically ill patients with severe pulmonary disease. 2 17 18 Our case was unique as she had no respiratory symptoms and an otherwise uncomplicated clinical course; however, she still presented with a thrombotic complication in an unusual site.

OVT is a rare entity that is most commonly seen in the postpartum period. Other causes of OVT include pelvic Unusual presentation of more common disease/injury inflammatory disease, recent gynaecological or abdominal surgery, hypercoagulable state and underlying malignancy. 5 An underlying hypercoagulable state has been reported in 50% of the cases with OVT. 19 Regardless of the aetiology, rightsided OVT accounts for 70%-90% of the cases. It can likely be related to dextrotorsion of the uterus that compresses the right ovarian vein, antegrade flow and relatively more incompetent valves of the right ovarian vein. 20 The most common symptoms are fever (80%) and right-sided pelvic pain (55%). 21 Our patient was unusual as she did not have a fever on presentation, and the venous thrombosis was on the left side. This condition can be fatal due to the serious life-threatening complication from thrombus extension into the systemic veins and subsequent pulmonary artery embolisation. The incidence of OVT complicated by pulmonary embolism is reported to be approximately 25%. 22 Our case was diagnosed with OVT and subsequent pulmonary embolism. It is unclear if the pulmonary embolus occurred secondary to embolisation of ovarian thrombosis or a primary thrombus as a result of hypercoagulability state due to COVID-19, specifically in the absence of lower extremity DVT. The treatment for OVT is anticoagulation for 3-6 months. However, no clear guideline is available about the duration of therapy, and non-vitamin K antagonist oral anticoagulants have not yet been studied in such cases. 5 20 The only widely available treatment in COVID-19-associated coagulopathy is prophylactic dose of low molecular weight heparin, which should be considered in all patients (including non-critically ill) who require hospital admission for COVID-19 infection. 23 Use of higher-intensity, non-standard anticoagulation currently lacks efficacious evidence in COVID-19. 10 A study by Klok et al 2 showed a 31% incidence of thrombotic complications in ICU patients with COVID-19 infection despite being on prophylactic anticoagulation. Considering this remarkably high incidence of VTE, it is suggested to increase the intensity of anticoagulation despite the lack of randomised evidence to support the practice. Current evidence suggests D-dimer, an indicator of fibrin breakdown, can be used to assess severity of clot burden and guide initiation and monitoring of therapy. 1 24 In summary, we present an interesting case with an unusual presentation of COVID-19 who presented with abdominal pain and no significant respiratory symptoms and was diagnosed with thrombosis of the left ovarian vein. Our case emphasises the high risk of coagulopathy in COVID-19 cases, even without a severe systemic infection. Evaluation and risk stratification for thrombosis with coagulation markers and D-dimer should be incorporated in the management of COVID- 19. 25 Learning points ► This is the first case report of ovarian vein thrombosis secondary to COVID-19-associated coagulopathy (CAC). ► CAC can present with thromboembolic complications even in the absence of typical respiratory symptoms. ► CAC is associated with poor prognosis and prompts prophylactic anticoagulation in all patients who require hospitalisation. ► Coagulopathy is independently indicative of severe illness even in the absence of lung involvement. Prothrombin time/ partial thromboplastin time/international normalised ratio, fibrinogen and D-dimer should be monitored in all patients with COVID-19 requiring hospitalisation.

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis

Ovarian vein thrombosis: incidence of recurrent venous thromboembolism and survival

Ovarian vein thrombosis: a rare cause of abdominal pain outside the peripartum period

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Venous thrombosis and arteriosclerosis obliterans of lower extremities in a very severe patient with 2019 novel coronavirus disease: a case report

Endothelial cell infection and endotheliitis in COVID-19

Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China

Bidirectional relation between inflammation and coagulation

Lupus anticoagulant is frequent in patients with Covid-19

Infectious origin of the antiphospholipid syndrome

Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study

Postpartum ovarian vein thrombosis

Postpartum ovarian vein thrombosis: an unpredictable event: two case reports and review of the literature

Acute appendicitislike symptoms as initial presentation of ovarian vein thrombosis

Ovarian vein thrombosis in the nonpregnant woman: an overlooked diagnosis

ISTH interim guidance on recognition and management of coagulopathy in COVID-19

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

D-Dimer is associated with severity of coronavirus disease 2019: a pooled analysis

Contributors Supervised and reviewed by AK. Patient was under the care of MV. Report was written by MV, AJ and PP.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.Competing interests None declared.

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