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15 January 2007
A Case Report and Literature Review of Portal Vein Thrombosis Associated with Cytomegalovirus Infection in Immunocompetent Patients
Department of Clinical Medicine, University of Insubria, Varese, Italy
We describe a young man with acute portal vein thrombosis (PVT) and cytomegalovirus (CMV) infection, and we review the literature regarding the association between PVT and CMV in immunocompetent patients. Published data suggest that CMV hepatitis and, possibly, other types of acute viral hepatitis could be a local risk factor for acute PVT.
Received 3 July 2006; accepted 15 August 2006; electronically published 14 December 2006.
Several local and systemic factors are involved in the pathogenesis of acute portal vein thrombosis (PVT). In particular, intra‐abdominal inflammatory processes, such as acute and chronic pancreatitis, cholecystitis, and appendicitis, are well recognized risk factors of PVT [1]. Neither acute hepatitis nor acute cytomegalovirus (CMV) infection—which is both a hypothesized systemic procoagulant risk factor and a certain cause of viral hepatitis—is usually reported as a potential risk factor for PVT [1–3]. We describe a young immunocompetent man who experienced prompt resolution of an asymptomatic acute PVT in a highly likely case of CMV infection and review the available evidence of the natural history of acute CMV‐mediated PVT.
Case report.
A 34‐year‐old white man with an echographic diagnosis of PVT was admitted to a tertiary care hospital (Ospedale di Circolo, Varese, Italy) on 26 March 2005. His past medical, family, and social history was unremarkable, apart from a spontaneous pneumothorax at the age of 13 years. In the 2 weeks prior to his admission to the hospital, he was unsuccessfully treated with antibiotic therapy (ampicillin and erythromycin) by a general practitioner for a persistent fever associated with cough. He was initially referred to the emergency department of a primary care hospital, where abdominal color Doppler ultrasonography was performed after the detection of elevated transaminase, lactate dehydrogenase, and D‐dimer levels. The ultrasound revealed a partial thrombosis of the left branch of the portal vein and a moderately enlarged liver and spleen. For this reason, he was transferred to the Department of Clinical Medicine at Ospedale di Circolo.
At admission, the patient was asymptomatic; in particular, he did not report any abdominal symptoms. He was still receiving antibiotic therapy and was not receiving any additional medication. On physical examination, his blood pressure was 140/90 mm Hg, he had a regular pulse rate of 96 beats/min, his body temperature was 38.3°C, and his blood oxygen saturation level on breathing air was 97%. Abdominal palpation revealed a mild enlargment of the liver and of the spleen during deep inspiration. Serum testing revealed a mild elevation of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels (57 U/L, 94 U/L, and 866 U/L, respectively) and a marked elevation of the D‐dimer level (1010 μg/L; cutoff value, <200>
An urgent computed tomographic scan of the abdomen using intravenous iodine contrast medium confirmed a nonenhancing filling defect within the lumen of the left branch of the portal vein. Organ masses, which are possible local causes of portal vein thrombosis, were excluded, apart from 1‐cm‐diameter lymphonodes located at the hepatic ileum. The patient was given a full therapeutic dose of low molecular weight heparin, enoxaparin (8000 IU twice daily), and, few days later, 5 mg of warfarin. He continued to receive warfarin, with a target international normalized ratio of 2.5, for the following 6 months.
During the patient's hospitalization, an extensive serological screening was performed with the aim to identify any possible viral cause of hepatitis and persistent fever; test results for hepatitis B surface antigen, antihepatitis B core antigen IgG, hepatitis C virus IgG, hepatitis A virus total immunoglobulin and IgM, Toxoplasma gondii IgM, Epstein‐Barr anti–viral capsid antigen IgM, HIV‐1 and ‐2 total IgG, and parvovirus B19 antiantigen recombinant VP2 IgM antibodies were all negative. Rubella IgM and herpes simplex 1 and 2 IgM index test results were not conclusive. The CMV IgM index value was 2.5 (cutoff value, >1.1), the IgG antibody level was 1.3 UI/mL (cutoff value, >1.0 UI/mL), and IgG avidity was 10% (low avidity, <35%);>
On 5 April 2005, an abdominal CT using iodine contrast medium revealed a complete resolution of the PVT. At discharge from the hospital, on 7 April 2005, the patient was asymptomatic and afebrile, but alanine aminotransferase and aspartate aminotransferase levels remained increased (164 and 479 IU/dL, respectively). The conclusive diagnosis was acute PVT associated with a probable acute CMV infection, because no other obvious causes could explain clinical and laboratory data.
Extensive screening for thrombophilia was performed after discontinuation of oral anticoagulation therapy—that is, 8 months after the diagnosis of thrombosis. The results of this screening were negative. Wild‐type factor II and V genes were present, protein C resistance was absent, a screening test for protein C and S had negative results, antithrombin activity was 102%, factor VIII activity was 150% (reference range, 50%–200%), homocysteine level was 9.7 μmol/L, and normal levels of IgM and IgG anticardiolipin antibodies, normal levels of IgM and IgG anti–β glycoprotein 1 antibodies, as well as negative lupus anticoagulant (activated thromboplastin time and dilute Russell’s viper venom time), were present. At that time, aspartate aminotransferase and alanine aminotransferase levels were within the reference range (20–29 IU/L). The results of an HIV test were negative.
Discussion.Venous thromboembolism is a disease with multiple causes, often involving acquired or environmental risk factors, as well as a genetic predisposition [4]. As with PVT, single or multiple prothrombotic disorders are frequently associated with local precipitating factors, such as cirrhosis, cancer, or local inflammation [2]. In our patient, it is likely that both a systemic procoagulant state and local inflammation coexisted.
Acute infections are associated with a transient increased risk of venous thromboembolic events [5]. In particular, some viral infections almost invariably lead to hemostatic abnormalities that range from insignificant laboratory changes to severe disseminated intravascular coagulation [6]. A direct infection of endothelial cells and systemic inflammation lead to an activation of coagulation due to tissue factor‐mediated thrombin generation, down‐regulation of physiological anticoagulant mechanism, and inhibition of fibrinolysis [3]. In vitro studies indicate that CMV has a procoagulant effect: endothelial cells turn in a procoagulant state as CMV directly infects endothelium and causes membrane perturbation. Intrinsic CMV procoagulant properties start and/or amplify the hemostatic imbalance [3].
Furthermore, as in other acute viral infections, systemic inflammatory response syndrome and inflammatory changes in the surrounding tissues could be associated with viral acute hepatitis; propagation of acute liver inflammation to the endothelium of the portal vein system by contiguity could activate the coagulation system and increase the risk of PVT. To further support our hypothesis that acute viral hepatitis is a relevant pathogenetic factor in developing acute PVT and, in particular, in developing acute CMV‐mediated PVT, we performed an extensive literature search of the Embase and Medline databases for articles published up to May 2006, to correctly describe the natural history of acute CMV‐mediated PVT. No language restrictions were applied, and reference lists of all included studies were manually searched for other potential eligible studies. Our search results revealed that no case‐control or cohort studies of acute CMV‐mediated PVT have been published. We identified only 10 published case reports, all of which involved immunocompetent patients, 1 of whom was an infant [7–15] (table 1). Including our case, adult patients had a mean age of 34 years, and 6 patients were male (60%). Three patients (30%) did not complain of abdominal pain. Known venous thromboembolic risk factors were absent in 4 patients (40%). Eight patients (80%) experienced a complete recanalization of the portal vein that was evident at the radiologic follow‐up, which was performed a median of 3 months after the PVT. Two patients (20%) experienced a complete resolution of PVT in <12>
1.Published cases of acute portal vein thrombosis (PVT) associated with cytomegalovirus (CMV) infection.Why is viral hepatitis not usually reported as a cause of acute PVT? Published data suggest that a rapid resolution of the thrombus can occur, even without anticoagulation therapy [8]. This does not occur in more usual sites of venous thrombosis: 38.8% of patients with a deep venous thrombosis of the lower limbs experienced resolution of the thrombus after 6 months of anticoagulation therapy [16]. Moreover, mild symptomatic or asymptomatic clinical presentation can occur: 30% of acute PVT cases were detected accidentally, because patients did not complain of any abdominal pain. In our patient, PVT was completely asymptomatic; it was discovered inadvertently by ultrasonography, and it resolved completely after 10 days of antithrombotic therapy.
In conclusion, our case report reinforces the available evidence that suggests that, at the very least, acute CMV hepatitis—and, possibly, acute viral hepatitis—should be added to the list of risk factors of acute PVT. As well, these conditions should be routinely investigated in etiological clinical studies to definitively assess their causal role in acute PVT in immunocompetent patients.
Acknowledgments
We thank Professors D. Valla and N. Casadevall for providing a full paper of a published case report.
Potential conflicts of interest.All authors: no conflicts.
References
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Pulmonary embolism and portal vein thrombosis in an immunocompetent adolescent with acute cytomegalovirus hepatitis.
1: J Thromb Thrombolysis. 2008 Dec 31. [Epub ahead of print]Related Articles, Links
Pulmonary embolism and portal vein thrombosis in an immunocompetent adolescent with acute cytomegalovirus hepatitis.
Ladd AM, Goyal R, Rosainz L, Baiocco P, Difabrizio L.
Department of Internal Medicine, Lenox Hill Hospital, New York, NY, USA, dr_ladd25@yahoo.com.
Cytomegalovirus infection is usually asymptomatic or resembles infectious mononucleosis with fever, pharyngitis, arthralgias, lymphadenopathy, and atypical lymphocytosis. Even though primary CMV infection is usually self-limited in healthy individuals, significant complications can develop in immunocompromised patients. Venous or arterial thromboembolic phenomena are uncommon, yet very serious complications of CMV infection. Most published reports describe immunosupressed patients after organ transplantation or in the presence of HIV co-infection. However, thrombotic events in CMV infected immunocompetent individuals may occur. We describe the case of an immunocompetent adolescent with acute cytomegalovirus hepatitis that was complicated with pulmonary embolism and portal vein thrombosis. To our knowledge, this is the first reported case in which these two thrombotic phenomena occurred simultaneously in an adolescent with no obvious predisposing factors for thrombosis in the setting of an acute CMV infection.
PMID: 19116696 [PubMed - as supplied by publisher]
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