Portal vein thrombosis is a rare but serious condition where a blood clot forms in the portal vein, restricting blood flow to the liver. Its causes are often linked to liver disease, coagulation disorders, or abdominal infections. However, emerging discussions suggest infections like Lyme disease could be a contributing factor. Could Lyme disease trigger changes in blood flow or immune responses that lead to clot formation? This article explores the known causes of portal vein thrombosis and delves into the possibility of Lyme disease as a risk factor, offering insights into an often-overlooked connection.
The Link Between Lyme Disease and Portal Vein Thrombosis: What Research Says
Portal vein thrombosis (PVT) is a medical condition characterized by the formation of a blood clot in the portal vein, a crucial blood vessel that carries nutrient-rich blood from the gastrointestinal tract and spleen to the liver. This condition can obstruct blood flow, leading to significant complications, such as increased pressure in the portal vein system (portal hypertension), spleen enlargement, and reduced liver function. Although PVT is considered rare, its impact on health can be profound, warranting a deeper understanding of its causes and risk factors.
The causes of portal vein thrombosis are multifaceted, often involving a combination of underlying conditions and triggering events. Common risk factors include cirrhosis, malignancies, and coagulation disorders that predispose individuals to abnormal blood clotting. Surgical procedures, infections, and trauma to the abdominal region may also contribute to the development of this condition. However, in some cases, the root cause remains unclear, highlighting the need for further research.
Traditionally, portal vein thrombosis has been closely associated with liver-related diseases, especially cirrhosis. In these cases, the liver's impaired ability to regulate blood flow and clotting increases the likelihood of clot formation in the portal vein. Yet, recent studies suggest that other factors, such as systemic infections and inflammatory conditions, may also play a role in the development of PVT, even in individuals without pre-existing liver disease.
One emerging area of interest is the potential connection between portal vein thrombosis and infections like Lyme disease. Lyme disease, caused by the bacterium Borrelia and transmitted through tick bites, is known to cause widespread inflammation and vascular complications in severe or untreated cases. Could this inflammatory response extend to the portal vein, increasing the risk of thrombosis?
In this article, we will delve into a specific case of a patient with Lyme disease who developed portal vein thrombosis, exploring the potential connection between the two conditions. By examining this case and discussing relevant medical insights, we aim to shed light on the possible links between Lyme disease and this rare but serious condition.
Thrombosis of the Portal Vein and its Branches in a Patient Seropositive for Borrelia Antigens
Authors:
Reznik EV, Prushkovskaya MP, Presnova ED, Novikova NA, Ivaschenko RA, Dedov EI, Nikitin AE, Nikitin IG
DOI: 10.26442/terarkh201890114-89
Abstract:
Lyme borreliosis, commonly contracted via tick bites, remains an acute global health issue. Delayed or absent medical intervention can result in severe complications, including thrombosis in various venous regions. Portal vein thrombosis (PVT) is a condition with high morbidity and mortality, and infections have been identified as risk factors. However, its association with Lyme borreliosis has not been extensively explored. Herein, we describe the case of a 34-year-old male presenting with thrombosis of the portal, splenic, and superior mesenteric veins in conjunction with Borrelia antigen seropositivity. This case underscores the necessity of Borrelia antigen screening in patients with splanchnic vein thrombosis (SVT) and fever.
Introduction:
Lyme borreliosis, caused by spirochetes of the genus Borrelia (notably Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii), primarily transmitted via tick bites, is a multi-systemic infectious disease affecting skin, the nervous system, musculoskeletal system, and cardiovascular systems. Rarely, it can involve other organs, including the liver, kidneys, and bronchial systems. Manifestations range from erythema migrans to systemic involvement without overt signs such as a tick bite or erythema. Diagnosing borreliosis often requires comprehensive serological and molecular methods due to low spirochete concentrations in tissues.
Portal vein thrombosis, often associated with cirrhosis or malignancies, represents a significant clinical concern. Its etiologies include infections; however, cases involving Lyme borreliosis remain exceptionally rare. This report details such a case, exploring the diagnostic challenges, therapeutic approaches, and the implications of coexisting borreliosis and splanchnic thrombosis.
Case Report:
A 34-year-old man presented with an 11-day history of fever (maximum 38.7°C) and persistent epigastric pain. He had chronic helicobacter-associated gastritis and gallstones. Notably, the patient had attended a forest picnic shortly before symptom onset, though no tick bite was documented.
Clinical Presentation and Diagnostics:
The patient exhibited mild leukocytosis (11.2 x 10⁹/L), elevated lymphocyte percentage (70%), increased C-reactive protein (34.6 mg/L), and a borderline procalcitonin level (0.195 ng/mL). D-dimer was elevated at 1.98 μg/mL, and antithrombin III levels were reduced (75%). Serological and molecular investigations ruled out viral hepatitis, systemic autoimmune diseases, and thrombophilia. Multi-slice computed tomography (MSCT) revealed thrombosis in the portal vein, splenic vein, and superior mesenteric vein.
The patient’s coagulation profile demonstrated elevated fibrin-monomer complexes (RFMK 11.0 mg/100 mL) and decreased protein S (49%). Genetic analysis identified polymorphisms in folate cycle genes (e.g., MTHFR and MTRR), which may predispose to hyperhomocysteinemia and thrombosis.
Serological Testing:
Borrelia-specific IgM titers were significantly elevated (62.2 U/mL initially, rising to 190 U/mL). Immunoblotting confirmed IgM antibodies against Borrelia antigens OspA (p31) and OspC (p25), indicative of active infection.
Therapeutic Intervention:
The patient was treated with anticoagulants (enoxaparin transitioning to rivaroxaban) and doxycycline (100 mg twice daily for 14 days). This regimen resulted in resolution of fever, normalization of inflammatory markers, and regression of thrombosis on follow-up imaging.
Discussion:
This case highlights the rare but significant association between Lyme borreliosis and portal vein thrombosis. Although Borrelia is not a common cause of splanchnic thrombosis, the patient’s clinical response to doxycycline supports a causal link. The pathophysiological mechanisms may involve endothelial dysfunction and immune-mediated vascular damage. Histopathological studies in Lyme disease have identified perivascular lymphocytic infiltrates, endothelial colonization by Borrelia, and microvascular thrombosis. These findings align with the thrombogenic potential observed in this patient.
The diagnostic challenge lies in the absence of hallmark symptoms (e.g., erythema migrans). Negative results in PCR testing of biological samples often complicate early diagnosis due to low spirochete loads. Serological assays remain the cornerstone of diagnosis, with immunoblotting providing confirmatory evidence.
Literature Context:
Few reports have documented venous thrombosis in Lyme disease. Ansari et al. described cerebral venous sinus thrombosis in a pediatric patient with Lyme borreliosis. Adamaszek and Blažina reported similar cases without detailed serological confirmation. Demirok et al. noted retinal vessel occlusion in a patient with Borrelia seropositivity.
An Unexpected Intersection: Lyme Disease and Portal Vein Thrombosis
Case and Clinical Relevance
The described case of a 34-year-old male presenting with portal vein thrombosis (PVT) alongside seropositivity for Borrelia antigens is both unusual and medically significant. This case bridges two rarely connected domains of infectious disease and hematological complications, underscoring the need for vigilance in diagnosing atypical manifestations of Lyme borreliosis. The patient's resolution with doxycycline and anticoagulation highlights the importance of targeted therapy based on robust diagnostic evidence.
Diagnostic Challenges
Lyme borreliosis presents a diagnostic challenge due to its polymorphic clinical manifestations and low spirochete concentrations in blood and tissues. In this case, the absence of hallmark signs like erythema migrans and the lack of a documented tick bite complicated initial diagnostic efforts. However, elevated Borrelia-specific IgM titers and confirmatory immunoblotting against Borrelia antigens were pivotal. This demonstrates the critical role of serological diagnostics in identifying atypical Lyme disease presentations.
Molecular diagnostic methods like PCR often suffer from low sensitivity in Lyme borreliosis, particularly in cases without significant spirochetemia. The false negatives frequently associated with PCR highlight the necessity of complementing it with serological tests to improve diagnostic yield.
Pathophysiological Mechanisms
The case report highlights possible mechanisms linking Borrelia infection to thrombosis, including:
- Endothelial Dysfunction: Borrelia's colonization of vascular endothelium can incite inflammatory cascades and disrupt vascular homeostasis.
- Immune-Mediated Damage: Cross-reactivity between Borrelia antigens and host proteins can exacerbate vascular injury.
- Hypercoagulability: Secondary effects of infection, such as elevated inflammatory markers, can tip the coagulation balance towards thrombosis.
These mechanisms align with histopathological findings of vascular infiltration and thrombosis in Lyme disease and emphasize the broader systemic impact of Borrelia infection beyond its classical manifestations.
Therapeutic Implications
The successful use of doxycycline in conjunction with anticoagulants showcases a dual therapeutic strategy addressing both the infectious and thrombotic components. The decision to initiate doxycycline despite a lack of definitive clinical features of Lyme disease was substantiated by serological evidence and demonstrates the importance of clinical acumen in complex cases.
Additionally, long-term anticoagulation with rivaroxaban was essential to ensure resolution of thrombosis and prevent recurrence, reflecting best practices in managing PVT regardless of its etiology.
Literature and Context
This case contributes to a small but growing body of evidence linking Lyme disease to venous thrombosis:
- Ansari et al.: Cerebral venous sinus thrombosis in a pediatric patient with Lyme disease, emphasizing the neurological spectrum of thrombotic complications.
- Demirok et al.: Retinal vein occlusion in a Borrelia-seropositive patient, demonstrating the diverse vascular presentations of Lyme disease.
These reports, combined with the current case, suggest a need for broader epidemiological studies to elucidate the prevalence and risk factors for thrombosis in Lyme disease patients.
Future Directions
- Research: Controlled studies are needed to explore the incidence of thrombosis in Lyme disease and validate proposed mechanisms.
- Diagnostics: Enhanced serological panels and improved molecular methods can reduce diagnostic delays in atypical cases.
- Clinical Awareness: Healthcare providers should consider Lyme disease in patients with unexplained thrombosis, especially in endemic regions or those with suggestive epidemiological exposure.
Conclusion
This case underscores the complex interplay between infectious and thrombotic processes, illustrating the importance of considering Borrelia infection in the differential diagnosis of splanchnic vein thrombosis. The favorable outcome highlights the efficacy of an integrated approach combining antimicrobial and anticoagulant therapies, paving the way for improved diagnostic and management protocols in similar cases.