Acute/atypical Signs of Budd Chiari Syndrome Secondary to Multi-thrombotic Causes

doi:10.21203/rs.3.rs-2835740/v1

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Case Report

Acute/atypical Signs of Budd Chiari Syndrome Secondary to Multi-thrombotic Causes

https://doi.org/10.21203/rs.3.rs-2835740/v1

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Budd-Chiari syndrome is a rare medical condition that affects one in a million people and can be caused by various thrombotic and non-thrombotic factors. In rare instances, multiple factors may contribute to its development, with coagulation factor deficiencies being a less commonly implicated cause. This case report presents a case of BCS associated with protein C deficiency and antiphospholipid syndrome (APLS). The patient is a 30-year-old woman who was brought in due to sudden abdominal distension. She had a three weeks history of intractable vomiting and loose stools. There was also a history of repeated miscarriages. The laboratory findings revealed slightly elevated liver enzymes, a positive Anti-β2 GPI screening, moderately decreased Protein C level and activated protein C resistance/FV Leiden. The patient was discharged after 21 days of inpatient treatment with symptomatic improvement.

Gastroenterology & Hepatology

budd-chiari-syndrome

protein-c-deficiency

antiphospholipid syndrome (APLS)

Budd-Chiari syndrome (BCS) is an unusual clinical entity that arises due to thrombotic or non-thrombotic hepatic venous outflow obstruction. Abdominal pain, ascites, and hepatomegaly usually represent clinical presentation. The prevalence of BCS is relatively low, estimated to be less than 1 case per 100,000 individuals in the general population. BCS is rare in Western countries, with a reported incidence of one in 2.5 million cases. However, the prevalence of BCS is higher in Asia, particularly in Nepal, China, and India, where it ranges from 6.8 to 12 cases per 100,000 individuals in China. (1)

There are known to be two types of BCS: Primary BCS and Secondary BCS. The primary is due to thrombosis and obstruction originating in the vein, while external contraction (by a tumour or an abscess) is known to be the reason for secondary causes. (2) There have been many reports about different etiological factors, of which more than one factor may play a role in 25% of the patients. (3) BCS can have various underlying causes, with myeloproliferative neoplasms being the most common culprit (accounting for 39% of cases), followed by JAK2 mutation accounting for 29%, antiphospholipid syndrome (APLS) about 25%, paroxysmal nocturnal hemoglobinuria (PNH) about 19%, protein C deficiency roughly 4%, and protein S deficiency being least common with 3%. (4)

Here we report a case of BCS due to multiple thrombotic causes in a 30-year-old woman brought to the emergency department of Civil Hospital Karachi.

A 30-year-old woman was brought to the emergency department of Civil Hospital Karachi by her husband when she developed a sudden onset of abdominal distension. According to her history, she had intractable vomiting and loose stools for three weeks and was treated with intravenous antibiotics, after which her abdomen started distending. There was no active complaint of fever, diarrhea, vomiting, itching and bleeding, although she had mild abdominal discomfort and difficulty breathing. The patient is a mother of 4 children, with three miscarriages at 3, 1 and 1.5 months, respectively. Her last baby was born in June 2021 through spontaneous vaginal delivery. Her systemic review was unremarkable, and there was no history of alcohol or tobacco consumption relevant to drugs or hepatotoxic chemicals. On examination, the patient was conscious with GCS 15/15. She was of average height with no signs of anemia, jaundice, edema, or coagulopathy. Her abdomen was symmetrically distended, measuring 38.6 inches, with no scar marks or distended veins. There was no visceromegaly; however, shifting dullness and fluid thrill was joyous, showing signs of moderate ascites. The rest of the examination was unremarkable.

Her lab parameters showed cbc and coagulation study in the normal range (white blood cell count of 8.8 × 103/µL (normal range 4–11 × 103/µL) (64.0% neutrophils), hemoglobin of 12.5 gm/dL(normal range 13–17 gm/dL), hematocrit was 40%, and platelet count was 462 × 103/µL (normal range 150–400 × 103/µL), prothrombin time (PT) was 12.1 seconds, international normalized ratio (INR) of 1.16 (normal range 0.8–1.2) and the activated partial thromboplastin time (APTT) ratio was 26.0 seconds). Biochemistry tests showed a slight elevation of liver enzymes (aspartate transaminase (AST) 68 IU/L (normal range 14–63 IU/L); alanine transaminase (ALT) 129 IU/L (normal range < 34 IU/L); alkaline phosphatase (ALP) 292 IU/L (normal range 60–240 IU/L); and, total bilirubin 1.1 mg/dL (normal range 0–1.1 mg/dL) IU/L) and albumin 3 gm/dL (normal range 3.8–5.4 gm/dL), with no jaundice or kidney dysfunction and creatinine being 0.7 mg/dL. The serum level of C-reactive protein was markedly elevated (78.5mg/L). The ascitic fluid study revealed protein 2.5 gm/dL, albumin 1.4 gm/dL, Serum ascites albumin gradient (SAAG) was 1.6, Acid fast bacilli (AFB) and Gram-stain-negative. Serological tests were negative for hepatitis A, B, C, E, and HIV. Serum ferritin and ceruloplasmin are within normal limits. Blood and urine cultures were negative.

Abdominal ultrasonography showed normal measuring liver, spleen and portal vein (1.0 cm) with gross ascites. A focal thrombus was seen at porta hepatis, and color doppler showed no flow, suggesting a thrombus (See Fig. 1). A computed Tomography scan of the abdomen showed a mottled appearance involving the liver with non-visualization of the hepatic vein, and intrahepatic IVC also appeared collapsed. Filling defect within the portal vein and Inferior Vena Cava suggested that the thrombus extends up to the suprarenal region, confirming Budd Chiari Syndrome. (See Fig. 2)

On Autoimmune Workup, Antinuclear antibody (ANA), Anti-Mitochondrial antibody (AMA), Anti-Smooth Muscle antibody (ASMA), Anti-Gatric parietal cell antibody (AGPCA), Anti-SS-A/Ro antibody, rheumatoid factor, anti-double-stranded DNA antibody, anti-Sm antibody, and myeloperoxidase antineutrophil cytoplasmic antibodies were negative. Regarding Antiphospholipid antibodies, the lupus anti-coagulant (1.07) (normal 0.8–1.2) ) and anti-cardiolipin antibody were Negative. However, Anti-β2 GPI screening was positive, with IgA and IgG under reference ranges (12.176 RU/ml and 2.062 RU/ml), respectively. However, IgM is 34.261 RU/ml (normal < 20 RU/ml). Her complement level was C3 1.08 g/L (normal range 0.79-1.51g/L ), C4 0.11 g/L (normal range 0.16–0.38 g/L), while her Serum IgA level was 3.14 g/L (normal range 0.82–4.53 g/L), Serum IgG level was increased, i.e. 23.1g/L (normal range 7.51–15.6 g/L ) and Serum IgM level slightly increased 3.23g/L (normal range 0.46–3.04 g/L). Thrombophilia Workup revealed Protein S in the normal range, 94.2%. At the same time, Protein C levels were moderately decreased, 46% (normal range 70–140%), as proven that ProC Global/FV, a susceptible test to detect activated protein C resistance/FV Leiden (100%) and protein C deficiency (90%) (5), was also decrease being 0.38 (normal range 0.86–1.1) proving deficiency of Protein C.

The patient was started on Diuretics Furosemide 40 mg thrice daily and Spironolactone 100 mg twice daily. Rivoraxaban10mg was added once a day after the thrombophilia workup, and fluid restriction was advised. The patient was discharged after 21 days of inpatient treatment with symptomatic improvement. On follow-up after six weeks, the patient was clinically stable, and her repeated protein c levels were in the normal range (76%).

Budd-Chiari syndrome (BCS) is an uncommon but clinically challenging disorder characterized by the occlusion of the hepatic venous outflow tract, including the small hepatic veins, the large hepatic veins, or the inferior vena cava. (6) This rare disorder has many etiological bases and can be classified as primary or secondary BCS. Primary BCS originates within the lumen of the vein, and the major risk factors include hypercoagulable states and thrombosis, which may be caused by multiple inherited and acquired disorders such as myeloproliferative disorders, protein C deficiency, protein S deficiency, Behcet’s disease, antiphospholipid syndrome or IVC webs (more common in Asia). Secondary BCS originates from compression and obstruction external to the vein, such as tumoral invasion, abscess, or cyst. (7) Prothrombotic risk factors are present in 90% of the individuals though 46% have multiple concurrent risk factors. (8) Many other risk factors, such as ulcerative colitis, use of oral contraceptive pills, malnutrition, and pregnancy, have also been identified. However, the cause of BCS remains unknown in numerous cases. In a case series of 164 patients, the etiology was either unidentified or inadequately established in 70.1% of the cases. (9)

The classical clinical presentation of BCS includes abdominal pain, ascites, hepatomegaly, jaundice, and leg swelling. (10, 11) About 15–20% of patients are asymptomatic. (7, 10) Furthermore, serum aminotransferase levels and bilirubin levels are elevated. (12) In our case, a 30-year-old woman presented with the main complaints of abdominal distention and associated abdominal discomfort and difficulty breathing. There were elevated liver enzymes and bilirubin, while albumin levels were decreased. Nevertheless, these are nonspecific, and further workup was done to determine the underlying cause.

A radiographic analysis is required to check for the patency of hepatic veins/IVC and is critical to establish a diagnosis. Ultrasonography coupled with Doppler studies are the preferred modality. (13) The ultrasound findings most commonly include hepatosplenomegaly, an enlarged caudate lobe, intrahepatic collaterals, a compressed IVC, and ascites. Computed tomography (CT) and magnetic resonance imaging (MRI) can provide detailed images of the liver and hepatic vasculature to help recognize the underlying cause of BCS and determine the extent of the disease. In our case, abdominal ultrasonography showed a normal-looking liver and spleen with massive ascites. The absence of flow within the hepatic vein on color Doppler and the lack of visualization of the hepatic vein with the collapsed intrahepatic IVC seen on CT established the diagnosis of BCS.

Some further attempts are required to identify the cause of the hypercoagulable state. An additional autoimmune evaluation was conducted, which revealed elevated antiphospholipid antibodies (Anti-β2 GPI), suggesting antiphospholipid syndrome (APS). This syndrome can be secondary to systematic lupus erythematosus, other connective tissue diseases, malignant tumors, or prolonged drug treatment. (14) However, APS can be primary and occur without any of these conditions (13). This syndrome is clinically associated with recurrent thrombosis, miscarriages, and thrombocytopenia. (15, 16) The association of APS with BCS seems to be rare. Ibrahim. et al. (17) describe a case of primary APS presenting as BCS with positive aCL-IgM (anti-cardiolipin IgM) antibodies and aCLIgA (anti-cardiolipin IgA) antibodies. This is in contrast to our study, where anti-cardiolipin antibodies along with lupus anti-coagulant yielded negative results. A thrombophilia workup was also performed, which demonstrated lowered levels of Protein C.

The ultimate aim of therapeutic interventions in BCS is to relieve portal and IVC hypertension, remove the diseased hepatic vein/IVC, decrease cirrhosis, and prevent a recurrence. Treatment is done stepwise, ranging from medical management to a liver transplant when necessary. Medical management includes anticoagulation, sodium restriction, diuretic therapy, and paracentesis. Trans jugular intrahepatic portosystemic shunt (TIPS) placement has become increasingly popular in patients and has become the option of treatment wherever a shunting procedure is indicated. Angioplasty and stent placement are valuable adjuncts. (18). Our patient was started on anti-coagulants and diuretics and improved significantly with no reports of recurrence.

In conclusion, this case report presents a case of BCS associated with APS and protein C deficiency. Owing to its rarity, BCS is likely to be misdiagnosed or underdiagnosed. Due to this, it is of utmost importance for physicians and clinicians to consider BCS in patients presenting with symptoms of hepatomegaly, splenomegaly, or ascites and perform an extensive workup. To correctly determine the etiology of BCS, it is crucial to assess all prothrombotic factors and an extensive autoimmune workup. Nevertheless, a timely diagnosis and treatment of BCS are vital to prevent long-term complications and improve outcomes.

The patient has given their consent to participate in this study and have it published

Ethics approval and consent to participate:

Not applicable as no intervention was performed as a part of the research in any case.

Consent for publication:

Consents were obtained for publication from the patients upon stabilization of their psychotic illnesses.

Availability of data and materials:

Not applicable.

Competing interests:

None to declare.

Funding:

None to declare.

AUTHOR’S CONTRIBUTIONS

Conception and design: SMFZ, BSR

Acquisition of data: SMFZ, AQ

Drafting of the manuscript: BSR, AQ

Critical revision for important intellectual content: MTA

Final approval of the study: AQ, SMFZ, BSR, MTA

ACKNOWLEDGEMENTS:

Not applicable.

Zu M, Xu H, Zhang Q, Gu Y, Wei N, Xu W, et al. Review of Budd-Chiari Syndrome. Journal of interventional medicine [Internet]. 2020 May 1 [cited 2023 Apr 5];3(2):65–76. Available from: https://pubmed.ncbi.nlm.nih.gov/34805910/
Mancuso A. An update on the management of Budd-Chiari syndrome: The issues of timing and choice of treatment. Eur J Gastroenterol Hepatol. 2015 Mar 6;27(3):200–3.
Aydinli M, Bayraktar Y. Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. World J Gastroenterol [Internet]. 2007 May 21 [cited 2023 Apr 5];13(19):2693–6. Available from: https://pubmed.ncbi.nlm.nih.gov/17569137/
Adams DH. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. Vol. 56. 2007. 1175–1175 p.
Dati F, Hafner G, Erbes H, Prellwitz W, Kraus M, Niemann F, et al. ProC® Global: the first functional screening assay for the complete protein C pathway. Clin Chem [Internet]. 1997 Sep 1 [cited 2023 Apr 5];43(9):1719–23. Available from: https://academic.oup.com/clinchem/article/43/9/1719/5640948
Murad SD, Plessier A, Hernandez-Guerra M, Fabris F, Eapen CE, Bahr MJ, et al. Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Intern Med [Internet]. 2009 Aug 4 [cited 2023 Apr 9];151(3):167–75. Available from: https://pubmed.ncbi.nlm.nih.gov/19652186/
Ferral H, Behrens G, Lopera J. Budd-Chiari syndrome. AJR Am J Roentgenol [Internet]. 2012 Oct [cited 2023 Apr 9];199(4):737–45. Available from: https://pubmed.ncbi.nlm.nih.gov/22997363/
Boyer TD, Lindor KD, Sanyal AJ, Terrault NA. Zakim and Boyer’s Hepatology: A Textbook of Liver Disease E-Book. 2016 [cited 2023 Apr 9]; Available from: https://books.google.com.eg/books?id=epe_DQAAQBAJ
Hoyumpa AM, Schiff L, Helfman EL. Budd-Chiari syndrome in women taking oral contraceptives. Am J Med [Internet]. 1971 [cited 2023 Apr 9];50(1):137–40. Available from: https://pubmed.ncbi.nlm.nih.gov/5539574/
Okuda H, Yamagata H, Obata H, Iwata H, Sasaki R, Imai F, et al. Epidemiological and clinical features of Budd-Chiari syndrome in Japan. J Hepatol [Internet]. 1995 [cited 2023 Apr 9];22(1):1–9. Available from: https://pubmed.ncbi.nlm.nih.gov/7751574/
Ye QB, Huang QF, Luo YC, Wen YL, Chen ZK, Wei AL. Budd-Chiari syndrome associated with liver cirrhosis: A case report. World J Clin Cases [Internet]. 2021 Apr 4 [cited 2023 Apr 9];9(12):2937. Available from: /pmc/articles/PMC8058661/
Zahn A, Gotthardt D, Weiss KH, Richter G, Schmidt J, Stremmel W, et al. Budd-Chiari Syndrome: Long term success via hepatic decompression using transjugular intrahepatic porto-systemic shunt. BMC Gastroenterol [Internet]. 2010 Mar 1 [cited 2023 Apr 9];10(1):1–7. Available from: https://bmcgastroenterol.biomedcentral.com/articles/10.1186/1471-230X-10-25
Asherson RA, Cervera R. Antiphospholipid Syndrome. Journal of Investigative Dermatology. 1993 Jan 1;100(1):S21–7.
Vincent T, Mackworth-Young C. The Primary Antiphospholipid Syndrome. Hughes Syndrome [Internet]. 2000 [cited 2023 Apr 9];111–26. Available from: https://link.springer.com/chapter/10.1007/978-1-4471-3666-8_12
Harris EN, Boey ML, Mackworth-Young CG, Gharavi AE, Patel BM, Loizou S, et al. Anti-cardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet [Internet]. 1983 Nov 26 [cited 2023 Apr 9];2(8361):1211–4. Available from: https://pubmed.ncbi.nlm.nih.gov/6139567/
Yun YY, Yoh KA, Yang HI, Park SH, Lee SH, Cho CS, et al. A case of Budd-Chiari syndrome with high antiphospholipid antibody in a patient with systemic lupus erythematosus. Korean J Intern Med [Internet]. 1996 [cited 2023 Apr 9];11(1):82–6. Available from: https://pubmed.ncbi.nlm.nih.gov/8882480/
Ibrahim MB, Kinsara AJ. Primary antiphospholipid syndrome presenting as Budd-Chiari syndrome. Ann Saudi Med [Internet]. 1998 [cited 2023 Apr 9];18(2):154–7. Available from: https://pubmed.ncbi.nlm.nih.gov/17341949/
Horton JD, San Miguel FL, Ortiz JA, John Horton CD, Beaumont Army W. Budd–Chiari syndrome: illustrated review of current management. Liver International [Internet]. 2008 Apr 1 [cited 2023 Apr 9];28(4):455–66. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1478-3231.2008.01684.x

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Acute/atypical Signs of Budd Chiari Syndrome Secondary to Multi-thrombotic Causes

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