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Year : 2014  |  Volume : 57  |  Issue : 2  |  Page : 329-331
Inferior vena cava thrombosis in a case of amoebic liver abscess: Is hypercomplementemia responsible for this rare entity?

1 Department of Pediatric Critical Care, PGIMER and Associated Dr. Ram Manohar Lohia Hospital, New Delhi, India
2 Department of Microbiology, Vardhman Mahavir Medical College and Associated Safdarjung Hospital, New Delhi, India
3 Department of Pediatric Cardiology, PGIMER and Associated Dr. Ram Manohar Lohia Hospital, New Delhi, India

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Date of Web Publication19-Jun-2014


Among the liver abscesses, thrombosis of the inferior vena cava (IVC) has been reported mainly in amoebic liver abscess (ALA) caused by Entamoeba histolytica (E.H). It is an unusual complication especially in paediatric age group. Association of hypercomplementemia and IVC thrombosis has not been discussed previously. Published data suggest that E.H can activate the complement system and can cause hypercomplementemia. A very few studies suggest that complement activation and hypercomplementemia are associated with thrombus formation. We describe a paediatric case of ALA complicated by IVC thrombosis extending to the right atrium and discuss the possible role of hypercomplementemia in causation of IVC thrombosis in cases of ALA.

Keywords: Amoebic liver abscess, complement proteins 3 and 4, inferior vena cava thrombosis

How to cite this article:
Chandelia S, Jain S, Yadav DK, Dubey NK. Inferior vena cava thrombosis in a case of amoebic liver abscess: Is hypercomplementemia responsible for this rare entity?. Indian J Pathol Microbiol 2014;57:329-31

How to cite this URL:
Chandelia S, Jain S, Yadav DK, Dubey NK. Inferior vena cava thrombosis in a case of amoebic liver abscess: Is hypercomplementemia responsible for this rare entity?. Indian J Pathol Microbiol [serial online] 2014 [cited 2023 Sep 27];57:329-31. Available from:

   Introduction Top

Among the liver abscesses, thrombosis of the inferior vena cava (IVC) has been reported mainly in amoebic liver abscess (ALA) which is an unusual complication especially in the pediatric age group. Its pathogenesis is not much clear. The role of the complement cascade has been discussed by a very few authors in cases of intestinal and hepatic ameobiasis. [1],[2],[3],[4],[5] Similarly its role in the genesis of thrombus has been reported scarcely in diseases other than amoebiasis. [6],[7],[8] To the best of our knowledge, the following case report describes for the first time the possible association between hypercomplemenetemia and IVC thrombosis in patients of ALA.

   Case report Top

A 3-year-old female child presented complaining high grade fever and pain in the abdomen for 20 days along with abdominal distension for 3 days. There was no history of jaundice, diarrhea, vomiting or gastro-intestinal bleeding. On examination, her temperature, heart rate (HR), respiratory rate (RR) and blood pressure was 103°F, 104/min, 38/min and 104/72 mmHg respectively. There was decreased air entry and dull percussion note on the right side of the chest. Abdomen was distended with tender hepatomegaly (liver size was 6 cm below the costal margin). Her preliminary investigations showed hemoglobin-8.0 g/dl, total leucocyte count-50000/mm 3 (Polymorphs-83%) and platelets-4.8 lacs/mm 3 . Her aspartate and alanine transaminase, alkaline phosphatase, blood urea, creatinine and serum electrolytes were normal. Sonography revealed a large liver abscess of 280 cc and right pleural effusion. The abscess was drained and a pigtail catheter was left in situ. She received broad spectrum intravenous antibiotics along with metronidazole and showed signs of clinical improvement. Meanwhile, the amoebic serology (IgG antibody by enzyme linked immunosorbent assay [ELISA]) was reported to be positive. Blood and pus culture were sterile. So a diagnosis of ALA with sympathetic pleural effusion was made.

On 5 th day of admission, she developed breathlessness, bradycardia (HR-60/min), tachypnoea and chest pain. An echocardiographic examination revealed a mobile thrombus (1.8 cm × 1.0 cm) in the right atrial cavity extending from IVC, but there was no evidence of pulmonary embolism [Figure 1]. Emergency thrombectomy with simultaneous check laparotomy was planned and anticoagulation with heparin was started immediately. Meanwhile, the patient improved and her vital signs stabilized (HR-89/min and RR-20/min) with other supportive treatment (oxygen, antipyretics and blood transfusion). Therefore, the surgery was deferred. In a week's time, the size of thrombus decreased to 0.8 cm × 0.7 cm. Similarly, the abscess responded to the treatment and decreased to 66 cc along with the normalization of leukocyte counts.
Figure 1: Arrow showing thrombus in right atrium during

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Subsequently in view of second time hospitalization (history of pneumonia 6 months ago) and a large complicated abscess; her HIV ELISA, complement proteins complement component 3 (C3), C4 and immunoglobulin levels (mg/dl) were done to rule out any immunodeficiency. HIV serology was non-reactive. To our surprise, the levels of IgG (1562.3 {610-1380}), IgM (146.9 {20-134}) and IgA (251.4l {30-240}) were high. Her C4 and C3 levels were also high (52 mg/dl {20-40} and 187 mg/dl {80-160} respectively). The child was discharged in good condition on warfarin for 6 months with a target international normalized ratio of 2.5. At 3 months of follow up, complete resolution of abscess, thrombus and pleural effusion was documented.

   Discussion Top

Amoebiasis is a life endangering disease affecting 50% of the population in tropics. Around 3-9% patients are at risk of developing ALA. Since IVC thrombosis has been mainly associated with ALA, it needs explanation. Mechanical compression, ongoing inflammation and contiguous spread are considered to be associated. Increased tendency for thrombosis may be related to complement proteins. Complement and coagulation system act together and enhance each other's effects which are crucial for defence against infective agents. Complement system is activated through the (1) classical, (2) lectin and (3) alternative pathways that unite at the C3 convertase level cleaving C3 to C3a and C3b. C3a activates platelets, enhances their aggregation and adhesion. C3b further adds to the formation of C5 convertase, which cleaves C5 to C5a and C5b. C5a enhances blood thrombogenicity, mainly through the upregulation of tissue factor (TF) (main trigger for coagulation) and plasminogen activator inhibitor-1 (inhibitor of fibrinolysis) on various cell types. C5b contributes to the formation of the C5b-9, which when incorporates into the membrane of platelets leads to altered polarization where clotting can occur. C5b-9 also induces the release of microparticles bearing TF on their surface. C3b binds to P-selectin (increasing more adhesion), the expression of which is induced on platelets by C1q (classical pathway). In turn thrombin and activated platelets, cleave C3 and C5 to further amplify the activation of complement. Additionally platelets contribute to the activation of complement through the phosphorylation of C3b and thrombin triggers release of P-selectin. Furthermore, impairment of fibrinolysis by complements occurs. Thus, both complement and coagulation system act in conjunction to augment each other's final outcome. [9] Entamoeba histolytica (E.H) can activate both classic and alternative pathways of the complement system and thus can lead to IVC thrombosis. [10]

Our patient had raised levels of complement C4 and C3 proteins which is in agreement with the results of few studies done in cases of intestinal amoebiasis and ALA as shown in [Table 1]. [1],[2],[3],[4],[5] A positive correlation between large size of ALA and C3 has also been proposed by Ahmed. [3] Muñoz and Salazar also found same results in cases who received only medical management while the cases requiring drainage of the abscess showed low C3 levels. They proposed that patients requiring drainage reflect a more invasive nature of infection where C3 gets consumed. [2] No other study describes such differences in the complement levels due to different management or stages of amoebiasis, making this a basis for further research. So we observe that E.H can activate complement, can cause high levels of C3 and C4 but a direct causal relation between it and thrombosis cannot be elicited. However a few studies, done in non-communicable diseases support this hypothesis.
Table 1: Published studies of amoebiasis associated with hypercomplementemia

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Savelli et al. evaluated two groups of patients of antiphospholipid antibodies with and without thrombosis and observed that the incidence of thrombosis was significantly higher in patients with raised Complement levels (C4 and C3 [P - 1.3 × 10 -8 and 0.013 respectively]). [6] Similarly Kourtzelis et al. showed that the recurring complement activation contributes to thrombosis in dialyzed patients by generation of the anaphylatoxin C5a and the induction of granulocyte colony stimulating factor which augments platelet aggregation, thus further increasing clot size. [7]

In addition, Khoudary et al. suggested that C3 may be related to the formation and stabilisation of thrombus through its assembly to hemostatic markers. They also proposed an association between C4 and thrombus development factors like factor VIIc and fibrinogen. [8]

In conclusion, this case suggests that while treating large ALA, a high degree of suspicion should be kept in mind and every effort should be made to rule out right heart thrombus before the patient develops pulmonary embolism. Although at this stage, it is difficult to say if C3 and C4 can be used as markers for suspecting IVC thrombosis, Future studies should be planned to define the role of these factors in cases of ALA so that patients developing thrombosis and their prognosis can be predicted.

   References Top

1.Hussein AA, Shani WS. Serum levels of IL-4, immunoglobulins and complements during human amoebiasis. Basrah J Sci (B) 2006;24:112-1192.  Back to cited text no. 1
2.Muñoz LE, Salazar OG. Complement activation in patients with amebic liver abscess. J Hepatol 1987;5:30-6.  Back to cited text no. 2
3.Ahmed L. Serum immunoglobulins and complement in patients suffering from amoebic liver abscess. J Egypt Soc Parasitol 1990;20:23-8.  Back to cited text no. 3
4.Oyeyinka GO, Onyemelukwe GC. Amoebic liver abscess: Serum immunoglobulins and complement in Northern Nigerian patients. Ann Trop Med Parasitol 1983;77:293-6.  Back to cited text no. 4
5.Gupta AK, Mahajan RC, Ganguly NK, Sharma S. Serum immunoglobulins, complement levels and cell-mediated immune status in patients with amoebic liver abscess. J Assoc Physicians India 1982;30:597-9.  Back to cited text no. 5
6.Savelli SL, Roubey RA, Wu Y, Yang Y, Kitzmiller KJ, Nagaraja HN, et al. Contrasting roles of complement C4 and C3 in human antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). American College of Rheumatology. Abstract Poster Presented in Annual Scientific Meeting; 2008. Available from: [Last accessed on 2013 Jun 11].  Back to cited text no. 6
7.Kourtzelis I, Markiewski MM, Doumas M, Rafail S, Kambas K, Mitroulis I, et al. Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis. Blood 2010;116:631-9.  Back to cited text no. 7
8.Khoudary SR, Shields KJ, Chen HY, Matthews KA, Tyrrell KS. Complement proteins C3 and C4 are associated with higher levels of hemostatic markers in women at midlife: The study of women's health across the nation. (Poster Abstract Presentations.) Circulation 2013;127:AP287. Available from: [Last accessed on 2013 Jun 11].  Back to cited text no. 8
9.Markiewski MM, Nilsson B, Ekdahl KN, Mollnes TE, Lambris JD. Complement and coagulation: Strangers or partners in crime? Trends Immunol 2007;28:184-92.  Back to cited text no. 9
10.Calderon J, Schreiber RD. Activation of the alternative and classical complement pathways by Entamoeba histolytica. Infect Immun 1985;50:560-5.  Back to cited text no. 10

Correspondence Address:
Sudha Chandelia
402, PGIMER, Academic Building, Dr. Ram Manohar Lohia Hospital, New Delhi - 110 001
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.134734

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