Case report
Congenital hypoplasia of the inferior vena cava and inherited
thrombophilia: rare associated risk factors for idiopathic
deep vein thrombosis. A case report
Massimiliano Bianchia, Danilo Gianninib, Alberto Balbarinib and
Maido Giovacchino Castiglionia
In young patients, acquired and genetic causes of deep
vein thrombosis frequently interact. The association of
congenital hypoplasia of the inferior vena cava with
antithrombin III deficiency has never been described in
the literature as a causal factor of proximal deep vein
thrombosis in young patients. We report the case of an
18-year-old patient affected by deep vein thrombosis
due to this rare association without other common risk
factors. J Cardiovasc Med 9:101–104 Q 2008 Italian
Federation of Cardiology.
Introduction
Of the three mechanisms of thrombosis defined by
Virchow in the 19th century – i.e. vessel wall injury,
stasis, and ‘changes in the composition of blood’ (hyper-
coagulability) – the last two predominate in venous
thrombosis. Hypercoagulability can be inherited or
acquired (Table 1). The inherited type, which is also
termed ‘inherited thrombophilia’ (common: factor V
Leiden, G20210A mutation in the prothrombin gene,
homozygous C677T mutation in the methylenetetra-
hydrofolate reductase gene; rare: antithrombin, protein
C and S deficiency; and very rare: dysfibrinogenaemia,
homozygous homocystinuria) should be suspected when
a patient has venous thromboembolism, family history of
venous thrombosis, is younger than 45 years of age, or has
no apparent acquired risk factors, or is a female with a
history of multiple abortions, stillbirth or both [1,2]. In
young patients, acquired and genetic causes of deep vein
thrombosis (DVT) frequently interact. In addition to
circumstantial risk factors [3,4] and inherited thrombo-
philia, some anomalies of the inferior vena cava (IVC)
with inefficacious venous drainage have been found in
young subjects suffering from idiopathic DVT [3,5–7].
The anomalies of the IVC have an estimated prevalence
of 0.07–8.7% in the general population [4]. They become
apparent in infants when combined with heart failure or
visceral malformations [8]. In adults, IVC anomalies are
commonly seen incidentally in abdominal surgery or
radiological workup [4,9,10]. Some case reports, however,
have identified patients with anomalies of the IVC who
became symptomatic because of proximal, idiopathic
DVT of the lower extremities [10–15].
1558-2027 ß 2008 Italian Federation of Cardiology
Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.
Journal of Cardiovascular Medicine 2008, 9:101–104
Keywords: deep vein thrombosis, inferior vena cava, thrombophilia
a
Internal Medicine, General Medicine Department and bUnit of Angiology, Cardio-
Thoracic Department, University of Pisa, Azienda Ospedaliera Universitaria
Pisana, Pisa, Italy
Correspondence to Dr Massimiliano Bianchi, Dipartimento di Medicina Generale,
Università degli Studi, Azienda Ospedaliera Pisana, Via Paradisa 2, 56124 Pisa, Italy
Tel/fax: +39 050 996855; e-mail: massimilianobianchi3@tin.it
Received 11 September 2006 Revised 22 November 2006
Accepted 27 November 2006
Case report
An 18-year-old man was admitted to our department with
a history of painfully swollen right leg after strenuous
muscular exercise. An idiopathic DVT involving the
femoral and popliteal veins was diagnosed by colour
Doppler duplex ultrasonography (using 5–7 MHz linear
transducers, Esaote AU5, Esaote Biomedica, Genoa,
Italy), revealing the extension of the thrombus to the
inguinal and iliac region, above the femoral ligament [16].
As part of the diagnostic protocol for assessing thrombus
extension, when compression B-mode ultrasonography
displays a thrombus extending above the femoral liga-
ment, magnetic resonance imaging with intravenous con-
trast is performed.
Contrast-enhanced magnetic resonance venography
showed iliac vein thrombosis and congenital anomaly
of the IVC (hypoplasia) with enlargement of the azy-
gous venous system. Magnetic resonance also displayed
a developed deep venous collateral system, which
drained the blood from the lower extremities to the
heart (Fig. 1).
Screening for inherited thrombophilia (factor V Leiden,
G20210A mutation in the prothrombin gene, homozy-
gous C677T mutation in the methylenetetrahydrofolate
reductase gene, antithrombin III, protein C and S
deficiency, dysfibrinogenaemia, homozygous homocysti-
nuria) showed antithrombin III deficiency. Doppler ultra-
sound examination showed no evidence of cardiac or
great vessel malformation. The patient was efficaciously
treated with subcutaneous fractionated heparin followed
 102 Journal of Cardiovascular Medicine 2008, Vol 9 No 1

Table 1 Inherited and acquired causes of venous thrombosis the presence of hypoplasia of the IVC with partial azygous
Inherited continuation in one of the patient’s family members
Common (16-year-old sister). Screening for inherited thrombophilia
G169A mutation in the factor V gene (factor V Leiden)
G20219A mutation in the prothrombin (factor II) gene
revealed antithrombin III deficiency in all the patient’s
Homozygous C677T mutation in the methylenetetrahydrofolate reductase family members. None of them had common risk factors
gene other than thrombophilia. The clinical characteristics of
Rare
Antithrombin deficiency
the patient and his family members are reported in Table 2.
Protein C deficiency
Protein S deficiency Discussion
Very rare
Dysfibrinogenaemia A computerised Medline search for English-language
Homozygous homocysteinuria reports published from January 1966 to December
Probably inherited
Increased levels of factor VII, IX, XI or fibrinogen
2005 resulted in only a few cases of DVT in young
Acquired patients with congenital malformation of the IVC and
Surgery and trauma inherited thrombophilia, suggesting that this association
Prolonged immobilisation
Older age is exceedingly rare. Table 3 [7,17–25] summarises the
Cancer major clinical features and diagnostic data of other
Myeloproliferative disorders reported cases. In particular, the association of hypo-
Previous thrombosis
Pregnancy and the puerperium plasia of the IVC with antithrombin III deficiency has
Use of contraceptives or hormone replacement therapy never been described in the literature.
Resistance to activated protein C (not due to alterations in the factor V gene)
Antiphospholipid antibodies
Mild to moderate hyperhomocysteinaemia In clinical practice, the usual laboratory and echo lab tools
(screening tests for inherited thrombophilia and com-
pression B-mode ultrasonography) should be integrated
by warfarin treatment. There were no recurrences of with the assessment of the abdominal veins whenever
DVT in the subsequent 5 years. proximal extension of vein thrombosis above the femoral
ligament is present. In fact, these clinical findings should
The same methodology was applied to evaluate the prompt the clinical suspicion of inadequate blood drai-
patient’s family members (four consecutive patients). nage from the abdominal veins. The rare anomalies of the
Duplex ultrasonography of the inferior limbs and magnetic IVC were accurately shown by magnetic resonance veno-
resonance venography of the abdominal veins disclosed graphy, which is a highly sensitive and specific technique
without use of ionising radiation [26]. Data from the
Fig. 1 literature show that these vascular anomalies are caused
by aberrant development in the sixth to eighth weeks of
gestation. During this period, complex embryological
development of the IVC with anastomosis, disappearance
and replacement of vessels may result in different mal-
formations [4,27]. However, if the deep venous collateral
system is sufficiently developed and drains efficaciously
the venous blood from the lower extremities to the heart,
symptoms are likely to be prevented in this subset of
patients [12–14]. In our case, strenuous muscular exer-
cise may have triggered the acute thrombotic event.

Furthermore, we found antithrombin III deficiency in all

Gadolinium-enhanced magnetic resonance venogram of the abdominal
veins showing anomaly of the inferior vena cava (IVC) in patient 3. The
hemiazygous vein (HAV) is enlarged to compensate for the IVC
anomaly and collects the venous blood return from a markedly dilated
paravertebral venous collateral vessel (PVC). LRV, left renal vein; SV,
splenic vein.
the patient’s family members and hypoplasia of the IVC
in two of them (patients 3 and 4, Table 2), but none had
experienced any venous thrombotic event. Patients with
persistent risk factors and symptomatic DVT are at high
risk for thrombotic recurrence requiring long-term oral
anticoagulation. Economic evaluations have shown that
prophylactic measures are cost-effective in preventing
recurrent thromboembolism compared with no prophy-
laxis or surveillance and selective treatment of venous
thromboembolism [28].
This study has some limitation because the association of
antithrombin III deficiency with hypoplasia of the IVC is

Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.

 DVT in IVC hypoplasia and inherited thrombophilia Bianchi et al. 103

Table 2 Clinical characteristics of the five study patients

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5

Sex Male Female Male Male Female

Age (years) 39 39 18 19 16
Vein affected None None Bilateral femoral-iliac None None
Precipitating factors No No No No Yes
Hypoplasia of the IVC No No Yes No Yes
Coagulation abnormalitiesa Yes Yes Yes Yes Yes
Additional risk factorsb No No No No No
Total follow-up 5 years

IVC, inferior vena cava. a Antithrombin III, protein C, protein S, plasminogen, thrombin time, antiphospholipid antibodies, homocysteine serum concentration, factor V Leiden.
b
Smoking, obesity, diabetes, hypertension.

Table 3 Major clinical features of other reported cases in the literature

Author No. patients Sex (M/F) Age (years) DVT IVC hypoplasia Thrombophilia testing

Halbmayer et al. [7], 1993 1 1/0 24 Yes 1 FXII deficiency

Ruggeri et al. [17], 2001 75 3/1 <30 Yes 4 No
Siragusa et al. [18], 2001 21 1/1 <21 Yes 2 2 FV Leiden
Chee et al. [19], 2001 60 2/2 20–40 Yes 3 1 FV Leiden
Schneider et al. [20], 2002 1 1/0 44 Yes 1 FV Leiden
Obernosterer et al. [21], 2002 97 3/2 51  19 Yes 5 1 Protein S deficiency
Parma et al. [22], 2003 1 1/0 18 Yes 1 FV Leiden (C677T)
Vidra et al. [23], 2003 1 1/0 25 Yes 1 FV Leiden (G20210A)
Garcia-Fuster et al. [24], 2004 110 3/3 16–50 Yes 4 3 PT G20210A, 2 APA
Sakellaris et al. [25], 2005 1 1/0 10 Yes 1 No

APA, antiphospholipid antibodies; DVT, deep vein thrombosis; F, female; FV, factor V; FXII, factor XII; IVC, inferior vena cava; M, male; PT, prothrombin.

exceedingly rare, and common genes could be investi-
gated in the family members. It is difficult to explain why
the other two family members with the same alterations
did not ever experience any venous thrombotic event.
In conclusion, our report suggests that, in young patients
(<30 years) affected by proximal DVT of the inferior
limbs, the assessment of inherited thrombophilia should
be integrated with a complete evaluation of the abdomi-
nal veins, as coexistence of congenital anomalies of the
IVC cannot be ruled out a priori.
Acknowledgement
We wish to thank Virginia Adams for her contribution
to the editing of the manuscript and for English review-
ing.
References
1 Rosendaal FR. Thrombosis in the young: epidemiology and risk factors. A
focus on venous thrombosis. Thromb Haemost 1997; 78:1–6.
2 Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis.
N Engl J Med 2001; 344:1222–1231.
3 Matzdorff AC, Green D. Deep vein thrombosis and pulmonary embolism:
prevention, diagnosis, and treatment. Geriatrics 1992; 47:48–52.
4 Kellman GM, Alpern MB, Sandler MA, Craig BM. Computed tomography of
vena caval anomalies with embryologic correlation. Radiographics 1988;
8:533–556.
5 Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999;
353:1167–1173.
6 De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia:
pathogenesis, clinical syndromes, and management. Blood 1996;
87:3531–3544.
7 Halbmayer WM, Radek J, Duschet P, Lindeck G, Gschnait F, Czembirek H,
et al. Recurrent venous thromboses in hypoplasia of the vena cava inferior and
factor XII deficiency. Dtsch Med Wochenschr 1993; 118:1561–1566.
8 Muelheims GH, Mudd JG. Anomalous inferior vena cava. Am J Cardiol
1962; 9:945–952.
9 Baldridge ED Jr, Canos AJ. Venous anomalies encountered in aortoiliac
surgery. Arch Surg 1987; 122:1184–1188.
10 Klessen C, Deutsch HJ, Karasch T, Landwehr P, Erdmann E. Thrombosis of
the deep leg and pelvic veins in congenital agenesis of the inferior vena
cava. Dtsch Med Wochenschr 1999; 124:523–526.
11 Saito H, Sano N, Kaneda I, Arakawa M, Ishida S, Takahashi S,
et al. Multisegmental anomaly of the inferior vena cava with thrombosis
of the left inferior vena cava. Cardiovasc Intervent Radiol 1995;
18:410–413.
12 Dougherty MJ, Calligaro KD, DeLaurentis DA. Congenitally absent inferior
vena cava presenting in adulthood with venous stasis and ulceration: a
surgically treated case. J Vasc Surg 1996; 23:141–146.
13 Shah NL, Shanley CJ, Prince MR, Wakefield TW. Deep venous thrombosis
complicating a congenital absence of the inferior vena cava. Surgery 1996;
120:891–896.
14 Salgado Ordonez F, Gavilan Carrasco JC, Bermudez Recio FJ, Aguilar
Cuevas R, Fuentes Lopez T, Gonzales Santos P. Absence of the inferior
vena cava causing repeated deep venous thrombosis in an adult – a case
report. Angiology 1998; 49:951–956.
15 Tiesenhausen K, Amann W, Thalhammer M, Aschauer M. Aplasia of the
inferior vena cava as a cause for recurring thrombosis of the lower
extremities and pelvic veins. Vasa 1999; 28:289–292.
16 White RH, McGahan JP, Daschbach MM, Hartling RP. Diagnosis of deep-
vein thrombosis using duplex ultrasound. Ann Intern Med 1989; 111:297–
304.
17 Ruggeri M, Tosetto A, Castaman G, Rodeghiero F. Congenital absence of
the inferior vena cava: a rare risk factor for idiopathic deep-vein thrombosis.
Lancet 2001; 357:441.
18 Siragusa S, Anastasio R, Falaschi F, Bonalumi G, Bressan MA. Congenital
absence of inferior vena cava. Lancet 2001; 357:1711.
19 Chee YL, Culligan DJ, Watson HG. Inferior vena cava malformation as a risk
factor for deep venous thrombosis in the young. Br J Haematol 2001;
114:878–880.
20 Schneider JG, Eynatten MV, Dugi KA, Duex M, Nawroth PP. Recurrent
deep venous thrombosis caused by congenital interruption of the inferior
vena cava and heterozygous factor V Leiden mutation. J Intern Med 2002;
252:276–280.
21 Obernosterer A, Aschauer M, Schnedl W, Lipp RW. Anomalies of the
inferior vena cava in patients with iliac venous thrombosis. Ann Intern Med
2002; 136:37–41.

Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.

 104 Journal of Cardiovascular Medicine 2008, Vol 9 No 1

22 Parma M, Belotti D, Marinoni S, Pogliani EM. Congenital absence of the

inferior vena cava and genetic coagulation abnormalities: a rare associated
risk factor for recurrent idiopathic deep vein thrombosis. Clin Appl Thromb
Hemost 2003; 9:347–348.
23 Vidra T, Szomor A, Battyani I, Muhl D, Losonczy H. Agenesis of inferior vena
cava combined with multiple genetic predisposition on the case of deep
venous thrombosis in a young male. Orv Hetil 2003; 144:2283–2286.
24 Garcia-Fuster MJ, Fernandez C, Forner MJ, Vaya A. Risk factors and clinical
characteristics of thromboembolic venous disease in young patients: a
prospective study. Med Clin (Barc) 2004; 123:217–219.
25 Sakellaris G, Tilemis S, Papakonstantinou O, Bitsori M, Tsetis D, Charissis
G. Deep venous thrombosis in a child associated with an abnormal inferior
vena cava. Acta Paediatr 2005; 94:242–244.
26 Thornton MJ, Ryan R, Varghese JC, Farrell MA, Lucey B, Lee MJ. A three-
dimensional gadolinium-enhanced MR venography technique for imaging
central veins. AJR Am J Roentgenol 1999; 173:999–1003.
27 Chuang VP, Mena CE, Hoskins PA. Congenital anomalies of the inferior
vena cava. Review of embryogenesis and presentation of a simplified
classification. Br J Radiol 1974; 47:206–213.
28 Prandoni P, Lensing AW, Cogo A, Cuppini S, Villata S, Carta M, et al. The
long-term clinical course of acute deep venous thrombosis. Ann Intern Med
1996; 125:1–7.

Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited.