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Hamostaseologie 2017; 37(S 01): S26-S31
DOI: 10.5482/HAMO-17-03-0012
Case Report
Schattauer GmbH

A rare case of unprovoked venous thromboembolism manifestation in a young patient with antithrombin Type IIB deficiency combined with inferior vena cava anomaly from Lithuania

Seltener Fall einer Venenthrombose bei einem jungen Patientenaus Litauen mit Antithrombin Typ IIB Mangel in Kombination mit einer Anomalie der Vena cava
Sonata Saulytė-Trakymienė
1   Vilnius University, Faculty of Medicine, Institute of Clinical Medicine, Clinic of Pediatrics
2   Children’s Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius
,
Irina Adomaitienė
2   Children’s Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius
,
Susanne Unkrig
3   Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Germany
,
Johannes Oldenburg
3   Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Germany
,
Vytautas Ivaškevičius
3   Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Germany
› Author Affiliations
Further Information

Publication History

received: 05 March 2017

accepted in revised form: 22 August 2017

Publication Date:
28 December 2017 (online)

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Summary

Hereditary antithrombin (AT) deficiency is an autosomal-dominant disorder predisposing to venous and arterial thrombosis. Homozygosity resulting in severe AT deficiency is not compatible with life, apart from homozygous mutations affecting the heparin-binding site representing the most severe thrombophilia. Patients and methods: A 12-year-old previously healthy boy of Romani origin presented with a swollen, painful left leg and fever. Imaging revealed signs of inferior vena cava (IVC) thrombosis, the presence of interrupted intrahepatic IVC with azygos continuation and bilateral iliofemoral thrombosis with enlargement of the azygous and hemiazygos venous system. In addition, right pleural effusion and signs of bilateral renal pericortical cysts, possibly caused by retroperitoneal lymphangiectasia, were disclosed. Thrombophilia screening involving protein C, Protein S, Antithrombin (chromogenic assays based on the inhibition of FIIa and FXa, antigen concentration), APC resistance, prothrombin mutation and Lupus anticoagulants was performed using standard laboratory methods. Genetic analysis of the SERPINC1 gene was done by direct sequencing. Results: Thrombophilia screening showed isolated decreased AT activity at 21% (RR 80–120%). AT levels were retested and remained decreased (33–36%) on two consecutive occasions. SERPINC1 gene analysis revealed a previously described homozygous mutation (Budapest III) causing type IIB deficiency (c.391C>T; p.Leu131Phe). A family study confirmed the same mutation in both parents and three siblings. The patient improved significantly following warfarin therapy and over the past 2.5 years did not experience new thromboembolism. Conclusions: This case represents a rare combination of two risk factors provoking manifestation of spontaneous venous thromboembolism at a young age requiring permanent anticoagulant therapy.

Zusammenfassung

Der hereditäre Antithrombinmangel ist eine autosomal-dominante Gerinnungsstörung, die zu venösen sowie arteriellen Thromboembolien prädisponiert. Homozygotie, die zu einem schweren Antithrombin-Mangel führt, ist mit Ausnahme der die Heparin-Bindungsstelle betreffenden Mutationen, welche dann zu einer schweren Thrombophilie führen, mit dem Leben nicht vereinbar. Patienten und Methode: Ein 12-jähriger, zuvor gesunder Knabe aus einer Roma-Familie wurde mit Beinschwellung links, Schmerzen und Fieber vorgestellt. Bildgebende Verfahren wie-sen eine Thrombose der Vena cava inferior (VCI), eine Unterbrechung der intrahepatischen VCI mit Fortsetzung in der V. azygos und eine beidseitige iliofemorale Thrombose mit Erweiterung des Azygos-/Hemiazygos-Venen-systems nach. Zusätzlich wurden ein rechts-seitiger Pleuraerguss und beidseitige Zysten im Bereich der Nierenrinde, möglicherweise infolge retroperitonealer Lymphangiektasien, beschrieben. Ein Thrombophiliescreening unter Berücksichtigung von Protein C, Protein S, Antithrombin (Aktivitäts- und Antigen-Bestimmung), APC-Resistenz, Prothrombinmutation und Lupus-Antikoagulantien wurde im Standard-Laborverfahren durchgeführt. Die genetische Analyse des SERPINC1-Gens erfolgte durch direkte Sequenzierung. Ergebnisse: Das Thrombophiliescreening zeigte eine isolierte Verminderung der Antithrombinaktivität auf 21% (Referenzbereich: 80–120 %). Zwei Verlaufskontrollen des Antithrombinspiegels bei Folgeuntersuchungen bestätigten die Verminderung (33–36%). Die molekulargenetische Untersuchung des SERPINC1-Gens ergab eine homozygote Mutation (Budapest III) als vorbeschriebene Ursache des Typ-IIB-Mangels (c.391C>T; p.Leu131Phe). Eine Untersuchung der Familie bestätigte das Vorliegen derselben Mutation bei beiden Eltern und bei drei Geschwistern. Unter Warfarintherapie besserte sich der klinische Zustand des Patienten signifikant und im weiteren Beobachtungszeitraum traten über bisher 2.5 Jahre keine weiteren thromboembolischen Ereignisse und keine Zunahme der Restthrombuslast auf. Schlussfolgerungen: Die Falldarstellung beschreibt die Kombination zweier seltener Risikofaktoren, welche im Kindesalter zur Entstehung einer spontanen Venenthrombose führten und trotz des jugendlichen Alters eine Dauerantikoagulation erforderlich machten.

Keywords

Antithrombin deficiency - vena cava anomaly - venous thromboembolism

Schlüsselwörter

Hereditäre Antithrombinmangel - Vena cava Anomalie - Venenthrombose
 

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