Recurrent thrombosis despite anticoagulation in a man with monocytosis

Summary

Recurrent thromboembolism despite oral anticoagulation is primarily suspicious of overt or occult neoplasia. We report on a man (age: 67 years) who presented with severe thrombophilia which was only controlled when the patient was set on a combined anticoagulation with low molecular weight heparin in supratherapeutic dosage and phenprocoumon with a target INR of 2.0. Despite repeated evaluation over about two years, a malignant tumour could never be demonstrated. However, the patient suffered in addition to a protein S deficiency from an antiphosphospholipid syndrome and a chronic myelomonocytic leukaemia.

We postulate that the accepted strong thrombogenicity of antiphosphospholipid syndrome was further increased by protein S deficiency and a possibly procoagulatory effect of the abnormal monocytes explaining the severe thrombophilia resistant to standard therapeutic anticoagulation with a vitamin K antagonist and usual therapeutic doses of low molecular weight heparin, respectively.

Zusammenfassung

Rezidivierende Thromboembolien trotz adäquater Antikoagulation sind in erster Linie verdächtig auf ein Tumorleiden. Wir berichten über einen 67-jährigen Mann, dessen Thromboseneigung sich einzig durch eine kombinierte Antikoagulation mit einem niedermolekularen Heparin in supratherapeutischer Dosis und einem Coumarinderivat mit Ziel-INR 2,0 kontrollieren ließ. Ein Tumorleiden konnte nie nachgewiesen werden, hingegen fanden sich nebst einem Protein-S-Mangel ein Antiphospholipid-Syndrom und eine chronische myelomonozytäre Leukämie. Wir postulieren, dass die bekannterweise ausgeprägte Thrombogenizität des Antiphospholipid-Syndroms zusätzlich verstärkt wurde durch den Protein-S-Mangel und einen möglicherweise prokoagulatorischen Effekt abnormer Monozyten und sich entsprechend durch eine übliche Antikoagulation nicht beherrschen ließ.

Keywords

Thrombosis - monocytosis - anticoagulation

Schlüsselwörter

Thrombose - Monozytose - Gerinnungshemmung

^* Present address: Division of Haematology, University Hospital, 8000 Zürich, Switzerland

• References

• 1 Ansell J, Hirsh J, Dalen J. et al. Managing oral anticoagulant therapy. Chest 2001; 119: 22S-38S.
• 2 Cervera R, Piette JC, Font J. et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arth Rheum 2002; 46: 1019-27.
• 3 Falanga A, Rickles FR. Pathophysiology of the thrombophilic state in the cancer patient. Sem Thromb Hemost 1999; 25: 173-82.
• 4 Khamashta MA, Cuadrado MJ, Mujic F. et al. The management of thrombosis in the antiphospholipid syndrome. N Engl J Med 1995; 332: 993-7.
• 5 Merrill JT. What causes the antiphospholipid syndrome?. Curr Rheumatol Rep 2001; 3: 293-300.
• 6 Monreal M, Prandoni P. Venous thromboembolism as first manifestation of cancer. Sem Thromb Hemost 1999; 25: 131-6.
• 7 Oosting JD, Derksen RH, Bobbink IW. et al. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism?. Blood 1993; 81: 2618-25.
• 8 Osterud B. Tissue factor expression by monocytes: regulation and pathophysiological roles. Blood Coagul Fibrinol 1998; 9 (Suppl. 01) S9-14.
• 9 Parke AL, Weinstein RE, Bona RD. et al. The thrombotic diathesis associated with the presence of phospholipid antibodies may be due to low levels of free protein S. Am J Med 1992; 93: 49-56.
• 10 Reverter JC, Tassies D, Font J. et al. Hypercoagulable state in patients with antiphospholipid syndrome is related to high induced tissue factor expression on monocytes and to low free protein S. Arterioscler Thromb Vasc Biol 1996; 16: 1319-26.
• 11 Roubey RA. Tissue factor pathway and the antiphospholipid syndrome. J Autoimmun 2000; 15: 217-20.
• 12 Singh AK. Immunopathogenesis of the antiphospholipid antibody syndrome: an update. Curr Op Nephrol Hypertens 2001; 10: 355-8.
• 13 Trousseau A. Phlegmasia alba dolens. In: Baillière JB. (ed). Clinique Médicale de l’Hôtel-Dieu de Paris. Paris: 1865: 654-712.