Chronic disseminated intravascular coagulation in a patient with antiphospholipid antibodies and acquired protein S deficiency

C. Dicke, K. Holstein, M. Voigtländer, F. Stahl, U. Schnoor, C. Bokemeyer, F. Langer (Hamburg, Germany)

Acquired problems and alterations of coagulation
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: We describe the rare case of a 76-year-old woman presenting with a thrombohemorrhagic syndrome due to disseminated intravascular coagulation (DIC) in the context of elevated antiphospholipid antibodies and acquired protein S deficiency.

Methods: We measured coagulation inhibitors, activated protein C resistance (APC-R), factor V gene mutation Leiden, lupus anticoagulant (LA), and IgG/IgM antibodies to cardiolipin (aCL) and beta2-glycoprotein I (anti-β2-GPI) by standard laboratory tests. Mixing studies with normal human plasma (NHP) were used to screen for a functional protein S inhibitor. Tissue factor (TF)-specific procoagulant activity (PCA) of plasma microvesicles (MVs) was assessed by single-stage clotting assay.

Results: At presentation, a diffuse and painful reticular erythema indicated severely impaired microcirculation. Coagulation tests revealed DIC with consumptive coagulopathy: prothrombin time 45.5% (normal: 80-130%), fibrinogen 0.5 g/L (1.8-4.0 g/L), D-dimer 34 mg/L (< 0.5 mg/L). Platelet count was normal (166 x 109/L). Surgical and antibiotic treatment of sigmoid diverticulitis did not resolve DIC, and overt malignancy was excluded by endoscopy and FDG-PET/CT. The coagulopathy was controlled by application of enoxaparin (2 x 40 mg/d), or apixaban (2-3 x 5 mg/d), but reoccurred within 24 hours after cessation of anticoagulation. Titers of IgM-aCL were elevated, ranging from 17 U/mL (< 10 U/mL) at presentation to 90 U/mL during follow-up. Antinuclear antibodies were negative, as were tests for LA and anti-β2GPI. There was APC-R with a ratio of 1.7 (> 2.0) in the absence of factor V gene mutation Leiden. Free and total protein S antigen were normal, but protein S activity was severely reduced to 14% (55-125%) with no appropriate correction upon mixing with NHP. Significant MV-associated TF PCA was detected. No underlying rheumatologic or malignant disease evolved over the next two years. A short-term course of oral glucocorticoids was ineffective.

Conclusion: In this patient, generation of MV-associated TF PCA, possibly due to monocyte activation by antiphospholipid antibodies, in combination with acquired APC-R and severe depletion of protein S activity caused a systemic coagulopathy characterized by clotting factor consumption and microvascular thrombosis, which could only be controlled by uninterrupted systemic anticoagulation.