Late onset of thrombosis in siblings with homozygous protein C deficiency

C. Wermes, M. Suslovych, C. Detering, M. von Depka (Hannover, Germany)

Pediatric and neonatal thrombosis and hemostasis
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: Homozygous protein C (PC) deficiency is an extremely rare life-threatening coagulopathy presenting in the neonatal period with extensive purpura fulminans and very high rates of morbidity and mortality. Prenatal onset of thrombotic events is a common situation that worsens the prognosis of these patients.

Methods: Here we demonstrate a case report of two siblings, 1 year and 14 years old, with a homozygous PC deficiency (PC<10%) with the mutation c.925G>A (p.Ala309Thr, historic Ala267Thr, Exon 9, PROC-Gene). The younger sister had been clinically inconspicuous so far but the older girl suffered from a sinus venous thrombosis at the age of two. Therefore, she was successfully treated with low-molecular-weight heparin (LMWH). Her medical history demonstrated the presence of repeated mild headache and dermal necrosis in recent years. Further laboratory parameters did not show any abnormal values except for the well-known PC deficiency and a mild reduction of protein S (56.5%). Due to the older sisterĀ“s medical history and the very high risk of thromboembolic events due to the homozygous PC deficiency we decided to implement a primary prophylaxis with Warfarin in the younger girl although she did not show any thromboembolic events so far. In the older sister we also started a long-term anticoagulation treatment with Warfarin. In both patients a PC replacement therapy and an anticoagulation with a LMWH was given additionally due to the known abnormal thrombotic risk during upitration of Warfarin.

Results: Both girls showed a very good response to Warfarin with a stable INR value of 2-3 after a few days so the concomitant therapy with PC replacement and LMWH was stopped. During therapy no clinical complications or adverse events occurred so far.

Conclusion: In these patients with homozygous PC deficiency a late onset of thromboembolic events was observed which is very uncommon for this type of disease. Anticoagulation treatment should have been given early in childhood before life-threatening complications could occur. A combination of Warfarin therapy and an additional PC replacement therapy as wells as an anticoagulation during upitration phase seems to offer an efficacious and safe treatment as secondary prophylaxis as well as primary prophylaxis for recurrent purpura fulminans and thromboembolic events in PC deficient patients.