PB0302 - Preventing thrombosis in moderate-severe protein C deficiency: the effects of different treatment regimens in a boy with protein C level of 4 IU/dl.

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Idske C.L Kremer Hovinga, MD PhD

Pediatric Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands

Co-Author(s)

Kathelijn Fischer, MD, PhD (she/her/hers)

Pediatric Hematologist
Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, The Netherlands
Utrecht, Utrecht, Netherlands

Background: Moderate-severe protein C deficiency (MSPCD) is defined as a protein C level of 1-20 IU/dl. MSPCD has variable age and symptoms of presentation. The best treatment to prevent thrombosis in MSPCD is unknown.

Aims: The aim of this report is to demonstrate the effect of different treatment regimens in a boy with MSPCD.

Methods: The boy presented at the age of two with hematomas and swelling on the thigh. He never had thrombosis. The laboratory parameters demonstrated a coagulopathy including increased d-dimers (38 mg/l) and decreased fibrinogen levels (0,5 g/l) together with factor consumption. Protein C activity was 4 IU/dl. Genetic testing showed compound heterozygous mutations of the PROC genes.

Treatment: In the course of 2,5 years, he received:
1. no treatment
2. low molecular weight heparin (LMWH) dalteparin
3. direct oral anticoagulant (DOAC) rivaroxaban
3a. combination of rivaroxaban and plasma-derived protein C concentrate (Ceprotin) 62.5 IU/kg intravenously during a period of sickness, followed by a dose of 30 IU/kg the day after.
4. combination of rivaroxaban and Ceprotin subcutaneously

Results: Figure 1 shows the effect of the different treatment regimens on d-dimers and fibrinogen levels. This demonstrates that dalteparin and rivaroxaban were evenly effective, but did not lead to complete normalization of fibrinogen and d-dimers. Addition of Ceprotin 3 times a week led to almost complete normalization of laboratory parameters. The child did not develop symptomatic thrombosis nor purpura fulminans. With Ceprotin 30 IU/kg subcutaneously he had a protein C activity level of 25 IU/dl after 12 hours and 14 IU/dl after 48 hours.

Conclusion(s): Coagulopathy in a boy with MSPCD improved during treatment with subsequently LMWH, DOAC and combination of Ceprotin and DOAC. The optimal treatment based on clinical features, laboratory parameters and treatment burden in this boy was Ceprotin 3 times a week subcutaneously combined with rivaroxaban in therapeutic dose.