Summary: Since the first description of subcutaneous protein C concentrate as treatment for severe protein C deficiency in 1996, further cases have been reported but there is no uniform approach to this form of treatment. In order to assess the safety and effectiveness of subcutaneous protein C concentrate and suggest recommendations for future use, patients who had received subcutaneous protein C concentrate were identified from the literature, by contacting the manufacturers and by personal communication. Treatment details were available from 14 cases. Apart from one case where the infusion interval was inadvertently increased, no thrombotic events occurred even when doses were subsequently reduced. Initially, a trough protein C level of >0·25 iu/ml should be aimed for. Subsequently, a smaller dose of subcutaneous protein C concentrate, especially if taken with an oral anticoagulant, may be protective maintenance treatment. The treatment was well tolerated with few side effects. Subcutaneous protein C concentrate on its own or combined with an oral anticoagulant appears to be safe and effective as maintenance treatment of severe protein C deficiency. A major advantage is the avoidance of central venous access devices. The incidence of neurodevelopmental handicap was high with blindness affecting the majority of patients.

Zusammenfassung: Im Kindesalter werden wie bei Erwachsenen hämorrhagische Diathesen und thrombotische Erkrankungen beobachtet. Die Ursachen sind angeboren oder erworben. Schwerere angeborene Störungen mit Blutungsfolgen manifestieren sich meist im Kleinkindalter, während angeborene thrombophile Störungen meist in Kombination mit zusätzlichen Risikofaktoren das Entstehen von Thrombosen mit Gipfeln im Neugeborenen- und Pubertäts- bzw. Adoleszentenalter begünstigen. Zur Beurteilung von Hämostaseparametern in Verbindung mit klinischem Befund ist die Kenntnis einiger kindlicher Besonderheiten, wie die Altersabhängigkeit der Gerinnungswerte, wichtig. Nur so können adäquate Therapieentscheidungen getroffen werden.

Background: Familial multiple coagulation factor deficiencies (FMCFDs) are a group of inherited hemostatic disorders with the simultaneous reduction of plasma activity of at least two coagulation factors. As consequence, the type and severity of symptoms and the management of bleeding/thrombotic episodes vary among patients. The aim of this study was to identify the underlying genetic defect in patients with FMCFDs. Methods: Activity levels were collected from the largest cohort of laboratory-diagnosed FMCFD patients described so far. Genetic analysis was performed using next-generation sequencing. Results: In total, 52 FMCFDs resulted from coincidental co-inheritance of single-factor deficiencies. All coagulation factors (except factor XII (FXII)) were involved in different combinations. Factor VII (FVII) deficiency showed the highest prevalence. The second group summarized 21 patients with FMCFDs due to a single-gene defect resulting in combined FV/FVIII deficiency or vitamin K–dependent coagulation factor deficiency. In the third group, nine patients with a combined deficiency of FVII and FX caused by the partial deletion of chromosome 13 were identified. The majority of patients exhibited bleeding symptoms while thrombotic events were uncommon. Conclusions: FMCFDs are heritable abnormalities of hemostasis with a very low population frequency rendering them orphan diseases. A combination of comprehensive screening of residual activities and molecular genetic analysis could avoid under- and misdiagnosis.