Management of SCPCD

Severe congenital protein C deficiency (SCPCD) is a rare autosomal recessive disorder that usually presents within hours after birth.^1,2 Management of SCPCD may require both acute and long-term prophylactic treatment options.^1,3,4

The treatment options discussed in this article may not be in line with approved product labels in all countries and are not intended as recommendations for treatment. Please consult your local prescribing information.

Management of SCPCD may require both acute and long-term treatment options^1,3,4

Babies with SCPCD may present with symptoms soon after birth, which require emergency management.^1-4 In the acute setting, it is recommended that protein C replacement should be started promptly, ideally with a protein C concentrate, although anticoagulant therapy may be used.^1,3,4

Management of SCPCD goes beyond emergency treatment in infancy – long-term prophylaxis may be needed to prevent symptom recurrence.^1,3,4 Protein C concentrate is preferred for long-term treatment, although vitamin K antagonists are an alternative if availability is limited.^3,4 Liver transplantation is potentially curative, but the risks and benefits should be carefully considered.^3,5

What treatments are available for SCPCD?

The symptoms of SCPCD, which include purpura fulminans and large-vessel thrombosis, usually present soon after birth and may be rapidly progressive, requiring emergency treatment.^1-4 In survivors, SCPCD can result in severe sequelae, and long-term treatment options may be required to prevent recurrence of symptoms.^1,3,4 Read on to learn more about acute and long-term treatment options, and key recommendations for management according to guidance from the International Society on Thrombosis and Haemostasis in 2022.³

Acute treatment of SCPCD symptoms

Protein C replacement

Protein C replacement is an established method for SCPCD symptom management, and should start promptly upon suspicion of an SCPCD diagnosis in babies, once an appropriate diagnostic sample has been obtained.^3,4,6,7

Two sources of protein C are available for replacement therapy – protein C concentrates or fresh frozen plasma.^1,3,4

Protein C concentrates

Intravenously administered (IV) plasma-derived, viral-inactivated protein C concentrates are the preferred protein C source for replacement therapy in the acute setting, and there is one treatment in the UK for SCPCD.^3,4,8 An initial loading dose should achieve a target plasma protein C activity of 1 IU/mL, with dosing gradually reduced following a satisfactory response to maintain trough protein C activity above 0.25 IU/mL.^3,8

Fresh frozen plasma

If protein C concentrate is unavailable or delayed, fresh frozen plasma is the preferred alternative source for protein C replacement.^3,4,9 However, patients should be carefully monitored during treatment, and fresh frozen plasma should be switched to protein C concentrate once an SCPCD diagnosis is confirmed.^1,3,4,10

Protein C replacement with IV protein C concentrate is recommended for acute treatment of SCPCD symptoms^1,3,4

Whatever the source of protein C, replacement therapy in the acute setting should continue until purpura fulminans lesions have resolved (usually around 4–8 weeks) and plasma concentrations of coagulation markers such as D-dimers have normalised.^3,4,9

Anticoagulant therapy

Anticoagulants, including oral vitamin K antagonists (VKAs), unfractionated heparin (UH), and low-molecular-weight heparin (LMWH), are sometimes used for acute treatment of purpura fulminans, but should be used with caution in the acute neonatal setting due to an increased risk of bleeding caused by depletion of procoagulation factors.³ UH or LMWH with age-appropriate dosing are preferred, particularly if large-vessel thrombosis is present.³

Long-term management

Protein C replacement

Protein C concentrate is the preferred option for long-term management of SCPCD (Figure 1).³ The goal of prophylactic protein C therapy is to prevent relapse or occurrence of clinical manifestations of SCPCD.⁷

VKAs

If protein C concentrate is unavailable or too expensive, VKAs are the recommended alternative for long-term SCPCD management, although use in young children may be difficult (Figure 1).³ Blood tests should be carefully monitored during VKA treatment to assess the risk of bleeding or purpura fulminans recurrence.³

Liver transplant

Liver transplant is a potentially curative option in SCPCD and may be an alternative to long-term protein C replacement (Figure 1).^3,5 However, given the long-term risks associated with this procedure, the risks and benefits should be carefully discussed with the patient’s family.³

Figure 1. A summary of the available acute and long-term treatment options for patients with SCPCD.³
Abbreviations: CVL, central venous line; FFP, fresh frozen plasma; IV, intravenous; LMWH, low-molecular-weight heparin; PF, purpura fulminans; SCPCD, severe congenital protein C deficiency; UH, unfractionated heparin; VKA, vitamin K antagonist.

SCPCD management is complex, and clinicians should make management decisions based on the individual patient’s clinical presentation, taking side effects, cost, and suitability for each family into consideration³

References

1. Goldenberg and Manco-Johnson, 2008. Protein C deficiency. https://www.doi.org/10.1111/j.1365-2516.2008.01838.x
2. Marlar, 1989. Diagnosis and treatment of homozygous protein C deficiency. Report of the working party on homozygous protein C deficiency of the subcommittee on protein C and protein S, international committee on thrombosis and haemostasis. https://www.doi.org/10.1016/s0022-3476(89)80688-2
3. Minford, 2022. Diagnosis and management of severe congenital protein C deficiency (SCPCD): Communication from the SSC of the ISTH. https://www.doi.org/10.1111/jth.15732
4. Chalmers, 2011. Purpura fulminans: Recognition, diagnosis and management. https://www.doi.org/10.1136/adc.2010.199919
5. Boucher, 2018. Successful liver transplantation for homozygous protein C deficiency with a type II mutation using a heterozygous living related donor. https://www.doi.org/10.1002/ajh.24998
6. Knoebl, 2008. Severe congenital protein C deficiency: The use of protein C concentrates (human) as replacement therapy for life-threatening blood-clotting complications. https://doi.org/10.2147/btt.s1954
7. Kroiss and Albisetti, 2010. Use of human protein C concentrates in the treatment of patients with severe congenital protein C deficiency. https://www.doi.org/10.2147/btt.s3014
8. CEPROTIN Summary of Product Characteristics. https://www.emcpi.com/grp/96?utm_medium=pi-url
9. Williams, 2002. The investigation and management of neonatal haemostasis and thrombosis. https://www.doi.org/10.1046/j.1365-2141.2002.03674.x
10. Pescatore, 2001. Clinical management of protein C deficiency. https://www.doi.org/10.1517/14656566.2.3.431