Protein C Deficiency Treatment & Management

Updated: Jan 04, 2019
  • Author: Shamudheen Rafiyath, MD; Chief Editor: Perumal Thiagarajan, MD  more...
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Treatment

Medical Care

A substantial proportion of individuals with protein C deficiency remain asymptomatic throughout life and require no specific therapy. However, thromboprophylaxis may be considered for such individuals, particularly if they have a strong family history of thrombosis, in situations associated with a high thrombotic risk, such as pregnancy and the postpartum state, surgery, and trauma.

A case report by Milleret and colleagues describes 2 years of successful prophylaxis in a patient with neonatal severe protein C deficiency, using warfarin oral suspension. The international normalized ratio (INR) was measured by home monitoring, with a target INR of 2.5 to 3.5. [69]

For those patients who do develop clinical manifestations of hereditary protein C deficiency, treatment depends on the particular clinical syndrome: venous thromboembolism (VTE), warfarin-induced skin necrosis (WISN), or neonatal purpura fulminans (NPF).

Venous thromboembolism

VTE in patients with protein C deficiency is managed in much the same way as it is for patients with VTE due to other causes. Because the risk of recurrent VTE in protein C–deficient patients may be as high as 60%, [22] long-term anticoagulation is often recommended, particularly following a spontaneous thromboembolic event.

In protein C deficiency, caution should be taken to reduce the risk of warfarin-induced skin necrosis while choosing the anticoagulant agent. Preventive measures include the use of an oral anticoagulant other than warfarin, use of warfarin with a lower starting dose, and longer duration of overlapping heparin or low molecular weight heparin (LMWH) administration.

Because of the availability of and familiarity with the use of direct oral anticoagulants (DOACs), the preference is to use DOACs for anticoagulation in patients with a typical VTE presentation. However, in massive pulmonary embolism and other severe clinical presentations such as hypoxemia/shock, or deep vein thrombosis with a proximal clot burden and in patients with concerns about adherence, the preference would be to administer heparin or an LMWH and then transition to warfarin, with the goal of keeping the international normalized ratio (INR) in the high end of the therapeutic range.

Warfarin-induced skin necrosis

WISN is a medical emergency that requires treatment as soon as it is recognized. Therapy consists of immediate discontinuation of warfarin, administration of vitamin K, and initiation of therapeutic doses of heparin. If the patient is protein C deficient, exogenous protein C should be administered, either in the form of fresh frozen plasma or, preferably, as purified protein C concentrate (Ceprotin) with the goal of expeditiously normalizing plasma protein C activity. [70]

In adult patients with protein C deficiency who have experienced WISN, dabigatran, rivaroxaban apixaban, or edoxaban have been used successfully for subsequent anticoagulation. A case report describes the effective and safe use of rivaroxaban in a teenage patient, with thrombin generation assays used to adjust the dosage. [71]

Neonatal purpura fulminans

Like WISN, NPF is a medical emergency that requires rapid normalization of plasma protein C activity. Although fresh frozen plasma has been used as a source of exogenous protein C in the treatment of NPF, frequent dosing is required to maintain adequate plasma levels, thereby limiting its usefulness in this setting. Highly purified protein C concentrate represents an attractive alternative that does not subject patients to the high volume and protein load of fresh frozen plasma. [72, 73, 74]

After treatment of the acute phase of NPF, patients are transitioned to anticoagulation therapy, which they must remain on indefinitely. Warfarin may be used in this setting, provided that exogenous protein C is administered during its initiation in order to avoid the development of WISN. [75] For patients with breakthrough thrombosis despite anticoagulation, protein C concentrate may be infused at home. A subcutaneous formulation of protein C requiring administration every 3 days has been used successfully in this context. [76]

Living donor liver transplantations have been successfully performed in NPF, resulting in a permanent cure. [77]  

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Consultations

Consultation with a hematologist is warranted for the care of patients with congenital protein C deficiency.

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Diet and Activity

There are no special dietary requirements for individuals with protein C deficiency. However, patients on warfarin should consume a steady diet and avoid large day-to-day fluctuations in the amount of vitamin K–containing foods (ie, dark green leafy vegetables) they ingest.

There are no specific restrictions with respect to physical activity that are recommended for individuals with protein C deficiency. All individuals should ambulate regularly during prolonged travel to reduce the risk of VTE. Patients on anticoagulation therapy should avoid contact sports to reduce the risk of trauma and major bleeding.

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