Protein C Deficiency

Jan 9, 2020
5 min read

Updated: Oct 17

Protein C Deficiency is a rare inherited condition that increases the risk of abnormal blood clot formation in the veins and lungs. The disorder results from a mutation in the PROC gene, which reduces or impairs the body’s natural anticoagulant function. While many carriers never develop symptoms, others face recurring venous thromboembolism that demands lifelong monitoring and anticoagulant therapy. Recent research has improved early genetic detection and established clearer management guidelines, ensuring that high-risk patients—especially women during pregnancy or those with family histories of thrombosis—receive timely, targeted care.

Protein C Deficiency: Causes, Diagnosis, and Treatment

Protein C deficiency is a rare but serious disorder that increases the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). It may be inherited through genetic mutation or acquired due to another medical condition. Many people with the deficiency never develop symptoms, but in others, the lack of sufficient protein C can lead to severe and even life-threatening clotting events.

Overview

What is Protein C Deficiency?

Protein C deficiency occurs when the body lacks enough functional protein C, a natural anticoagulant that prevents excessive clotting. Protein C helps regulate coagulation by inactivating key clotting factors (Va and VIIIa). When levels are low or the protein is defective, this balance breaks down, allowing abnormal clots to form—most commonly in the legs and lungs.

Without adequate regulation, blood can clot too easily inside veins, cutting off circulation and oxygen to tissues. This can result in DVT, PE, or in severe cases, multi-organ complications.

How Common Is Protein C Deficiency?

A mild (heterozygous) form of the disorder affects roughly 1 in 200 to 500 people, while the severe (homozygous) form occurs in about 1 in 500,000 to 750,000 individuals. Both men and women are affected equally.

The true prevalence may be higher than reported due to underdiagnosis, especially in patients who experience unexplained blood clots but are never genetically tested.

Symptoms

What Are the Signs and Symptoms of Protein C Deficiency?

Mild deficiency often remains silent until a triggering event, such as surgery, pregnancy, or prolonged immobility, initiates clot formation.

Common signs of DVT include:

Persistent leg pain or tenderness
Swelling
Warm, discolored, or reddish-purple skin

If a clot travels to the lungs (PE), symptoms may include:

Sudden shortness of breath
Chest pain
Rapid heartbeat
Coughing, sometimes with blood
Fainting or lightheadedness

In newborns with severe deficiency, life-threatening clotting may develop within hours to days of birth, often appearing as:

Widespread purplish skin patches (purpura fulminans)
Internal bleeding in affected tissues
Signs of disseminated intravascular coagulation (DIC)

Causes

What Causes Protein C Deficiency?

Protein C deficiency results from a mutation in the PROC gene, which provides the instructions for making protein C.

Type I: Low levels of protein C in the blood.
Type II: Normal levels, but the protein does not function properly.

A person who inherits one defective gene (heterozygous) usually has a mild form of the condition and may never experience a clot. Inheriting two defective copies (homozygous) causes a severe deficiency that presents at birth.

Protein C deficiency can also be acquired through conditions that reduce protein C levels, including:

Vitamin K deficiency
Warfarin therapy
Severe liver disease
Sepsis or DIC, where protein C is consumed during widespread clotting

Even though inherited deficiency is uncommon, acquired causes can temporarily mimic the same dangerous hypercoagulable state—especially in critically ill patients.

Diagnosis and Testing

How is Protein C Deficiency Diagnosed?

Diagnosis requires a careful combination of clinical history and specialized laboratory testing. Because many individuals remain asymptomatic until a triggering event occurs, identifying an inherited clotting disorder often begins with unexplained or recurrent blood clots.

Your healthcare provider may evaluate for Protein C deficiency based on:

Personal history of deep vein thrombosis (DVT), pulmonary embolism (PE), or other venous clots—especially at a young age or in the absence of common risk factors.
Family history of venous thromboembolism (VTE) or known hereditary thrombophilia.
Protein C activity testing, which measures how effectively the protein functions in your blood.
Protein C antigen testing, which measures the actual amount of protein present.
Genetic testing for PROC gene mutations, which can confirm inheritance but is not required for diagnosis or management.

Because Protein C levels can be temporarily reduced by warfarin therapy, severe illness, pregnancy, or DIC, testing should be performed under stable conditions for accurate results.

Management and Treatment

How is Protein C Deficiency Treated?

Treatment depends on the severity of deficiency, clinical history, and presence of active or prior clots.

For most individuals with mild or heterozygous deficiency:

No continuous therapy is required unless additional risk factors are present (e.g., surgery, trauma, pregnancy, prolonged immobility).
Anticoagulants (blood thinners) are prescribed if a thrombotic event occurs.
- If warfarin is used, treatment must begin with heparin bridging to prevent warfarin-induced skin necrosis—a rare but serious complication caused by sudden depletion of protein C.
- Direct oral anticoagulants (DOACs) such as apixaban or rivaroxaban are increasingly favored for many patients due to lower risk of this reaction and ease of monitoring.
All anticoagulation should be managed under close medical supervision; never stop or change dosage without consulting your provider.

For newborns or infants with severe (homozygous) deficiency:

Protein C concentrate (Ceprotin®) or fresh frozen plasma may be administered to replace missing protein C and control life-threatening clotting, including purpura fulminans.

Complications

Complications of Protein C Deficiency

If untreated or mismanaged, Protein C deficiency can lead to serious outcomes, including:

Warfarin-induced skin necrosis, which begins as painful red or purple lesions—often on the torso, arms, or legs—that may progress to tissue death if not promptly addressed.
Venous thromboembolism (VTE), where clots form in deep veins and can dislodge, traveling to the lungs and causing pulmonary embolism (PE).
Purpura fulminans in newborns, a rapidly fatal clotting crisis without urgent intervention.
Fluid overload in infants receiving plasma infusions for replacement therapy.

Outlook / Prognosis

What Can I Expect If I Have Protein C Deficiency?

Severe congenital deficiency carries a grave prognosis in infancy, with high mortality even when treated due to complications such as fluid overload from repeated transfusions.
Mild or heterozygous deficiency generally allows a normal lifespan but increases risk for recurrent deep vein thrombosis or pulmonary embolism, particularly under stress conditions like surgery, immobility, or hormone therapy.
Long-term outcomes depend on adherence to preventive care, timely treatment, and careful monitoring by a hematologist.

Prevention

Can Protein C Deficiency Be Prevented?

The inherited form cannot be prevented, but early recognition and management can significantly reduce risk. Family members may benefit from genetic counseling and laboratory testing.

The acquired form can sometimes be avoided by addressing underlying triggers and minimizing external risks, such as:

Estrogen-containing medications, including birth control and hormone therapy.
Smoking, which damages vascular endothelium.
Obesity and inactivity, which impair circulation.
Pregnancy or postpartum recovery, when clotting risk naturally increases.

In some cases, clinicians may prescribe preventive low-dose anticoagulation during high-risk periods.

Additional Common Questions

Do Blood Clots Develop in the Arteries in People with Protein C Deficiency?

While Protein C deficiency primarily affects the venous system, rare reports suggest an association with arterial clots and ischemic stroke. The data are limited, and the connection remains under investigation.

What Can Trigger Clots in Protein C Deficiency?

Common triggers include:

Prolonged inactivity (bed rest, long travel)
Pregnancy or postpartum recovery
Major surgery or trauma
Serious illness or infection

For those with Protein C deficiency, these situations should always be managed with heightened vigilance and, when appropriate, preventive anticoagulation.