Protein C and Protein S are natural anticoagulants made by your liver. They work together as a team to prevent your blood from clotting too much. Think of them as the "brakes" on your clotting system.

Protein S acts as a cofactor (helper) for activated protein C, enhancing its ability to break down activated clotting factors. When you have a deficiency in either protein, your blood has a tendency to clot more easily than it should. This is called thrombophilia - a condition where you're at higher risk for developing blood clots in your veins.

These deficiencies are relatively rare:

Together, hereditary protein C and protein S deficiencies account for about 5-10% of people with thrombophilia.

Protein C Deficiency: The PROC gene on chromosome 2q14.3 provides instructions for making protein C. About 160 different mutations in this gene have been identified. There are two types:

Protein S Deficiency: The PROS1 gene on chromosome 3q11.1 controls protein S production. This is more complex because there's also a PROS2 pseudogene (an inactive copy). Approximately 200 known mutations have been identified in the PROS1 gene. There are three types:

Both conditions are typically inherited in an autosomal dominant pattern - you only need one abnormal gene from one parent to have the condition. About 50% of people with hereditary protein S deficiency will experience a blood clot by age 45 without preventive measures.

Protein S circulates in two forms in your blood:

Only the free form is functional, which is why measuring free protein S is important for diagnosis.

You can also develop these deficiencies later in life (acquired) due to:

Important note: Newborns naturally have lower levels of these proteins at birth - protein C can be as low as 35% in healthy full-term babies and gradually increases over the first 6 months of life.

The clinical presentation can vary widely - from no symptoms at all to life-threatening complications.

Common presentations:

Severe protein C deficiency - Neonatal Purpura Fulminans: This is a rare but life-threatening condition that occurs in newborns with extremely low or absent protein C (homozygous deficiency). It presents within hours to days after birth with:

Special complication - Warfarin-Induced Skin Necrosis: When starting warfarin in someone with severe protein C deficiency, the drug initially drops protein C levels even faster than the clotting factors, creating a temporary hypercoagulable state. This can cause painful skin necrosis, typically within 3-5 days of starting warfarin. This is why heparin must be given first when starting warfarin in these patients.

When to test: Testing should be considered if you have:

The tests:

Critical timing issues: These tests should NOT be done:

Wait at least 2-4 weeks after stopping anticoagulation and after acute illness has resolved. If you test positive, repeat testing is recommended to confirm the diagnosis.

Special considerations for protein S testing: Because protein S levels are affected by age, sex, and hormonal status, interpreting results requires considering these factors. Women naturally have lower protein S levels than men, and levels vary with the menstrual cycle.

If you've never had a clot: Usually, no medication is needed. Focus on avoiding risk factors:

If you've had a clot:

Special situations:

The prognosis is generally good with proper management. Here's what to know:

The molecular basis for protein S deficiency is highly diverse - there are many different mutations that can cause it, each potentially affecting protein expression differently.

✓ Protein C and S work together as your body's natural blood thinners
✓ Deficiency can be inherited or acquired
✓ Many people never have symptoms
✓ First clot typically occurs before age 45-50
✓ For protein S deficiency, hormones (pregnancy, birth control) are major risk factors ✓ Avoid high-risk factors like birth control pills (especially for protein S) and smoking
✓ Always use heparin first before warfarin to prevent skin complications
✓ Testing should be done at the right time (not during clots, pregnancy, or on blood thinners)
✓ Free protein S level is the most important measurement for protein S deficiency ✓ With proper management, most people live normal, healthy lives

References:

I hope you found this helpful! Click the subscribe button below to receive more content straight to your inbox!