How does C (complement) and S (properdin) protein deficiency manifest?

Clinical Manifestations of Protein C and Protein S Deficiency

Protein C and S deficiencies primarily manifest as venous thromboembolism, with the most serious presentations being deep vein thrombosis, pulmonary embolism, and in severe cases, graft thrombosis in transplant recipients. 1

Thrombotic Manifestations

Venous Thrombosis

• Deep vein thrombosis and pulmonary embolism are the hallmark presentations of protein C and S deficiency 1
• Cerebral venous thrombosis can occur, particularly in patients with inherited protein C or S deficiency 1
• Portal vein thrombosis (PVT) and Budd-Chiari syndrome (BCS) are recognized complications, especially when combined with other precipitating factors 1

High-Risk Clinical Scenarios

• Renal transplant recipients with protein C or S deficiency face significantly increased risk of allograft thrombosis 1
• In one transplant study, protein S deficiency was found in 1.5% of recipients and was associated with early graft failure and graft thrombosis 1
• Pregnancy and postpartum period represent particularly high-risk windows, with postpartum thrombotic risk of 1.76% in women with protein S deficiency and positive family history 2, 3

Age and Presentation Patterns

• First thrombotic events typically occur in young adults, though presentation can range from neonatal period to adulthood 1
• Neonatal presentations of homozygous protein deficiency manifest as severe thrombotic complications requiring immediate intervention with fresh frozen plasma (10-20 mL/kg every 12 hours) or protein concentrate 2

Diagnostic Considerations

Testing Limitations

• Diagnosis can be challenging because decreased protein C and S levels may reflect underlying liver disease or acute thrombosis rather than true inherited deficiency 1
• Normal prothrombin levels or positive family history are required to establish inherited deficiency, as many patients cannot receive definitive diagnosis without these criteria 1
• Pregnancy significantly lowers protein S levels, so testing should be deferred until at least 6 weeks postpartum 3

Associated Conditions

• Protein C and S deficiencies are classified among the inherited thrombophilias alongside Factor V Leiden, prothrombin gene mutation, and antithrombin deficiency 1
• These deficiencies show autosomal-dominant inheritance patterns in most cases 1

Critical Pitfalls to Avoid

• Do not confuse with complement deficiencies: The question may refer to complement proteins, which present entirely differently with recurrent neisserial infections rather than thrombosis 1, 4
• Avoid testing during acute thrombosis or pregnancy, as levels will be artificially low and non-diagnostic 1, 3
• Recognize that asymptomatic carriers exist: Not all individuals with protein C or S deficiency will experience thrombosis, particularly without additional risk factors 2, 3

---

Note on Complement vs. Coagulation Proteins: If the question refers to complement protein deficiencies (terminal complement components C5-C9, or properdin), the manifestations are completely different: recurrent Neisseria meningitidis infections (often with rare serogroups), with onset before 6 months or after 5 years of age, and potential for fulminant septic shock 1, 4, 5, 6, 7. Properdin deficiency specifically carries high risk of fulminant meningococcal disease 5, 7.