Protein C Deficiency Clinical Presentation
- Author: Adam Cuker, MD, MS; Chief Editor: Perumal Thiagarajan, MD more...
Patients with previously diagnosed or suspected protein C deficiency should be queried about their personal history, family history, and laboratory testing.
The following questions should be asked:
- Does the patient have a previous history of venous thromboembolism (VTE)? If so, at what anatomic site(s)? At what age(s) did VTE occur? Were there any antecedent provoking factors (eg, postoperative state, pregnancy, postpartum state, trauma, estrogen therapy, immobilization), or did VTE occur spontaneously?
- Has the patient experienced previous thrombotic challenges (eg, surgeries, pregnancies, traumas, use of estrogen therapy, immobilization) without developing VTE? If so, at what age(s) did these occur? Was thromboprophylaxis used?
- Has the patient been treated with anticoagulation in the past? Is there a history of warfarin-induced skin necrosis (WISN)? Was there bleeding or other complications of anticoagulation therapy?
- Is there a history of pregnancy loss or other obstetric complications (eg, prematurity, preeclampsia, eclampsia)? At what gestational age(s) did pregnancy loss occur? Was a cause of pregnancy loss ever identified?
The following questions should be asked:
- Is there a family history of VTE? In which family member(s)? At what anatomic site(s)? At what age(s)? Were there any antecedent provoking factors, or did VTE occur spontaneously?
- Have family members been treated with anticoagulation? Is there a family history of WISN?
- Is there a family history of pregnancy loss or other obstetric complications (eg, prematurity, preeclampsia, eclampsia)? At what gestational age(s) did pregnancy loss occur? Was a cause of pregnancy loss ever identified?
- Is there a family history of neonatal purpura fulminans (NPF)?
The following questions should be asked:
- In the past, what laboratory tests (ie, functional and/or immunologic protein C assays) (see Workup, Laboratory Studies) were performed and what were the results? Have abnormal tests been repeated? Have family members been tested?
- Was a cause of acquired protein C deficiency (see Acquired Protein C Deficiency in Causes) present during laboratory testing? If so, laboratory testing generally must be repeated in the absence of such causes before a diagnosis of hereditary protein C deficiency can be rendered.
- Was laboratory testing performed to assess for other hypercoagulable states (eg, factor V Leiden, prothrombin gene mutation, protein S deficiency, antithrombin deficiency, antiphospholipid antibody syndrome, dysfibrinogenemia)?
Patients with symptomatic hereditary protein C deficiency may present with VTE or WISN. Homozygotes and compound heterozygotes frequently present with NPF during the first hours of life.
Findings of acute VTE on physical examination are discussed in topics elsewhere (see Further Reading). Deep venous thrombosis of the lower extremity may be complicated by postthrombotic syndrome, a chronic condition associated with swelling, pain, discoloration, and venous insufficiency of the lower extremity.
Warfarin-induced skin necrosis
The skin lesions of WISN occur on the extremities, torso, breasts, and penis. They begin as erythematous macules and, if appropriate therapy is not initiated promptly, evolve to become purpuric and necrotic bullae. See image below.
Neonatal purpura fulminans
Affected neonates present with diffuse ecchymoses which, similar to the lesions of WISN, progress to form necrotic bullae if appropriate therapy is not rapidly instituted. See image below.
Protein C deficiency may be congenital or acquired. The genetic basis of congenital protein C deficiency is reviewed in Pathophysiology, above.
Acquired Protein C Deficiency
Causes of acquired protein C deficiency include:
- Acute thrombosis
- Warfarin therapy
- Liver disease
- Vitamin K deficiency
- Certain chemotherapeutic agents (eg, L-asparaginase)
Cases of acquired protein C deficiency in association with the development of a protein C auto-antibody and hematopoietic stem cell transplantation have also been reported. A severe form of acquired protein C deficiency associated with purpura fulminans may be observed in patients with meningococcemia and other causes of severe sepsis.
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