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Protein C Deficiency Clinical Presentation

  • Author: Adam Cuker, MD, MS; Chief Editor: Perumal Thiagarajan, MD  more...
 
Updated: Jan 21, 2016
 

History

Patients with previously diagnosed or suspected protein C deficiency should be queried about their personal history, family history, and laboratory testing.

Personal history

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?

Family history

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)?

Laboratory testing

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)?
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Physical

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.

Venous thromboembolism

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.

A patient with warfarin-induced skin necrosis. A patient with warfarin-induced skin necrosis.

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.

A patient with neonatal purpura fulminans. A patient with neonatal purpura fulminans.
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Causes

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:

Cases of acquired protein C deficiency in association with the development of a protein C auto-antibody[52] and hematopoietic stem cell transplantation[53] 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.[54]

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Contributor Information and Disclosures
Author

Adam Cuker, MD, MS Assistant Professor of Medicine, Assistant Professor of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine

Adam Cuker, MD, MS is a member of the following medical societies: American College of Physicians, American Society of Hematology, Anticoagulation Forum, Hemostasis and Thrombosis Research Society, International Society on Thrombosis and Haemostasis

Disclosure: Received consulting fee from Genzyme for consulting; Received consulting fee from Amgen for consulting; Received grant/research funds from T2 Biosystems for other; Received grant/research funds from Spark Therapeutics for other. .

Coauthor(s)

Eleanor S Pollak, MD Associate Director of Special Coagulation, Associate Professor, Department of Pathology and Laboratory Medicine, Section of Hematology and Coagulation, University of Pennsylvania

Eleanor S Pollak, MD is a member of the following medical societies: American Society of Hematology, College of American Pathologists, National Multiple Sclerosis Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Society for Clinical Investigation, Association of American Physicians, American Society for Biochemistry and Molecular Biology, American Heart Association, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

David Aboulafia, MD Medical Director, Bailey-Boushay House, Clinical Professor, Department of Medicine, Division of Hematology, Attending Physician, Section of Hematology/Oncology, Virginia Mason Clinic; Investigator, Virginia Mason Community Clinic Oncology Program/SWOG

David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, AMDA - The Society for Post-Acute and Long-Term Care Medicine, American Society of Hematology, Infectious Diseases Society of America, Phi Beta Kappa

Disclosure: Nothing to disclose.

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The protein C pathway. APC = activated protein C; PC = protein C; S= protein S; T = thrombin; TM = thrombomodulin; Va = factor Va; VIII = factor VIIIa.
A patient with warfarin-induced skin necrosis.
A patient with neonatal purpura fulminans.
 
 
 
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