Diseases » Goodpasture syndrome

Purpura Fulminans

Purpura Fulminans: Excerpt from The 5-Minute Pediatric Consult

David F. Friedman, MD

Purpura Fulminans - BASICS

Purpura Fulminans - description

• Congenital, acquired, or idiopathic condition of rapidly progressive microvascular hemorrhage into the skin
• Associated with an underlying acquired or congenital disorder of coagulation
• May lead to skin necrosis as well as acral amputations

Purpura Fulminans - epidemiology

Depends on underlying cause

Purpura Fulminans - incidence

• Neonatal purpura fulminans related to homozygous protein C deficiency: 1 in 250,000–500,000 births
• Homozygous protein S deficiency is more rare.

Purpura Fulminans - prevalence

Purpura frequently seen in bacterial sepsis with meningococcus and other pathogens

Purpura Fulminans - risk factors

Purpura Fulminans - genetics

• Deficiencies of protein C and protein S are autosomally inherited with variable penetrance.
• Many different genetic mutations, leading to both qualitative and quantitative defects of the proteins
• Heterozygous protein C and S deficiency states usually cause a hypercoagulable condition, with increased risk of venous or arterial thrombosis throughout life.
• Homozygous protein C or S deficiency states lead to severe deficiency (<5% of normal factor activity) and neonatal purpura fulminans and are usually fatal.
• Factor V Leiden:
  • Known risk factor for thrombosis
  • May predispose to infection-associated purpura fulminans
  • May also predispose to purpura fulminans in patients who are heterozygotes for protein C or S deficiency
• Other genetic predispositions to thrombosis, such as prothrombin mutations, may also contribute to risk for purpura fulminans.

Purpura Fulminans - pathophysiology

Common features of purpura fulminans:

• Inflammation: Endothelial injury from bacterial endotoxin or other trigger may initiate secretion of inflammatory cytokines or activation of coagulation and complement proteins.
• Purpura: Extravasation of formed elements of the blood from injured capillaries into the skin
• Dermal vascular thrombosis: Formation of microthromboses in blood vessels of the skin, leading to hemorrhage in the skin (purpura), necrosis of skin, and gangrene

Purpura Fulminans - etiology

• Infection-associated purpura fulminans:
  • Overwhelming sepsis, usually bacterial; Neisseria meningitidis most common
  • May be a complication of varicella infection
  • Disseminated intravascular coagulation: State of sustained activation of coagulation cascade and fibrinolytic mechanisms, leading to consumption of platelets, fibrinogen, and often formation of microthromboses
• Inherited defect of coagulation presenting as neonatal purpura fulminans:
  • Deficiency of protein C: Leads to a loss of important inhibitory regulation of coagulation and uncontrolled clotting
  • Protein C slows (“brakes”) the coagulation cascade at two steps: By degrading activated coagulation factor Va in the common part of the coagulation pathway and by degrading factor VIIIa in the intrinsic pathway
  • Protein S is a cofactor for protein C.
• Idiopathic:
  • Postinfectious complication—formation of antibodies to protein S causing protein S deficiency has been described as a postinfectious autoimmune phenomenon.
  • Complication of warfarin (Coumadin) therapy
  • Other unknown mechanisms

Purpura Fulminans - DIAGNOSIS

Purpura Fulminans - signs & symptoms

Purpura Fulminans - history

• Current bacterial sepsis: Fever, weakness, dizziness, nausea, vomiting, onset of petechial rash:
  • Family history suggestive of hypercoagulable state
  • Blood clots or thromboses at an early age, such as stroke, deep vein thrombosis, pulmonary embolism
  • Family members taking warfarin (Coumadin) or heparin
• Previous affected child with purpura fulminans or hypercoagulable state
• Prior exposure to heparin, therapeutically or via IV Hep-Lock
• Medications, including anticoagulation

Purpura Fulminans - physical exam

• Signs of sepsis:
  • Fever
  • Hypotension
  • Tachycardia
  • Poor perfusion
  • Cool extremities
  • Decreased pulses
  • Shock
• Nonblanching purpura
• Acral purpura and necrosis: Check fingers, nose, toes, and penis for black areas.
• An erythematous border may surround purpuric areas.
• Bullae may form over purpuric skin.
• Oozing at sites of venipuncture
• Pain, ischemia, and edema of extremities or internal organ dysfunction may result from deep vein thrombosis or arterial thrombosis, depending on location and severity.

Physical examination trick:

• Depress the purpuric area with a glass slide to determine whether it blanches.

Purpura Fulminans - tests

Purpura Fulminans - lab

Screening:

• CBC:
  • Platelet count may be low.
  • Hemoglobin may be low.
• Prothrombin time: Prolonged as in disseminated intravascular coagulation
• Partial thromboplastin time: Prolonged as in disseminated intravascular coagulation
• Fibrinogen: Decreased with consumption and fibrinolysis
• Fibrin split products: Increased fibrinolysis as in disseminated intravascular coagulation

Etiologic:

• Protein C activity in patient and parents
• Protein S antigen (total and free) in patient and parents
• Test for antiphospholipid antibodies: Usually lupus anticoagulant or anticardiolipin antibody
• Factor V Leiden mutation assay

False positives: Protein C and S levels may decrease because of consumption during a thrombotic episode that is not related to an underlying deficiency. Low measurements often need to be repeated at baseline after recovery. Protein C and S levels may be below adult normal ranges for the first 3–6 months of life in healthy infants.

Purpura Fulminans - imaging

To document presence and extent of suspected large vessel thrombosis:

• Ultrasound with Doppler flow study
• CT
• MRI: Better for visualization of vessels
• Angiography: Most invasive, requires vascular injury for access

Imaging is potentially useful to:

• Distinguish thrombosis from other pathology
• Judge age of thrombus (based on collateralization)
• Assess clot size prior to anticoagulant or thrombolytic therapy
• Distinguish baseline old clot from new thrombosis

The most useful imaging strategy depends on location and clinical situation.

Purpura Fulminans - differencial diagnosis

• Infection:
  • Neisseria meningitidis, most common infectious cause of purpura fulminans
  • Streptococci
  • Haemophilus species
  • Staphylococci
  • Gram-negative bacteremia: Escherichia coli, Klebsiella, Proteus, Enterobacter
  • Rickettsia: Rocky Mountain spotted fever
  • Varicella
• Environmental:
  • Warfarin (Coumadin)-induced skin necrosis: 1 in 500–1,000 individuals starting warfarin therapy develop necrosis in subcutaneous fat.
  • Thought to be caused by relative depletion of anticoagulant protein C (a vitamin K–dependent factor) during the initial phase of warfarin effect
• Tumor: Myeloid leukemia
• Congenital: Inherited deficiencies of protein C and protein S:
  • Only severe, homozygous (<5% activity) deficiencies of proteins C and S are associated with purpura fulminans.
  • Milder, heterozygous deficiencies of protein C and protein S, as well as deficiency of antithrombin III, dysfibrinogenemias, the carrier state for factor V Leiden, and other prothrombotic defects all give rise to hypercoagulable states, but not neonatal purpura fulminans.
  • Patients with one or more risk factors for thrombosis may be more likely to develop purpura fulminans with an environmental stimulus.
• Immune
• Heparin-induced thrombocytopenia: Antibody to heparin-platelet complex causes platelet activation, thrombocytopenia, and microthrombosis, including dermal vessels.
• Antiphospholipid antibody syndrome: Predisposition to thrombosis can include skin necrosis.
• Miscellaneous:
  • Thrombotic thrombocytopenic purpura
  • Paroxysmal nocturnal hemoglobinuria
  • Henoch–Schönlein purpura

Purpura Fulminans - TREATMENT

Purpura Fulminans - general measures

Purpura Fulminans - diet

Patients on warfarin (Coumadin) therapy may need to avoid foods with high vitamin K content, especially if there is variation in the dose of warfarin required to maintain adequate anticoagulation.

Purpura Fulminans - medication

Contraindications, precautions, and significant possible interactions:

• Many drugs can affect warfarin (Coumadin) metabolism.
• Chronic infusion therapy for neonates may run into access problems.

Purpura Fulminans - first line

• Anti-infective agents depending on underlying cause
• Fresh frozen plasma q12h to replace proteins C and S in acute disseminated intravascular coagulation of purpura fulminans
• Periodic fresh frozen plasma infusions for chronic replacement
• Prothrombin complex concentrates also have thrombogenic potential.
• Protein C concentrate is shown to be of benefit in meningococcemia and severe sepsis in adults but not yet approved for this use in pediatric patients.
• Protein C has half-life of 10 hours in circulation.
• Protein C replacement by periodic infusion of protein C concentrate
• Oral warfarin (Coumadin) therapy indefinitely usually recommended for documented protein C or S deficiency
• Low-molecular-weight heparin is also a commonly used option for long-term anticoagulation therapy.

Purpura Fulminans - FOLLOW UP

Purpura Fulminans - prognosis

• Related to underlying cause of purpura fulminans
• Overall, poor for homozygous deficiencies of proteins C and S

Purpura Fulminans - complications

• Skin necrosis and gangrene
• Scarring
• Acral amputations, from tips of digits to whole limbs
• Thrombosis in internal organs
• Death

Purpura Fulminans - patient monitoring

• When to expect improvement: Related to underlying cause of purpura fulminans
• Signs to watch for:
  • Spread of purpura
  • Hypotension
  • Gangrene
• Pitfalls:
  • Individuals with protein C and protein S deficiency may have increased risk of warfarin (Coumadin)-induced skin necrosis when starting warfarin. Patients should be heparinized for several days prior to the start of oral anticoagulation.
  • Management of an infant on oral anticoagulation is difficult because of the practical problem of obtaining reliable measurements of PT, the increased risk associated with deep venipunctures for blood samples, and difficulty in establishing a stable warfarin (Coumadin) dose. Low-molecular-weight heparin by injection is usually the preferred anticoagulant therapy in infants.

Purpura Fulminans - bibliography

1. Adcock DM, Brozna J, Marlar RA. Proposed classification and pathologic mechanisms of purpura fulminans and skin necrosis. Semin Thromb Hemost. 1990;16:333.
2. Francis RB. Acquired purpura fulminans. Semin Thromb Hemost. 1990;16:310.
3. Gerson WT, Dickerman JD, Boville G, et al. Severe acquired protein C deficiency in purpura fulminans associated with disseminated intravascular coagulation: Treatment with protein C concentrate. Pediatrics. 1993;91:418.
4. de Kleijn ED, de Groot R, Hack CE, et al. Activation of protein C following infusion of protein C concentrates in children with severe meningococcal sepsis and purpura fulminans: A randomized, double-blinded, placebo-controlled dose-finding study. Crit Care Med. 2003;31:1839–1847.
5. Leclerc F, Leteurtre S, Cremer R, et al. Do new strategies in meningococcemia produce better outcomes? Crit Care Med. 2000;28:S60.
6. Marlar RA, Neumann A. Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies. Semin Thromb Hemost. 1990;16:299.
7. Patha N, Faust SN, Levin M. Pathophysiology of meningococcal meningitis and septicaemia. Arch Dis Child. 2003;88:601–607.
8. Rivard GE, David M, Farrell C, et al. Treatment of purpura fulminans in meningococcemia with protein C concentrate. J Pediatr. 1995;126:646.
9. Smith OP, White B. Infectious purpura fulminans: Diagnosis and treatment. Br J Haematol. 1999;104:202.
10. Vincent JL, Nade S, Kutsogiannis DJ, et al. Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: A retrospective analysis of patients enrolled in recent clinical trials. Crit Care. 2005;9:R331–R343.

Purpura Fulminans - CODES

Purpura Fulminans - icd9

286.6 Defibrination syndrome, purpura fulminans

Purpura Fulminans - FAQ

• Q: What is the risk of a second affected child with protein C or S deficiency?
• A: If the diagnosis is confirmed by family studies that show both parents to be carriers of the deficiency and the affected child to be homozygous, there is a 25% chance that each subsequent infant would have purpura fulminans and a 50% chance that each child would be a carrier. However, other hypercoagulable states have been described that may be risk factors for purpura fulminans.
• Q: Should a child with purpura fulminans be followed by a specialist?
• A: Generally yes, with a pediatric hematologist, to assist in acute management of purpura, establishment of diagnosis, and management of long-term anticoagulation.

>>

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About Goodpasture syndrome

• Back to disease: Goodpasture syndrome: Introduction
• Next Book Extract About Goodpasture syndrome: Surveys relating to Goodpasture syndrome
• More Book Extracts: All Online Books for Goodpasture syndrome

More Medical Textbooks Online about Goodpasture syndrome

Review other book chapters online related to Goodpasture syndrome:

Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

---

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

 » Next page: Surveys relating to Goodpasture syndrome

Rate This Website

What do you think about the features of this website? Take our user survey and have your say:

Website User Survey

Medical Tools & Articles:

Next articles:

• Surveys relating to Goodpasture syndrome
• Ask Question about Goodpasture syndrome

Tools & Services:

• Bookmark this page
• Symptom Search
• Symptom Checker
• Medical Dictionary
• Give your feedback

Medical Articles:

• Disease & Treatments Search
• Misdiagnosis Center
• Full list of interesting articles

Forums & Message Boards

• Ask or answer a question at the Boards:
• I cannot get a diagnosis. Please help.
• Tell us your medical story.
• Share your misdiagnosis story.
• What is the best treatment for my condition?
• See all the Boards.

Enter your search terms Submit search form
Search The Web Search wrongdiagnosis.com

homepage | back to top

Common Health Mistakes

Choose ... Alzheimers & Dementia Asthma Child ADHD ADHD in Adults Allergy Hypertension Bipolar Breast Cancer Celiac Disease Crohns Disease Colon Cancer Contraception Diabetes Cancer Depression Erectile Disorder Cholesterol COPD GERD Heartburn/Reflux Metabolic Syndrome Migraine/Headache Multiple Sclerosis Obesity Osteoporosis Overactive Bladder Psoriasis Sexual Disorder Sleep Disorders Smoking The Pill Ulcerative Colitis All Common Mistakes

Symptom
Checker

Choose... Fever Rash Pain Headache Fatigue Cough Other symptoms

Search Specialists by State and City

Choose... GENERAL PRACTICE CARDIAC HEALTH WOMEN'S HEALTH CANCER CARE RADIOLOGY MENTAL HEALTH PATHOLOGY EAR, NOSE, THROAT MEDICINE GENETICS NEUROLOGY DIALYSIS CARE SURGERY ORTHOPEDICS/SPORTS MEDICINE CHILDREN'S HEALTH OTHER SPECIALTIES