Clinical presentation of purpura fulminans is characterized by a sudden onset of initially erythematous macules and petechiae which progress within hours into massive ecchymoses with irregular and sharp borders, distributed on various parts of the body. In addition to skin lesions, symptoms that may appear include fever, hypotension, and often shock, if purpura fulminans is a complication of an acute infection. Neonatal purpura fulminans develops within the first 72 hours after birth, with a similar clinical presentation, and in all patients, because of massive infarction of the skin and organs, major organ dysfunction may occur, presenting with symptoms related to the target organ. In severe cases that accompany DIC, vascular thrombosis and pulmonary embolism may occur, and persistent bleeding from wounds and puncture sites is also observed. In severe cases, gangrene and necrosis of extremities may be observed, requiring amputation of fingers and even limbs.

• Sepsis

  […] a sepsis-mortality protective agent. [clinicaladvisor.com]

  Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock. Intensive Care Med. 2001; 27: 1853-1859 Hack C.E. [amjmedsci.com]

  Purpura fulminans secondary to pneumococcal sepsis in a healthy infant is described. [ncbi.nlm.nih.gov]

• Fever

  PF though common with rocky mountain spotted fever (RMSF) is rarely seen in association with Indian tick typhus, the usual cause of spotted fever in India. [jpgmonline.com]

  […] in North America, and various hemorrhagic fevers in other parts of the world and in travelers. [clinicaladvisor.com]

  (se Scarlet Fever, [[Scarlet Fever]]) Streptococcal Pharyngitis (see Streptococcus, [[Streptococcus]]): Streptococcus species are the most common etiology in adults Upper Respiratory Infection Varicella (see Varicella-Zoster Virus, [[Varicella-Zoster [mdnxs.com]

• Acutely Ill Patient

  The acutely ill patient with fever and rash. [amjmed.com]

  In addition, it describes the manifestations in acutely ill patients in the ICU, as well as severe cutaneous manifestations occurring during pregnancy, after sun exposure, in cold weather, as a result of extreme poverty, and in other situations. [books.google.it]

• Pallor

  He was noted to have pallor and icterus. An extensive purpuric rash with areas of hemorrhage was seen over both the legs, hands, and the trunk [Figure 1]. Rest of the systemic examination was normal. [jpgmonline.com]

  Physical examination revealed pallor, pedal edema, palpable purpuric spots on both the lower limbs. Her blood pressure was low (80/50 mm of Hg), progesterone receptor - 118/min, and risk ratio - 20/min. [ijccm.org]

• Low Fever

  They were accompanied by the onset of a low-grade intermittent fever and night sweats. One month after his initial presentation, the lesions had spread to involve the distal, dorsal surface of his feet and toes. [jmedicalcasereports.biomedcentral.com]

• Easy Bruising

  There is evidence of bleeding under the skin, with easy bruising and the development of petechiae. In the acute form there may be bleeding from any of the body orifices, such as hematuria, nosebleed, vaginal bleeding, and bleeding gums. [medical-dictionary.thefreedictionary.com]

• Pneumonia

  (see Klebsiella Pneumoniae, [[Klebsiella Pneumoniae]]) Neisseria Meningitidis (see Neisseria Meningitidis, [[Neisseria Meningitidis]]): common etiology Moraxella Catarrhalis (see Moraxella Catarrhalis, [[Moraxella Catarrhalis]]) Proteus Mirabilis (see [mdnxs.com]

  We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans. [ncbi.nlm.nih.gov]

  Streptococcus pneumoniae mostly presents with community-acquired pneumonia. We present a case of PF secondary to DIC related to Pneumococcal sepsis in an otherwise healthy and immunocompetent patient. [eprints.bice.rm.cnr.it]

  (Korean J Med 70:725-728, 2006) Key Words : Purpura fulminans, Streptococcus pneumoniae, Sepsis, Splenectomy, Disseminated intravascular coagulation [ekjm.org]

  Blood cultures came back as predominantly gram positive cocci in chains consistent with Streptococcus pneumoniae. [actasdermo.org]

• Hypotension

  Patients present with high-grade fever, petechial or purpuric rash and rapid progression to purpura fulminans and hypotension [1]. [clinmedjournals.org]

  FOLLOW-UP RECOMMENDATIONS When to expect improvement: related to underlying cause of purpura fulminans Signs to watch for: Spread of purpura Hypotension Gangrene Treatment dur... Goldenberg NA, Manco-Johnson MJ. Protein C deficiency. [5minuteconsult.com]

  He progressed into hypotension, disseminated intravascular coagulation and refractory shock despite resuscitation and early antibiotic commencement. [ncbi.nlm.nih.gov]

  fever, and disseminated intravascular coagulation, usually following an infectious illness. purpura fulminans A life-threatening condition of acute onset occurring in infants, which is characterised by cutaneous haemorrhage and necrosis, hypotension [medical-dictionary.thefreedictionary.com]

• Vascular Disease

  disease.2 Purpura fulminans (PF) is a life-threatening disorder characterised by rapidly progressive cutaneous haemorrhage and necrosis caused by vascular thrombosis and disseminated intravascular coagulation. [pmj.bmj.com]

  Cutaneous vascular diseases. In: James WD, Berger TG, Elston DM, editors. Andrew’s diseases of the skin: clinical dermatology. 10th ed. Philadelphia, Pa: Saunders; 2006. 2. Rintala E, Kauppila M. [westjem.com]

  diseases (Kawasaki disease, other vasculitis) diseases, and adverse drug reactions are often kept in mind, and the index of suspicion for rickettsial illness is quite low. [scienceopen.com]

  CAPILLARITIS OF UNKNOWN CAUSE These are vascular diseases of undetermined cause with different manifestations and share the same histopathological features. [drmhijazy.com]

• Purpura

  Retiform purpura in patient with sepsis, DIC, and acquired protein C deficiency. Figure 2. More retiform purpura in same patient. [clinicaladvisor.com]

  In adults, purpura fulminans is most commonly caused by severe infection. However, the primary risk to life and limb is often the purpura fulminans (rather than the underlying infection). [emcrit.org]

  Related Images Left Arrow Button Right Arrow Button Figure 67-9 Purpura fulminans in a patient with meningococcemia. Figure 67-9 Purpura fulminans in a patient with meningococcemia. [5minuteconsult.com]

  A unique subset of inherited coagulation defects leading to fulminant purpura in neonates has also been well documented. [journals.lww.com]

• Cutaneous Manifestation

  September 1988 Purpura Fulminans: A Cutaneous Manifestation of Severe Protein C Deficiency Arch Dermatol. 1988;124(9):1387-1391. doi:10.1001/archderm.1988.01670090043009 Full Text • Protein C, when activated, is a vitamin K-dependent serine protease that [jamanetwork.com]

  MD, FACP doi: 10.1097/IPC.0000000000000485 Case Reports Abstract In Brief Author Information Authors Article Metrics Metrics Purpura fulminans is a rapidly progressing clinical syndrome of hematologic and cutaneous manifestations accompanied by an underlying [journals.lww.com]

  Purpura fulminans is a cutaneous manifestation of disseminated intravascular coagulation.1 It most commonly is a result of sepsis related to meningococcal, streptococcal or other bacterial infection. [scielo.br]

  Purpura fulminans is a cutaneous manifestation of disseminated intravascular coagulation. 1 It most commonly is a result of sepsis related to meningococcal, streptococcal or other bacterial infection. [bjid.org.br]

  We report the case of a 25-year-old female patient who presented with purpura fulminans as a manifestation of primary antiphospholipid syndrome. Purpura fulminans is considered a rare cutaneous manifestation of antiphospholipid syndrome. [ncbi.nlm.nih.gov]

• Petechiae

  The patient's condition aggravated, with need for invasive mechanical ventilation and intermittent haemodialysis, and evolution from a petechiae-like rash to purpura and gangrene, culminating in bilateral lower limb amputation. [ncbi.nlm.nih.gov]

  […] purpura [ per´pu-rah ] a hemorrhagic disease characterized by extravasation of blood into the tissues, under the skin, and through the mucous membranes, and producing spontaneous bruises, ecchymoses, and petechiae (small hemorrhagic spots) on the skin [medical-dictionary.thefreedictionary.com]

  Cutaneous examination revealed multiple erythematous, petechiae and ecchymotic patches over upper and lower extremities [Figure 1] and trunk. [ijpd.in]

  Often there is pain followed by petechiae. Ecchymoses develop and evolve into painful indurated, well-demarcated purple papules with erythematous borders (as you can see in the image this lesions are coalescent). [unboundedmedicine.com]

  BMJ 316:276–9 [CrossRef] [PubMed] [Google Scholar] Mandl KD, Stack AM, Fleischer GR (1997) Incidence of bacteremia in infants and children with fever and petechiae. [afmu.revuesonline.com]

• Hemorrhagic Bullae

  A and B, Initial presentation of localized erythema on the left leg and nonblanching retiform purpura, edema, and hemorrhagic bullae on both legs. [mdedge.com]

  Skin lesions enlarge rapidly and may evolve into hemorrhagic bullae with subsequent necrosis and black eschar formation. [jpgmonline.com]

  Later in the course, hemorrhagic bullae may form, which contribute to the classic hard eschars characteristic of NPF. Differential diagnosis with necrotizing fasciitis should be performed. Treatment of NPF should be multidisciplinary. [jpnim.com]

• Skin Rash

  rash for two days. [scielo.br]

  Full Text A 45-year-old male presented with history of fever for four days and a skin rash for two days. The rash was present primarily at the extremities and had progressed to acquire a blackish hue at the time of presentation ( Figs. 1 and 2 ). [bjid.org.br]

  English Dictionary – Complete and Unabridged, 12th Edition 2014 © HarperCollins Publishers 1991, 1994, 1998, 2000, 2003, 2006, 2007, 2009, 2011, 2014 pur•pu•ra (ˈpɜr pyʊər ə) n. a skin rash of purple or brownish red spots resulting from the bleeding [thefreedictionary.com]

• Stroke

  (see “APC in severe sepsis” and “APC in ischemic stroke”). [doi.org]

  Acute tissue injuries such as certain snakebites, necrotising enterocolitis, freshwater drowning, heat stroke, brain and crush injury, massive tissue destruction, and renal homograft rejection. [dermnetnz.org]

• Burning Sensation

  The lesions were painful with a burning sensation but were not pruritic. The patient also reported intermittent fevers, chills, myalgia, nausea, and shortness of breath. Enlarged lymph nodes were present in the right cervical chain. [mdedge.com]

  Burning sensation and pain may be mild or sometimes severe depending on the site and extent of the lesions. Arthralgia and swollen joints. Kidney involvement : leads to manifestations of glomerulonephritis. [drmhijazy.com]

• Anuria

  She received bilateral lower extremities escharotomy but developed acute renal failure with anuria 24 h later. [hindawi.com]

  The patient completed the antibiotic regimen and afterwards, she was maintained only in supportive treatment, performing daily hemodialysis due to anuria and frequent need for transfusion of red blood cells due to anemia. [scielo.br]

  The patient rapidly developed hypotension, anuria, and worsening metabolic acidosis, despite receipt of aggressive fluid resuscitation and levarterenol. His skin became mottled, and purpura developed over his lips and knees. [academic.oup.com]

After suspicion towards purpura fulminans arises, workup should involve a complete blood count (CBC), particularly focusing on the evaluation of platelet count. In addition to blood count, a coagulation panel including prothrombin time (PT) and activated partial thromboplastin time (aPTT) should be obtained, alongside values of fibrinogen and D-dimers. This is required in order to gain a full view of the coagulation cascade, and try to determine the cause [14]. 

Vital information can be obtained from patient history, which may reveal that the patient suffers from enzyme deficiencies, or had signs of infection prior to the development of purpura fulminans, which may indicate meningococcal infection. Physical examination should be performed, and together with laboratory findings, the cause of this condition will be identified. Idiopathic cases have been observed and are considered to have been caused by a latent viral or bacterial infection [15].

• Neutrophilia

  Initial laboratory investigation confirmed anemia (hemoglobin - 9.3 g/dl), total lung capacity 8.9 × 10 9 /L with neutrophilia, (neutrophil - 83%, lymphocyte - 11%, and eosinophil - 1%), and platelets 139 × 10 9 /L. [ijccm.org]

  The septic screen showed neutrophilia. WFT was positive for Ox-2 and Ox-19 Ag. Other relevant investigations were normal [Table 1]. [idoj.in]

  Neutrophilia or eosinophilia may occur. Hypocomplementaemia is usual. Circulating immune complexes are often demonstrated. [drmhijazy.com]

• Staphylococcus Aureus

  Aureus (see Staphylococcus Aureus, [[Staphylococcus Aureus]]): recently identified etiology [ MEDLINE ] Streptococcus Agalactiae (Group B Strep) (see Streptococcus Agalactiae, [[Streptococcus Agalactiae]]) Streptococcus Pneumoniae (Pneumococcus) (see [mdnxs.com]

  Purpura fulminans in a premature neonate resulting from Staphylococcus aureus septicemia is illustrated. Unfortunately, the baby succumbed to septicemia. © 2012 Wiley Periodicals, Inc. [ncbi.nlm.nih.gov]

  […] caused by Staphylococcus aureus, Arch Intern Med, 1941, vol. 68 (pg. 851 - 75 ) 20 Community-acquired Staphylococcus aureus bacteraemia in patients who do not abuse intravenous drugs, QJM, 1998, vol. 91 (pg. 41 - 7 ) 21 Immunochemical assays for toxic [academic.oup.com]

• Leukocytosis

  The purpuric rash covered approximately 70% TBSA in the next afternoon, and the platelet count was 9 × 109/L, haemoglobin was 31 g/L, and leukocytosis was 27.28 × 109/L. [hindawi.com]

  Laboratory investigations include CBC which showed leukocytosis with neutrophilic predominance, thrombocytopenia and hemoglobinemia. Prothrombin time and Activated partial thromboplastin time revealed no coagulation after 180 seconds of the test. [herdin.ph]

  Laboratory data included leukocytosis, thrombocytopenia, and significant metabolic acidosis with a lactate of 10mmol/L. [journal.chestnet.org]

  On investigation, complete blood count revealed normocytic normochromic anemia with neutrophilic leukocytosis. WFT was positive for Ox-19 antigen. Other relevant investigations were within normal limits [Table 1]. [idoj.in]

  Hemogram showed leukocytosis (13000/cmm) with 35% bands, platelets 76,000/ml and sedimentation rate of 98 mm. The prothrombin time and partial thromboplastin time were prolonged and the fibrin degradation products were grossly elevated. [westjem.com]

Treating purpura fulminans is achieved through elimination of the underlying cause, since purpura itself cannot be treated by any means. 

While the cause is being investigated, replacement therapy must be initiated, including:

• Platelet transfusion, due to a potentially excessive rapid loss of thrombocytes.
• Cryoprecipitate transfusion for replacement of fibrinogen and factor VIII
• Fresh frozen plasma, which increases levels of natural anticoagulants and other clotting factors, including antithrombin, and proteins C and S
• Heparin can be sometimes useful, but under specific indications, because it is not advised to give patient with purpura fulminans that have excessive bleeding. However, for patients with prothrombotic symptoms such as venous thrombosis, may benefit from heparin.

If the cause is suspected to be an infection, broad-spectrum intravenous antibiotic therapy is absolutely necessary, and should primarily target Neisseria meningitidis, for which ceftriaxone is the primary choice, usually as 2gr q12h for at least 7 days. Other cause-related therapies include administration of intravenous immunoglobulins, while amputations may also be necessary in the case of severe gangrene.

Prognosis of purpura fulminans solely depends on the underlying cause, but the conditions accompanied by it are usually extremely severe. Neonatal forms of purpura fulminans are 100% fatal without replacement of deficient clotting factors, while meningococcal sepsis can still be a fatal condition, even despite therapy. Improvements in supportive therapy have been made within the last few decades and have improved patient outcomes, including prevention of secondary infections, and transfusion of necessary blood products.

Disorders of the coagulation system and purpuric lesions may occur due to various causes, but purpura fulminans implies a major coagulation disorder and has been observed in the following conditions:

• Disseminated intravascular coagulation (DIC) - Abnormal and excessive generation of prothrombotic factors in the circulation can occur because of various reasons, including infections, surgical complications, malignant diseases, and enzyme deficiencies. Depending on the rate and severity of DIC, it may either cause venous thrombosis, pulmonary embolism, with low rates of bleeding (slowly evolving), or it may cause thrombocytopenia and depletion of clotting factors (rapidly evolving), leading to bleeding and multiorgan failure. Regardless of the type, purpura fulminans can arise as a manifestation of this disorder. 
• Infection - Meningococcal infection [6] and the development of sepsis caused by Neisseria meningitidis is a life-threatening infection that is most commonly encountered in children [7], and is characterized by very high fever and constitutional symptoms. In 15-25% of the cases, abrupt development of disseminated purpuric lesions is observed. Despite all treatment strategies, this infection can still be fatal, due to its abrupt onset and severe damage to blood vessels and coagulation system [8].
• Neonatal purpura fulminans (congenital deficiency of protein C or S) - Although it is very rare [9], neonates who are born with a deficiency of either protein C or S develop extensive purpuric lesions on their first day of life, and the condition may be life-threatening if not supplemented with appropriate enzymes [10]. 
• Drug-induced  - Purpura fulminans can be caused by medications. Several drugs, including sulfonamides, penicillins, and phenytoin have been mentioned as potential causes of this disorder, through mechanisms still not fully understood [11].
• Thrombocytopenia - Any disease which accelerates platelet consumption, or decreases platelet production can predispose patients to purpura fulminans [12], including idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and malignant diseases which deplete platelets.
• Clotting factor deficiencies - Purpura can often be a manifestation of clotting factor deficiencies, and purpura fulminans can be observed in severer cases. Examples include von Willebrand disease, hemophilia A and B, antithrombin III deficiency, and other clotting factor deficiencies.

Purpura fulminans can be observed among patients of any age and gender, depending on the cause. This disorder is observed in neonates, young children, and adults of any age, because the conditions in which this disorder appears, may occur at any point in life.

Purpuric lesions on the skin occur due to extravasation of blood from blood vessels into the surrounding environment. This "pooling" of blood under the skin can occur either due to uncontrolled activation of the coagulation cascade, and subsequent depletion of platelets leading to massive bleeding, or due to slow and excessive activation of prothrombotic factors, leading to thrombosis and vascular infarctions, which cause blood vessel rupture and release of blood from the vessels.

In the case of clotting factor deficiency, the coagulation pathway cannot perform its regular functions, leading to a decreased capacity of blood for coagulation, resulting in bleeding. In cases of malignancies, such as lymphomas, or after chemotherapy, thrombocytes may be depleted, thus leading to purpura fulminans through a similar mechanism.

Infections, particularly meningococcal sepsis, cause rapid and possibly lethal damage to the vascular system. Proinflammatory cytokines, including tumor necrosis factor alpha (TNF)–α, and interleukin 1 (IL-1), rapidly consume clotting factors, and the effects of bacterial endotoxins lead to the development of microemboli in the circulation and widespread disruption of the endothelial barrier [13]. 

It is important to mention that purpura fulminans can occur only if the coagulation cascade is severely impaired, and should not be confused with the development of purpura and purpuric lesions that are commonly seen in some other disorders, such as Henoch-Schonlein purpura, autoimmune vasculitis, and some other diseases.

In order to prevent the development of purpura fulminans, early signs of this disorder must be identified, so that complications may be prevented. However, it is difficult to establish the diagnosis early because of the sudden onset of the purpuric rash. Nevertheless, in all patients who have predisposing conditions, such as clotting factor deficiencies, or disease-related thrombocytopenias, regular checkups should be performed in order to evaluate the status of the coagulation system. Proper management of existing conditions, such as ITP and TTP, may reduce the risk of this potentially fatal disorder.

Purpura fulminans arises due to severe damage of the coagulation system [1], and is one of the clinical manifestations of disseminated intravascular coagulation (DIC) [2], which develops as a result of various conditions, such as infections, autoimmune diseases and congenital enzyme deficiencies affecting the coagulation cascade. The pathogenesis comprises severe imbalance of coagulation factors and platelets, leading to extravasation of blood from the vessels, and cutaneous hemorrhage. In the case of massive vascular thrombosis, gangrenous tissue necrosis develops [3] and extensive damage to the skin and the surrounding tissues may occur.  Depending on the cause, purpura fulminans may be observed in patients of all ages, including neonates, children, and adults [4]. The clinical presentation is the sudden and abrupt appearance of initially small petechiae, accompanied by cutaneous pain. As the disease progresses, extensive and massive ecchymoses (purpura) with sharp and irregular borders are exhibited, either deep purple or blue in color. Symptoms such as fever and hypotension may be observed, as well as shock and gangrenous necrosis of extremities. Laboratory tests should include a full blood count (with an emphasis on platelet count), biochemical parameters including fibrinogen, D-dimer, as well as PT and PTT, to determine the status of the coagulation system. Patient history, as well as physical examination, may point to the underlying cause, and immediate treatment is absolutely necessary in order to achieve a good prognosis, which depends on the cause. Treatment also includes replacement therapy of necessary blood products, including platelets, coagulation factors and activated protein [5], which may be life-saving. 

Purpura fulminans is a form of skin rash which occurs in diseases which profoundly damage the coagulation system, and if this condition is observed on physical examination, it should be treated as a medical emergency. Purpura fulminans manifests as a deep purple to blue rash that develops on numerous locations on the body within hours and is usually accompanied by pain. This rash occurs because of the imbalance between the factors which are responsible for normal blood coagulation, resulting in leakage of blood from blood vessels. This blood concentrates under the skin, and bleeding into the external environment may occur.

This disorder may be seen in neonates and children who are suffering from deficiencies of some of the factors in the coagulation system, in patients suffering from meningococcal infection, or in those that are suffering from conditions that impair the number of thrombocytes or platelets. Diseases that cause this condition may be fatal, which is why a prompt diagnosis is necessary. Through patient history, physical examination, as well as certain laboratory tests, suspicion towards this disorder arises and immediate treatment must be initiated. Treatment should be directed at the underlying cause, but it also aims at replenishing blood products that are depleted, such as platelets and coagulation factors. Because of the rapid and abrupt course of this disease, prevention is not really possible, but patients with disorders known to cause purpura fulminans should manage their illnesses adequately, in order to prevent potentially life-threatening consequences. 

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