Purpura fulminans is a life-threatening, massive infarction of the skin, which occurs due to severe impairment of the coagulation system, and manifests as extensive purpuric skin lesions. This disorder is most commonly seen in patients who develop disseminated intravascular coagulation due to various causes.
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.
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].
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:
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:
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.