RARE DISEASE
Acquired purpura fulminans
Acquired purpura fulminans
Acquired purpura fulminans
Drug discovery
2
drugs
With orphan designations
Overview
Acquired purpura fulminans (APF) is a life-threatening thrombotic disorder characterized by rapidly progressing skin necrosis, disseminated intravascular coagulation (DIC), and multi-organ failure. It arises from severe infections (e.g., Neisseria meningitidis, Streptococcus pneumoniae) or idiopathic autoimmune mechanisms, often involving acquired deficiencies of protein C/S [6][8][16]. Management requires aggressive anticoagulation, protein replacement therapies, and infection control [1][5][8].
Therapies
Immediate interventions: Fresh frozen plasma (10–20 mL/kg) or protein C concentrate to restore anticoagulant proteins [1][5][8].
Anticoagulation: Heparin or warfarin (after initial plasma replacement) [1][4][8].
Adjunctive care: Surgical debridement for necrosis, antibiotics for sepsis, and critical care support [1][3][8].
Categories: rare hematological diseases
Research Papers
84 drug discovery papers about Acquired purpura fulminans, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
84 drug discovery papers about Acquired purpura fulminans, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
cell therapies
2023-09-21 | Case report: Blotchy skin in a puffy neonate: is there a new association?
Purpura fulminans in the neonatal population is a rare but potentially life-threatening condition complicated by thrombosis, resultant vital organ necrosis, and gangrene of the extremities. Considering the rapid evolution of the pathogenetic mechanism, an index of suspicion, early identification, and prompt intervention are imperative for improved outcomes. The majority of purpura fulminans cases have an infectious etiology, but it is essential to consider other congenital and acquired causes.We present a clinical case of a female neonate to emphasize the correlation between purpura fulminans, congenital chylothorax, involvement of the PAK2 gene, and the occurrence of retinal detachment in both eyes. After draining the congenital chylothorax, the neonate developed purpura fulminans due to a loss of protein C, S, and antithrombin factors, previously not reported in the literature. The purpuric lesions resolved after the administration of fresh frozen plasma. Subsequently, no recurring purpura fulminans lesions were noted following the normalization of the antithrombotic factor levels in the serum. Subsequently, the child also developed retinal detachment in both eyes.
1967-12-04 | Blood and Blood Components in the Prevention and Control of Bleeding
Banked blood contains many of the factors necessary for hemostasis. The most important components which are not present in stored blood are factor VIII (antihemophilic factor) and platelets. Methods are now available whereby significant concentrations of these components can be achieved from fresh donor blood by the hospital blood bank.
small molecules
2025-05-01 | Vascular Compromise in Toxic Shock Syndrome: A Case of Purpura Fulminans
Abstract Introduction: Purpura fulminans (PF) is a rare, potentially fatal manifestation of disseminated intravascular coagulation (DIC) characterized by tissue thrombosis and hemorrhagic skin necrosis. The pathophysiology of PF involves severe acquired protein C deficiency, leading to uncontrolled coagulation and thrombosis. It can be triggered by bacterial infections; less commonly, by viral infections, toxic shock syndrome (TSS), pressors, and genetic abnormalities. In this submission, we describe a case of PF in a patient requiring pressor support for Group A streptococcus (GAS) toxic shock syndrome. Case: A 49-year-old woman with past medical history of alcohol use disorder presented with 2 days of knee pain after a fall. She was hypotensive and tachycardic on arrival with elevated lactate. Aspiration of the knee revealed septic arthritis, and blood cultures grew GAS. Norepinephrine, vasopressin, and Angiotensin II were started for management of shock. She was empirically treated with vancomycin/cefepime/clindamycin, then transitioned to linezolid/ceftriaxone and IVIG. On presentation, her hands and feet were noted to be cool and dusky; within 24 hours, she developed extensive distal digital necrosis, an isolated purpuric lesion on the thigh, and pulselessness in the bilateral ulnar and radial arteries. She was thrombocytopenic and coagulopathic and had evidence of fibrinolysis with normal fibrinogen. Within 72 hours, she developed superimposed bullae over purpuric skin patches and diagnosed with purpura fulminans. She was managed with a heparin drip and platelet transfusions to maintain platelets >30,000 and ultimately required right below-the-knee amputation, right transradial forearm amputation, and a left transmetatarsal amputation. Discussion: Purpura fulminans (PF) is a rare but significant complication associated with TSS, which can arise from infections with both Staphylococcus aureus or Streptococcus pyogenes. These pathogens produce superantigens, which elicit an exaggerated immune response, leading to DIC. The use of vasopressors to manage shock during the acute phase of illness exacerbates microvascular thrombosis and subsequent skin necrosis. Patients typically present with hypotension, multi-organ failure, and rapidly progressive purpuric skin lesions, with those localized to the distal extremities being particularly indicative of pressor-induced ischemia. Management of PF in this context includes aggressive antibiotic therapy targeting toxin-producing organisms, judicious downtitration of vasopressors as hemodynamic stability improves, and treatment of coagulopathy. In severe cases, surgical intervention may be necessary, including debridement or even amputation, to facilitate the use of prosthetics and enhance functional recovery. Early recognition and a comprehensive treatment strategy are crucial in improving outcomes for patients experiencing PF in the context of TSS.
2023-07-03 | Use of hyperbaric oxygen therapy of purpura fulminans in an extremely low birth weight preterm: A case report.
Purpura fulminans (PF) is a rare and fatal complication of septic shock or diffuse intravascular coagulation (DIC) resulting in skin and soft tissue necrosis. PF can be caused by congenital or acquired protein C (PC) or protein S (PS) deficiency. The most common cause of PF in a neonate is sepsis. In our extremely low birth weight preterm case, due to PF that started in the right-hand fingers, examination was made and protein S deficiency was detected as well as MTHFR (A1298C) and Factor V Leiden (R506Q) homozygous mutations. While being unresponsive to fresh frozen plasma (FFP) and unfractionated heparin (UFH) therapy, we want to highlight the curative treatment with hyperbaric oxygen (HBOT), which has not previously been used in extremely low birth weight preterm infants for this purpose.
2018-05-09 | Rare presentation of rickettsial infection as purpura fulminans: a case report
Purpura fulminans is an acute life-threatening disorder characterized by intravascular thrombosis and hemorrhagic infarction of the skin complicated with disseminated intravascular coagulation. It is commonly seen in acute infections following meningococcal and streptococcal infections. Few cases of purpura fulminans following rickettsial infections have been described in the literature.We report a case of a 55-year-old Sri Lankan woman who presented to Teaching Hospital Peradeniya with a febrile illness, headache, and myalgia that progressed to an erythematous rash starting over the bilateral lover limbs and hands and that became black and necrotic with a few hemorrhagic blebs. She had normocytic anemia, platelet clumps, and monocytosis as well as a deranged clotting profile. The result of immunofluorescence antibody testing for rickettsial immunoglobulin G was strongly positive for Rickettsia conorii with a rise in titer convalescent sera, and a diagnosis of purpura fulminans following rickettsial infection was made. The patient made an excellent recovery with chloramphenicol treatment.The treating physician should consider the rare but very treatable condition of rickettsial infection as a differential diagnosis in the etiological diagnostic workup of patients presenting with severe purpuric and hemorrhagic rash with fever.
2018-04-09 | An ADAM-10 dependent EPCR shedding links meningococcal interaction with endothelial cells to purpura fulminans
Purpura fulminans is a deadly complication of Neisseria meningitidis infections due to extensive thrombosis of microvessels. Although a Disseminated Intra-vascular Coagulation syndrome (DIC) is frequently observed during Gram negative sepsis, it is rarely associated with extensive thrombosis like those observed during meningococcemia, suggesting that the meningococcus induces a specific dysregulation of coagulation. Another specific feature of N. meningitidis pathogenesis is its ability to colonize microvessels endothelial cells via type IV pili. Importantly, endothelial cells are key in controlling the coagulation cascade through the activation of the potent anticoagulant Protein C (PC) thanks to two endothelial cell receptors among which the Endothelial Protein C Receptor (EPCR). Considering that congenital or acquired deficiencies of PC are associated with purpura fulminans, we hypothesized that a defect in the activation of PC following meningococcal adhesion to microvessels is responsible for the thrombotic events observed during meningococcemia. Here we showed that the adhesion of N. meningitidis on endothelial cells results in a rapid and intense decrease of EPCR expression by inducing its cleavage in a process know as shedding. Using siRNA experiments and CRISPR/Cas9 genome edition we identified ADAM10 (A Disintegrin And Metalloproteinase-10) as the protease responsible for this shedding. Surprisingly, ADAM17, the only EPCR sheddase described so far, was not involved in this process. Finally, we showed that this ADAM10-mediated shedding of EPCR induced by the meningococcal interaction with endothelial cells was responsible for an impaired activation of Protein C. This work unveils for the first time a direct link between meningococcal adhesion to endothelial cells and a severe dysregulation of coagulation, and potentially identifies new therapeutic targets for meningococcal purpura fulminans.
2006-01-01 | Purpura Fulminans in an Adult Patient with Haemophilus Influenzae Sepsis: Case Report and Review of the Literature
Purpura fulminans is a rare complication of a coagulopathy or an infection. Haemophilus influenzae infection, which has decreased since the haemophilus influenzae type B vaccine was initiated, is an unusual initiating cause of purpura fulminans. This case is the first reported in the literature of an adult who developed purpura fulminans after Haemophilus influenzae sepsis. Her elevated beta2 glycoprotein 1 ratio may have contributed to the severity of her disease. Although rare, Haemophilus influenzae may precipitate purpura fulminans. Current therapy is directed at control of precipitating factors, removal of nonviable tissue, treatment of secondary infections, and physiologic support. There also is evidence that patients respond well to hyperbaric oxygen therapy, with decreasing limb and tissue loss.
proteins
2026-06-08 | Post-infectious Purpura Fulminans in a Healthy Child: A Case Report
Introduction: Purpura fulminans (PF) is a rare and life-threatening thrombohemorrhagic disorder characterized by rapidly progressive purpuric skin lesions caused by dermal microvascular thrombosis and disseminated intravascular coagulation. Post-infectious PF is an uncommon variant in children and is typically associated with transient acquired deficiencies of natural anticoagulant proteins. Case Presentation: A previously healthy 3-year-old girl presented with rapidly progressive painful violaceous plaques on both shins. She was afebrile and hemodynamically stable. Laboratory studies revealed disseminated intravascular coagulation and severe acquired Protein S deficiency with anti-Protein S antibodies. Diagnosis of PF was made. Microbiological testing was positive for Streptococcus species and metapneumovirus, suggesting a post-infectious trigger. Despite early treatment with antibiotics, anticoagulation, fresh frozen plasma, and intravenous immunoglobulins, the lesions progressed to full-thickness skin necrosis requiring surgical debridement and split-thickness skin grafting. Coagulation parameters and Protein S levels normalized within two weeks. Conclusion: Post-infectious PF should be suspected in children presenting with rapidly progressive purpuric lesions following recent infection. Early recognition and aggressive multidisciplinary management are essential to prevent life-threatening complications and limit permanent tissue damage.
2026-03-01 | 1509: PURPURA FULMINANS IN PNEUMOCOCCAL SEPSIS: A FATAL COMPLICATION IN A PATIENT WITH SICKLE CELL TRAIT
Introduction: Purpura fulminans is a rare rapidly-progressive thrombotic disorder characterized by disseminated intravascular coagulation (DIC), tissue necrosis, and multiorgan failure. It is precipitated by severe bacterial infection, especially in functionally asplenic or immunocompromised patients. Though most commonly associated with meningococcemia, Streptococcus pneumoniae is also a known inciting pathogen. Description: A 36-year-old man with known sickle cell trait and undiagnosed asplenia was found unresponsive after two days of rigors and poor sleep. His children were recently sick with fever and cough. He was febrile to 105.2°F and encephalopathic with laboratory studies notable for leukocytosis, lactate (9.8 mmol/L), coagulopathy, acute kidney injury, and transaminitis. Imaging revealed right lower lobe consolidation and evidence of autosplenectomy. Blood cultures grew Streptococcus pneumoniae. Despite broad-spectrum antibiotics, his condition deteriorated with rising creatinine (5.2 mg/dL) and rhabdomyolysis (CK >59,000 U/L) prompting CRRT initiation. He developed a diffuse purpuric rash and laboratory features consistent with DIC: thrombocytopenia, prolonged PTT, schistocytes, and low fibrinogen. Arterial dopplers showed loss of distal perfusion with compartment syndrome suspected in all extremities. Fasciotomy was deferred due to instability. Unfortunately, the patient suffered cardiac arrest in the setting of refractory hyperkalemia, shock, and multiorgan failure. Discussion: This case highlights the severity of purpura fulminans due to pneumococcal sepsis in a patient with sickle cell trait. The combination of functional hyposplenism in the absence of prior vaccination, systemic inflammation, and hypercoagulability created a prothrombotic storm unresponsive to standard interventions. Early recognition of purpura fulminans is critical to provide optimal antimicrobial coverage to improve outcomes. Acquired protein C deficiency may contribute to the pathophysiology of this condition; although this patient received plasma without notable improvement, protein C replacement therapy may be beneficial in some cases. Optimal vaccination, prompt antibiotic therapy, and aggressive DIC management remain the cornerstones of prevention and care in such high-risk populations.
2025-07-25 | Real-world use of protein C concentrate for the treatment of patients with protein C deficiency: an international registry.
Published reports on the real-world use of protein C concentrate have been limited to case reports or small case series. To collect and assess data on the medical diagnoses, treatment regimens, safety outcomes, and treatment outcomes of patients receiving protein C concentrate in routine clinical practice. This was a prospective, open-label, registry-based study conducted at 26 sites in Europe and the USA. Data were collected from the medical records of patients of all ages who received treatment with protein C concentrate. The primary endpoints were medical diagnoses associated with protein C concentrate treatment, treatment regimens, and the safety of protein C concentrate (incidence of related adverse events [AEs] and all serious AEs [SAEs]). Between June 23, 2010, and June 22, 2015, 43 patients, including 25 with severe congenital protein C deficiency (SCPCD) and 18 with severe acquired protein C deficiency, were enrolled in the study, all of whom were included in the analysis. In total, 306 treatment courses of protein C concentrate were documented during the study, for treatment of acute thrombotic episodes, short-term replacement, and long-term prophylaxis. Most patients (76%) with SCPCD were receiving long-term prophylaxis. Overall, 124 AEs were reported in 27 patients (63%); 17 patients experienced SAEs. Only 2 AEs (SAEs of abdominal pain and lower extremity pain) in 1 patient were considered possibly related to protein C concentrate. The results of this study provide insights into the real-world use of protein C concentrate in clinical practice in Europe and the USA.
2025-05-01 | Loss of Flow and Purple Hands: That's What I Call Fulminans
Abstract Our patient was a 78-year old female with no known medical history who presented with shortness of breath and a painful rash of the right arm. The rash began approximately two weeks prior to respiratory symptoms. She rapidly deteriorated within several hours of presentation and became febrile and hypotensive. Within 48 hours, she developed diffuse, flaccid bullae and purpura over all extremities and anterior trunk. Blood cultures resulted positive for Group A Streptococcus pyogenes within 24 hours. Despite prompt initiation of broad spectrum and antitoxic antibiotics, multiorgan failure rapidly ensued. Shortly thereafter she developed necrosis of the oral and nasal mucosa, digits of the hands and feet, as well as small vessel thrombi leading to loss of blood flow to her feet and hands. It was also noted her CRRT filter clotted at an abnormally rapid rate, approximately 6-8 hours. Her clinical picture was consistent with purpura fulminans (PF), an even more rapidly progressive subtype of disseminated intravascular coagulation (DIC) that has an overwhelming mortality rate. The mechanism of PF remains poorly understood. Despite all that is unknown about PF, there is a wide consensus that PF occurs predominantly in children. Of the limited literature that exists, PF is believed to result from a number of etiologies including sepsis, inherited deficiency of proteins C (PC) and S (PS), or in the post-infectious period due to acquired autoantibodies against PC and PS. Unsurprisingly, there is not a general consensus regarding work up for PF. Multiple case reports and limited data suggest that lab findings of PF are largely consistent with DIC, which include prolonged PTT and PT, elevated D-dimer, and decreased fibrinogen. Interestingly, our patient's fibrinogen remained within normal limits but with prolonged PTT and PT. A small study by Lorelle et al. found a linear relationship between antithrombin (AT) and PC, which raises the question: can PC concentrate or anticoagulation treat PF? Again, no PF-specific studies exist to answer this question, but a study by Zarychanski et al investigating infection-associated DIC found no change in all cause mortality in those treated with heparin versus placebo or usual care. Unfortunately, our patient declined too rapidly for these investigations to be performed before her family elected to initiate comfort care measures. Especially considering the inevitably unfavorable outcome of PF, rapid recognition of PF is paramount and goes without saying that potential therapies including protein C supplementation and anticoagulation need be explored.
cell therapies
2023-09-21 | Case report: Blotchy skin in a puffy neonate: is there a new association?
Purpura fulminans in the neonatal population is a rare but potentially life-threatening condition complicated by thrombosis, resultant vital organ necrosis, and gangrene of the extremities. Considering the rapid evolution of the pathogenetic mechanism, an index of suspicion, early identification, and prompt intervention are imperative for improved outcomes. The majority of purpura fulminans cases have an infectious etiology, but it is essential to consider other congenital and acquired causes.We present a clinical case of a female neonate to emphasize the correlation between purpura fulminans, congenital chylothorax, involvement of the PAK2 gene, and the occurrence of retinal detachment in both eyes. After draining the congenital chylothorax, the neonate developed purpura fulminans due to a loss of protein C, S, and antithrombin factors, previously not reported in the literature. The purpuric lesions resolved after the administration of fresh frozen plasma. Subsequently, no recurring purpura fulminans lesions were noted following the normalization of the antithrombotic factor levels in the serum. Subsequently, the child also developed retinal detachment in both eyes.
1967-12-04 | Blood and Blood Components in the Prevention and Control of Bleeding
Banked blood contains many of the factors necessary for hemostasis. The most important components which are not present in stored blood are factor VIII (antihemophilic factor) and platelets. Methods are now available whereby significant concentrations of these components can be achieved from fresh donor blood by the hospital blood bank.
small molecules
2025-05-01 | Vascular Compromise in Toxic Shock Syndrome: A Case of Purpura Fulminans
Abstract Introduction: Purpura fulminans (PF) is a rare, potentially fatal manifestation of disseminated intravascular coagulation (DIC) characterized by tissue thrombosis and hemorrhagic skin necrosis. The pathophysiology of PF involves severe acquired protein C deficiency, leading to uncontrolled coagulation and thrombosis. It can be triggered by bacterial infections; less commonly, by viral infections, toxic shock syndrome (TSS), pressors, and genetic abnormalities. In this submission, we describe a case of PF in a patient requiring pressor support for Group A streptococcus (GAS) toxic shock syndrome. Case: A 49-year-old woman with past medical history of alcohol use disorder presented with 2 days of knee pain after a fall. She was hypotensive and tachycardic on arrival with elevated lactate. Aspiration of the knee revealed septic arthritis, and blood cultures grew GAS. Norepinephrine, vasopressin, and Angiotensin II were started for management of shock. She was empirically treated with vancomycin/cefepime/clindamycin, then transitioned to linezolid/ceftriaxone and IVIG. On presentation, her hands and feet were noted to be cool and dusky; within 24 hours, she developed extensive distal digital necrosis, an isolated purpuric lesion on the thigh, and pulselessness in the bilateral ulnar and radial arteries. She was thrombocytopenic and coagulopathic and had evidence of fibrinolysis with normal fibrinogen. Within 72 hours, she developed superimposed bullae over purpuric skin patches and diagnosed with purpura fulminans. She was managed with a heparin drip and platelet transfusions to maintain platelets >30,000 and ultimately required right below-the-knee amputation, right transradial forearm amputation, and a left transmetatarsal amputation. Discussion: Purpura fulminans (PF) is a rare but significant complication associated with TSS, which can arise from infections with both Staphylococcus aureus or Streptococcus pyogenes. These pathogens produce superantigens, which elicit an exaggerated immune response, leading to DIC. The use of vasopressors to manage shock during the acute phase of illness exacerbates microvascular thrombosis and subsequent skin necrosis. Patients typically present with hypotension, multi-organ failure, and rapidly progressive purpuric skin lesions, with those localized to the distal extremities being particularly indicative of pressor-induced ischemia. Management of PF in this context includes aggressive antibiotic therapy targeting toxin-producing organisms, judicious downtitration of vasopressors as hemodynamic stability improves, and treatment of coagulopathy. In severe cases, surgical intervention may be necessary, including debridement or even amputation, to facilitate the use of prosthetics and enhance functional recovery. Early recognition and a comprehensive treatment strategy are crucial in improving outcomes for patients experiencing PF in the context of TSS.
2023-07-03 | Use of hyperbaric oxygen therapy of purpura fulminans in an extremely low birth weight preterm: A case report.
Purpura fulminans (PF) is a rare and fatal complication of septic shock or diffuse intravascular coagulation (DIC) resulting in skin and soft tissue necrosis. PF can be caused by congenital or acquired protein C (PC) or protein S (PS) deficiency. The most common cause of PF in a neonate is sepsis. In our extremely low birth weight preterm case, due to PF that started in the right-hand fingers, examination was made and protein S deficiency was detected as well as MTHFR (A1298C) and Factor V Leiden (R506Q) homozygous mutations. While being unresponsive to fresh frozen plasma (FFP) and unfractionated heparin (UFH) therapy, we want to highlight the curative treatment with hyperbaric oxygen (HBOT), which has not previously been used in extremely low birth weight preterm infants for this purpose.
2018-05-09 | Rare presentation of rickettsial infection as purpura fulminans: a case report
Purpura fulminans is an acute life-threatening disorder characterized by intravascular thrombosis and hemorrhagic infarction of the skin complicated with disseminated intravascular coagulation. It is commonly seen in acute infections following meningococcal and streptococcal infections. Few cases of purpura fulminans following rickettsial infections have been described in the literature.We report a case of a 55-year-old Sri Lankan woman who presented to Teaching Hospital Peradeniya with a febrile illness, headache, and myalgia that progressed to an erythematous rash starting over the bilateral lover limbs and hands and that became black and necrotic with a few hemorrhagic blebs. She had normocytic anemia, platelet clumps, and monocytosis as well as a deranged clotting profile. The result of immunofluorescence antibody testing for rickettsial immunoglobulin G was strongly positive for Rickettsia conorii with a rise in titer convalescent sera, and a diagnosis of purpura fulminans following rickettsial infection was made. The patient made an excellent recovery with chloramphenicol treatment.The treating physician should consider the rare but very treatable condition of rickettsial infection as a differential diagnosis in the etiological diagnostic workup of patients presenting with severe purpuric and hemorrhagic rash with fever.
2018-04-09 | An ADAM-10 dependent EPCR shedding links meningococcal interaction with endothelial cells to purpura fulminans
Purpura fulminans is a deadly complication of Neisseria meningitidis infections due to extensive thrombosis of microvessels. Although a Disseminated Intra-vascular Coagulation syndrome (DIC) is frequently observed during Gram negative sepsis, it is rarely associated with extensive thrombosis like those observed during meningococcemia, suggesting that the meningococcus induces a specific dysregulation of coagulation. Another specific feature of N. meningitidis pathogenesis is its ability to colonize microvessels endothelial cells via type IV pili. Importantly, endothelial cells are key in controlling the coagulation cascade through the activation of the potent anticoagulant Protein C (PC) thanks to two endothelial cell receptors among which the Endothelial Protein C Receptor (EPCR). Considering that congenital or acquired deficiencies of PC are associated with purpura fulminans, we hypothesized that a defect in the activation of PC following meningococcal adhesion to microvessels is responsible for the thrombotic events observed during meningococcemia. Here we showed that the adhesion of N. meningitidis on endothelial cells results in a rapid and intense decrease of EPCR expression by inducing its cleavage in a process know as shedding. Using siRNA experiments and CRISPR/Cas9 genome edition we identified ADAM10 (A Disintegrin And Metalloproteinase-10) as the protease responsible for this shedding. Surprisingly, ADAM17, the only EPCR sheddase described so far, was not involved in this process. Finally, we showed that this ADAM10-mediated shedding of EPCR induced by the meningococcal interaction with endothelial cells was responsible for an impaired activation of Protein C. This work unveils for the first time a direct link between meningococcal adhesion to endothelial cells and a severe dysregulation of coagulation, and potentially identifies new therapeutic targets for meningococcal purpura fulminans.
2006-01-01 | Purpura Fulminans in an Adult Patient with Haemophilus Influenzae Sepsis: Case Report and Review of the Literature
Purpura fulminans is a rare complication of a coagulopathy or an infection. Haemophilus influenzae infection, which has decreased since the haemophilus influenzae type B vaccine was initiated, is an unusual initiating cause of purpura fulminans. This case is the first reported in the literature of an adult who developed purpura fulminans after Haemophilus influenzae sepsis. Her elevated beta2 glycoprotein 1 ratio may have contributed to the severity of her disease. Although rare, Haemophilus influenzae may precipitate purpura fulminans. Current therapy is directed at control of precipitating factors, removal of nonviable tissue, treatment of secondary infections, and physiologic support. There also is evidence that patients respond well to hyperbaric oxygen therapy, with decreasing limb and tissue loss.
proteins
2026-06-08 | Post-infectious Purpura Fulminans in a Healthy Child: A Case Report
Introduction: Purpura fulminans (PF) is a rare and life-threatening thrombohemorrhagic disorder characterized by rapidly progressive purpuric skin lesions caused by dermal microvascular thrombosis and disseminated intravascular coagulation. Post-infectious PF is an uncommon variant in children and is typically associated with transient acquired deficiencies of natural anticoagulant proteins. Case Presentation: A previously healthy 3-year-old girl presented with rapidly progressive painful violaceous plaques on both shins. She was afebrile and hemodynamically stable. Laboratory studies revealed disseminated intravascular coagulation and severe acquired Protein S deficiency with anti-Protein S antibodies. Diagnosis of PF was made. Microbiological testing was positive for Streptococcus species and metapneumovirus, suggesting a post-infectious trigger. Despite early treatment with antibiotics, anticoagulation, fresh frozen plasma, and intravenous immunoglobulins, the lesions progressed to full-thickness skin necrosis requiring surgical debridement and split-thickness skin grafting. Coagulation parameters and Protein S levels normalized within two weeks. Conclusion: Post-infectious PF should be suspected in children presenting with rapidly progressive purpuric lesions following recent infection. Early recognition and aggressive multidisciplinary management are essential to prevent life-threatening complications and limit permanent tissue damage.
2026-03-01 | 1509: PURPURA FULMINANS IN PNEUMOCOCCAL SEPSIS: A FATAL COMPLICATION IN A PATIENT WITH SICKLE CELL TRAIT
Introduction: Purpura fulminans is a rare rapidly-progressive thrombotic disorder characterized by disseminated intravascular coagulation (DIC), tissue necrosis, and multiorgan failure. It is precipitated by severe bacterial infection, especially in functionally asplenic or immunocompromised patients. Though most commonly associated with meningococcemia, Streptococcus pneumoniae is also a known inciting pathogen. Description: A 36-year-old man with known sickle cell trait and undiagnosed asplenia was found unresponsive after two days of rigors and poor sleep. His children were recently sick with fever and cough. He was febrile to 105.2°F and encephalopathic with laboratory studies notable for leukocytosis, lactate (9.8 mmol/L), coagulopathy, acute kidney injury, and transaminitis. Imaging revealed right lower lobe consolidation and evidence of autosplenectomy. Blood cultures grew Streptococcus pneumoniae. Despite broad-spectrum antibiotics, his condition deteriorated with rising creatinine (5.2 mg/dL) and rhabdomyolysis (CK >59,000 U/L) prompting CRRT initiation. He developed a diffuse purpuric rash and laboratory features consistent with DIC: thrombocytopenia, prolonged PTT, schistocytes, and low fibrinogen. Arterial dopplers showed loss of distal perfusion with compartment syndrome suspected in all extremities. Fasciotomy was deferred due to instability. Unfortunately, the patient suffered cardiac arrest in the setting of refractory hyperkalemia, shock, and multiorgan failure. Discussion: This case highlights the severity of purpura fulminans due to pneumococcal sepsis in a patient with sickle cell trait. The combination of functional hyposplenism in the absence of prior vaccination, systemic inflammation, and hypercoagulability created a prothrombotic storm unresponsive to standard interventions. Early recognition of purpura fulminans is critical to provide optimal antimicrobial coverage to improve outcomes. Acquired protein C deficiency may contribute to the pathophysiology of this condition; although this patient received plasma without notable improvement, protein C replacement therapy may be beneficial in some cases. Optimal vaccination, prompt antibiotic therapy, and aggressive DIC management remain the cornerstones of prevention and care in such high-risk populations.
2025-07-25 | Real-world use of protein C concentrate for the treatment of patients with protein C deficiency: an international registry.
Published reports on the real-world use of protein C concentrate have been limited to case reports or small case series. To collect and assess data on the medical diagnoses, treatment regimens, safety outcomes, and treatment outcomes of patients receiving protein C concentrate in routine clinical practice. This was a prospective, open-label, registry-based study conducted at 26 sites in Europe and the USA. Data were collected from the medical records of patients of all ages who received treatment with protein C concentrate. The primary endpoints were medical diagnoses associated with protein C concentrate treatment, treatment regimens, and the safety of protein C concentrate (incidence of related adverse events [AEs] and all serious AEs [SAEs]). Between June 23, 2010, and June 22, 2015, 43 patients, including 25 with severe congenital protein C deficiency (SCPCD) and 18 with severe acquired protein C deficiency, were enrolled in the study, all of whom were included in the analysis. In total, 306 treatment courses of protein C concentrate were documented during the study, for treatment of acute thrombotic episodes, short-term replacement, and long-term prophylaxis. Most patients (76%) with SCPCD were receiving long-term prophylaxis. Overall, 124 AEs were reported in 27 patients (63%); 17 patients experienced SAEs. Only 2 AEs (SAEs of abdominal pain and lower extremity pain) in 1 patient were considered possibly related to protein C concentrate. The results of this study provide insights into the real-world use of protein C concentrate in clinical practice in Europe and the USA.
2025-05-01 | Loss of Flow and Purple Hands: That's What I Call Fulminans
Abstract Our patient was a 78-year old female with no known medical history who presented with shortness of breath and a painful rash of the right arm. The rash began approximately two weeks prior to respiratory symptoms. She rapidly deteriorated within several hours of presentation and became febrile and hypotensive. Within 48 hours, she developed diffuse, flaccid bullae and purpura over all extremities and anterior trunk. Blood cultures resulted positive for Group A Streptococcus pyogenes within 24 hours. Despite prompt initiation of broad spectrum and antitoxic antibiotics, multiorgan failure rapidly ensued. Shortly thereafter she developed necrosis of the oral and nasal mucosa, digits of the hands and feet, as well as small vessel thrombi leading to loss of blood flow to her feet and hands. It was also noted her CRRT filter clotted at an abnormally rapid rate, approximately 6-8 hours. Her clinical picture was consistent with purpura fulminans (PF), an even more rapidly progressive subtype of disseminated intravascular coagulation (DIC) that has an overwhelming mortality rate. The mechanism of PF remains poorly understood. Despite all that is unknown about PF, there is a wide consensus that PF occurs predominantly in children. Of the limited literature that exists, PF is believed to result from a number of etiologies including sepsis, inherited deficiency of proteins C (PC) and S (PS), or in the post-infectious period due to acquired autoantibodies against PC and PS. Unsurprisingly, there is not a general consensus regarding work up for PF. Multiple case reports and limited data suggest that lab findings of PF are largely consistent with DIC, which include prolonged PTT and PT, elevated D-dimer, and decreased fibrinogen. Interestingly, our patient's fibrinogen remained within normal limits but with prolonged PTT and PT. A small study by Lorelle et al. found a linear relationship between antithrombin (AT) and PC, which raises the question: can PC concentrate or anticoagulation treat PF? Again, no PF-specific studies exist to answer this question, but a study by Zarychanski et al investigating infection-associated DIC found no change in all cause mortality in those treated with heparin versus placebo or usual care. Unfortunately, our patient declined too rapidly for these investigations to be performed before her family elected to initiate comfort care measures. Especially considering the inevitably unfavorable outcome of PF, rapid recognition of PF is paramount and goes without saying that potential therapies including protein C supplementation and anticoagulation need be explored.
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Drug Discovery Landscape
2 orphan drug designations for Acquired purpura fulminans.
2 orphan drug designations for Acquired purpura fulminans.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
eptifibatide and iloprost | small molecules | FDA | — | Thrombologic |
Protein C concentrate | proteins | FDA | — | Immuno Clinical Research Corp. |
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