Treatment Of Purpura Fulminans Research Articles

FOOLED BY FIBRINOGEN, DISTRACTED BY ESCHERICHIA COLI: AN UNEXPECTED PRESENTATION OF PURPURA FULMINANS

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Purpura fulminans (PF) is a rare, life-threatening dermatologic manifestation of disseminated intravascular coagulation (DIC) most often precipitated by severe sepsis from meningococcemia in children or Group A Streptococcus in adults. It is classically characterized by a classic pattern of cutaneous purpura leading to rapidly progressive skin necrosis and multi-system organ failure due to thrombosis of small and medium-sized blood vessels (1). CASE PRESENTATION: A 28 year old male with acquired immunodeficiency syndrome (AIDS, CD4 count 75), Kaposi’s sarcoma on doxorubicin, and adrenal insufficiency was admitted to the intensive care unit (ICU) for septic shock after being found at home in a pool of liquid stool. He was immediately intubated for profound metabolic acidosis and respiratory failure. The patient was initiated on vasopressors and broad spectrum antibiotics, but developed multi-organ failure requiring continuous renal replacement therapy, ischemic hepatitis, and DIC (Internationalized Normalized Ratio (INR) 4.5, Partial Thromboplastin Time (PTT) 52.8 seconds, D-Dimer 41,857 ng/mL, fibrinogen 280 mg/dL). Blood cultures grew Escherichia coli, likely from gastrointestinal source in the setting of diarrhea. On hospital day two, the patient developed large bullae over a base of well-defined purpuric patches on bilateral lower extremities, scrotum, and left dorsal arm. PF was suspected and definitively diagnosed by dermal biopsy showing scattered late-stage fibrin thrombi in small dermal vascular channels with epidermal and dermal necrosis. The patient survived the ICU admission with gradual resolution of his multi-organ failure but required quadruple amputations due to PF and vasopressor-related digit ischemia. DISCUSSION: Here we describe a case of PF with an unusual causative organism and a non-classic coagulation profile. PF is typically caused by meningococcus, Streptococcus or less commonly Staphylococcus, Vibrio, or Varicella through hypothesized thrombotic pathways involving over activation of tissue factor and relative depletion of protein C and S (1,2). Escherichia coli associated PF is exceptionally rare with only three reported cases (1,3-4). An additional unusual feature of this case was that the patient maintained persistently normal levels of fibrinogen despite the development of fulminant DIC. Low fibrinogen levels have been advocated as a useful diagnostic marker of DIC; however, plasma levels may remain normal for prolonged periods despite ongoing consumption as fibrinogen also acts as an acute-phase reactant (5). Up to 57% of patients with DIC may have normal fibrinogen levels (6). CONCLUSIONS: As early recognition and treatment of PF is vital to reduce mortality, this case provides an important reminder that clinicians should not be deterred in considering a diagnosis based on an atypical feature or laboratory value. Reference #1: 1. Ahmed M, Samotowka M, Habis S, Mahmoud A, & Saeed R (2018). Escherichia coli Bacteremia-induced Purpura Fulminans: A Case Report. Cureus. Reference #2: 2. Lécuyer H, Borgel D, Nassif X, & Coureuil M (2017). Pathogenesis of meningococcal purpura fulminans. Pathogens and Disease, 75(3). 3. Ichimiya M, Takita Y, Yamaguchi M, & Muto M (2007). Case of purpura fulminans due to septicemia after artificial abortion. The Journal of Dermatology, 34(11), 786–789. Reference #3: 4. Huemer G M, Bonatti H, & Dunst K M (2004). Purpura fulminans due to E. coli septicemia. The Central European Journal of Medicine, 116(3), 82–82. 5. Levi M, Toh C H, Thachil J, & Watson H G (2009). Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Journal of Haematology, 145(1), 24–33. 6. Spero J, Lewis J, & Hasiba U (1980). Disseminated Intravascular Coagulation. Thrombosis and Haemostasis, 43(01), 28–33. DISCLOSURES: No relevant relationships by Lehman Godwin, source=Web Response No relevant relationships by Jenny Han, source=Web Response Previous consultant in 2017 relationship with Third Rock Ventures Please note: $20001 - $100000 Added 01/03/2020 by Stephen Linderman, source=Web Response, value=Consulting fee Removed 01/03/2020 by Stephen Linderman, source=Web Response Previous consultant 2017-2018 relationship with Third Rock Ventures Please note: $20001 - $100000 Added 01/03/2020 by Stephen Linderman, source=Web Response, value=Consulting fee No relevant relationships by Douglas Parker, source=Web Response No relevant relationships by Jeeyon Rim, source=Web Response

LIMB THREATENING CUTANEOUS MANIFESTATION OF CRYOGLOBULINEMIA: PURPURA FULMINANS

SESSION TITLE: Critical Care 2 SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/09/2018 05:00 PM - 06:00 PM INTRODUCTION: Purpura fulminans (PF) is a rare life-threatening disorder with mortality up to 80-100%. The most common causes include sepsis, hematologic malignancy, trauma, and obstetric emergencies. The diagnosis is often delayed and no standard treatment is available. We present a case of PF possibly due to human metapneumovirus (HMPV) in the setting of multiple myeloma and cryoglobulinemia. CASE PRESENTATION: A 60-year-old Caucasian female with a history of multiple myeloma on chemotherapy and biopsy proven cryoglobulinemia presented with cough, generalized weakness, and a diffuse purpuric rash. She developed a violaceous, bullous rash two days prior to admission that was present on her bilateral arms and ankles, face, and anterior right thigh (Figures 1, 2, 3). The patient was febrile, tachycardic, and hypoxic requiring 2 l/min of oxygen on admission. Initial labs revealed pancytopenia without any evidence of disseminated intravascular coagulopathy. Over the next few days, the skin rash worsened with significant epidermal sloughing resulting in admission into the burn unit. The patient eventually developed multi-organ dysfunction and was treated aggressively with plasmapheresis and intravenous immunoglobulin in addition to broad spectrum antibiotics. The patient survived, however she required multiple surgical debridements resulting in significant aesthetic disfigurement and long-term disability. DISCUSSION: Most cases of PF are secondary to infection. The pathophysiology is poorly understood but includes acquired deficiency of protein c and dysfunction of the protein c-thrombomodulin pathway which can result in diffuse thrombotic multi-organ dysfunction (1). Although bacterial infection is commonly present, rare cases of PF due to viral infections have been reported. To our knowledge, PF has never been associated with HMPV infection. Additionally, there are no reports of PF associated with cryoglobulinemia. The contribution of cryoglobulinemia to this patient's presentation is unclear. While there is no standard treatment of PF, the general approach should be to address the underlying infection, aggressive anticoagulation, and robust transfusion support aimed at correcting acquired deficiencies in natural anticoagulant proteins. Despite these efforts, the majority of patients do not survive. CONCLUSIONS: Early identification and intervention is crucial when taking care of a patient with purpura fulminans. Given the rarity of this potentially fatal condition, it should be on the differential diagnosis for a patient presenting with purpuric lesions and coagulopathy. Reference #1: Colling ME at al. Purpura Fulminans: Mechanism and Management of Dysregulated Hemostasis. Transfus Med Rev. 2017. DISCLOSURES: No relevant relationships by Stacey Burns, source=Web Response No relevant relationships by Hau Chieng, source=Web Response No relevant relationships by Amit Chopra, source=Web Response No relevant relationships by Alireza Nathani, source=Web Response No relevant relationships by Biplab Kumar Saha, source=Web Response

Registry Of Patients Treated With Protein C Concentrate (Human) In The United States and Europe: Interim Results

BackgroundProtein C (PC) is a naturally occurring, vitamin-K dependent anticoagulant produced by the liver. Deficiency of PC, which can be congenital or acquired, results in a hypercoagulable state. Patients with severe PC deficiency may manifest severe, often life-threatening, disseminated intravascular coagulation (DIC), purpura fulminans (PF), and/or thromboembolism. Highly purified protein C concentrate prepared from human donor plasma (Ceprotin; Baxter Healthcare Corporation, Westlake Village, CA) is an approved therapy for prevention and treatment of venous thrombosis and PF in patients with severe congenital PC deficiency (SCPCD) in the United States. It is indicated in patients with SCPCD for PF and coumarin-induced skin necrosis, and short-term prophylaxis in the European Union and other countries. Use of protein C concentrate (human) has been reported in patients with acquired PC deficiency. The Ceprotin Treatment Registry is a prospective, international, multi-center, open-label, non-interventional, observational study designed to examine the long-term safety and effectiveness of protein C concentrate (human) in the clinical setting. This is the first large, real-world assessment of the treatment of a rare disease with protein C concentrate (human). Here we report data from the first interim analysis in June 2013 covering a 3-year enrollment period. MethodsPatients of any age who received, or were initiating/receiving protein C concentrate are included. The study duration is 5 years (3-year enrollment period plus 2 years of follow-up). All study visits/assessments are in accordance with standard of care, with protein C concentrate dose, dose frequency, duration and route of administration determined by the investigator. The study objectives are to determine the most common medical diagnoses associated with protein C concentrate treatment, protein C concentrate treatment regimens, and safety information based on all serious adverse events (SAEs) and rate of treatment-related AE. Other objectives include: an examination of the relationship between protein C concentrate treatment and outcomes in all registry participants, as well as various subgroups. Descriptive statistical analyses are used. ResultsAt the time of data extraction, 34 patients were enrolled from 26 centers; 10 centers in the United States and 16 centers in Europe. Half of the patients were males. The primary diagnosis of PC deficiency was congenital in 25 patients (73.5%) and acquired in 9 patients (26.5%). The median age at diagnosis was 0.03 years (range 0–19.9). Mean plasma PC activity level was 9% (range 1–40.0). The most common (in ≥3 patients) thrombotic disease-associated conditions were PF (50.0%); blindness (44.1%); thromboembolic disease (41.2%), which included deep vein thrombosis, arterial thrombosis and DIC; stroke (32.4%), and renal dysfunction (8.8%). Of the 23 patients being treated with protein C concentrate, 15 were administered protein C concentrate intravenously, and 8 patients received protein C concentrate subcutaneously. The body weights of patients receiving subcutaneous treatment ranged from 10.0 kg to 57.9 kg. A total of 15 patients received an anticoagulant treatment in addition to protein C concentrate. Eight patients reported 23 SAEs, all of which were considered not related to treatment. Eighteen (52.9%) patients reported 72 AEs; only 1 of them, an episode of upper respiratory infection, was considered possibly treatment-related. In 18 patients in whom PC activity recovery was determined after protein C concentrate treatment, there were no patients documented with poor recovery. Protein C concentrate was used during 18 surgeries/invasive procedures and considered effective in all interventions for which data were available. ConclusionsData from the first interim analysis of the Ceprotin Treatment Registry demonstrate that patients with both congenital and acquired severe PC deficiency who are treated with protein C concentrate (human) have a low incidence of treatment related SAEs and AEs, and treatment with protein C concentrate appears to be effective when used during surgery/invasive procedures. Further patient follow up will shed light onto clinical treatment outcomes. Disclosures:Manco-Johnson:CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Biogen Idec: Membership on an entity's Board of Directors or advisory committees; Baxter BioScience: Membership on an entity's Board of Directors or advisory committees; Bayer HealthCare: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Research Funding. Knoebl:Novo Nordisk: Consultancy, Honoraria; Baxter: Consultancy, Honoraria. Shapiro:Cangene: Research Funding; Biogen Idec: Research Funding; Baxter BioScience: Research Funding; Bayer HealthCare: Research Funding. Finnerty:Baxter: Employment, Equity Ownership. Yel:Baxter: Employment, Equity Ownership. Gelmont:Baxter: Employment, Equity Ownership.

Diagnostic Value of Polymerase Chain Reaction Analysis of Skin Biopsies in Purpura Fulminans

Even though prompt diagnosis and treatment of purpura fulminans (PF) is essential to reduce mortality, early administration of antibiotics may preclude identification of the causative agent by standard bacterial cultures and thus render definitive diagnosis impossible. Here we present a case of an infant with PF and negative bacterial cultures for whom polymerase chain reaction (PCR) analysis of a cutaneous biopsy specimen obtained 4days after initiation of antibiotics identified the genomic sequence of Neisseria meningitidis genogroup C. When bacterial cultures fail to provide useful information, PCR of skin biopsy specimens can be a valuable diagnostic tool in PF.

Purpura Fulminans Associated with Streptococcus pneumoniae Septicemia in an Asplenic Pediatric Patient

Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans.

Human skin allografts as a useful adjunct in the treatment of purpura fulminans

The aim of this report is to discuss the role of human skin allografts in surgical coverage procedures for patients with purpura fulminans. We describe cases of purpura fulminans in three adults and one infant treated at our burns unit between October 2006 and January 2008. The application of cryopreserved human skin allografts allowed us to obtain immediate wound closure after necrosis excision and enabled our team to subsequently perform autografts on favourable graft recipient sites. Recourse to human skin allografts must be considered a pertinent therapeutic option in patients with purpura fulminans.

Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients

IntroductionPurpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels.MethodsIn Germany, patients receiving protein C concentrate (Ceprotin®, Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this national, retrospective, multi-centered study.ResultsComplete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03).ConclusionsThis retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial.

Modern Concepts of the Diagnosis and Treatment of Purpura Fulminans

Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin that is rapidly progressive and accompanied by vascular collapse and disseminated intravascular coagulation. It usually occurs in children, but this syndrome has also been noted in adults. The purpose of this collective review is to provide modern concepts on the diagnosis and treatment of neonatal purpura fulminans, idiopathic purpura fulminans, and acute infectious purpura fulminans. There are three forms of this disease that are classified by the triggering mechanisms. First, neonatal purpura fulminans is associated with a hereditary deficiency of the natural anticoagulants Protein C and Protein S as well as Antithrombin III. Idiopathic purpura fulminans usually follows an initiating febrile illness that manifests with rapidly progressive purpura. Deficiency of Protein S is considered to be central to the pathogenesis of this form of the disease. The third and most common type of purpura fulminans is acute infectious purpura fulminans. The mortality rate has decreased with better treatment of secondary infections, supportive care, and new treatments, but it remains a disabling condition often requiring major amputations.

AlloDerm Acellular Dermal Graft in the Treatment of Purpura Fulminans

AlloDerm Acellular Dermal Graft in the Treatment of Purpura Fulminans

Molecular and immunological mechanism of action of HBO in the treatment of purpura fulminans

Molecular and immunological mechanism of action of HBO in the treatment of purpura fulminans

Molecular and immunological mechanism of action of HBO in the treatment of purpura fulminans

Molecular and immunological mechanism of action of HBO in the treatment of purpura fulminans

Treatment of purpura fulminans in meningococcemia with protein C concentrate

Objective: To evaluate the clinical and laboratory effects of protein C concentrate as an adjunct to conventional therapy in the treatment of meningococcemia with purpura fulminans. Design: Case series (pilot study). Setting: Intensive care unit in a tertiary care pediatric hospital. Patients: Four children (aged 3 months to 15 years) requiring intensive treatment for meningococcemia with shock, disseminated intravascular coagulation, and purpura fulminans. Intervention: Intravenous administration of a protein C concentrate (100 IU/kg every 6 hours). Main outcome measures: Plasma protein C amidolytic activity, fibrinogen, and D-dimers; evolution of skin and limb lesions. Results: Treatment with protein C concentrate led to a rise in plasma protein C activity levels to within normal limits in all patients, associated with an increase in plasma fibrinogen and a bimodal decrease in D-dimers. No adverse effects were noted. All patients had reversal of organ dysfunction despite the severity of the initial illness. Two patients recovered completely with no sequelae; two required amputations. Conclusions: These encouraging clinical and laboratory results and the absence of side effects warrant the initiation of a double-blind, randomized controlled multicenter trial to determine the role of protein C replacement in the treatment of meningococcemia-associated purpura fulminans. ( J PEDIATR 1995; 126:646-52)

Use of topically applied nitroglycerin in the treatment of purpura fulminans

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