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Purpura Fulminans

Disease Details

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Description: Purpura fulminans is a rapidly progressing, life-threatening condition characterized by widespread blood clotting in small vessels, leading to tissue necrosis and hemorrhagic skin lesions.
Type: Purpura fulminans can be classified into two main types:
1. Acute infectious purpura fulminans
2. Neonatal purpura fulminans

The type of genetic transmission involved in purpura fulminans is primarily autosomal recessive. Neonatal purpura fulminans, specifically, is often associated with inherited deficiencies of protein C or protein S, which follow this pattern of genetic transmission.
Signs And Symptoms: Purpura fulminans is a severe and potentially life-threatening condition characterized by:

1. **Signs and Symptoms:**
- Sudden onset of widespread purplish spots or patches on the skin (purpura)
- Rapid progression to large areas of bruising and clotting under the skin
- Fever
- Shock and organ failure in severe cases
- Painful skin lesions
- Potential development of gangrene in affected areas

Immediate medical attention is critical to manage this condition.
Prognosis: Purpura fulminans lesions, once established, often progress within 24 to 48 hours to full-thickness skin necrosis or soft-tissue necrosis. Once purpura fulminans lesions progress to full-thickness skin necrosis, healing takes between 4–8 weeks and leaves large scars.Without treatment, necrotic soft tissue may become gangrenous, leading to loss of limbs. Purpura fulminans is often accompanied by micro-vascular thrombosis and haemorrhagic infarction in other tissues, such as the lungs, kidneys, central nervous system and adrenal glands, leading to multiple organ failure, and causes initial high mortality and long-term morbidity in survivors. Purpura fulminans may also lead to severe large vessel venous thrombosis if untreated in its early stages.Purpura fulminans secondary to severe infection is self-limiting. In cases of homozygous protein C deficiency, episodes of purpura fulminans and other thrombotic events are recurrent. Moreover, infant survival due to maintenance replacement therapy is often associated with intellectual disability or visual impairment. For post-infection purpura fulminans, new lesions will occur while neutralising autoantibodies are present (1–2 weeks after presentation).A multi-disciplinary care team is usually required for rehabilitation after purpura fulminans.
Onset: The onset of purpura fulminans can be acute and rapidly progressive. This condition is often characterized by the sudden appearance of large areas of purpura (bruising) and disseminated intravascular coagulation (DIC), which can evolve within hours to days. It is often associated with severe infections, particularly meningococcal septicemia, or can occur in the context of a genetic deficiency of protein C or S, or other coagulopathies. Early medical intervention is critical due to the rapid progression and potential for severe complications.
Prevalence: The prevalence of purpura fulminans is not well-documented due to its rarity. It is an uncommon but severe and life-threatening condition typically associated with severe infections, particularly sepsis, or genetic deficiencies in protein C or protein S.
Epidemiology: Purpura fulminans is rare and most commonly occurs in babies and small children but can also be a rare manifestation in adults when it is associated with severe infections. For example, Meningococcal septicaemia is complicated by purpura fulminans in 10–20% of cases among children. Purpura fulminans associated with congenital (inherited) protein C deficiency occurs in 1:500,000–1,000,000 live births.
Intractability: Purpura fulminans is often considered intractable due to its severe and rapidly progressing nature. This potentially life-threatening condition requires immediate and intensive medical intervention, including the use of antibiotics, anticoagulants, and supportive care such as intensive care unit admission. Despite aggressive treatment, the outcomes can be poor, especially if not addressed promptly.
Disease Severity: Purpura fulminans is a severe, life-threatening condition. It is characterized by sudden onset of widespread blood clots in small blood vessels, often leading to tissue necrosis and organ failure. The condition is often associated with infections, particularly meningococcal sepsis, and can also occur due to congenital or acquired deficiencies in protein C or protein S. Early diagnosis and treatment are critical for improving outcomes.
Healthcare Professionals: Disease Ontology ID - DOID:0060538
Pathophysiology: Regardless of the underlying cause of purpura fulminans, the mechanism of disease is similar with deficiency in protein C concentration or decrease in protein C activity which promotes blood clotting (thrombosis).In cases of severe sepsis, there is widespread activation of the acute systemic inflammatory response, including activation of the coagulation and complement pathways, as well as endothelial dysfunction. Activated protein C helps regulate the systemic inflammatory response. During sepsis, signalling by the inflammatory cytokines, interleukin-1 and tumour necrosis factor, mediate altered protein transcription in the systemic inflammatory response, resulting in decreased synthesis of the regulatory proteins antithrombin, protein C and protein S, with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen. Activated protein C binds to endothelial protein C receptor and subsequently cleaves the endothelial cell protease activated receptor-1, not only altering coagulation profiles but down-regulating pro-inflammatory and pro-apoptotic mediators, up-regulation of anti-inflammatory and anti-apoptotic pathways and stabilization of the endothelial cell barrier functions.Systemic coagulation activation may lead to depletion of circulating coagulation factors and platelets, which subsequently lead to bleeding. In early purpura fulminans, lesion progression correlates with the histological appearance of blockage of small skin blood vessels with blood clots causing capillary dilation and congestion with red blood cells. In later stage lesions, there is irreversible endothelial ischaemic injury with extravasation of blood cells into the dermis and gangrenous necrosis, sometimes with secondary infection.The depletion of anticoagulant and anti-inflammatory proteins, in particular, protein C and its co-factor, protein S, may also promote thrombus formation, inhibit fibrinolysis and lead to further activation of the inflammatory pathways.
Carrier Status: Purpura fulminans is not primarily associated with a carrier status as it is an acute and severe form of disseminated intravascular coagulation (DIC) and not a hereditary condition. It is often linked to infections, especially with Neisseria meningitidis, or a thrombotic disorder due to congenital or acquired deficiencies in proteins C or S. Carrier status is not applicable to this condition.
Mechanism: Purpura fulminans is a severe and life-threatening condition characterized by intravascular thrombosis and hemorrhagic infarction of the skin, often following infections or coagulation disorders. The mechanism involves several key components:

1. **Pathophysiology**:
- **Acute Inflammatory Response**: It often follows severe infections, particularly with Neisseria meningitidis, Streptococcus pneumoniae, or Varicella. This triggers a systemic inflammatory response.
- **Coagulation Cascade Activation**: The inflammation leads to widespread activation of the coagulation cascade, resulting in extensive microvascular thrombosis.

2. **Molecular Mechanisms**:
- **Protein C Pathway Dysfunction**: A critical molecular component involves the protein C pathway. Protein C, a natural anticoagulant, is often deficient or dysfunctional in purpura fulminans. Infections or genetic mutations can lead to reduced activation or function of protein C, impeding its ability to regulate clot formation.
- **Endothelial Cell Damage**: The infectious agents and inflammatory cytokines cause direct damage to endothelial cells, increasing vascular permeability and promoting a procoagulant state.
- **Increased Tissue Factor Expression**: Endothelial damage and inflammatory cytokines elevate the expression of tissue factor, a key initiator of the coagulation cascade, further accentuating clot formation.

These mechanisms collectively result in the hallmark findings of purpura fulminans: widespread microvascular clotting, skin necrosis, and hemorrhagic infarction. Early recognition and aggressive management are essential to improve outcomes.
Treatment: Early stage sepsis-associated purpura fulminans may be reversible with quick therapeutic intervention. Treatment is mainly removing the underlying cause and degree of clotting abnormalities and with supportive treatment (antibiotics, volume expansion, tissue oxygenation, etc.). Thus, treatment includes aggressive management of the septic state.Purpura fulminans with disseminated intravascular coagulation should be urgently treated with fresh frozen plasma (10–20 mL/kg every 8–12 hours) and/or protein C concentrate to replace pro-coagulant and anticoagulant plasma proteins that have been depleted by the disseminated intravascular coagulation process.Protein C in plasma in the steady state has a half life of 6- to 10-hour, therefore, patients with severe protein C deficiency and presenting with purpura fulminans can be treated acutely with an initial bolus of protein C concentrate 100 IU/kg followed by 50 IU /kg every 6 hours. A total of 1 IU/kg of protein C concentrate or 1 mL/kg of fresh frozen plasma will increase the plasma concentration of protein C by 1 IU/dL. Cases with comorbid pathological bleeding may require additional transfusions with platelet concentrate (10–15 mL/kg) or cryoprecipitate (5 mL/kg).Established soft tissue necrosis may require surgical removal of the dead tissue, fasciotomy, amputation or reconstructive surgery.
Compassionate Use Treatment: Purpura fulminans is a severe and rapid-onset condition characterized by blood clotting and skin necrosis. For compassionate use treatment, off-label, or experimental treatments, the following options might be considered:

1. **Protein C Concentrate**: Replacement therapy with protein C concentrate can be used, especially in patients with congenital protein C deficiency.

2. **Recombinant Activated Protein C (drotrecogin alfa)**: Though previously used for severe sepsis and showing some efficacy for clotting disorders, its use has been discontinued due to a lack of sufficient benefit.

3. **Antithrombin III**: This can be considered for severe clotting issues, as it inhibits thrombin and other serine proteases.

4. **Heparin and Low Molecular Weight Heparin (LMWH)**: These anticoagulants may be administered, under careful monitoring, to manage disseminated intravascular coagulation (DIC) associated with purpura fulminans.

5. **Fresh Frozen Plasma (FFP)**: This provides clotting factors that may be deficient in patients, especially in those with acute DIC or significant bleeding.

6. **Intravenous Immunoglobulin (IVIG)**: In some cases, IVIG is considered, particularly for idiopathic or autoimmune-related purpura fulminans.

7. **Eculizumab**: This monoclonal antibody, though primarily used for conditions like atypical hemolytic uremic syndrome (aHUS), may be contemplated if complement-mediated pathways are implicated.

8. **Adjunctive Therapies**: Other supportive measures, including antibiotics for infectious causes, wound care, and intensive care support, may be essential for managing systemic effects.

Due to the critical nature of purpura fulminans, treatment decisions often require a multidisciplinary approach and are individualized based on the underlying cause and patient condition.
Lifestyle Recommendations: Purpura fulminans is a severe condition that requires immediate medical attention and primarily managed in a hospital setting. Lifestyle recommendations are generally not applicable for the acute management of this condition. However, for individuals at risk or recovering from an episode, general health tips might include:

1. **Adherence to Treatment**: Strictly follow medical advice, medication regimens, and any recommended follow-up appointments or procedures.
2. **Infection Prevention**: Maintain good hygiene, stay up-to-date on vaccinations, and avoid exposure to infections to minimize the risk of conditions that could trigger purpura fulminans.
3. **Healthy Diet**: Eat a balanced diet to support overall health and immune function.
4. **Regular Exercise**: Engage in appropriate physical activity, as recommended by a healthcare provider, to promote general wellness.
5. **Avoid Smoking and Limit Alcohol**: These can impair immune function and overall health.
6. **Monitor for Symptoms**: Be vigilant for any signs of recurrent issues, such as unusual bruising, bleeding, or symptoms of infections, and seek prompt medical attention if they occur.

These recommendations should complement professional medical care and are intended to support overall health rather than serve as primary treatment.
Medication: Purpura fulminans is a rare, life-threatening condition characterized by widespread blood clotting and skin necrosis. Treatment typically includes the following medications:

1. **Anticoagulants**: Heparin is often used to prevent further clotting.
2. **Antibiotics**: Broad-spectrum antibiotics are administered if the condition is associated with an infection, such as meningococcal septicemia.
3. **Protein C Concentrates**: In cases related to protein C deficiency, protein C concentrates may be administered.
4. **Intravenous Immunoglobulin (IVIG)**: Used in certain cases, such as autoimmune or inflammatory causes.
5. **Vasoactive Agents**: These are used to support blood pressure and improve circulation.
6. **Analgesics or Sedatives**: Given for pain management and to provide comfort.

Immediate medical intervention is crucial, and treatment plans often need to be tailored to the individual patient based on the underlying cause and overall condition.
Repurposable Drugs: There is limited information on the repurposable drugs for purpura fulminans, a rare condition characterized by acute, severe thrombosis and skin necrosis often associated with severe infections or protein C deficiency. Some therapies potentially considered for repurposing based on their mechanism of action might include:

1. **Activated Protein C (Drotrecogin alfa)**: Used in severe sepsis, it may address the coagulation issues.
2. **Heparin**: An anticoagulant that can be used to prevent further thrombotic events.
3. **Fresh Frozen Plasma (FFP)**: Replenishes deficient coagulation factors.
4. **Antibiotics**: Crucial in cases triggered by a bacterial infection.

These are not definitive repurposable drugs but are treatments considered based on the symptoms and underlying mechanisms of purpura fulminans. Always consult a healthcare professional for specific medical advice.
Metabolites: Purpura fulminans is a severe, rapidly progressive, and often fatal condition characterized by hemorrhagic skin lesions and disseminated intravascular coagulation. Relevant metabolic abnormalities may include elevated levels of D-dimer, fibrin degradation products, and decreased levels of anticoagulant proteins like Protein C and Protein S. Hypofibrinogenemia or acquired deficiencies in antithrombin III can also be observed. These changes reflect the underlying coagulopathy and systemic inflammatory response associated with the disease.
Nutraceuticals: Purpura fulminans is a severe, life-threatening condition marked by the sudden onset of widespread bleeding into the skin (purpura) and rapid progression to disseminated intravascular coagulation (DIC). Nutraceuticals (food-derived products with potential health benefits) are not a standard treatment for purpura fulminans. Instead, the management typically involves immediate medical interventions such as antibiotics (if caused by infection), anticoagulants, supportive care, and sometimes plasma exchange or protein C replacement therapy. Prompt treatment in a clinical setting is crucial.
Peptides: Peptides in the context of purpura fulminans can refer to therapeutic agents or biomarkers in clinical research. For instance, certain peptide-based treatments may target coagulation pathways to manage or mitigate symptoms. The abbreviation "nan" is unclear in this context and may need further specification for an accurate response.