Recombinant human activated protein C in the treatment of children with meningococcal purpura fulminans

Meningococcal purpura fulminans (MPF) produces high mortality and morbidity, despite appropriate standard therapy. Administration of recombinant human activated protein C (rhAPC) has been successfully applied in adults with MPF and pediatric studies are under way. We report three pediatric patients with MPF treated with rhAPC as compassionate therapy. In two of these patients, positive clinical and laboratory effects were observed and both children achieved full recovery. The remaining patient died after 36 hours from refractory multiorgan failure. No rhAPC-related adverse effects were detected. The reported cases highlight the usefulness of rhAPC in children with MPF at least as a rescue compassionate treatment. Further clinical trials are needed to better delineate its efficacy and administration schedule in children.     

Management of neonatal purpura fulminans with severe protein C deficiency

Neonatal purpura fulminans is a life threatening clinical entity characterized by extensive subcutaneous thrombosis and disseminated intravascular coagulation usually manifesting shortly after birth. We report an autosomal recessive form of the disease in a neonate who was diagnosed with compound heterozygosity for mutations in his protein C gene as the molecular basis of his disorder.     

Neonatal purpura fulminans due to homozygous protein C deficiency

Severe and recurrent purpura fulminans developed in a Turkish boy at 1 week of age. Initial coagulation studies performed were compatible with disseminated intravascular coagulation. Subsequent investigations showed that the patient had homozygous and his healthy parents had heterozygous protein C deficiency. The episodes of purpura fulminans were controlled by infusions of fresh frozen plasma and heparinization. Oral anticoagulant therapy was given in the symptom-free period.     

A novel protein C mutation causing neonatal purpura fulminans

Background

Neonatal purpura fulminans due to congenital protein C deficiency is a rare disorder.

Case characteristics

A four-day-old neonate presented with multiple necrotic skin lesions with abnormal coagulation profile.

Intervention and outcome

Skin lesions responded to repeated plasma transfusions but the neonate developed bilateral retinal detachment. A novel homozygous PROC gene mutation was noted in the neonate.

Message

Molecular diagnosis and prenatal counseling in neonatal purpura fulminans are vital considering the poor outcome.

     

Activated protein C concentrate reverses purpura fulminans in severe genetic protein C deficiency

Severe genetic protein C deficiency is rare and is associated with severe, often fatal thrombosis. The authors report the use of recombinant activated protein C (APC) to treat an episode of purpura fulminans (PF) in a teenage girl with severe protein C deficiency who had developed anaphylaxis to fresh-frozen plasma that was given in the past to treat recurrent episodes of PF. Concomitant with an infusion of APC, 20 microg/kg/h for 10 hours, a d-dimer level that was markedly positive (6,450 ng/mL) prior to the onset of PF decreased to 847 ng/mL following the APC. The teenager was treated with heparin along with warfarin for four days until the INR was more than 3.5 and the d-dimer level was less than 230 ng/mL. At the end of the APC infusion all skin lesions of PF were resolved. There were no adverse reactions to APC. APC was safe and effective for treatment of PF in severe genetic protein C deficiency.     

Idiopathic purpura fulminans with transient protein S deficiency

Idiopathic purpura fulminans produces rapidly progressive hemorrhagic necrosis of the skin with disseminated intravascular coagulation in individuals without known abnormalities of the protein C pathway or acute infections. The disease mainly affects children and in 90 % of cases is preceded by a benign infection. Its pathogenesis involves a temporary autoimmune protein S deficiency that provokes a state of hypercoagulability. We present the case of a previously healthy 2-year-old boy with hemorrhagic skin lesions characteristic of purpura fulminans and disseminated intravascular coagulation without sepsis. Severe, temporary protein S deficiency was confirmed. The patient received daily replacement therapy with fresh frozen plasma for 12 days and anticoagulation with heparin for 3 months. Evolution was favorable. Although the other parameters returned to normal, protein S remained low for 50 days despite treatment. The patient has made a complete recovery.     

暴发性紫癜的治疗进展

暴发性紫癜(purpura fulminans,PF)征候群又名坏疽性紫癜、坏死性紫癜、出血性紫癜,系儿科危重症,主要为广泛血管内血栓形成,临床表现酷似弥漫性血管内凝血(DIC)。其临床特征为:突然迅速进展的对称性皮肤紫癜,累及全身皮肤,以下肢密集,与其他暴发性皮肤损伤不同的是皮疹可在几小时内由瘀点迅速增大融合为直径为数厘米的瘀斑,基底肿胀坚硬与周围组织分界清楚,颜色由鲜红渐变为暗紫色,坏死后成为黑色焦痂,浆液坏死区发生水泡或血泡,可融合成大泡,发疹的肢体可出现明显肿胀疼痛[1]。本病病因不明,可发生于以下3种情况:急性感染引起的急性感染…     

A case of purpura fulminans secondary to transient protein C deficiency as a complication of chickenpox infection

Purpura fulminans is a rare but dramatic disease which occurs most commonly during or after an infection. It is characterized by extensive involvement of the skin and extremities and involvement of visceral organs. Purpura fulminans, when occurring after a viral infection such as varicella, is usually characterized by purpuric lesions involving the trunk, usually with sparing of the visceral organs. In this report we describe a child with purpura fulminans due to a transient protein C deficiency as a complication of chickenpox infection. A seven-year-old girl developed bruise-like lesions on her extremities on the fifth day after eruption of varicella exanthem. She had no previous history of bleeding tendency or thrombosis. Family history was also negative. On the seventh day of her illness she was admitted to Marmara University Hospital with widespread echymotic an partially crusted chickenpox lesions. CBC, urinalysis and blood chemistries were within normal limits. She had a prolonged aPT and apt with low serum fibrinogen and high D-dimers suggestive disseminated intravascular coagulation (DIC). Protein C activity was low. Punch skin biopsy was consistent with purpura fulminans. She was treated with heparin and fresh frozen plasma which helped her to recover clinically as well as hematologically. She was discharged with still low protein C activity that returned to normal by the next follow-up visit.     

Meningococcal purpura fulminans treated with medicinal leeches.

INTRODUCTION: Meningococcal septicemia remains one of the most common infectious causes of admission to a pediatric intensive care unit. Numerous treatment strategies aimed at the thromboembolic complications inducing purpura fulminans and limb/digital ischemia have been attempted, with variable results. The successful use of medicinal leeches for pneumococcal purpura fulminans has been described, and we present a similar case of meningococcal purpura fulminans. PATIENT AND INTERVENTION: A 5-wk-old female infant with meningococcal meningitis and septicemia and progressive purpura fulminans of the left hand was treated with medicinal leeches. Medicinal leeches were applied to the left dorsal hand on a daily basis for 4 consecutive days. RESULT: The swelling and limited functionality visibly improved after 48 hrs, and by 120 hrs, perfusion in the distal phalanges of the thumb and middle finger was evident. Reperfusion of the distal phalanges was not fully sustained, and at 6 wks the plastic surgery department debrided the distal phalanges of her left hand, excluding the thumb. She fully recovered from the meningococcal septicemic shock; the functionality of her left thumb was preserved, and she has limited functionality of her left hand. CONCLUSION: The unique combination of salivary products in leech therapy has theoretical benefits and requires future study.     

Purpura fulminans in severe congenital protein C deficiency: Monitoring of treatment with protein C concentrate

This report describes the successful use of protein C concentrate to treat severe purpura fulminans in a homozygous protein C-deficient infant for 8 months until oral anticoagulation was initiated. While fresh frozen plasma was previously used in such cases to replace protein C in the acute phase, the availability of a monoclonal antibody purified protein C concentrate now allows specific replacement of protein C, avoiding problems of fluid overload. An occlusive-hydrocolloid bandage proved to be effective in local treatment of skin lesions. D-dimer, fibrin monomer, thrombin-antithrombin complex and prothrombin fragment 1+2 were useful markers in monitoring and optimizing protein C replacement therapy.     

Diagnosis and management of neonatal purpura fulminans

Neonatal purpura fulminans is a rare, life-threatening condition, caused by congenital or acquired deficiencies of protein C or S. The condition is often fatal unless there is early recognition of the clinical symptoms, prompt diagnosis, and judicious replacement therapy is initiated. The clinical presentation is that of acute disseminated intravascular coagulation and hemorrhagic skin necrosis. The management includes an acute phase of replacement therapy with fresh frozen plasma or protein C concentrate and a maintenance therapy that includes anticoagulation with warfarin or low molecular weight heparin. This review focuses on the management of severe protein C deficiency.     

Purpura fulminans in a Chinese boy with congenital protein C deficiency

Severe and recurrent purpura fulminans developed in a Chinese boy at one day of age. Results of coagulation studies performed on the patient during attacks were compatible with the diagnosis of disseminated intravascular coagulation. Subsequent investigations have revealed that the patient is homozygous and that his parents are heterozygous for protein C deficiency. Cryoprecipitate and fresh frozen plasma induced a remission, and administration of warfarin has been successful in preventing recurrence of attacks for as long as 8 months without infusion of any plasma components. None of the family members who are heterozygous for protein C deficiency have had thrombotic episodes.     

Purpura fulminans in a case of protein C deficiency

We report a case of protein C deficiency which presented with purpura fulminans. The inheritance of protein C deficiency is discussed and the importance of warfarin (Coumadin) treatment in this condition is emphasized.Abbreviations DIC disseminated intravascular coagulation - PT prothrombin time     

Severe protein S deficiency associated with heterozygous factor V Leiden mutation in a child with purpura fulminans

Homozygous or compound heterozygous protein S (PS) deficiency is very rare in the population; only 8 patients from 6 different families have been reported. On the other hand, the factor V Leiden (FVL) mutation is a frequent cause of inherited prothrombotic disorder. Here the authors report a case of patient with severe PS deficiency associated with the FVL mutation who has had purpura fulminans since the age of 10 days. She is the first child of a consanguineous marriage. Her father is double heterozygous for PS deficiency and FVL mutation and has recurrent thrombosis. This is the first case of severe PS deficiency combined with the FVL mutation. This suggests the need for complete evaluation of patients with purpura fulminans for thrombotic factors.     

High-dose heparin in a patient with purpura fulminans following varicella

We report on a 3 1/2 year old girl with purpura fulminans after varicella who made a complete recovery on treatment with an appropriate high-dose heparin regimen and other supporting measures. Several attempts to reduce the heparin dosage from the initial high level (85 IU/kg/hour) to the usual level (25 IU/kg/hour) were followed each time by an immediate deterioration in the clinical condition.