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.     

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     

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.     

Long-term survival of a child with homozygous protein C deficiency successfully treated with living donor liver transplantation

Abstract:  Homozygous protein C deficiency is an autosomal recessive disorder often presenting with purpura fulminans. Fresh frozen plasma and oral anticoagulation have been used in the treatment of this disease. Lately, protein C concentrate has become the treatment of choice. However, protein C concentrate is not yet widely available in many countries. We report a six-month-old girl with homozygous protein C deficiency who had suffered from frequent thrombotic episodes. She was successfully treated with living donor liver transplantation. Eight years after the transplantation, she remains symptom free. As described here, the liver transplantation offers an alternative curative treatment for children with homozygous protein C deficiency.     

Renal transplantation experience in a patient with factor V Leiden homozygous,MTHFR C677T heterozygous,and PAI heterozygous mutation

Vascular complications are important causes of allograft loss in renal transplantation. A two and a half‐month‐old boy was diagnosed with posterior urethral valve and progressed to end‐stage renal disease at eight yr of age. During the HD period, a central venous catheter was replaced three times for repeated thrombosis. The boy was found to be homozygous for FVL and heterozygous for both MTHFR (C677T) and PAI. At the age of 12, renal transplantation was performed from a deceased donor. Postoperative anticoagulation therapy was initiated with continuous intravenous administration of heparin at the dose of 10 IU/kg/h. HD was performed for the first three days. By the fourth day of transplantation, his urine output had increased gradually. Heparin infusion was continued for 18 days during hospitalization at the same dosage. Thereafter, he was discharged with LMWH. On the third month after transplantation, his serum creatinine level was 1.1 mg/dL and eGFR was 75.7 mL/min/1.73 m². He has still been using LMWH, and his eGFR was 78.7 mL/min/1.73 m² eight months after transplantation. Postoperative low‐dose heparin treatment is a safe strategy for managing a patient with multiple thrombotic risk factors.     

Diagnosis and treatment of a newborn with homozygous protein C deficiency

The case is reported of a seriously affected newborn with homozygous protein C deficiency who developed neonatal purpura fulminans. Foetal ultrasound at 33 wk of gestation revealed ventriculomegaly. The first lesions appeared on the scalp 48 h after birth. She was initially treated with fresh-frozen plasma and, after the diagnosis was confirmed, with purified protein C concentrate. After skin necrosis had healed, therapy was continued with oral warfarin. The infant was homozygous for protein C W380G mutation. Diagnosis at the DNA level gave the parents an option of reliable prenatal diagnosis in their subsequent pregnancy. CONCLUSION: Difficulties in reaching an accurate diagnosis are discussed since early diagnosis and urgent therapy with protein C replacement are crucial to avoid further damage after delivery.     

Coexistence of acquired protein S and protein C deficiency and the Arg506Gln mutation in factor Va in a child with severe thromboembolic disease

An 11-y-old girl who presented with cellulitis and clinical signs of deep vein thrombosis (DVT) is reported here. She developed staphylococcal sepsis, recurrent septic emboli and a large vegetation on the tricuspid valve. The patient was found to be heterozygous for the Arg506Gln mutation in factor Va and had low levels of protein C and protein S during the sepsis. The coexistence of the two thrombophilic states may explain the severe thromboembolic manifestations.     

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.     

Cerebral sinus thrombosis in a child with active ulcerative colitis and factor V Leiden

Ulcerative colitis (UC) is a rare cause of cerebral sinus thrombosis. We describe a 10‐year‐old patient with UC who developed cerebral sinus thrombosis during an acute exacerbation of his colitis and was found to be heterozygous for factor V Leiden. He was successfully treated with enoxaparin. Enoxaparin was then used for prophylaxis during acute exacerbations of his UC without any recurrence/progression of cerebral venous thrombosis. This report describes a cerebral thrombotic event in a child with UC and factor V Leiden. Pediatr Blood Cancer 2009;52:867–869. © 2009 Wiley‐Liss, Inc.     

Portal vein thrombosis in association with factor V Leiden mutation in a patient with hepatocellular carcinoma

We report a case of hepatocellular carcinoma associated with portal vein thrombosis. Analysis of whole cellular DNA demonstrated heterozygosity for the factor V Leiden mutation. The patient also had marked protein C deficiency. The presence of the mutation associated with protein C deficiency may increase the risk of thrombosis in this patient with hepatocellular carcinoma. Med. Pediatr. Oncol. © 1997 Wiley-Liss, Inc.     

Deep venous thrombosis in a child with nephrotic syndrome associated with a circulating anticoagulant and acquired protein S deficiency.

Thromboembolic events occur with a frequency of 3-5% in children with nephrotic syndrome (NS). Although numerous abnormalities in all phases of coagulation have been described in NS, the pathogenesis of clotting abnormalities remains poorly understood in this group of patients. We describe a child with long-standing NS in whom a severe deep venous thrombosis and pulmonary embolism secondary to acquired protein S deficiency and a strong lupus-type circulating anticoagulant developed. In addition, this patient had a markedly decreased plasma level of C4b binding protein. Although acquired protein S deficiency has been described in various clinical disorders including NS, our patient is unusual in having C4bBP deficiency, and his is the only reported pediatric case of NS complicated by thromboembolism in which a circulating anticoagulant has been implicated, to our knowledge.     

Successful living domino liver transplantation in a child with protein C deficiency

PC is produced in the liver and inhibits blood coagulation by catalyzing active factors V and VIII. PC deficiency causes abnormal blood clotting that is difficult to regulate by anticoagulative treatments. Four reports of PC deficiency treated with LTx have been published; however, no report of DLT as a therapy for PC deficiency is available. We describe a case of a 23‐month‐old girl who received DLT for compound heterozygous PC deficiency. Her PC activity was below 5%. She developed intracranial lesion and frequent refractory purpura fulminans. Both her parents had heterozygous mutations of PC genes and were excluded as living donors. Furthermore, she was a low priority on the waiting list of deceased‐donor transplantation. We performed living DLT using the liver from a patient with MSUD. Activated PC concentrate safely supported the perioperative period. After DLT, she maintained normal PC activities and BCAA levels. This is the first case of PC deficiency successfully treated by living DLT with MSUD. We propose that DLT using liver from patients with MSUD is a treatment option for PC deficiency.     

Successful renal transplantation in a patient with heterozygous prothrombin gene, factor V Leiden mutation and heparin-induced thrombocytopenia using r-hirudin as anticoagulant

Vascular complications remain the most common cause of early renal allograft loss in patients with end-stage renal failure. Underlying thrombophilic disorders increase the risk of early graft thrombosis. A male adolescent with high-risk thrombophilia because of combined heterozygous factor V Leiden (G1691A) and prothrombin gene (G20210A) mutation developed HIT II. Hemodialysis and subsequent renal transplantation were undertaken using recombinant hirudin, a direct and selective thrombin inhibitor, as an anticoagulant. Primary function in the transplanted kidney was excellent. No thrombotic or hemorrhagic events have occurred and follow-up showed excellent long-term graft survival. Patients on HD have an increased risk for the development of HIT, and therefore, they need repetitive screening for the development of acquired thrombotic risk factors (e.g. HIT II or lupus anticoagulant). R-hirudin is efficacious and safe on both HD and following renal transplantation.     

Anticardiolipin and acquired protein S deficiency in early childhood

A 27 month old child presented with left hemiplegia and was found to have deep cerebral venous thrombosis. The deep cerebral venous thrombosis resolved on warfarin. Elevated and fluctuating anticardiolipin antibodies as well as protein S deficiency were detected.     

Successful treatment with cyclosporin A in a child with acquired pure amegakaryocytic thrombocytopenic purpura

Idiopathic acquired pure amegakaryocytic thrombocytopenic purpura (APATP) in young patients (non-neonates) is a rare disorder with a variable clinical course. Cure is unusual. A 13.5-year-old boy with idiopathic APATP was treated with cyclosporin A. Apparently effective, the treatment resulted in the reappearance of marrow megakaryocytes and normalization of platelet count.     

Mesenteric venous thrombosis in a child with type 2 protein S deficiency

A 5-year-old girl presented with abdominal pain and bloody stools 2 weeks after suffering from influenza A infection. Enhanced computed tomographic scan showed widespread splanchnic venous thrombosis and small intestine necrosis. She recovered after the necrotic bowel was resected. The patient continues to receive anticoagulant therapy. Thrombophilia screening after the complete resolution consistently showed mildly decreased protein S (PS) activity with normal PS antigen levels. Sequence analysis detected a heterozygous K196E mutation in the PROS1 gene. Type 2 PS deficiency was diagnosed. This is the first report of mesenteric vein thrombosis in a child with a type 2 PS deficiency.     

Postinfection purpura fulminans in a patient heterozygous for prothrombin G20210A and acquired protein S resistance

Purpura fulminans usually consists of large, often symmetrical, spreading ecchymosis, which may later develop into extensive areas of skin necrosis and peripheral gangrene. Postinfectious purpura fulminans associated with an autoantibody directed against protein S has been described. The interaction and the contribution of recently described mutations such as factor V Leiden and prothrombin G20210A to the development and progression of postinfectious purpura fulminans and venous thrombosis is not known. The authors describe a patient heterozygous for prothrombin G20210A who developed purpura fulminans and extensive venous thrombosis secondary to acquired protein S deficiency.     

Catheter-associated recurrent intracardiac thrombosis and factor V Leiden mutation in a child with non-Hodgkin's lymphoma

Patients with cancer have an increased risk for thromboembolism, which might be related to several factors including central venous catheters and chemotherapeutics. Congenital prothrombotic risk factors might also contribute to thrombotic events. In this report, we present a catheter-related recurrent intracardiac thrombosis in a boy with non-Hodgkin's lymphoma and factor V Leiden mutation. Screening for factor V Leiden mutation in children with cancer and recurrent thrombotic events is recommended. Periodic echocardiography may be considered for a group of patients if the catheter tip is in the right atrium and therapy includes L-asparaginase and corticosteroids.     

Impaired IgG responses in a child with homozygous C2 deficiency and recurrent pneumococcal septicaemia

Homozygous deficiency of the second component of complement (C2) is the most common inherited deficiency of complement. Although C2 deficiency has been detected in asymptomatic individuals, patients usually present with either autoimmune disease or recurrent pyogenic infection, particularly due to encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis. Interestingly, infection is the most common mode of presentation of C2 deficiency in young children (1). An association between C2 deficiency and IgG subclass deficiency has also been previously described. We now report a female child with C2 deficiency that presented at the age of 3 mo with recurrent pneumococcal septicaemia. Although IgG subclass levels were normal, specific IgG responses to vaccination against S. pneumoniae and H. influenzae were significantly impaired.