Multiple arterial and venous thromboembolism in a male patient with hereditary protein C deficiency: A case report.

RATIONALE: Hereditary protein C deficiency has a high prevalence in Asian populations, being the important risk factor associated with thrombophilia. Traditionally, conservative medication is the first choice for patients with hereditary protein C deficiency. However, there are few reports on whether aggressive surgical treatment can be performed when patients continue to develop life-threatening ischemic symptoms after adequate anticoagulant and thrombolytic therapy. PATIENT CONCERNS: A 40-year-old male presented with right lower extremity pain for 1 week. DIAGNOSIS: Computed tomography angiography (CTA) of lower extremity indicated arterial embolization of the right superficial femoral artery. Vascular ultrasonography showed old extensive thrombus in the deep vein of the left lower extremity. Electrocardiogram reported old anterior myocardial infarction. Sequencing of the gene encoding protein C (PROC) gene revealed that a heterozygous in-frame deletion mutation (c.577-579delAAG, p.192delK). Based on these findings, the diagnosis of hereditary protein C deficiency was made. INTERVENTIONS: The patient was given low-molecular-weight heparin (LMWH) anticoagulation and urokinase treatment immediately. Then we performed the Fogarty catheter embolectomy with about 18.5 cm thrombus being removed and utilized the balloon catheter to dilate the anterior tibial artery. Despite given adequate anticoagulant and thrombolytic therapy postoperatively, the patient still had new thrombosis, and eventually underwent arterial embolectomy and amputation. OUTCOMES: The patient was discharged with good wound healing and continued rivaroxaban treatment at a dose of 20 mg daily. The patient was followed-up monthly until 1 year: there was no adverse ischemic events occurred. LESSONS: Aggressive surgical treatment may be the effective attempt for life-saving when conservative treatment as the first choice had unsatisfactory results in hereditary protein C deficiency patients. The novel oral anticoagulants (NOACs) could be more suitable than warfarin for the treatment and prevention of recurrence in patients with hereditary protein C deficiency.

Liver transplantation for congenital protein C deficiency with initial poor graft function: a case report with literature review.

Congenital deficiency of protein C (PC) is a rare disease that causes thrombophilia during the neonatal and infantile periods. Despite anticoagulative treatments, purpura fulminans and major vessel thrombosis often occur. We report a 7-year-old girl with congenital PC deficiency who underwent deceased donor liver transplantation (LT) and experienced complications accompanied by initial poor graft function (IPGF). Before LT, she had cerebral and ophthalmic hemorrhage, and seven episodes of purpura fulminans. The operation was successfully performed; however, the liver graft developed IPGF. Hyperammonemia and coagulopathy required continuous hemodiafiltration and infusion of fresh frozen plasma. It took 22 days for PC activity to reach reference levels. The changes in clotting and anticlotting activities in the patient's plasma were revealed using clot waveform analysis and the HemosIL ThromboPath® assay. PC activity remained normal for 5 years after LT. Even when IPGF occurs, liver function including PC activity can remain normal for a long time after recovery from IPGF. LT can be a curative treatment for congenital PC deficiency.

Protein C Deficiency.

Protein C (PC) deficiency is a heritable or acquired risk factor for thrombophilia, with presentations varying from asymptomatic to venous thromboembolism to neonatal purpura fulminans, a life-threatening disorder. Hereditary PC deficiency is caused by mutation in the PC (PROC) gene located on chromosome 2q14.3. Heterozygous and acquired PC deficiencies are more common than homozygous deficiency. The recommended initial laboratory test measures PC activity using either clot-based or chromogenic methods. There are numerous potential interferences in PC activity testing that may result in either false-positive (falsely low activity) or false-negative (falsely normal or elevated activity) results. In the present review, we discuss common clinical presentations; laboratory testing, with a focus on potential assay interferences; treatment options; and prognosis in patients with PC deficiency.

Homozygous protein C deficiency presenting as neonatal purpura fulminans: management with fresh frozen plasma, low molecular weight heparin and protein C concentrate.

Purpura fulminans in neonates is a rapidly progressive thrombotic disorder manifesting as hemorrhagic skin infarction and disseminated intravascular coagulation. Being inherited in an autosomal dominant manner, it is a medical emergency. Clinical presentations of patients may vary depending on the genetic mutations. Retinal and intracranial hemorrhages are the worst clinical scenarios with persistent morbidity. During acute phase, fresh frozen plasma, protein C concentrates and anticoagulant therapy should be administered rapidly. Here we report a patient with homozygous protein C deficiency.

Perioperative management of severe congenital protein C deficiency.

: Perioperative care of congenital protein C deficiency has not been well established. Here, we describe a patient with congenital protein C deficiency who underwent laparoscopic fundoplication and gastrostomy at 2 years of age. Preoperatively, we stopped warfarin, administered fresh frozen plasma, and activated protein C. These procedures were performed without bleeding or clotting events, and at 3 days after the procedures, we restarted warfarin. Several episodes of abdominal hemorrhage and purpura fulminans occurred 2-4 weeks postoperatively, and the events were managed conservatively. We conclude that an invasive procedure can be performed in patients with protein C deficiency with appropriate supportive therapy, and postoperative observation for a sufficient length of time is essential to minimize the risk of complications.

Arterial thrombosis in "protein C deficiency"--a rare event.

We report here a case of a 35 year old male with protein C deficiency who presented with acute right sided hemiparesis with right sided facial palsy due to cerebral arterial thrombosis. He was treated with anticoagulation therapy and improved. This case is interesting as arterial thrombosis is rarely observed event in protein C deficiency.

[Sepsis-associated Purpura Fulminans International Registry--Europe (SAPFIRE)]. / Ein europäisches Register für sepsisassoziierte Purpura fulminans (SAPFIRE).

BACKGROUND: Purpura fulminans is a rare life-threatening condition which is characterized by disseminated thrombosis in dermal and systemic microcirculation, cutaneous hemorrhages with progressing necrosis and multiple organ failure. The underlying pathogenesis is based on the disruption of the intrinsic anticoagulation cascade, with protein C deficiency being considered the leading factor in this process. In the majority of cases, the condition emerges as consumptive coagulopathy associated with severe sepsis. OBJECTIVES: Epidemiological data on sepsis-associated purpura fulminans (SAPF) are scarce and evidence-based treatment guidelines have not been established yet. While restoration of the balance in the coagulation cascade is a declared therapeutic goal, evaluations of the efficacy of different therapeutic approaches in randomized clinical trials are still lacking. The causal role of individual microbial pathogens also requires comprehensive evaluation. METHODS: A prospective multicenter Sepsis-Associated Purpura Fulminans International Registry-Europe (SAPFIRE) will be established in the first quarter of 2015. For the first time, participating centers will systematically collect information on etiology, clinical course, biomarkers, treatment, morbidity, and mortality of SAPF. RESULTS: The SAPFIRE data will be periodically evaluated and disseminated. Retrospective analysis of each center's data and regular access to aggregated information collected by other centers will enable the participants to monitor and update care quality standards.

HIV-associated thromboembolic phenomenon due to protein C deficiency.

HIV-infected individuals are at a high risk of developing arterial and venous thromboembolism. Opportunistic infections, protease inhibitors, low CD4 count, antiphospholipid antibodies, protein S, and protein C deficiencies are some important risk factors associated with it. However, thromboembolic phenomenon due to protein C deficiency has been rarely reported. We report a case of a 12-year-old girl with facial palsy due to middle cerebral artery infarct because of HIV infection and associated protein C deficiency.

Long-term follow-up of homozygote protein C deficiency after multimodal therapy.

Homozygous protein C deficiency is an extremely rare condition presenting in the neonatal period with purpura fulminans, with very high rates of morbidity and mortality. Optimal treatment for this condition is highly complex, poorly understood, and often limited by cost and product supply. We report a child who presented 2 days after birth with purpura fulminans and severe prenatal eye damage, but no cerebral lesions. He was treated with novel multimodal therapy culminating in liver transplant at 3 years of age. The patient is now 12 years of age, well, with blindness as his only long-term deficit.

Hypoimmunoglobulinemia and protein C deficiency in a girl with Jacobsen syndrome: a case report.

Jacobsen syndrome is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. The typical clinical manifestations include physical growth retardation, mental retardation,facial dysmorphisms, congenital heart disease, thrombocytopenia, or pancytopenia. A Thai-Australian girl was born with multiple abnormalities. Typical features and her karyotype, 46, XX, del(ll) (q23-qter), confirmed Jacobson syndrome. She had many uncommon findings including upslanting palpebral fissures, tortuousity of retinal vessels and hypogammaglobulinemia. In addition, this case also presented with protein C deficiency, which has not been reported previously in Jacobsen syndrome. The patient was treated with phototherapy, intravenous antibiotic injection, and platelet transfusion in neonatal period. Cranioplasty was performed for prevention of the increased intracranial pressure at three months of age. Surgical correction for strabismus was in the treatment plan.

Neonatal asphyxia and renal failure as the presentation of non-inherited protein C deficiency.

Inherited or acquired protein C (PC) deficiency leads to thromboembolic events. Plasma PC activity in infancy is physiologically lower than in adults. We describe a case of neonatal asphyxia and acute renal failure associated with isolated PC deficiency. A full-term male infant was born to a healthy mother by caesarean section because of fetal distress. The small-for-gestational age infant showed 2 and 7 of Apgar scores at 1 and 5 minutes, respectively. Hypercoagulability required repeated infusions of fresh frozen plasma. Coagulation study revealed PC activity, 6%, protein S activity, 61%, and high D-dimer levels, along with normal factor VII activity and absent vitamin K deficiency. Anticoagulant and activated PC therapy improved coagulopathy and nephropathy. Imaging analyses indicated no visceral infarctions. Renal function and PC activity have been slowly normalized until 6 months of age. He had no PROC mutation or PC-deficient parents. Selective PC deficiency may occur as an acquired cause of hypercoagulable crisis in the stressed newborn.

Predicting the risk of venous thromboembolism recurrence.

Venous thromboembolism (VTE) is a chronic disease with a 30% ten-year recurrence rate. The highest incidence of recurrence is in the first 6 months. Active cancer significantly increases the hazard of early recurrence, and the proportions of time on standard heparin with an APTT ≥ 0.2 anti-X(a) U/mL, and on warfarin with an INR ≥ 2.0, significantly reduce the hazard. The acute treatment duration does not affect recurrence risk after treatment is stopped. Independent predictors of late recurrence include increasing patient age and body mass index, leg paresis, active cancer and other persistent VTE risk factors, idiopathic VTE, antiphospholipid antibody syndrome, antithrombin, protein C or protein S deficiency, hyperhomocysteinemia and a persistently increased plasma fibrin D-dimer. A recommendation for secondary prophylaxis should be individualized based on the risk for recurrent VTE (especially fatal pulmonary embolism) and bleeding. The appropriateness of secondary prophylaxis should be continuously reevaluated, and the prophylaxis stopped if the benefit no longer exceeds the risk.

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.

Protein C deficiency: a case review.

Protein C (PC) deficiency is a rare but life-threatening bleeding disorder that can present in the immediate neonatal period. This article presents the case of a baby girl with acute and progressive neonatal purpura fulminans as the presenting feature of PC deficiency. Other common complications of this disease include ophthalmic problems and central nervous system (CNS) changes. Management consists of correcting the coagulopathy, intensive wound care including negative-pressure dressings and skin grafting, and supportive care for the ophthalmic and CNS issues. Long-term follow-up consists of lifelong anticoagulant therapy to avoid recurrence of these complications.

Duplication of the inferior vena cava in a patient presenting for IVC filter placement.

Given the complex embryogenesis of the inferior vena cava (IVC), anatomic variations are commonly encountered. Duplication of the IVC occurs in up to 2.8% of the population. Though asymptomatic, a duplicated IVC has important clinical implications when attempting caval filtration. We present the case of a 45- year-old male with factor V leiden and protein C deficiency, who required cessation of warfarin anticoagulation in preparation for cervical laminectomy. The patient had a duplicated IVC and required placement of a caval filter in each IVC.

Varicella-associated purpura fulminans and multiple deep vein thromboses: a case report.

Varicella-associated purpura fulminans is a rare syndrome associated with substantial morbidity and mortality. General supportive care, heparinization, and plasma infusions are the mainstays of treatment. A patient aged 8 years and 8 months with purpura fulminans and multiple deep vein thromboses after varicella infection because of deficiencies of proteins C and S is presented in this case report.

Treatment of inherited protein C deficiency by replacement therapy with the French purified plasma-derived protein C concentrate (PROTEXEL).

BACKGROUND/OBJECTIVES: A multicentre retrospective study was performed to assess the efficacy/safety of a French purified plasma-derived protein C (PC) concentrate in inherited PC deficiency. MATERIALS AND METHODS: Nine patients were enrolled, five children aged < 5 weeks, among whom four with a severe deficiency were homozygous, and four patients < 37 years with PC levels ranging 14-25%, including one compound heterozygous. RESULTS: Thirty replacement therapy courses were recorded with mean PC dosages ranging between 24-90 IU/kg/day for prophylactic courses and 51-209 IU/kg/day for treatment courses. Recoveries varied between 0.8 and 1.12% IU/kg in preventive situations and between 1.09 and 1.91% IU/kg for treatment courses; 23 treatment courses were performed in patients aged 1 day to 18 years, 19 out of 23 treatments resulted in complete recovery with no sequelae. Treatment efficacy was difficult to assess in four out of 23 cases because the thrombotic event was not confirmed in one case and due to late treatment initiation in the three other cases. Seven prophylactic treatments were used either in association of vitamin K antagonists or to prevent thrombotic events due to vitamin K antagonist introduction or withdrawal. The safety assessed during 914 infusions was excellent. No abnormal bleeding was reported, including with high doses, during surgery, with heparin therapy. CONCLUSIONS: Replacement therapy with this French PC concentrate is safe and effective in patients with inherited PC deficiency.