Long-term Follow-up of Homozygote Protein C Deficiency After Multimodal Therapy

Monagle, Kate; Ignjatović, Vera; Hardikar, Winita; Newall, Fiona; Monagle, Paul

doi:10.1097/mph.0000000000000032

Cited by 15 publications

(11 citation statements)

References 20 publications

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“…Liver transplantation has been successful in the management of severe PC deficiency, but the evidence is limited to few cases . In general, pediatric liver transplantation shows excellent long‐term survival (75–90%) for most conditions, so is an attractive option for severe PC deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…Such a discrepancy between two PC activity assays has been previously described in two patients, one with a rare PC variant [14] and another in a patient on PC replacement. [15] Such a discrepancy has to be kept in mind while interpreting PC assays. Index case remained thrombosisfree with trough PC activity of 15-25% (chromogenic) or 8-15% (clotting).…”

Section: Pc Activitymentioning

confidence: 99%

“…Liver transplantation has been successful in the management of severe PC deficiency, but the evidence is limited to few cases. [15][16][17][18] In general, pediatric liver transplantation shows excellent long-term survival (75-90%) for most conditions, [19] so is an attractive option for severe PC deficiency. However, complications related to immunosuppression, transplant-related mortality, and secondary malignancies should be considered.…”

Section: Liver Transplantmentioning

confidence: 99%

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Severe Congenital Protein C Deficiency: Practical Aspects of Management

Shah

Ferreira

Karmali

et al. 2016

Pediatr Blood Cancer

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Subcutaneous (SC) protein C (PC) was used in a child with purpura fulminans secondary to severe congenital PC deficiency. For maintenance, PC 80-120 IU/kg, given over 60-90 min SC Q48hr, has been successful as a home therapy for more than 3 years. The treatment was monitored by measuring trough PC chromogenic activity (target ≥15%) and D-dimer levels. No change in clinical course was appreciated after discontinuing enoxaparin (and leaving the patient on prophylactic PC replacement alone). A significant discrepancy between clotting-based and chromogenic-based PC activity is shown.

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Section: Discussionmentioning

confidence: 99%

Section: Pc Activitymentioning

confidence: 99%

Section: Liver Transplantmentioning

confidence: 99%

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Severe Congenital Protein C Deficiency: Practical Aspects of Management

Shah

Ferreira

Karmali

et al. 2016

Pediatr Blood Cancer

View full text Add to dashboard Cite

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“…The rarity of severe PC deficiency and inherent risks with liver transplantation make this curative therapy exceptional. Only seven case reports of this intervention exist in the literature . For all but one of these, the transplanted organs, both cadaveric and living, came from otherwise healthy donors to ensure resolution of the PC deficiency.…”

Section: Protein C Baseline Testing For Affected Family Membersmentioning

confidence: 99%

Successful liver transplantation for homozygous protein C deficiency with a type II mutation using a heterozygous living related donor

et al. 2018

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“…LT is a well‐established curative treatment for congenital PC deficiency . In addition to the clear economical advantage over the costly life‐long Ceprotin treatment, endogenous PC produced by the graft liver requires less frequent monitoring.…”

mentioning

confidence: 99%

Successful ABO‐incompatible pediatric living donor liver transplantation in an infant with protein C deficiency

Yeh

Yen²,

Lin

et al. 2017

Pediatric Blood & Cancer

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described a case of protein C (PC) deficiency maintained successfully by daily subcutaneous infusions of Ceprotin (human PC concentrate).They mentioned liver transplantation (LT) as another treatment option.Here, we present a case and rationale in support of early referral for transplantation. F I G U R E 1 Protein C supplementation (blue bar, right axis, IU/day) and serum D-dimer levels (gray line, left axis, mcg/dl) decreased while serum protein C activity levels (orange line, left axis, %) rose steadily after living donor liver transplantation (arrow) A male term baby, ABO blood group O, developed pulmonary hemorrhage with disseminated intravascular coagulation shortly after birth. Purpura fulminans with necrotic skin lesions soon developed.Aggressive transfusion of fresh frozen plasma (FFP) was given. His serum PC activity was <5%. Genetic testing revealed compound heterozygous PROC gene mutations (c.532G>C/c.679G>T). Multiple intracranial hematomas with right subretinal hematoma were found on magnetic resonance imaging. The patient was treated with regular subcutaneous Ceprotin and oral warfarin. At age 4 months, LT was considered due to unstable disease and a large Ceprotin requirement.His uncle (blood group B) was selected as a living related donor as the parents were heterozygotes. Due to previous massive FFP transfusions, the patient's serum anti-B IgG titer was 1:256, which was successfully lowered to 1:64 after transfusing type AB FFP (20 ml/kg/day).Ceprotin (2,000-4,000 IU/day), enoxaparin (300 IU/kg/day), and vitamin K1 (1 mg/day) were continued. A reduced lateral segment graft was implanted at age 5 months and 19 days. The body weight at LT was 5.9 kg and graft weight was 205 g (graft-recipient weight ratio 0.0346).Tacrolimus and steroid were used for immunosuppression. Ceprotin was given intraoperatively (6,000 IU) and gradually reduced with therapeutic targets of serum D-dimer <20 mcg/ml, trough serum PC activity level >50%, and INR around 1.5. His PC activity level increased steadily ( Fig. 1). At last follow-up, age 28 months, he had been weaned off tacrolimus for 6 months. Recent biopsy showed no evidence of rejection. The anti-B IgG titer remained low (1:1).LT is a well-established curative treatment for congenital PC deficiency. [2][3][4][5][6][7] In addition to the clear economical advantage over the costly life-long Ceprotin treatment, endogenous PC produced by the graft liver requires less frequent monitoring. The procedure obviates the risk of recurrent coagulation derangement and its organ damaging hemorrhagic and thrombotic events, 3,4,6,7 some of which may preclude receiving LT. The long-term survival of LT in infants has improved and is now comparable to older children. 8 The concern of long-term immunosuppression has been addressed by our recent report on successful minimization/withdrawal of tacrolimus, 9 in which most of the participants tolerated dose reduction, and one-third were stably weaned off the drug. Lastly, it is well known that infants do not require any specific measure...

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Long-term Follow-up of Homozygote Protein C Deficiency After Multimodal Therapy

Cited by 15 publications

References 20 publications

Severe Congenital Protein C Deficiency: Practical Aspects of Management

Severe Congenital Protein C Deficiency: Practical Aspects of Management

Successful liver transplantation for homozygous protein C deficiency with a type II mutation using a heterozygous living related donor

Successful ABO‐incompatible pediatric living donor liver transplantation in an infant with protein C deficiency

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