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.

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.

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.

Intestinal lymphangiectasia with protein-losing enteropathy in Waldenstrom macroglobulinemia.

Gastrointestinal complications of Waldenstrom macroglobulinemia (WM) are unusual but often treatable. We report a case of WM associated with significant gastrointestinal involvement manifest as chronic diarrhea with protein-losing enteropathy and recurrent venous thromboses. Small bowel biopsy was negative for amyloidosis but revealed intestinal lymphangiectasia with deposition of monoclonal IgM. The patient was treated with cyclophosphamide, vincristine, and prednisone with rapid and complete resolution of the peripheral edema and diarrhea. We follow the case report with a retrospective analysis of patients with WM and gastrointestinal symptoms seen at our institution, and review the available literature on this unusual association. An increased awareness of the gastrointestinal manifestations of WM may help to explain and to treat the chronic, debilitating, and potentially life-threatening symptoms in patients with this lymphoproliferative disorder.

Cardiopulmonary bypass for a coronary artery bypass graft patient with heterozygous protein C deficiency and protein S deficiency.

Cardiopulmonary bypass (CPB) poses great risks for hypercoagulable patients and requires management techniques to ensure an optimal outcome free from thrombotic events. This case report reviews perfusion management techniques that may contribute to a safer CPB experience for a patient deficient in both protein C and protein S. A patient with heterozygous protein C deficiency is at increased risk of thrombosis, especially in the venous circulation. Since it is an essential cofactor for activated protein C, deficiency of free protein S is also linked to a hypercoagulable condition. A 52-year-old male presented to our institution with a past medical history of hypercoagulable state, multiple deep vein thromboses, pulmonary embolisms, and stroke. He was scheduled for two-vessel coronary artery bypass graft surgery to be followed by right carotid endarterectomy (RCEA) before discharge. The anesthesia and perfusion teams worked closely together to ensure that fresh frozen plasma (FFP) was given intraoperatively at appropriate times. Heparin dose response and protamine dosage was determined with hemostasis management system (HMS) analysis. The closed CPB circuit and cannulae were Carmeda bonded. Rapid autologous priming, along with the use of a hemoconcentrator, kept the hematocrit above 21 during CPB. Zero-balance ultrafiltration and leukocyte depletion were initiated during rewarming to aid in attenuation of the inflammatory response. To conserve coagulation factors, all pump blood was ultrafiltrated post-CPB and returned to the patient. Laboratory samples drawn on postoperative day (POD) one measured normal protein C activity with subnormal protein S activity. On POD six, the patient underwent RCEA and he was discharged on POD eight without complications.

[Paradox: when a prothrombotic disorder is responsible for an upper gastrointestinal bleeding. Case report of hepatoportal sclerosis]. / Paradoxe: lorsqu'un état prothrombotique est responsable d'une hémorragie digestive. Observation d'un cas de sclérose hépatoportale.

Variceal bleeding is frequently the initial presentation of a previously unknown cirrhosis. Portal hypertension and its complications without liver cirrhosis should raise the possibility of presinusoidal portal hypertension, and the diagnosis of hepatoportal sclerosis. These patients need to be investigated for coagulation disorders. A hypercoagulable state is often associated. Risks and benefits of anticoagulation should be further investigated in these patients.

Use of aprotinin during cardiopulmonary bypass in a patient with protein C deficiency.

This case study reviews cardiopulmonary bypass (CPB) management in a Protein C deficient patient undergoing reoperation for an atrioventricular (AV) valve replacement with the use of aprotinin. Protein C inhibits factors Va and VIIIa in the coagulation cascade and inactivates tissue plasminogen activator inhibitor, thus maintaining hemostasis. Protein C deficiency can cause hypercoagulability and may result in thrombotic episodes, especially in areas of low blood flow or during activation of the coagulation cascade. A 17-year-old male presented with a functional single ventricle and AV valve regurgitation. The patient had a history of three previous AV valve replacements. Protein C deficiency was first diagnosed after thrombosis of the first valve prosthesis. Other case studies in protein C deficient patients suggested the use of fresh frozen plasma (FFP) before bypass to restore protein C levels, ATIII replacement before heparin administration, and avoidance of aprotinin because of its known competitive inhibition of activated protein C. Two units of FFP were given by anesthesia before the administration of aprotinin, and two units of FFP were added to the pump prime. The full Hammersmith loading dose of aprotinin was administered just before initiation of CPB. The same dose of aprotinin was added to the pump prime just before initiation of CPB. Additional heparin (100 U/kg) was administered every hour during bypass. Activated clotting time tests (ACTs) were performed every 15 min, and thromboelastographs (TEGs) were performed every hour. The patient recovered from surgery without major complications, and there were no perioperative thrombotic events. The patient was discharged on day 41 and is doing well. Postoperative atrial arrhythmias were a contributing factor to his delayed discharge. The use of aprotinin in a protein C deficient patient undergoing open-heart surgery may be safe if protein C levels are restored before administration of aprotinin, and anticoagulation is carefully monitored.

Ischemic heart disease associated with protein C deficiency.

Three patients of ischemic heart disease associated with protein C deficiency are reported. Although delayed diagnosis of protein C deficiency resulted in the failure of repeated interventions, coronary artery bypass grafting performed after making the correct diagnosis has led to satisfactory mid-term results under strict anticoagulation therapy. The level of protein C should be measured more frequently in the field of ischemic heart disease and earlier diagnosis of its deficiency should be made, because measurement of protein C does not cost much.

Relentless progression of venous obstruction in a case of Budd-Chiari syndrome related to heterozygous protein C deficiency.

A 28-year-old man with heterozygous protein C deficiency presented with Budd-Chiari syndrome resulting from hepatic vein obstruction. Over the next 40 months, standard oral anticoagulant therapy and multiple percutaneous interventions aimed at relieving hepatic vein obstruction could not prevent progression of the disease ultimately to cirrhosis and death. Serial angiography provided unique documentation of the relentless progression of hepatic venous obstruction, which was related to the disease and to iatrogenic factors. Operative findings obtained during unsuccessful mesocaval shunt surgery revealed that venous disease in protein C deficiency can be far more extensive than is clinically anticipated. The ineffectiveness of therapy in this patient may be related to standard oral anticoagulant therapy being insufficient to offset the risk of recurrent thrombosis and progression to an advanced stage of vascular damage.