Severe congenital protein C deficiency: the use of protein C concentrates (human) as replacement therapy for life-threatening blood-clotting complications

Abstract

The protein C pathway has an important function in regulating and modulating blood coagulation and ensuring patency of the microcirculation. Protein C deficiency leads to macro- and microvascular thrombosis. Congenital severe protein C deficiency is a life-threatening state with neonatal purpura fulminans and pronounced coagulopathy. Patients with heterozygous protein C deficiency have an increased risk for thromboembolic events or experience coumarin-induced skin necrosis during initiation of coumarin therapy. Replacement with protein C concentrates is an established therapy of congenital protein C deficiency, resulting in rapid resolving of coagulopathy and thrombosis without reasonable side effects. This article summarizes the current knowledge on protein C replacement therapy in congenital protein C deficiency.

Activated Protein C Inhibits Pancreatic Islet Inflammation, Stimulates T Regulatory Cells, and Prevents Diabetes in Non-obese Diabetic (NOD) Mice

“…Considering that aPC is thought to have a biological half-life of ϳ20 min (39), it is noteworthy that its protective effect persisted for at least 10 weeks after the last treatment. This suggests that aPC treatment between 6 and 16 weeks of age permanently ameliorated the autoimmune process leading to ␤ cell destruction.…”

Neonatal dermatological emergencies

“…The levels above 0.03-0.05 IU/ ml are sufficient to ameliorate the symptoms of PF. [61] Increased D-dimer levels, low fibrinogen, increased fibrinogen degradation products (FDP), low platelet count, and prothrombin fragment 1.2 indicate DIC. These parameters along with clinical response are useful in monitoring and optimizing Protein C therapy.…”

“…[61] Acute infectious PF can be managed with immediate heparinization, and infusion of FFP (15 ml/kg every 12 h) along with the resuscitation measures for septic shock. [57] Prostacycline, a thromboxane A 2 antagonist, in the initial dose of 5 ng/kg/min, then increased and maintained at 15 ng/kg/min for 48 h has been used successfully in the treatment of acute infectious PF.…”

“…It has beneficial effects on pulmonary hypertension and thromboxane-induced platelet aggregations which occur in septicemia. [63] The mortality is almost 100% in untreated hereditary neonatal PF, [61] whereas acute infectious PF is associated with 50% mortality. [60] B. Kawasaki disease Kawasaki disease is a systemic vasculitis predominantly affecting younger children less than 4 years of age with peak age of onset of 6 to 11 months.…”

A Novel Heparin-dependent Inhibitor of Activated Protein C That Potentiates Consumptive Coagulopathy in Russell's Viper Envenomation

“…From our results, we can imply that if APC is replenished in Russell's viper bite patients, the concentrations of RVV-X and RVV-V needed for the induction of consumptive coagulopathy would be much higher. Since severely envenomed patients develop bleeding disorders (fibrinogen consumption and microvascular occlusion with fibrin thrombi) similar to that seen in patients with severe sepsis and homozygous PC deficiency (40,41), administration of PC concentrate (Ceprotin) or recombinant APC (Drotrecogin ␣-activated or Xigris) before the consumption of coagulation factors should be able to pacify, if not prevent, the development of DIC or DIC-like symptoms in envenomed patients (48,49). This, in addition to treatments with antivenom, should reduce fibrin depositions in the glomerular capillaries, and should subsequently ameliorate the damage done to the kidneys.…”