Fulminant meningococcemia is characterized by acute onset of fever and petechiae with rapid progression to generalized purpura, septic shock, and multisystem organ failure (MSOF). Microvascular thrombosis due to disseminated intravascular coagulation (DIC) has a major role in the pathogenesis of MSOF. Endotoxin enhances the release of plasminogen activator inhibitor - 1 (PAI-1) which impairs fibrinolysis. Elevation of PAI-1 correlates with development of shock, renal failure, and death. Rt-PA interferes specifically with PAI-1, induces a clot-selective fibrinolysis and has no direct effect on hemodynamics. Therefore rt-PA may safely lead to the dissolution of microvascular thromboses and restore organ perfusion in patients with sepsis and DIC.

A 4 mo. infant presented with septic shock, stupor, anuria, purpura fulminans and DIC. Blood cultures grew. N. meningitidis. The patient had marked thrombocytopenia, prolonged PT and APTT, decreased fibrinogen, and elevated D-dimer and fibrin split products. Despite aggressive therapy with ceftriaxone, mechanical ventilation, colloid and blood product infusions, NaHCO3 infusion, high dose vasopressor and inotropic infusions(dopamine, dobutamine, and epinephrine), and stress dose steroids the patient remained severely oliguric with deteriorating hemodynamic status and increasing metabolic acidosis. An rt-PA infusion, total dose 1.25 mg/kg, was given over 4 hours with dramatic improvement in hemodynamics, urine output, and metabolic acidosis as noted in Table 1. The infant eventually recovered although will require skin grafting and possible amputation of distal extremities. A PAI-1 level obtained 18 hours after presentation was 1402 ng/ml suggesting lethal disease.

Table 1
Full size table

In our patient use of rt-PA resulted in improved organ perfusion and cardiac performance. Selective use of rt-PA in the treatment of fulminant meningococcemia merits further investigation.