Microvascular thrombosis is a characteristic of a variety of conditions (T.able...,.3)> including DIC, thrombotic thrombocytopenic purpura, and the purpura ulminans syndrome. These conditions may also be associated with large-vessel thrombotic manifestations, both arterial and venous. In DIC clinical attention is often directed towards the bleeding manifestations; microvasular thrombosis causing endorgan damage may go unrecognized unless it is overt. The microangiopathic process in thrombotic thrombocytopenic purpura causes widespread small-vessel platelet thrombi with neurological, renal, and other endorgan damage, as well as hemolysis, red cell fragmentation, and thrombocytopenia. Thrombotic thrombocytopenic purpura differs from the hemolytic uremic syndrome in which the microvascular thrombosis is restricted to the kidney. The pathogenesis of thrombotic thrombocytopenic purpura is unknown, but both high-molecular-weight multimers of von Willebrand factor and calpain, a calcium-dependent cysteine protease, have been implicated. The mainstay of treatment is early and intensive plasma exchange with fresh frozen plasma replacement (Rockefa/ 1991), to which about 70 per cent of patients respond. Refractory patients may benefit from the use of either cryosupernatant or solvent-detergent-treated plasma, which lack high-molecular-weight multimers of von Willebrand factor. Antiplatelet agents, steroids, and other immunosuppressive agents may also have a role in the management of these patients. Thrombotic thrombocytopenic purpura is associated with infections, pregnancy, drugs, HIV, malignancy, organ transplants, and collagen vascular disorders.
t^aMÉd hqu D^IIMMII indnliM V*UXII1<MHHIÉ ftuccutod HTt- t^livrf ^iori^-i
Table 3 Medical disorders predisposing to microvascular thrombosis
Purpura fulminans includes a group of heterogeneous conditions associated with rapidly progressive widespread thrombosis in the subcutaneous microcirculation, leading to necrosis of the dermis and subcutaneous fat and peripheral gangrene. It may occur in neonates as a result of homozygous or compound heterozygous deficiencies of proteins C and S. The severity of this potentially lethal condition is proportional to the functional protein C or S levels, which may be very low or undetectable. Acquired purpura fulminans generally occurs as a complication of infection. It is a cardinal feature of meningococcal sepsis, where there is usually laboratory evidence of consumptive coagulopathy and reductions in levels of all the naturally occurring anticoagulants, with the latter appearing to correlate with disease severity. In an attempt to improve the prognosis of this often fatal disorder, intensive plasma replacement and the recently available protein C concentrates have been administered to a few severely affected children. Although plasma protein C levels can be normalized using this approach, the impact on morbidity and mortality awaits prospective controlled clinical trials. Purpura fulminans also occurs in other bacterial infections including group A and B hemolytic streptococci, Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae, and Hemophilus egyptius.
In a third group of patients, purpura fulminans occurs a few days to weeks after the onset of a febrile illness. The illness may be complicated by impaired perfusion of limbs or digits, peripheral gangrene, and major endorgan dysfunction due to thromboembolic phenomena affecting the lungs, heart, or kidneys. This condition has been shown to occur in chidren in association with primary herpes zoster infection where it is caused by an acquired protein S deficiency due to autoantibodies directed against protein S. Leyinefal (1995) reported five such cases; in four of these the acquired protein S deficiency was precipitated by varicella, and in the fifth after a non-specific viral-like illness. Immediate heparinization, aggressive plasma replacement therapy, and, in cases complicated by major vessel thrombosis, tissue plasminogen activator have been used to limit thromboembolic complications.
Was this article helpful?