alpha-chymotrypsin and Disseminated-Intravascular-Coagulation

Values of mean antiproteases were studied in 60 children with meningococcal sepsis. At illness onset, increased levels of alpha-1 antiquimotrypsin (p less than 0.001) and decreased of alpha-2 macroglobulin (p less than 0.001) were found. Moreover, patients who were complicated with a disseminated intravascular coagulation (DIC) also showed a decrease of antithrombin III (p less than 0.001) and inter alpha-1 trypsin inhibitor (p less than 0.001). There was not relationship between antiproteases levels and mortality. In 33 cases the measures were repeated 24 hours later, but no homogeneous results were found, in spite of alpha-2 macroglobulin fall in patients complicated with DIC (p less than 0.05). Phenotypic variants of alpha-1 antitrypsin were studied in 47 cases by isoelectric focusing. Results did not provide evidence that "abnormal phenotypes" (no-Pi MM) could facilitate meningococcal sepsis or DIC, but an increased number of "abnormal phenotypes" (5/9) were found in dead patients (p less than 0.025).

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; alpha-Macroglobulins; Antithrombin III; Child, Preschool; Chymotrypsin; Disseminated Intravascular Coagulation; Humans; Infant; Meningococcal Infections; Phenotype; Protease Inhibitors

The effect of experimental trypanosomiasis on coagulation was studied because a patient in this hospital with Rhodesian trypanosomiasis developed thrombocytopenia with disseminated intravascular coagulation. Rats injected intraperitoneally with this strain of Trypanosoma rhodesiense consistently developed trypanosomiasis and severe thrombocytopenia without changes in hematocrit or concentration of fibrinogen or fibrin split products. At the time of 50% mortality (4-5 days) mean platelet counts per cubic millimeter of infected rats were 18,000+/-9,000 (+/-2 SEM) compared to 1,091,000+/-128,000 in uninfected controls. In vitro, concentrated trypanosomes and trypanosomefree supernates of disrupted organisms added to normal rat, rabbit, or human blood produced platelet aggregation within 30 min. This platelet aggregation was not blocked by inhibitors of ADP, kinins, or early or late components of complement. In vivo thrombocytopenia also occurred in infected rabbits congenitally deficient in C6 and in infected, splenectomized rats. Although the aggregating substance obtained from disrupted trypanosomes is heat-labile, it is active in the presence of complement inhibitors, suggesting that this trypanosomal product may be a protein enzyme or toxin. Since the phenomenon is independent of immune complexes, complement, ADP, and kinins, it appears to represent a new mechanism of microbial injury of platelets and the induction of thrombocytopenia.

Topics: Adenosine; Adenosine Diphosphate; Animals; Blood Cell Count; Blood Platelets; Chymotrypsin; Complement System Proteins; Disseminated Intravascular Coagulation; Edetic Acid; Fibrin; Fibrinogen; Hematocrit; Humans; In Vitro Techniques; Male; Microscopy, Electron; Platelet Adhesiveness; Rabbits; Rats; Thrombocytopenia; Trypanosomiasis; Trypsin; Trypsin Inhibitors