Levels of serum tumor necrosis factor alpha in relation to clinical involvement and treatment among Thai adults with Plasmodium falciparum malaria.

Concentrations of tumor necrosis factor alpha (TNF-alpha) in serum were measured in 17 Thai men infected with Plasmodium falciparum malarial infections to determine whether they were affected by severity of infections or exchange transfusions. Twelve patients were considered having complicated malarial infections, eight of whom had cerebral malaria. Five patients had uncomplicated malarial infections. The results showed that malarial infection markedly raised TNF-alpha level above normal values (mean +/- SEM 406 +/- 38 vs 15 +/- 5, p = 0.004). In complicated malaria, cerebral involvement appeared to significantly increase concentration of TNF-alpha when compared to values in uncomplicated malaria (mean +/- SEM 496 +/- 64 vs 339 +/- 12, p = 0.01). Degree of parasitemia, intravenous quinine (day 0 value vs day 7 value) and exchange transfusion did not significantly affect TNF-alpha levels. Conclusion: Serum level of TNF-alpha is increased in Plasmodium falciparum malarial infections and may be a useful index to predict severity of malarial infection, cerebral malaria in particular.

Pleomorphic large cell hemato-lymphoma (the so-called "malignant histiocytosis"): clinicopathological and immunophenotypic studies in 35 cases.

Thirty-five patients diagnosed with "malignant histiocytosis" from 1984 to 1989 were studied for clinical, laboratory, histopathological features as well as survival and response to therapy, Immunocytochemistry and immunophenotypic studies were performed in 12 cases using the paraffin immunoperoxidase method. The staining included alpha-1 antichymotrypsin, muramidase, immunoglobulins and monoclonal antibodies specific for T, B lymphocytes and macrophage. From the clinical features, responsiveness to therapy and survival, the patients were divided into 2 groups: the non-responders (25 cases) and responders (10 cases) groups. Very short median survival of 1.25 months was found in the non-responders, whereas, longer median survival of 14.15 months was found in the responder group. Important different clinical and laboratory features were observed among these two groups. Unresponsiveness to treatment; rapidly progressive pancytopenia, increased hemophagocytosis, presentation of immature cells in blood with extensive infiltration of malignant cells in the bone marrow; severe jaundice and deterioration of hepatic function accompanied by early extranodal involvement were almost exclusively observed initially in the non-responder group. Satisfactory response to treatment was observed only in the responder group. Similarity of histopathology, cytology and immunophenotype was observed in these two groups. The immunophenotypic study in 12 cases showed 5 cases of B-cell lymphoma, 3 cases of T-cell (with 1 Ki-1 -positive) lymphoma; 1 case of Ki-1 positive non-T, non-B anaplastic large cell lymphoma; and 3 cases of undetermined cell lineage. From this study, so-called "malignant histiocytosis" appears to be a disorder of heterogeneity. The immunophenotypes of malignant cells indicated that their origin belonged mostly to lymphoid cell lineage. Based on their clinical feature of the early hematogenous spread along with the distinct histopathological and immunophenotypic findings, the term "pleomorphic large cell hematolymphoma" is proposed to be used instead of the old misnomer, "malignant histiocytosis" (MH).

Exchange transfusion therapy in severe complicated malaria.

Nine cases of severe complicated falciparum malaria treated by exchange transfusion were studied. Eight patients survived and one patient died. Multisystemic complications were found in all cases. The CNS complications, acute renal failure, pulmonary insufficiency, jaundice, bleeding, sepsis, and DIC were found in 9, 7, 5, 7, 2, 4 and 1 cases, respectively. The fatal case presented with severe multisystemic complications together with 40% parasitemia. In eight survivors, whose parasitemia ranged from 0.3%, to 90%, had milder degrees of systemic complications. With the use of blood exchange 10-15 units, the parasitemia was decreased to less than 5% within 24 hours in all expect one who had parasitemia 90%. In comparison with the other 10 matched non-exchanged patients, there was no significant difference in survival rate between these two group (89% vs 80%). However, in the patients with ARDS the survival rate in the group who received the exchange transfusion therapy was superior (75% vs 0%). The exchange transfusion therapy is therefore strongly recommended in the treatment of malarial patients who present with parasitemia > 30% and severe systemic complications, particularly those who have severe acute renal failure or have lung complications. The amount of blood used for exchange transfusion should at least 1.2 times the blood volume for rapid removal of parasites and toxic metabolites from the circulation.

Abnormal hemostasis in dengue hemorrhagic fever.

Abstract. Abnormal hemostasis in dengue hemorrhagic fever includes:- 1. Vasculopathy which occurs during the early febrile to pre-shock and shock phase. The evidences support are: 1.1 Increased anaphylatoxin, released by complement activation causing leakage of intravascular fluid in to serous space. 1.2 Positive tourniquet test, some of which occur preceeding thrombocytopenia in the acute phase of DHF. 1.3 Excessive increased in PGI2 which is the most potent vasodilator and platelet aggregation inhibitor. 2. Platelets: 2.1 Thrombocytopenia due to 2.1.1 The bone marrow hypocellularity with increased in all forms of megakaryocytes but the vacuolated and disintegrated ones. 2.1.2 Destruction by the liver and spleen. 2.1.3 Immune-mediated injury as demonstration of dengue antibody complexes on the platelet surface. 2.1.4 The in vitro spontaneous aggregation to vascular endothelial cell pre-infected by dengue virus inducing platelet aggregation, causing lysis and platelet destruction. 2.2 Dysfunction shown by 2.2.1 Increased release of betathromboglobulin (BTG), PF4 and PGI2. 2.2.2 In vitro hypoaggregation stimulated by ADP and defect in ADP-releasing ability. 3. Coagulopathy including: 3.1 Prothrombin complex deficiency due to liver damage. 3.2 Consumptive coagulopathy due to the activation by mononuclear phagocytes, PF3 released from platelet aggregation. DIC is seen in prolonged shock cases of DSS.

Clinical manifestations and therapy of heat stroke: consumptive coagulopathy successfully treated by exchange transfusion and heparin.

This report of 8 cases (6 severe and 2 mild) heat stroke patients seen during the hot summer of 1987 at Pramongkutklao Hospital, Bangkok, represent the first report of this syndrome in Thailand. Severe cases presented with deep coma, shock, ARDS, DIC and other systemic complications. Two cases of mild heat stroke recovered completely with conventional treatment. Two of the 6 severe cases died with DIC, bleeding and acute renal failure. The other 4 surviving cases received early exchange transfusion and low dose heparin therapy. The clinical features of these 4 cases were as severe as those recorded for fatal heat stroke patients, including shock over 10 hours in 4, coma longer than 120 hours in 3, ARDS and DIC in 1. From these findings, early exchange transfusion plus low dose heparin should be considered as one effective treatment in severe fatal heat stroke patients.

Platelet function during the acute phase of dengue hemorrhagic fever.

Platelet aggregation, plasma betathromboglobulin (BTG) and platelet factor 4 (PF4) were studied in 35 children with dengue hemorrhagic fever. The suppression of platelet aggregation was demonstrated during acute phase of DHF in both shock and non-shock patients. Simultaneous with abnormal platelet aggregation, there was increased release of BTG and PF4 from platelets into plasma during the acute phase which lasted only 3-4 days after shock or subsidence of fever. Acute phase plasma during DHF infection was also shown to have a stimulatory effect on the aggregation of autologous platelets. In this study we showed that there was an increase in platelet secretory activity of BTG and PF4 along with an impairment of the platelet aggregation during acute phase of DHF.

Platelet dysfunction in malaria.

Platelet function tests including platelet aggregation, PF3, bleeding time and clot retraction were studied in 48 malarial patients. The suppression of platelet aggregation was demonstrated in both P. vivax and P. falciparum infection. However, this abnormality was more prominent in malarial patients who had systemic complications and bleeding. The recovery of the impaired platelet aggregation was observed at period of 7 and 14 days after parasitemia in malarial patients without and with systemic complications. The correlation between the suppression of platelet aggregation and thrombocytopenia was observed. From this study, bleeding in malaria are operated by two mechanisms: thrombocytopenia and severely depressed platelet aggregation.

Pure red cell aplasia in Thailand: report of twenty four cases.

Twenty four cases of pure red cell aplasia were reported. No underlying diseases were found in two cases. Of the 22 cases with secondary form, 10 were from infections, mostly gram negative organisms. Three cases had systemic lupus erythematosus, two had autoimmune hemolytic anemia. The following conditions were found in one each: thymoma, thyroid carcinoma, protein calorie malnutrition, rheumatoid arthritis, non-Hodgkin lymphoma and Sheehan's syndrome. Three patients died, two from uncontrolled infection, the other from uncontrolled SLE and subsequently systemic fungal infection. Only one of the 2 primary cases responded to immunosuppressive drugs. The majority of patients with underlying infections, PRCA resolved after the infections were treated. This is the first reported series of PRCA in Thailand.

Acute massive intravascular hemolysis and disseminated intravascular coagulation.

Two cases of acute intravascular hemolysis complicating acute disseminated intravascular coagulation were presented, one after normal delivery and the other after group A beta hemolytic streptococcal septicemia complicating acute myelomonoblastic leukemia. Neither case received heparin therapy. The first one survived while the latter succumbed. Intravascular hemolysis may not be a bad prognostic sign in such a condition.

Exchange transfusion in cerebral malaria complicated by disseminated intravascular coagulation.

A patient with cerebral malaria complicated by full-blown DIC, after failing to respond to other forms of treatment, was successfully treated by exchange transfusion. To the best of the authors' knowledge, this may be first reported case of full-blown DIC in malaria successfully treated by exchange transfusion.