Complement Changes and Disseminated Intravascular Coagulation in Plasmodium Falciparum Malaria

Srichaikul, Tanomsri; Puwasatien, Praparsri; Puwasatien, Prapaisri; Karnjanajetanee, Jul; Bokisch, ViktorA.

doi:10.1016/s0140-6736(75)92436-8

Cited by 73 publications

(40 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several international studies have found the prevalence of thrombocytopenia in vivax malaria between 72% and 86% (Srichaikul et al, 1975;Kelton et al, 1979;Makkar et al, 2002). Jadhav et al found that 65% of vivax malaria patients had platelet count between 50610 9 and 150610 9 /l (Jadhav et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Thrombocytopenia in vivax and falciparum malaria: an observational study of 131 patients in Karnataka, India

Saravu

Docherla

Vasudev

et al. 2011

Annals of Tropical Medicine & Parasitology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Thrombocytopenia in vivax and falciparum malaria: an observational study of 131 patients in Karnataka, India

Saravu

Docherla

Vasudev

et al. 2011

Annals of Tropical Medicine & Parasitology

View full text Add to dashboard Cite

“…Severe malaria develops as a consequence of capillaric sequestration of parasitized RBCs (pRBCs), [1][2][3] activation of complement [4][5][6] and coagulation, [7][8][9] and increases in vascular permeability, which together can lead to microcirculatory disturbances with comatous death as the ultimate outcome. 1,7,10,11 One unresolved puzzle relates to the fact that children with severe malaria frequently suffer from septicemia due to bacteria that otherwise play no major role in this potentially fatal affliction.…”

Section: Introductionmentioning

confidence: 99%

Digestive vacuoles of Plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes

Dasari

Reiß

Lingelbach

et al. 2011

Blood

View full text Add to dashboard Cite

Sequestration of parasitized erythrocytes and dysregulation of the coagulation and complement system are hallmarks of severe Plasmodium falciparum malaria. A link between these events emerged through the discovery that the parasite digestive vacuole (DV), which is released together with infective merozoites into the bloodstream, dually activates the intrinsic clotting and alternative complement pathway. Complement attack occurs exclusively on the membrane of the DVs, and the question followed whether DVs might be marked for uptake by polymorphonuclear granulocytes (PMNs). We report that DVs are indeed rapidly phagocytosed by PMNs after schizont rupture in active human serum. Uptake of malaria pigment requires an intact DV membrane and does not occur when the pigment is extracted from the organelle. Merozoites are not opsonized and escape phagocytosis in nonimmune serum. Antimalarial Abs mediate some uptake of the parasites, but to an extent that is not sufficient to markedly reduce reinvasion rates. Phagocytosis of DVs induces a vigorous respiratory burst that drives the cells into IntroductionSevere malaria develops as a consequence of capillaric sequestration of parasitized RBCs (pRBCs), 1-3 activation of complement [4][5][6] and coagulation, 7-9 and increases in vascular permeability, which together can lead to microcirculatory disturbances with comatous death as the ultimate outcome. 1,7,10,11 One unresolved puzzle relates to the fact that children with severe malaria frequently suffer from septicemia due to bacteria that otherwise play no major role in this potentially fatal affliction. [12][13][14] Approximately 50% of these infections are caused by nontyphoidal Salmonellae and other Enterobacteriae, indicating a gut origin. Current hypotheses regarding the causes underlying this general state of immune compromise focus mainly on disturbances in the function of macrophages, dendritic cells, and the adaptive immune system. 15 During its developmental cycle in the RBC, the malaria parasite ingests hemoglobin and packages the waste product hemozoin, which is also known as malaria pigment, in an organelle designated the digestive vacuole (DV). 16 Copious numbers of DVs are released into the bloodstream in patients with severe Plasmodium falciparum malaria, yet their biologic properties and fates have been only minimally studied. Hematin is widely regarded to be equivalent to hemozoin, 17,18 and most investigators have focused on the effects of this artificial molecule on the immune system. [19][20][21][22][23][24][25] However, hematin is not packaged within a membrane-bound organelle and any biologic activity deriving from the DV membrane would therefore be missed. In a different study, we have shown that the DV membrane, but not hemozoin itself, is endowed with the unique capacity to dually activate the alternative complement and the intrinsic clotting pathway (P.D., S. Heber, S. Baumeister, K.L., K.R., S.C.B., and S. Bhakdi, unpublished data, September 2011). Overactivation of these ancient enzyme cascades ...

show abstract

“…The authors noted that the patients with more severe thrombocytopenia also had DIC and that there was correlation between platelet count and C3 protein levels. However, the reduction in C3 was proportional to that in parasitaemia, suggesting that thrombocytopenia was not independently associated with C3 (Srichaikul et al 1975). In Manaus, 2004, a study with falciparum and vivax patients demonstrated a negative correlation between platelet counts, thrombinanti-thrombin complex and D-dimers, suggesting that the activation of coagulation could be partially responsible for thrombocytopenia (Marques et al 2005).…”

mentioning

confidence: 99%

Thrombocytopenia in malaria: who cares?

Lacerda

Mourão

Coelho

et al. 2011

Mem. Inst. Oswaldo Cruz

186

173

View full text Add to dashboard Cite

Key words: Plasmodium falciparum -Plasmodium vivax -malaria -thrombocytopenia -plateletsMalaria and thrombocytopenia • Marcus Vinícius Guimarães Lacerda et al. 53Data on the real burden of thrombocytopenia associated with malaria is contradictory in the literature and it is not usually considered when conducting patient selection. Table I shows the major publications estimating the frequency of thrombocytopenia. Most of these data were published in the late 1990s, probably in time with the surge in the availability of affordable automated machines capable of performing full blood counts (FBC). Manual platelet counting is time-consuming and usually needs to be requested by the physician with the routine blood count in most of the endemic areas for malaria. In only three publications is there an adequate randomised enrollment of patients with appropriate sample size calculation to estimate the frequency of bleeding and its association with the respective platelet count (Lacerda 2007, Silva 2009, Kochar et al. 2010. Only one study has ruled out other common causes of thrombocytopenia that are also endemic in the studied area (Lacerda 2007). There is a wide range of thrombocytopenia occurrence in these reports, which may be explained by distinct selection criteria of the enrolled patients. There are also differences in the selection of outpatients or inpatients from tertiary care centres that tend to present with severe thrombocytopenia. Furthermore, clinical manifestations of thrombocytopenia are usually described as case reports and most of these are due to P. vivax (Table II).In 2005, 138 of 684 (20.1%) malarial cases hospitalised in a tertiary care centre in Manaus had thrombocytopenia as the cause of admission, which corresponded to 6.8% of hospitalisations due to all causes in this reference institution (unpublished observations). Hospitalisation, however, does not add any benefit to the patient and because there is no evidence for any intervention, this simply increases public health costs in underdeveloped and under-resourced areas.Pathogenesis of malarial thrombocytopenia -Coagulation disturbances -A study based on 31 American soldiers in Vietnam with chloroquine-resistant falciparum malaria noted the following changes in the acute phase of the disease using the same patients as their own controls during convalescence: decrease in the platelet count and prothrombim activation time, increase in the activated thromboplastin time, and reduction in factors V, VII and VIII with normal fibrinogen (Dennis et al. 1967). This report suggested that thrombocytopenia was simply a consequence of the coagulation disorders presented by these patients, an idea that persisted for many decades in the literature. In another series of 21 patients with falciparum malaria, six had developed disseminated intravascular coagulation (DIC). The authors noted that the patients with more severe thrombocytopenia also had DIC and that there was correlation between platelet count and C3 protein levels. However, the reduction in C3 was pr...

show abstract

Complement Changes and Disseminated Intravascular Coagulation in Plasmodium Falciparum Malaria

Cited by 73 publications

References 13 publications

Thrombocytopenia in vivax and falciparum malaria: an observational study of 131 patients in Karnataka, India

Thrombocytopenia in vivax and falciparum malaria: an observational study of 131 patients in Karnataka, India

Digestive vacuoles of Plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes

Thrombocytopenia in malaria: who cares?

Contact Info

Product

Resources

About