Severe thrombocytopenia suggesting immunological mechanisms in two cases of vivax malaria

Yamaguchi, Sayuri; Kubota, Tatsumi; Yamagishi, Takahiro; Okamoto, Kiyoshi; Izumi, Takahiro; Takada, M; Kanou, Shigeyuki; Suzuki, Mamoru; Tsuchiya, Jun; Naruse, Takuji

doi:10.1002/(sici)1096-8652(199711)56:3<183::aid-ajh9>3.0.co;2-u

Cited by 65 publications

(45 citation statements)

References 9 publications

(10 reference statements)

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“…This finding is consistent with previously reported observations from South America and south Asia where P. vivax is endemic [2]. Clinical complications such as disseminated intravascular coagulation (DIC), platelet associated IgG increase (PAIgG), immune thrombocytopaenia purpura (ITP), acute renal failure, pulmonary oedema, splenomegaly, cerebral malaria, and seizures have been reported in P. vivax cases exhibiting profound thrombocytopaenia [15–19, 21]. In these cases, bleeding was observed in a few cases, indicating that thrombocytopaenia in P. vivax does not always lead to bleeding complications.…”

Section: Discussionsupporting

confidence: 91%

“…Various malaria-endemic countries, including Indonesia, Columbia, Kenya, India, and Pakistan, have documented high frequency of thrombocytopaenia in malaria patients [3–13]. Furthermore, case reports describing clinical manifestations of thrombocytopaenia due to P. vivax have been described indicating the significance of the respective parameter in vivax malaria [14–21]. Recent studies have also highlighted the usefulness of thrombocytopaenia as a plausible clinical marker of malaria diagnosis with significant sensitivity, specificity, positive, and negative predictive values [22–24].…”

Section: Introductionmentioning

confidence: 99%

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Tumour necrosis factor, interleukin-6 and interleukin-10 are possibly involved in Plasmodium vivax-associated thrombocytopaenia in southern Pakistani population

Raza

Khan

Ghanchi

et al. 2014

Malar J

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BackgroundIn Pakistan, Plasmodium vivax is endemic causing approximately 70% of the malaria cases. A number of haematological changes, especially thrombocytopaenia have been reported for P. vivax. Several host factors including cell-mediated immune cells, such as IL-1, IL-6 and IL-10 have been documented for P. vivax-induced thrombocytopaenia. However, study on correlation of cytokines and thrombocytopaenia in P. vivax, particularly in patients with severe signs and symptoms has not been reported from Pakistan.MethodsA case control study to correlate TNF, IL-6 and IL-10 in healthy controls and thrombocytopaenic P. vivax-infected patients (both uncomplicated and complicated cases) from southern Pakistan was carried out during January 2009 to December 2011. One Hundred and eighty two patients presenting with microscopy-confirmed asexual P. vivax mono-infection and 100 healthy controls were enrolled in the study at Aga Khan University Hospital, Karachi. Enzyme-linked immunosorbent assay (ELISA) was performed for determination of TNF, IL-6 and IL-10 levels.ResultsOut of 182 cases, mild thrombocytopaenia (platelet count 100,000-150,000 mm3) was observed in ten (5.5%), moderate (50,000-100,000 mm3) in 93 (51.1%), and profound thrombocytopaenia (<50,000 mm3) was detected in 79 (43.4%) patients. IL-6 and IL-10 levels were found approximately three-fold higher in the mild cases compared to healthy controls. Two-fold increase in TNF and IL-10 (p < 0.0001) was observed in profound thrombocytopaenic when compared with moderate cases, while IL-6 was not found to be significantly elevated.ConclusionCytokines may have a possible role in P. vivax-induced thrombocytopaenia in Pakistani population. Findings from this study give first insight from Pakistan on the role of cytokines in P.vivax-associated thrombocytopaenia. However, further studies are required to understand the relevance of cytokines in manifestations of thrombocytopaenia in P. vivax malaria.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Tumour necrosis factor, interleukin-6 and interleukin-10 are possibly involved in Plasmodium vivax-associated thrombocytopaenia in southern Pakistani population

Raza

Khan

Ghanchi

et al. 2014

Malar J

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“…One study identified an increased level of platelet-associated antibodies in thrombocytopenic malaria (falciparum) patients [46] as well as in vivax patients [47]. This was supported by a study that showed an association between polymorphisms in FccRIIa, the platelet IgG receptor and disease severity [48].…”

Section: Immune Mechanismsmentioning

confidence: 88%

The role of platelets in the pathogenesis of cerebral malaria

Cox

McConkey

2009

Cell. Mol. Life Sci.

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Malaria is a major cause of morbidity and mortality in the developing world and cerebral malaria is responsible for the majority of malaria-associated deaths. There is a strong association between thrombocytopenia and outcome in malaria, suggesting a role for platelets in the pathogenesis of malaria. This thrombocytopenia is likely due to platelet activation possibly through an interaction between PfEMP1 on plasmodium and CD36 on platelets. Platelet activation by plasmodium has two potential consequences. It can lead to the formation of micro-aggregates of infected red blood cells and platelets which can occlude blood vessels and it also leads to binding to and activation of the endothelium.

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“…Some studies suggest that the low platelet counts in malaria might be caused by activation [20] and/or apoptosis of platelets [14], thus leading to its removal by the immune system [12], [15]. Nonetheless, it has also been proposed that immune complexes generated by malarial antigen could lead to sequestration of the injured platelets in the spleen followed by phagocytosis by splenic macrophages [16]–[19].…”

Section: Introductionmentioning

confidence: 99%

Thrombocytopenia in Plasmodium vivax Malaria Is Related to Platelets Phagocytosis

et al. 2013

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BackgroundAlthough thrombocytopenia is a hematological disorder commonly reported in malarial patients, its mechanisms are still poorly understood, with only a few studies focusing on the role of platelets phagocytosis.Methods and FindingsThirty-five malaria vivax patients and eight healthy volunteers (HV) were enrolled in the study. Among vivax malaria patients, thrombocytopenia (<150,000 platelets/µL) was found in 62.9% (22/35). Mean platelet volume (MPV) was higher in thrombocytopenic patients as compared to non- thrombocytopenic patients (p = 0.017) and a negative correlation was found between platelet count and MPV (r = −0.483; p = 0.003). Platelets from HV or patients were labeled with 5-chloromethyl fluorescein diacetate (CMFDA), incubated with human monocytic cell line (THP-1) and platelet phagocytosis index was analyzed by flow cytometry. The phagocytosis index was higher in thrombocytopenic patients compared to non-thrombocytopenic patients (p = 0.042) and HV (p = 0.048). A negative correlation was observed between platelet count and phagocytosis index (r = −0.402; p = 0.016). Platelet activation was assessed measuring the expression of P-selectin (CD62-P) in platelets’ surface by flow cytometry. No significant difference was found in the expression of P-selectin between thrombocytopenic patients and HV (p = 0.092). After evaluating the cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17) in the patients’ sera, levels of IL-6, IL-10 and IFN-γ were elevated in malaria patients compared to HV. Moreover, IL-6 and IL-10 values were higher in thrombocytopenic patients than non-thrombocytopenic ones (p = 0.044 and p = 0.017, respectively. In contrast, TNF-α levels were not different between the three groups, but a positive correlation was found between TNF-α and phagocytosis index (r = −0.305; p = 0.037).Conclusion/SignificanceCollectively, our findings indicate that platelet phagocytosis may contribute to thrombocytopenia found in vivax malaria. Finally, we believe that this study opens new avenues to explore the mechanisms involved in platelet dysfunction, commonly found in vivax malaria patients.

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Severe thrombocytopenia suggesting immunological mechanisms in two cases of vivax malaria

Cited by 65 publications

References 9 publications

Tumour necrosis factor, interleukin-6 and interleukin-10 are possibly involved in Plasmodium vivax-associated thrombocytopaenia in southern Pakistani population

Tumour necrosis factor, interleukin-6 and interleukin-10 are possibly involved in Plasmodium vivax-associated thrombocytopaenia in southern Pakistani population

The role of platelets in the pathogenesis of cerebral malaria

Thrombocytopenia in Plasmodium vivax Malaria Is Related to Platelets Phagocytosis

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