Characterization of platelet count and platelet indices and their potential role to predict severity in malaria
TL;DR: It is shown that P. vivax malaria which has been traditionally regarded as ‘benign’ can be as sinister and menacing as P. falciparum malaria and hence warrants equal attention.
Abstract: The association of hematological parameters especially platelet parameters with disease severity in malaria is poorly understood. We aimed to characterize the platelet parameters across Plasmodium ...
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TL;DR: These evolving roles of platelets under four different infectious pathogen infections are discussed, of which are dengue, malaria, Esterichia coli (E. coli) and staphylococcus aureus S.Aureus, highlighting the complex interplay of these processes with hemostatic and thrombotic pathways.
Abstract: Platelets are anucleate cells produced by megakaryocytes. In recent years, a robust body of literature supports the evolving role of platelets as key sentinel and effector cells in infectious diseases, especially critical in bridging hemostatic, inflammatory, and immune continuums. Upon intravascular pathogen invasion, platelets can directly sense viral, parasitic, and bacterial infections through pattern recognition receptors and integrin receptors or pathogen: immunoglobulin complexes through Fc and complement receptors-although our understanding of these interactions remains incomplete. Constantly scanning for areas of injury or inflammation as they circulate in the vasculature, platelets also indirectly respond to pathogen invasion through interactions with leukocytes and the endothelium. Following antigen recognition, platelets often become activated. Through a diverse repertoire of mechanisms, activated platelets can directly sequester or kill pathogens, or facilitate pathogen clearance by activating macrophages and neutrophils, promoting neutrophil extracellular traps (NETs) formation, forming platelet aggregates and microthrombi. At times, however, platelet activation may also be injurious to the host, exacerbating inflammation and promoting endothelial damage and thrombosis. There are many gaps in our understandings of the role of platelets in infectious diseases. However, with the emergence of advanced technologies, our knowledge is increasing. In the current review, we mainly discuss these evolving roles of platelets under four different infectious pathogen infections, of which are dengue, malaria, Esterichia coli (E. coli) and staphylococcus aureus S. aureus, highlighting the complex interplay of these processes with hemostatic and thrombotic pathways.
136 citations
TL;DR: An increasing body of evidence is compiled showing the participation of platelet innate immune receptors, including PRRs, in infectious diseases, sterile inflammation, and cancer, and how innate immune receptor participate in platelet communication with leukocytes, modulating leukocyte‐mediated inflammation and immune functions is highlighted.
Abstract: Platelets are chief cells in hemostasis. Apart from their hemostatic roles, platelets are major inflammatory effector cells that can influence both innate and adaptive immune responses. Activated platelets have thromboinflammatory functions linking hemostatic and immune responses in several physiological and pathological conditions. Among many ways in which platelets exert these functions, platelet expression of pattern recognition receptors (PRRs), including TLR, Nod-like receptor, and C-type lectin receptor families, plays major roles in sensing and responding to pathogen-associated or damage-associated molecular patterns (PAMPs and DAMPs, respectively). In this review, an increasing body of evidence is compiled showing the participation of platelet innate immune receptors, including PRRs, in infectious diseases, sterile inflammation, and cancer. How platelet recognition of endogenous DAMPs participates in sterile inflammatory diseases and thrombosis is discussed. In addition, platelet recognition of both PAMPs and DAMPs initiates platelet-mediated inflammation and vascular thrombosis in infectious diseases, including viral, bacterial, and parasite infections. The study also focuses on the involvement of innate immune receptors in platelet activation during cancer, and their contribution to tumor microenvironment development and metastasis. Finally, how innate immune receptors participate in platelet communication with leukocytes, modulating leukocyte-mediated inflammation and immune functions, is highlighted. These cell communication processes, including platelet-induced release of neutrophil extracellular traps, platelet Ag presentation to T-cells and platelet modulation of monocyte cytokine secretion are discussed in the context of infectious and sterile diseases of major concern in human health, including cardiovascular diseases, dengue, HIV infection, sepsis, and cancer.
77 citations
TL;DR: The results demonstrate that not only the PLT counts but also the MPV, PDW and P-LCR indices significantly correlate with liver fibrosis in HCV-infected patients, therefore, these indices may be useful laboratory measures for evaluating Liver fibrosis progression.
Abstract: Aim A total of 241 patients with chronic HCV infection were recruited to investigate the association between liver fibrosis and PLT counts, as well as with MPV, PDW and P-LCR indices. Methods The determination of PLT indices was carried out using a Sysmex XT-1800i automated hematology analyzer. Serological tests for HA, LN, C-IV and PIIINP were performed in 210 patients. The liver stiffness was measured in 69 patients by transient elastography (FibroScan). Results The analysis showed that the four serum fibrosis markers were negatively correlated with PLT counts, but positively correlated with the MPV, PDW and P-LCR values. Moreover, a similar pattern was found after analyzing the FibroScan measurements, which were negatively correlated with PLT counts, but positively correlated with MPV, PDW and P-LCR values. We subdivided the HCV-infected patients into mild and advanced fibrosis groups. The PLT counts were significantly decreased and the MPV, PDW and P-LCR values were significantly increased in the advanced fibrosis group when compared with the mild fibrosis group. Conclusions Our results demonstrate that not only the PLT counts but also the MPV, PDW and P-LCR indices significantly correlate with liver fibrosis in HCV-infected patients. Therefore, these indices may be useful laboratory measures for evaluating liver fibrosis progression.
11 citations
Cites background from "Characterization of platelet count ..."
...The PLT count has been shown to be an important severity index in several diseases, such as malaria [5], colorectal cancer [6] and acute kidney injury [7]....
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TL;DR: Immature platelet fraction (IPF%) is raised in the case of severe malaria, and it was significantly more useful than MPV, and platelet indices are useful predictors of malaria severity.
Abstract: Purpose. Platelet parameter alteration such as platelet count and platelet indices are more common than in other blood cell lines due to diverse causative pathophysiological mechanisms in severe malaria infection. In malaria patients, no more studies evaluated platelet indices in relation to disease severity and prognosis. Therefore, this review assessed the current scientific knowledge on the potential role of platelet indices for the diagnostic marker of severe malaria infection. Results. Hence, after reviewing recent literatures, elevation of mean platelet volume and platelet distribution width in addition to decreased plateletcrit and platelet counts is the known potential risk factor associated with warning signs of severe malaria. Thus, thrombocytopenia<150×109/L, MPV≥9.05 fL, and PDW≥14.550% as well as significantly higher P-LCR and decrease in PCT are shown significant sensitivity and specificity as they are used as diagnostic and prognostic values in severe malaria infection. Conclusion. Platelet indices are useful predictors of malaria severity. Immature platelet fraction (IPF%) is raised in the case of severe malaria, and it was significantly more useful than MPV. Advanced research will further investigate the platelet index abnormality associated with specific age and gender among specific malaria species.
8 citations
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...6% to discriminate severe malaria [53, 54]....
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TL;DR: Most falciparum malaria infections among patients in Kosti city of the White Nile State – Sudan are of low-level parasitemia and leucopenia is not useful to predict falcipsiology, Nevertheless, fal ciparums malaria is significantly associated with anemia and thrombocytopenia with lower median values of Hb, RBC count, MCH, M CHC and platelet count.
Abstract: Hematological abnormalities are common features in falciparum malaria but vary among different populations across countries. Therefore, we compared hematological indices and abnormalities between Plasmodium falciparum-infected patients and malaria-negative subjects in Kosti city of the White Nile State, Sudan. A comparative, cross-sectional study was conducted at the Clinical Laboratory Unit of Kosti Teaching Hospital from June to December 2018. A total of 392 participants (192 P. falciparum-infected patients and 200 malaria-negative subjects) were recruited in the study. Hematological indices of hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and platelets were measured, and their median values were statistically compared. The majority of P. falciparum-infected patients (67.6%) showed a low-level parasitemia. The median values of Hb concentration, RBC count, mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC) were significantly lower in P. falciparum-infected patients, while the median red cell distribution width (RDW) was significantly higher in the patients compared to malaria-negative subjects. Anemia, low MCV, low MCH, low MCHC and high RDW were significantly associated with falciparum malaria, but parasitemia level was not significantly associated with anemia severity. The median total WBC count was non-significantly higher in P. falciparum-infected patients, with neutropenia being significantly associated with falciparum malaria. The median platelet count was significantly lower in P. falciparum-infected patients, with thrombocytopenia being significantly associated with falciparum malaria. Falciparum malaria among patients in Kosti city of the White Nile State, Sudan is predominantly of low-level parasitemia. It is significantly associated with anemia, low MCV, low MCH, low MCHC, high RDW, thrombocytopenia and neutropenia. However, parasitemia level is not a significant predictor of anemia severity. On the other hand, leucopenia is not useful to predict falciparum malaria. Further large-scale studies in community and healthcare settings and inclusion of patients with complicated or severe malaria and those with high parasite densities are recommended.
7 citations
References
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TL;DR: Children infected with Plasmodium falciparum malaria exhibited important changes in some haematological parameters with low platelet count and haemoglobin concentration being the two most important predictors of malaria infection in children in the study area.
Abstract: Malaria is the commonest cause of childhood morbidity in Western Kenya with varied heamatological consequences The t study sought to elucidate the haemotological changes in children infected with malaria and their impact on improved diagnosis and therapy of childhood malaria Haematological parameters in 961 children, including 523 malaria-infected and 438 non-malaria infected, living in Kisumu West District, an area of malaria holoendemic transmission in Western Kenya were evaluated The following parameters were significantly lower in malaria-infected children; platelets, lymphocytes, eosinophils, red blood cell count and haemoglobin (Hb), while absolute monocyte and neutrophil counts, and mean platelet volume (MPV) were higher in comparison to non-malaria infected children Children with platelet counts of <150,000/uL were 138 times (odds ratio) more likely to have malaria Thrombocytopaenia was present in 49% of malaria-infected children and was associated with high parasitaemia levels, lower age, low Hb levels, increased MPV and platelet aggregate flag Platelet aggregates were more frequent in malaria-infected children (25% vs 4%, p<00001) and associated with thrombocytopaenia rather than malaria status Children infected with Plasmodium falciparum malaria exhibited important changes in some haematological parameters with low platelet count and haemoglobin concentration being the two most important predictors of malaria infection in children in our study area When used in combination with other clinical and microscopy, these parameters could improve malaria diagnosis in sub-patent cases
236 citations
"Characterization of platelet count ..." refers result in this paper
...001) which was in accordance with other studies [22,23]....
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209 citations
TL;DR: The data show an association between thrombocytopenia and either severity or prognosis in childhood falciparum malaria in Dakar, Senegal, an area that is hypoendemic for malaria.
Abstract: Thrombocytopenia is a common finding in malaria, but its prognostic value has not been addressed in children. The relationship between thrombocytopenia (platelet count < 100,000/mm3 on admission) and severity and outcome was investigated prospectively in children hospitalized with falciparum malaria in Dakar, Senegal, an area that is hypoendemic for malaria. Of 288 falciparum cases, 215 matched the 2000 World Health Organization definition of severe malaria. Median platelet counts were lower (98,000/mm3 versus 139,000/mm3; P < 0.02) among severe cases than in mild cases, and in children who died than among those who recovered (68,500/mm3 versus 109,000/mm3; P < 0.002). In severe cases, children presenting with a platelet count < 100,000/mm3 were more likely to die (odds ratio [OR] = 6.31, 95% confidence interval [CI] = 2.0-26.0). Moreover, multivariate analysis identified thrombocytopenia as an independent predictor of death (OR = 13.3, 95% CI = 3.2-55.1). Our data show an association between thrombocytopenia and either severity or prognosis in childhood falciparum malaria.
165 citations
"Characterization of platelet count ..." refers background in this paper
...Previous studies have pointed out the utility of platelet count in assessing and predicting the severity of malaria [4,5]....
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TL;DR: More studies are needed to specifically clarify if thrombocytopenia is the cause or consequence of the clinical disease spectrum, and whether platelet counts usually revert to normal ranges a few days after efficacious antimalarial treatment.
Abstract: Despite not being a criterion for severe malaria, thrombocytopenia is one of the most common complications of both Plasmodium vivax and Plasmodium falciparum malaria. In a systematic review of the literature, platelet counts under 150,000/mm³ ranged from 24-94% in patients with acute malaria and this frequency was not different between the two major species that affected humans. Minor bleeding is mentioned in case reports of patients with P. vivax infection and may be explained by medullary compensation with the release of mega platelets in the peripheral circulation by megakaryocytes, thus maintaining a good primary haemostasis. The speculated mechanisms leading to thrombocytopenia are: coagulation disturbances, splenomegaly, bone marrow alterations, antibody-mediated platelet destruction, oxidative stress and the role of platelets as cofactors in triggering severe malaria. Data from experimental models are presented and, despite not being rare, there is no clear recommendation on the adequate management of this haematological complication. In most cases, a conservative approach is adopted and platelet counts usually revert to normal ranges a few days after efficacious antimalarial treatment. More studies are needed to specifically clarify if thrombocytopenia is the cause or consequence of the clinical disease spectrum.
163 citations
"Characterization of platelet count ..." refers background in this paper
...The incidence of thrombocytopenia in a literature review has been reported as 24–94% [14]....
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Journal Article•
TL;DR: Although absence of thrombocytopenia is uncommon in malaria, its presence is not a distinguishing feature between the two types, and can have therapeutic implications in context of avoiding unnecessary platelet infusions with the relatively more benign course in P. vivax malaria.
Abstract: AIM OF THE STUDY Malaria is a major health problem in the tropics with increased morbidity and mortality. Thrombocytopenia is a common finding in malaria. Although a reliable diagnostic marker, prognostic implications could vary in the two types of malaria. This study was undertaken to correlate the presence and severity of thrombocytopenia with the type of malaria. DESIGN A total of 1565 subjects were included in the study and identified positive for malaria parasites on peripheral smear examination with conventional microscopy. Platelet count was done on a fully automated, quantitative, hematology Coulter analyser. RESULTS Normal platelet count was noted in 21.6% cases. The mean platelet count in vivax malaria (n=973) was 1,15,390/microl (SD 64,580) with a range of 8000-5,73,000/microl, as against falciparum malaria (n=590) where the mean platelet count was 100,900/microl (SD 75,437) with a range of 2000-497,000/microl (Pearson coefficient 8.825, p < 0.0001). Platelet count < 20,000/microl was noted in only 1.5% cases in vivax malaria as against 8.5% cases of falciparum malaria, and none of the subjects with vivax malaria had a platelet count less than 5000/microl. CONCLUSION Although absence of thrombocytopenia is uncommon in malaria, its presence is not a distinguishing feature between the two types. Thrombocytopenia less than 20,000/microl can occur in P. vivax malaria although statistically more common with P. falciparum malaria. The above findings can have therapeutic implications in context of avoiding unnecessary platelet infusions with the relatively more benign course in P. vivax malaria.
145 citations
"Characterization of platelet count ..." refers result in this paper
...Similar rates of thrombocytopenia have been reported in other studies [8,12,13]....
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...This is in contrast to the usual belief that falciparum malaria causes more severe thrombocytopenia as shown by previous studies [8,13,15]....
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