Thrombocytopenia and Release of Activated von Willebrand Factor during Early<i>Plasmodium falciparum</i>Malaria

Mast, Quirijn de; Groot, Evelyn; Lenting, Peter J.; Groot, Philip G. de; McCall, Matthew; Sauerwein, Robert W.; Fijnheer, Rob; Ven, André van der

doi:10.1086/519844

Cited by 104 publications

(139 citation statements)

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“…During early stages of malaria, platelet agglutination as a result of endothelial cell activation and release of activated von-Willebrand factor occurs which may cause thrombocytopenia. 6 Occasionally platelets can be invaded by malarial parasites. Thrombocytopenia in malaria is rarely severe and treatment is focused on eradication of malarial parasite.…”

Section: Discussionmentioning

confidence: 99%

Study of febrile thrombocytopenia in Malwa region of India

Yadav

Singhai

2017

Asian J Med Sci

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Background: Febrile thrombocytopenia is the thrombocytopenia associated with fever. Diseases which commonly present with fever and thrombocytopenia are malaria, leptospirosis, septicemia, typhoid, arbovirus diseases such as dengue.Aims and Objectives: The study was intended to know the underlying etiology of febrile thrombocytopenia in Malwa region and its various presentations.Materials and Methods: This study was conducted at Department of General Medicine of a tertiary care centre for two years. Five-hundred adult patients (age >18 years) of febrile thrombocytopenia were evaluated for possible inclusion in this study. Routine investigations including complete blood counts, peripheral smear examination, kidney function tests, liver function tests, ultrasound of abdomen were done in all subjects. The specific investigations were done as and when indicated.Results: Out of 500 patients of febrile thrombocytopenia, 298 were male, while 202 were female. Commonest symptom after fever was malaise (83%) followed by nausea-vomiting (76%), headache (63.4%), jaundice (26.8%), easy fatigability (22.4%), bleeding manifestations (7.8%), cough (6.8%), dyspnea (5.8%), rash (2.4%) and delirium (1.4%). Dengue was found in 178 patients. Malaria was found in 122 patients. Other causes of febrile thrombocytopenia were septicemia (22 cases), leptospirosis (12 cases), chikungunya fever (10 cases), viral hepatitis (9 cases), enteric fever (9 cases), acute lymphoblastic leukemia (2 cases), non-hodgkin lymphoma (one case), disseminated tuberculosis (one case).Conclusion: Febrile thrombocytopenia is an important clinical condition commonly caused by infections, particularly viruses and malaria. Such studies will help in finding changing trends of locally prevalent infectious diseases and finding some new emerging diseases not prevalent in the particular region.Asian Journal of Medical Sciences Vol.8(5) 2017 83-86

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Section: Discussionmentioning

confidence: 99%

Study of febrile thrombocytopenia in Malwa region of India

Yadav

Singhai

2017

Asian J Med Sci

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“…Various mechanisms have been proposed to explain thrombocytopenia during malaria episodes, including platelet destruction by immune mechanisms 14,[18][19][20] ; low medullar platelet production 14,21,22 ; low thrombopoietin (TPO) synthesis 23 ; platelet sequestration in organs, such as the spleen 24,25 or brain [26][27][28] ; and systemic sequestration [29][30][31] . These changes are transient, and in general, patients recover completely after malaria treatment 32 .…”

Section: Introductionmentioning

confidence: 99%

Platelet profile is associated with clinical complications in patients with vivax and falciparum malaria in Colombia

Martinez-Salazar

Tobón-Castaño

2014

Rev. Soc. Bras. Med. Trop.

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Introduction: Thrombocytopenia is a common complication in malaria patients. The relationship between abnormal platelet profi le and clinical status in malaria patients is unclear. In low and unstable endemic regions where vivax malaria predominates, the hematologic profi les of malaria patients and their clinical utility are poorly understood. The aim of this study was to characterize the thrombograms of malaria patients from Colombia, where Plasmodium vivax infection is common, and to explore the relationship between thrombograms and clinical status. Methods: Eight hundred sixty-two malaria patients were enrolled, including 533 (61.8%) patients infected with Plasmodium falciparum, 311 (36.1%) patients infected with Plasmodium vivax and 18 (2.1%) patients with mixed infections. Results: The most frequently observed changes were low platelet count (PC) and high platelet distribution width (PDW), which were observed in 65% of patients; thrombocytopenia with <50,000 platelets/µL was identifi ed in 11% of patients. Patients with complications had lower PC and plateletcrit (PT) and higher PDW values. A higher risk of thrombocytopenia was identifi ed in patients with severe anemia, neurologic complications, pulmonary complications, liver dysfunction, renal impairment and severe hypoglycemia. The presence of thrombocytopenia (<150,000 platelets/µL) was associated with a higher probability of liver dysfunction. Conclusions: Young age, longer duration of illness and higher parasitemia are associated with severe thrombocytopenia. Our study showed that thrombocytopenia is related to malaria complications, especially liver dysfunction. High PDW in patients with severe malaria may explain the mechanisms of thrombocytopenia that is common in this group of patients.

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“…Contradictory data were presented showing aggregation impairment in severe falciparum patients after ADP addition in vitro (Srichaikul et al 1988). P. falciparum induces systemic acute endothelial cell activation and the release of activated von Willerbrand factor (vWF) immediately after the onset of the blood-stage infection (Mast et al 2007). Even without consumptive coagulopathy, the increase in soluble glycoprotein-1b (GP1b) concentrations results from vWF-mediated GP1b shedding, a process that may prevent excessive adhesion of platelets and parasitised erythrocytes (Mast et al 2010).…”

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Thrombocytopenia in malaria: who cares?

Lacerda

Mourão

Coelho

et al. 2011

Mem. Inst. Oswaldo Cruz

172

170

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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...

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Thrombocytopenia and Release of Activated von Willebrand Factor during EarlyPlasmodium falciparumMalaria

Abstract: P. falciparum induces systemic acute endothelial cell activation and release of activated vWF immediately after the onset of blood-stage infection. The resulting platelet agglutination may result in early thrombocytopenia and may play a role in the pathogenesis of malaria.

Cited by 104 publications

References 37 publications

Study of febrile thrombocytopenia in Malwa region of India

Study of febrile thrombocytopenia in Malwa region of India

Platelet profile is associated with clinical complications in patients with vivax and falciparum malaria in Colombia

Thrombocytopenia in malaria: who cares?

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