PB0742 - Functional changes in platelets and coagulation during asexual and sexual parasitemia in a controlled human malaria infection

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

SH

Shengshi Huang

PhD student
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Wv

Wouter van der Heijden

.
Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, the Netherlands;
Nijmegen, Gelderland, Netherlands
IR

Isaie Reuling

.
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands
Nijmegen, Gelderland, Netherlands
JW

Jun Wan

PhD student
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands;
Maastricht, Limburg, Netherlands
QY

Qiuting Yan

.
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Presenting Author(s)

Romy De Laat-Kremers, PhD

Post-doctoral Research Project Leader
Department of Data Analysis and Artificial Intelligence, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Co-Author(s)

AV

Andre Van der Ven

.
Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, the Netherlands;
Nijmegen, Gelderland, Netherlands
PG

Philip G. de Groot

Emeritus Professor
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
MAASTRICHT, Limburg, Netherlands
MM

Matthew McCall

.
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands;
Nijmegen, Gelderland, Netherlands
RS

Robert Sauerwein

.
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands;
Nijmegen, Gelderland, Netherlands
TB

Teun Bousema

.
Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, the Netherlands;
Nijmegen, Gelderland, Netherlands
Mark Roest, PhD

Clinical Director
Department of Platelet pathophysiology, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Marisa Ninivaggi, PhD

Research Project Leader
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Qd

Quirijn de Mast

.
Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, the Netherlands
Nijmegen, Gelderland, Netherlands
Bd

Bas de Laat, MD, PhD

General Director
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Background: Asexual Plasmodium falciparum parasitemia in a human malaria infection is associated with a drop in platelet number. It remains unknown whether this is related to acute and/or long-term functional changes in platelets and coagulation. Additionally, the impact of the malaria gametocytemia stage on platelets and coagulation has not yet been clarified.

Aims: We aimed to assess changes in the number and function of platelets, total and active VWF, and the coagulation system during early asexual parasitemia, subsequent gametocytemia and convalescence.

Methods: Sixteen individuals were enrolled in a controlled human malaria infection (CHMI) designed to induce gametocytemia. Blood samples were collected at baseline, at the peak of asexual blood stage parasitemia, during gametocytemia and at day 64. Platelet activation and reactivity was determined by flow cytometry and the activation of the coagulation system was quantified by coagulation factor levels, thrombin generation, and thrombin dynamics analysis.

Results: Platelet count was reduced during asexual blood stage infection but normalized during gametocytemia. Platelet P-selectin expression was slightly increased during asexual parasitemia, gametocytemia and on day 64, and platelets showed a marked decrease in reactivity to low dose collagen-related peptide-XL. During asexual parasitemia, the TG lag time is prolonged (+19.5%; p< 0.001). Thrombin dynamics analysis revealed a decreased prothrombin conversion (-12.9%, p=0.039) and a trend towards decreased prothrombin levels (-3.7%). At the time of gametocytemia and day 64, the thrombin generation ETP, peak height and velocity index were increased. Finally, concentrations of von Willebrand factor (VWF) and active VWF were markedly increased during asexual parasitemia, but normalized during gametocytemia.

Conclusion(s): We show that the early decrease in platelet count during asexual parasitemia is not associated with increased platelet reactivity but with endothelial activation leading to increased levels of active VWF which are able to form spontaneous VWF-platelet complexes and thereby increased platelet clearance.