During acute Plasmodium falciparum infection in man, plasma concentrations of platelet-specific proteins, β-thromboglobulin (βTG) and platelet factor 4 (PF4) were significantly elevated. For βTG, the mean concentration was 136.24 ± 71.58 ng/ml in patients, and 50.53 ± 25.42 ng/ml in control subjects (t = 5.3794; p = 0.0001), while for PF₄ mean values were, respectively, 75.35 ± 23.09 and 18.64 ± 13.42 ng/ml (t = -6.0897; p < 0.0001). Platelet LDH loss in vitro in response to stimulation with 0.5 U of thrombin was 57.0 ± 29.5% in patient samples and 24.8 ± 16.9% (control); the values being significantly different from each other (t = 2.888; p < 0.025). With serotonin (5HT) uptake and release however, the values were essentially normal, in spite of marginal difference observed in the uptake value of patients compared to control. The data indicate that there was in vivo platelet activation during the infection, with the haemostatic balance tilted towards hypercoagulability. There was also associated easy platelet lysis with stimulation. It is also suggested that the latter finding may be one of the mechanisms of reduced circulating platelet numbers observed in patients in the acute disease.

We had earlier reported altered ADP-induced platelet aggregation in man during acute malaria infection. The present study sought to determine (i) whether the changes suggested platelet hypersensitivity to ADP and (ii) whether such changes occurred in vivo or in vitro.The aggregation response of platelets (as citrated PRP) to addition of ADP from thirty patients with acute malaria infection has been compared with that of 29 control i.e., non-infected subjects. The age range of the subjects in both groups varied from 2 to 70 years. These tests were performed before the patients took any drugs. With addition of l.0μM ADP to 1 ml of PRP, the mean aggregation amplitude (as % light transmission) obtained from 8 patients, 39.8±27.1% was significantly greater than that from 9 control subjects (5.2±6.7%; t = 3.51; P < 0.005). With higher ADP concentrations (2.4 - 5.0μM) similar response in 22 subjects (mean 89.1±14.9%) was also significantly greater than that in 20 controls (77.8±16.5%; t = 12.45; P < 0.02). These results suggest that during acute malaria infection in man, circulating platelets become hypersensitive to ADP in vitro. No instances of spontaneous aggregation were however observed in the patients.βTG was determined in 7 patients and 6 controls. The mean plasma βTG in the patients (208.3±15.6 ng/ml) was significantly higher than that in controls (59.2±15.7 ng/ml; t = 13.44; P <0.001). These latter results suggest that the platelets were probably activated in vivo to release the βTG. They further suggest that the hypersensitive changes noted earlier also probably occurred in vivo.It is suggested that acute malaria (P.falciparum) infection in man is probably another clinical condition associated with platelet hypersensitivity.

SummaryDuring acute malaria infection, platelets in human platelet-rich plasma are hypersensitive to the addition of ADP between 1.0 uM and 5.0 uM, or adrenaline 0.11 uM as aggregating agents. The mean maximum aggregation amplitude (as % of light transmission) obtained from 8 subjects in response to added ADP (1.0 uM), 39.8 ± 27 (1SD), was significantly greater than the value in 6 controls (5.2±6.7 (1SD); t = 3, 51 P <0.005). A similar pattern of response was obtained with higher ADP concentrations (2.4,4.5 or 5.0 uM) in 22 patients and 20 control subjects (89.9±14.9% vs 77.8±16.5% (1SD) t = 2.45, P <0.02). Addition of 4.5 uM ADP to patient PRP usually evoked only a single aggregation wave (fused primary and secondary waves) while the typical primary and secondary wave pattern was usually obtained from controls.Mean plasma B-thromboglobulin (BTG) concentration in 7 patients (208.3 ± 15.6 ng/ml) was significantly higher than the value in 6 control subjects (59.2±15.7 ng/ml; t = 13.44, P <0.002).

We recently examined a possible role and extent of involvement of Plasmodium falciparum para-sitaemia in our earlier report of significantly lower circulating platelet numbers in healthy adult Nigerians (100 – 300x 103/ul) compared with matched Caucasians (150 – 140 χ 103/ml) ; (P<. 0.001), and in view of recently reported association of Plasmodium parasitaemia with thrombocytopaenia, consumptive coagulopathy (DIC) and other haemorrhagic syndromes. Ninety-eight febrile children aged between 8 months and 10 years whose fever was attributed to malaria parasitaemia only were admitted into the study. Platelet count, platelet aggregation, Factor VIII and FDP were determined on each blood sample which was collected before treatment was started. Tests were repeated 10-Hdays later. It was found that the mean platelet count of 132,000+61, 620/ul (1SD) during illness and immediately after treatment was significantly lower than the count of 234, 400+98, 480/ul, 10–14 days later, (t = 6.496 ; P<c 0.001 ). Significant thrombo cy topa emia (Platelets 70,000/ul) was observed only in Gfo of the subjects and none had any haemorrhagic symptoms. The effect was independent of age or degree of parasitaemia. Pre- and post-treatment leucocyte counts were similarly different (7952+2043 vs. 9221+3071 t = −2.81; P<0.05). Haematocrit values did not change significantly. However, in the response to platelet aggregating agents, it was found that the second wave of ADP-induced aggregation was regularly abolished during the parasitaemia.It is concluded that in hyperendemic Plasmodium falciparum environment, the malaria may often lead to mild depression of platelet count but that severe thrombocytopaenia is uncommon. The platelets may not be optionally functional.

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