ORIGINAL ARTICLE

Thrombocytopenia in Children with Vivax Malaria: A Studyfrom North India

Chandra Mohan Kumar & Shweta Singh & Rajnish Garg

Received: 29 June 2013 /Accepted: 17 October 2013# Dr. K C Chaudhuri Foundation 2013

AbstractObjectives To study incidence, severity and clinical significanceof thrombocytopenia and to study recovery pattern of plateletcounts in children with vivax malaria.Methods This was a retrospective hospital based descriptivecase series. Cases of confirmed vivax malaria were studiedand their Total Platelet Counts (TPC) evaluated daily tillrecovery and again after 1 wk on follow up visit.Results In this study out of 39 children of confirmed vivaxmalaria 22 had thrombocytopenia, having mean platelet count48×109/L on admission which showed a very quick recoveryon treatment and by day 3 of treatment it rose to 126.5×109/Lwithout platelet transfusion. In untreated cases the lowestplatelet counts was observed on day 5–6 and on treatment,platelet counts returned to normal without any platelettransfusion by 9th day. Even among children there arevariations in different age groups and younger ones showmore quicker recovery than older peers.Conclusions Vivax malaria is associated with transientthrombocytopenia which does not lead to significant bleedingin children.

Keywords Vivaxmalaria . Thrombocytopenia . Plateletcount . Transient

Introduction

Malaria, the most common and arguably the most importantparasitic disease in tropics is endemic in most parts of Indiaand is usually caused by P. falciparum and P. vivax . Althoughmild thrombocytopenia has been considered as common inboth falciparum and vivax malaria, severe thrombo-cytopenia, reported in P. falciparum malaria, is not commonlyassociated with P. vivax infection. Although thrombo-cytopenia is common in malaria, clinical bleeding is rare evenwith very low platelet counts, unless a co-existing coa-gulopathy is present [1].

This study aimed to find out association of thrombocytopenia,its clinical significance and recovery pattern of plateletcounts in confirmed cases of monoinfection vivax malaria.

Material and Methods

This retrospective hospital based descriptive case series studywas conducted from June 1st 2012 to November 30th 2012.All the children below 14 y hospitalised and attending OPD,diagnosed as vivax malaria by Advantage Malaria Card(Manufacturer J Mitra and Co Pvt Limited, New Delhi) Testand confirmed by thick and thin smear, were included in thestudy.

Cases who tested positive for dengue (by DengueDay1NS1 Test kit), P. falciparum (by Advantage MalariaCard and confirmed by peripheral thick and thin smear) orleptospira (by Advantage Leptospira IgM and IgG card) wereexcluded. Total platelet counts (TPC) were measured usingautomated cell counter (Swelab alpha manufactured by BouleMedical AB, Stolkholm, Sweden) and those with countsbelow 100×109/L were manually counted and confirmed.All cases were followed up and their TPC repeated daily tillthey crossed 100×109/L or had progressively increasing

C. M. Kumar (*)Department of Pediatrics, Hamdard Institute ofMedical Sciences andResearch, New Delhi 110029, Indiae-mail: cmkumar1@rediffmail.com

S. SinghDepartment of Biochemistry, Rama Medical College and ResearchCenter, Hapur, Ghaziabad, Uttar Pradesh, India

R. GargDepartment of Pathology, Gold Field Institute of Medical Sciencesand Research, Faridabad, Haryana, India

Indian J PediatrDOI 10.1007/s12098-013-1277-3

counts on two days. Platelet counts were repeated on 7th dayof discharge. The data was analysed by SPSS 19 and ‘t’ testwas applied for assessment of significance.

Results

Initially 136 malaria positive cases were recruited and afterapplying exclusion criteria 39 cases qualified to be included.Out of 39 cases positive only for vivax malaria (Table 1),22 (56.4 %) had thrombocytopenia i.e. , (platelets countbelow 150×109/L) (Table 2). Among these 22 children(mean age 6.73 y, median 7.5 y, mode 8 y, boys 12, girls 10)with thrombocytopenia, 21 (95.4 %) reported between daythree and five of fever. Mean duration of fever in prehospitalization phase was 3.18 d. Mean hemoglobin, totalleucocyte count and mean platelet counts on admission were9.6 g/dL, 5645/cumm and 48×109/L respectively. Meanplatelet counts of subset of patients presenting on 3rd, 4th and5th day of fever were 50×109/L, 58×109/L and 39×109/Lrespectively. Lowest platelet count encountered in this studywas 20×109/L. Out of 22 cases, 17 patients (77 %) wereafebrile by third day and five children who continued to have

spikes of fever after 3 d of chloroquin were treated withArtemether and Lumifantrine combination. TPC increased toa mean value of 69.5×109/L on day 2 and 126.5×109/L on day3 without any platelet transfusion ( p value-0.000 on pairedt test). Only 8 of them attended follow up visit to hospital after1 wk and all had TPC above 150×109/L. The mean TPC on1 wk follow up after discharge was 202×109/L.

Discussion

Malaria is a very common infection in children and a majorpublic health problem in India. Ninety five percent populationlives inmalaria endemic areas. There are about 1.5 to 2millioncases and 500–1,000 deaths are reported every year due to it inIndia [2]. Thrombocytopenia has been commonly reportedwith falciparum malaria but, its occurrence in vivax malariahas been reported as early as in 1985 by Santhanakrishnanet al. [3]. A few studies have also documented presence ofsevere thrombocytopenia in vivax malaria, the lowest TPC of5×109/L reported is from India, but that was in an adult case[4]. Lowest reported platelet counts in a child with vivaxmalaria was 8×109/L [5].

Table 1 Distribution of malarialparasite (MP) positive cases MP positive

casesP. vivaxpositive

P. falciparum/Dengue/Leptospira also positiveor couldn’t be ruled out

Confirmed isolatedvivax malaria

Vivax malaria withthrombocytopenia

136 64 25 39 22

Table 2 Age, sex and hematological values of the case of vivax malaria

Agegroup

Numberof cases

Pre hospitalduration offever (in days)

Mean Hb onadmission(g/dL)

Mean TLCon admission(per cmm)

Mean TPCon admission(×109/L)

Mean TPC on day2 of treatment(×109/L)

Mean TPC on day3 of treatment(×109/L)

Mean TPCon 1 wk afterdischarge(×109/L)#M F Total

1–4 y 3 3 6 3.16 9.53 5083 50.8 61 139 203.3

5–9 y 7 4 11 3.24 9.73 5642 49 72.1 130 232.5

10 andabove

2 3 5 3 9.38 6240 43.2 68 102 181.7

Total 12 10 22 3.18 9.6 5645 48.1 69.5 126.5 202.5

Paired samples test

Paired Differences

Mean Std. deviation Std. errorMean

95 % Confidence Interval ofthe difference

Lower Upper t df Sig. (2-tailed)

Pair 1 TPC onadmin—TPCDAY3

−0.78409 0.28122 0.05996 −0.90878 −0.65941 −13.078 21 0.000

TPC Total platelet count; TLC Total leucocyte count# Only 8 children came for follow up after 1 wk of discharge

Indian J Pediatr

Incidence of thrombocytopenia in vivax malaria has beenreported between 59 and 73 % in various studies in children[1, 6, 7] which compares well with 56.4 % in the index study.Higher incidence reported in adults has been attributed to theirincreased susceptibility [8]. Although exact mechanism ofthrombocytopenia in malaria is not known, immune mediatedlysis, dyspoeitic process in marrow with diminished plateletproduction and sequestration in spleen have been suggested as

probable explanations. Structural and functional abnormalitiesof platelets including invasion by malaria parasite have beendemonstrated [9].

The age distribution points that median age of affectedchildren was 7.5 y and the mode was 8 y. There was noremarkable difference between boys and girls as the ratio(6:5) remained comparable to the ratio observed in totalmalarial parasite (MP) positive cases.

Fig. 1 Scatogram and trendline of platelet. The trendline is going up. It cuts the thrombocytopenia cut off line (150×109/L) on day 9

Indian J Pediatr

It was an interesting observation that the TPC on admissionwas lower in children ≥10 y in comparison to <5 y olds (43.3×109/L vs. 50.8×109/L) and the rate of rise in TPCduring recoverywas slower. TPC on day 3 of treatment was 102×109/L inchildren above 10 y as compared to 139×109/L in childrenbelow 5 y. Thus the present study demonstrates a unique agedependent susceptibility and recovery rate of platelet countswhich have not been reported in earlier studies. The limitationof the present study is small sample size and therefore, thisobservation needs validation by larger studies.

The lowest platelet count recorded was 20×109/L with onlyone case having spontaneous bleeding. Interestingly the childwho bled, had a platelet count of 34×109/L and had only nasalbleed not requiring platelet transfusion. This observation is inline with studies done by Joshi et al. and Makkar et al. [7, 10].but in contrast to observation made by Harish R et al. in whichtwo cases had intracranial bleeding [5]. However, higherproportion of adults have been reported to have spontaneousbleeding [4, 10–12]. The platelet count recovery was quickand even though the mean value (126×109/L) remained belowthe definition criteria of thrombocytopenia still it showed asignificant rise from initial value of 48×109/L within 3 d oftreatment without platelet transfusion. As reported earlier [8],the index results suggest that thrombocytopenia in vivaxmalaria is a transient and a benign phenomenon. Figure 1shows the scatogram of platelet counts along with the trendline. The platelet counts had dipped to their trough on day 5–6(Mean 39×109/L for 7 untreated cases on day 5 and only oneuntreated case presented on day 6 at platelet count of 21×109/L)and the recovery was complete by 9th day of onset of fever.The present results concur with those of Jadhav et al. whoreported maximum fall in platelet count on day 5–6 returningto normal after 5–7 d of end of parasitemia [1]. The quick fallin platelet counts and the recovery within 10 d points towardsimmune mediated platelet destruction. The present studysuggests that as the thrombocytopenia associated with vivaxmalaria is transient and benign, these patients can be managedwithout any need to give platelet support therapy.

The leucocyte counts were in normal range and hemoglobinwas reduced very marginally consistent with the observationsof other workers who concluded that thrombocytopenia is anearly marker of vivax malaria and it appears much earlier thananemia and splenomegaly [13].

Contributions SS and RG: Collected the data and prepared themanuscript. CMK: Designed the study and written this paper. He willact as guarantor for this paper.

Conflict of Interest None.

Role of Funding Source None.

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