William Osler has said that “Humanity” has but 3 great enemies; fever, famine, and war; of these by far the greatest, by far the most terrible is fever”.

Malaria is the most important protozoal parasitic disease of humans. The word malaria derives its origin from the Italian “mal-aria” meaning bad air [1]. WHO estimated worldwide prevalence of malaria is about 300- 500 million per annum. It is present in more than 100 countries around the world. Most of these are developing countries or underdeveloped countries. [2]

Cases of malaria are known to be associated with variable degrees of coagulopathy as evident from abnormalities of screening coagulation assays in a large number of patients during the illness. However, attempts to use laboratory parameters as indicators of the severity of the underlying coagulopathy and for monitoring disease progression have met with only partial success [3]. Therefore, the authors wanted to revisit this subject in a prospective study involving a large number of malaria patients admitted at our tertiary care hospital in Ujjain and see if the platelet count is a good indicator of the underlying vasculopathy and of the hemorrhagic tendency and that normal screening coagulation assays are associated with the absence of hemorrhagic complications.

This study aimed to see if the elevation in D-Dimer levels and fibrin degradation products act as a marker of thrombosis and fibrinolysis respectively. Malaria affects almost all the organs of the body but the chief component affected is blood. Therefore, hematological changes play a major role in malaria pathology. The present study is an effort to correlate the laboratory changes in blood, and if they are the indicator of its clinical outcome.

Place of the study: Department of Pathology in Ruxmaniben Deepchand Gardi Medical College, Ujjain.

Duration and type of the study: The present prospective study was conducted over one and a half years i.e. January 2015 to July 2016.

Ethical considerations and permission: Ethical considerations and permission were met through the Institutional ethical committee.

Table-1: Age-wise distribution of P. vivax and P. falciparum cases.

83% of the total study cases had thrombocytopenia with platelet counts < 1,50,000/cumm, 97% of P. vivax and 64% patients of P. falciparum showed thrombocytopenia.

38 of total malaria positive patients, platelet counts ranged from 25,000 to <50,000/ μl. The P value is 0.000683 which is significant (Figure1).

Fig-1: Degree of thrombocytopenia.

Out of the total positive cases, PT was prolonged in 65% of total cases, Percentage positivity for prolonged PT for P.f and P.v is 60% and 68.5% respectively.

APTT was raised in 47% of malaria positive cases (P value> 0.05, not significant) with percentage positivity for P.f and P.v 48% and 45.7% respectively.

24 (18 P.v and 6 P.f) of the total malaria cases had isolated prolongation of PT, however, only 2 cases of P.v showed isolated prolongation of APTT. This shows that the extrinsic pathway of coagulation is affected more in malaria as compared to the intrinsic pathway.

The common pathway is affected giving rise to both prolongations in PT and APTT in a significant number of 54 cases (Figure 2).

In the present study, positive cases were observed in all the age groups although a maximum number of malaria cases were observed in the age group of 10 to 30 years and the least cases in the age group of 71 to 80. The frequency of malaria declined as the age increased. Similar findings were observed in a study carried out by Mohan Kashikunti et al [4] who reported a maximum number of malarial cases in the age group of 20 to 40 years.

The above results suggest that malaria affects the young and the population which is more exposed to the outdoor environment. In the present study, 16.6% of cases were in the age group of 0-10 years. These children play outdoors without wearing full clothes and in poor hygienic conditions and thus are vulnerable to mosquito bites.

In the present study, 52% of cases were of P. vivax and 48% of P. falciparum, our results are comparable to the study carried out by Kini Reshma G et al [5], which showed 60% cases of P. vivax. It corroborates with the fact that P. Vivax is the most common species of malaria in India followed by P. falciparum. Studies conducted by Himanshu Shekhar et al [6] and Mohan Kashikunty et al [4] show 54% and 76% of falciparum cases which may be due to difference in the geographical distribution of malarial species and show a rise in the incidence of P. falciparum over last few decades with a higher incidence of P.f as compared to P.v.

Anemia was reported in 62% of cases in the study carried by Himanshu Shekhar et al [6], whereas severe anemia was reported in 16%. Similarly, Sharma et al [7] reported anemia in 86.7% cases with severe anemia in 10% cases and Mohapatra et al [8] reported anemia in 59% of cases respectively. Our results are comparable to the studies carried out by them as anemia was found in 55% of the cases studied with severe anemia i.e hemoglobin < 6g/dl was seen in 13% of total cases. The mean hemoglobin value in patients with P. falciparum was 8.4g/dl lower than the mean hemoglobin value for P. vivax which was 11g/dL in the present study. (P-value <0.05).

83% of cases in the present study suffered from thrombocytopenia. Studies conducted by Sharma et al [7] who showed thrombocytopenia in 90% of their cases, Himanshu Shekhar Das et al [6] reported thrombocytopenia in 68% of cases, and Kini Reshma G et al [5] in 96% of their cases.

94% cases with positive FDP and all the cases with raised D-Dimer levels (P-value < 0.05)in the present study had platelet counts < 1,00x 10^3/ cumm suggesting that thrombocytopenia plays a critical role in the pathogenesis of thrombosis and fibrinolysis in malarial patients irrespective of the species involved causing DIC. These figures are comparable with a study conducted by Anirban Das Gupta et al [13].

It was observed that thrombocytopenia was seen in all the cases with deranged coagulation parameters. However, our findings were not in correlation with Ladhani et al [14]. They reported that thrombocytopenia was not the sole cause of DIC but other autoimmune mechanisms and increased peripheral destruction of platelet due to oxidative stress are also possible. However, they suggested that detailed platelet kinetic studies will be required to establish such observation.

5% of malaria cases in the present study presented with bleeding manifestations in the course of the disease and all had severe thrombocytopenia (platelet count < 20x 10^3/cumm) and elevated PT, APTT, and FDP. These observations were also reported in the studies carried out by Valluri Satya Prasad et al [15], Sahoo A.K, and Das A.K et al [12] with 10% and 8.8% cases with bleeding manifestations respectively.

There are many national programs like NVBDCP (National Vector Borne Disease Control Programme) implemented in India for the control of parasitic diseases like malaria. But, the inability to completely control and eliminate malaria, and it still exists as a burden, especially to economically reproductive ages.

As blood is the chief component affected by malaria, not only proper examination of peripheral smears is required for detection and species identification, but a careful evaluation of other laboratory parameters including platelet count, PT, APTT, FDP, and if required D- Dimer level estimation should be done irrespective of the malarial species for the early diagnosis of compensatory and non-compensatory consumptive coagulopathy and the life-threatening bleeding manifestations.