Life-saving coagulation panel tests in Malaria

Life-saving coagulation panel tests in Malaria

Editors:

  1. Dr. Praful B. Godkar (Ph.D)
    Eminent Author, Medical Biochemist and Scientist, Technical Education consultant. AGD Biomedicals (Pvt) LTD.
  2. Dr. Gauri Kulkarni MD (Pathology)
    Vice President, AGD Biomedicals (Pvt) LTD.

Malaria, especially P.falciparum greatly raises the risk of coagulopathy, which can cause both bleeding and clotting(1, 2).  Early malaria infection may increase thrombin generation, indicating a hypercoagulable state.  In cases of severe malaria, coagulopathy may advance to disseminated intravascular coagulation (DIC)(2,3).  DIC is a life-threatening disorder characterized by bleeding and microvascular thrombosis. Thrombocytopenia (decreased platelet count) is frequently observed in malaria and may elevate the risk of hemorrhage(1). (Refer to Case study). The activation of the coagulation system can lead to the formation of micro-blood clots in small blood vessels, which can block blood flow to various organs such as heart, liver, kidneys, brain, legs, etc., resulting in organ damage(3).  Rapid malaria diagnosis using advanced hematology analyzers like AGD HT 340, alongside hemogram and coagulation tests on AGD C-102, enables early anti-malarial treatment and correction of coagulation disorders that may be caused by malaria(6).

NOTE(6):

(1) Malaria remains a highly prevalent disease in more than 90 countries and accounts for at least 1 million deaths every year(1).

(2) Malaria is a mosquito-borne infectious disease that affects humans (vertebrates) and Anopheles mosquitoes. Malaria symptoms include headache, fever, fatigue, and vomiting, In severe cases, it can affect liver, kidneys and brain, leading to hepatic jaundice, seizures, and in severe cases coma and death.

(3) Malaria symptoms usually begin after being bitten by an infected Anopheles mosquito in 10 to 15 days. Without proper treatment, the patient may experience malaria recurrences within months.  

(4) The following five species of Plasmodium parasite infect humans: Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, Plasmodium  knowlesi and Plasmodium falciparum.

(5) Mild to moderate malaria is most commonly attributed to infection by the parasites Plasmodium ovale and Plasmodium malariae.  Severe malaria is caused by the Plasmodium falciparum parasite. Plasmodium vivax and Plasmodium knowlesi also can lead to severe disease, if diagnosed late.

(6) A medical emergency may result from undiagnosed or delayed treatment of uncomplicated malaria.

CASE STUDY

A 68-year-male was presented with fever (100-1010 F), severe headache, shivering, extreme fatigue and weakness for past two days (History as given by the patient). The attending physician after examination of the patient (with lethargy and extreme fatigue), recommended an urgent complete blood count (hemogram).

The complete hemogram report was as follows:

COMPLETE HEMOGRAM

PARAMETERRESULTNORMAL RANGE
Hemoglobin13.8 g/dl13–18 g/dl
Total erythrocyte count4.95 X 1012 /l5.0 ± 0.5 X 1012 /l
Total leukocyte count9.5 X 109/l7.0 ± 3.0 X 109/l
Differential leukocyte count
Neutrophils70%40–75%
Lymphocytes26%20–45 %
Eosinophils2%1–4 %
Monocytes2%2–8 %
PCV43%36–48%
MCV85.5 fL82–92 fL
MCH29 pg27–32 pg
MCHC32 %32–36 %
RDW1612–14
Platelet count34 X 109/l150–400 X 109/l
Metzer Index (MI)17.27< 13

STAINED PERIPHERAL BLOOD SMEAR EXAMINATION OBSERVATIONS:

Red blood cells: Predominantly Normocytic Normochromic

White Blood Cells: Normal

Platelets: Significantly decreased number. Occasional presence of giant platelets.

Impression: TROPHOZOITES AND SCHIZONTS FORMS OF PLASMODIUM VIVAX SEEN IN BOTH THICK AND THIN SMEAR

Malarial Parasite Index: 0.4%

DIAGNOSIS           

The patient was suffering from Malaria infection caused by Plasmodium vivax. A malaria parasite index of 0.4% suggested a low level of parasitaemia. The observation of a significantly very low platelet count indicated that it was necessary to admit the patient in the  hospital for prompt treatment.

NOTE

(1) Shivering during fever is a specific involuntary muscle contraction and relaxation which is a physical manifestation of chills. Shivering can last for 15 to 60 minutes.

 (2) Fever and shivering during malaria are directly related to the asexual reproductive cycle of the Plasmodium parasite within the red blood cells of the patient and the best phase to prepare thin and thick blood smears for the stained microscopic blood smears.

The following additional laboratory tests were advised upon admission to an emergency ward of a hospital:

COAGULATION PANEL TESTS

PARAMETER RESULT NORMAL RANGE
Prothrombin time (PT) 20 seconds 12–16 seconds
Activated partial thromboplastin time: (APTT) 42 seconds 35–40 seconds
Thrombin time (TT) 24 seconds 15–20 seconds

EVALUATION OF LABORATORY REPORTS(6)

(A) Patient was suffering from Malaria, and related thrombocytopenia, with marginally elevated PT,  APTT and TT.

(B) Prolonged PT, aPTT and TT signify a defect in the common pathway of the coagulation cascade which happens commonly in case of P falciparum malaria or severe cases of P.vivax malaria. .

(C ) Elevated TT, PT, and aPTT suggest a late-stage coagulation defect that raises bleeding risk(9),

NOTE

In severe malaria, continuous monitoring of coagulation parameters is crucial to detect early signs of coagulopathy and related appropriate management.

ROUTINE URINE EXAMINATION

PARAMETER RESULT NORMAL RANGE
Colour Yellow Normal colour
Protein ++ Absent
Bile pigments Present Absent
Bile salts Present Absent
Urobilinogen Increased Normal

LIVER FUNCTION TESTS (LFT)

PARAMETER RESULT NORMAL RANGE
Serum Total bilirubin 5.8 mg/dl Up to 1.0 mg/dl
Serum Direct bilirubin 4.5 mg/dl Up to 0.5 mg/dl
Serum indirect bilirubin 1.3 mg/dl Up to 0.5 mg/dl
SGPT 65 IU 5–35 IU
SGOT 78 IU 8-40 IU
Serum alkaline phosphatase 75 IU 20-80 IU

KIDNEY FUNCTION TESTS

PARAMETER RESULT NORMAL RANGE
Serum urea nitrogen 70 mg/dl 7–21 mg/dl
Serum creatinine 5.9 mg/dl 0.6–1.2 mg/dl
eGFR 60 > 90

NOTE

(1) Kidney and liver of the patient were infected by malarial parasites. Patient was suffering from fever (alternate day) for nearly eight days. However, he sought medical advice only on the seventh day. This miscommunication of case history (on the part of the patient) could have resulted in adverse patient outcome. Moreover, there were added financial implications.

(2) Upon admission to the emergency ward, when his blood was tested, his platelet count was only 24,000.00 and blood hemoglobin decreased to 12.2 g/dl (from initial 13.8 g/dl, a day prior to hospital admission. However, following appropriate treatment his platelet count increased steadily to normal levels, with significant improvements in liver and Kidney as indicated by the related laboratory tests.

References

(1) Butcher GA, Mitchell GH (September 2016). “The role of Plasmodium knowlesi in the history of malaria research”. Parasitology. 145 (1). Cambridge University Press: 6–17. doi:10.1017/S0031182016001888. PMID 27829470. S2CID 13209647.

(2) Blood Coagulation, Inflammation and Malaria. Ivo M. B. Francischetti1,*, Karl B. Seydel2, and Robson Q. Microcirculation. 2008 February ; 15(2): 81–107. doi:10.1080/10739680701451516.

(3) Miller LH, Baruch DI, Marsh K, Doumbo OK. The pathogenic basis of malaria. Nature 2002;415:673–679. [PubMed: 11832955].

(4). Newton CR, Taylor TE, Whitten RO. Pathophysiology of fatal falciparum malaria in African children.Am J Trop Med Hyg 1998;58:673–683. [PubMed: 9598460].

(5). Weatherall DJ, Miller LH, Baruch DI, Marsh K, Doumbo OK, Casals-Pascual C, Roberts DJ. Malaria and the red cell. Hematology Am Soc Hematol Educ Program 2002:35–57. [PubMed: 12446418]

(6) Godkar PB, Godkar DP. Text book of Medical laboratory technology (4th edition, 2024), Bhalani Publishers, Mumbai. India.

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