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 Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 3  |  Issue : 2  |  Page : 103-108

Role of red cell and platelet indices as a predictive tool for transfusions in dengue


Department of Transfusion Medicine, Manipal Hospital, Bengaluru, Karnataka, India

Date of Web Publication24-Oct-2018

Correspondence Address:
Dr. Ambuja Kantharaj
Department of Transfusion Medicine, Manipal Hospital, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_39_18

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  Abstract 


Review of literature and prevalent practices show the importance of red cell indices, especially hematocrit(HCT )in the diagnosis and prognosis of dengue. Platelet indices also may act as a tool to assess the prognosis and decide on the need for red cell and platelet transfusions in dengue. Platelet indices such as platelet count, mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) are simple indices which can be done by any 3-part differential cell counter. However, immature platelet fraction (IPF) can be done only at advanced centres using more advanced cell counters. In dengue fever, red cell indices give indirect information on whether the patient is bleeding or going into impending shock. An increased HCT suggests haemoconcentration and warrants treatment with bolus IV fluids while a decreased HCT in an unstable patient may indicate bleeding and act as a predictor for red cell transfusions, whereas it suggests recovery from disease in a stable patient. Platelet counts have no role in determining need for transfusion in dengue. Platelet indices give information on whether the platelet destruction is ongoing (necessitating an impending platelet transfusion) or whether the bone marrow is responsive and platelet transfusions can be put on hold. An increase MPV with falling platelets implies destruction of platelet and signals need for platelet transfusion while a decrease in MPV with low platelets <20,000/ul coupled with hemorrhagic tendency warrant need for red cell transfusions. An increase in IPF suggestive of responsive marrow and platelet transfusions could be possibly put on hold. Low platelet count, low MPV, low PCT, high PDW, and high P-LCR may be used as probable indicators for dengue in endemic area and also as a predictor of severity of dengue infection. However Platelet indices are still underutilised parameters both by the laboratory personnel as well as the clinicians due to various reasons like variability or lack of standardization in testing and reporting. Further platelet indices are not specific for (or predictive of) any particular pathological condition and large epidemiological, randomized, control studies are needed to establish utility of these parameters in dengue beyond doubt.

Keywords: Dengue, platelet indices, transfusion in dengue


How to cite this article:
Kantharaj A. Role of red cell and platelet indices as a predictive tool for transfusions in dengue. Glob J Transfus Med 2018;3:103-8

How to cite this URL:
Kantharaj A. Role of red cell and platelet indices as a predictive tool for transfusions in dengue. Glob J Transfus Med [serial online] 2018 [cited 2018 Nov 20];3:103-8. Available from: http://www.gjtmonline.com/text.asp?2018/3/2/103/243930




  Introduction Top


Dengue is a viral disease caused by dengue virus with four serotypes DEN-1–DEN-4 of the Flavivirus family transmitted through Aedes aegypti mosquito. More than 70% dengue is seen in lower- and middle-income countries.[1]

In majority of people, the illness is self-limiting and called simple dengue. However, dengue can be complicated by dengue shock syndrome (DSS) or dengue hemorrhagic fever (DHF) which warrants proper recognition and treatment without which, outcomes may be severe.

Review of literature and prevalent practices show the importance of red cell indices, (especially hematocrit [HCT]) in the diagnosis and prognosis of dengue. In addition, platelet indices also help assess the prognosis and decide on the need for transfusions.[2],[3]

Platelet indices such as platelet count, mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) are simple indices which can be done by any 3-part differential cell counter. However, immature platelet fraction (IPF) can be done only at advanced centers using more cell counters. Platelet indices are calculated and given by the cell counters but are often not reported. This is possibly due to underrecognition of the utility of these parameters both by the laboratory personnel as well as the treating physicians. Variability or lack of standardization in testing and reporting of these parameters could also be another reason. The clinical significance, reference values, and usefulness of some of these parameters are still under investigation.


  Platelet Indices Top


Mean platelet volume

Platelet volume is a marker of platelet function and activation. It is a calculated measure of platelet volume expressed in femtoliter (fL). When there is hypoproduction of platelets, immature platelets are activated and increase in size by pseudopod formation leading to increased MPV. Hence, increased MPV can be used as a marker of production rate and platelet activation. Normal range of MPV is reported to be between 7.2 and 11.7 fL. High MPV with ongoing thrombocytopenia represents peripheral destruction. Low MPV indicates underproduction/bone marrow suppression. MPV is inversely related to platelet counts. When marrow depression is the cause of thrombocytopenia, a rising trend in MPV heralds platelet recovery, and platelet transfusions may be put on hold.[4]

MPV is calculated by the formula,

MPV (fL) = ([PCT (%)/platelet count (×109/l)]) × 105.

Plateletcrit

PCT is the platelet equivalent of HCT. It is the volume of platelets expressed as a percentage of total blood volume and calculated according to the formula PCT = platelet count × MPV/10,000. The normal range for PCT is 0.22%–0.24%. PCT parallels the platelet count.

Platelet larger cell ratio

It is an indicator of circulating larger platelets (>12 fL), expressed as percentage. The normal percentage range is 15%–35%. It has also been used to monitor platelet activity. Platelet larger cell ratio (P-LCR) is inversely related to platelet count and directly related to PDW and MPV. It is decreased in patients with thrombocytosis and increased in thrombocytopenia. Further, studies have shown that P-LCR was significantly decreased in reactive thrombocytosis compared to neoplastic thrombocytosis. A greater increase in P-LCR is seen in destructive thrombocytopenia than those with hypoproliferative thrombocytopenia.[5]

Immature platelet fraction

IPF indicates the percentage of immature platelets containing higher concentration of RNA released into the circulation. It is measured in the reticulocyte/optical platelet channel of the 5-part differential hematology analyzer, Sysmex XE-2100 analyzer (Sysmex Corporation, Kobe, Japan) by flow cytometry, in which dye penetrates the cell membrane, staining the RNA in the cytoplasm of immature (or reticulated) platelets. IPF reference range is established between 1.1% and 6.1% in healthy individuals. An increased IPF is seen as production of platelets increases and low IPF indicate suppressed thrombopoiesis. It can be used as a tool to not only diagnose and monitor severity of thrombocytopenia but also as a predictor to recovery of thrombopoiesis in a previously thrombobocytopenic patient.[6]

Platelet distribution width

PDW directly measures variability in platelet size, changes with platelet activation, and reflects the heterogeneity in platelet morphology. It is an indicator of platelet anisocytosis. PDW is increased in the presence of platelet anisocytosis. The PDW reported varies markedly, with reference intervals ranging from 8.3% to 56.6%. There is a direct relation between MPV and PDW, that is, a high PDW is associated with a high MPV.[4],[7]

PDW and P-LCR are analyzed from a histogram of platelet size distribution. The distribution width at the level of 20% (the peak of the histogram is 100%) is defined as PDW, and the percentage of platelets with a size of more than 12fL was defined as P-LCR.

Mean platelet component (MPC)

Mean platelet component is a measure of mean refractive index of the platelets calculated by the new generation of blood cell analyzers (ADVIA 120 and ADVIA 2120) and provides direct information on density and granularity of platelets. Recent studies suggest that this parameter could correlate with the platelet activation state and become a potential predictive parameter for acute ischemic complications or thrombotic risk.[4],[8]

Composite platelet index (CPLI)

This is a conceptual index derived by multiplying platelet count (as decimal) with the mean platelet volume (e.g., platelet count of 1.5 × 105 mm3 and MPV of 10 fL, composite platelet index (CPLI) = 1.5 × 10 = 15) which can be used as an indicator of risk of bleeding. The rationale behind this index is fresh and large platelets would be more functional and hence counter the disadvantage of lower platelet count to certain extent. This means for a given platelet count, higher CPLI indicates higher MPV and hence better function and protection from bleeding.[9]

Normal ranges of platelet indices are shown in [Table 1].[10]
Table 1: Normal Range of platelet indices

Click here to view



  Pathophysiology of Dengue Hemorrhagic Fever Top


Hemorrhage in dengue is the result of low platelets and coagulopathy. Low platelets are due to direct bone marrow suppression of thrombopoiesis by dengue virus or destruction of platelets by anti-NS1 antibodies. Platelet transfusions have a limited role in the management of dengue[2],[3] and transfused platelets are as much likely to be destroyed by these antibodies as one's own platelets. Only indication for platelet transfusions in dengue is overt or internal mucosal bleeding. However, patient and doctors alike want platelet transfusions when the count drops below 10,000–20,000/ul.


  Pathophysiology of Dengue Shock Syndrome Top


Dengue virus causes increased capillary permeability and plasma leakage into extravascular space, leading to hemoconcentration.

Red cell indices give indirect information on whether the patient is bleeding (needing red cell transfusion) or going into impending shock (needing bolus intravenous [IV] fluids). Platelet indices give information on whether the platelet destruction is ongoing (necessitating an impending platelet transfusion) or whether the bone marrow is responsive and platelet transfusions can be put on hold.


  Role of Red Cell and Platelet Indices in Dengue Top


Role of red cell indices

Hematocrit

HCT forms the most important indicator in recognizing dengue complications. Increase in HCT over the baseline suggests hemoconcentration and possibly impending shock. This is caused by fluid leakage from capillaries that are seen in dengue. Such patients are more likely to develop DSS and need aggressive management with IV fluids.

Decrease in HCT in an unstable patient is suggestive of hemorrhage and may indicate internal bleeding secondary to DHF, whereas a decrease in HCT in a stable patient suggests recovery from disease [Figure 1].
Figure 1: Role of hematocrit in dengue

Click here to view


Therefore, a baseline HCT must be established in all patients with viral fevers.[2]

In the absence of baseline values the population mean may be used.

Role of reticulocyte production index

Reticulocyte production index (RPI) is believed to be good surrogate marker to predict the responsiveness of the bone marrow. A good correlation is seen between the increase in RPI and increase in postdengue platelet count.

Patients with an RPI greater than the cutoff (RPI >3) indicate a good bone marrow regenerative capacity and that the platelet count would eventually increase.[11]


  Role of Platelet Indices Top


Platelet count

Thrombocytopenia may be seen in dengue patients by day 4 or 5 of illness. The exact pathophysiology of thrombocytopenia in dengue is uncertain.

It could be due to direct bone-marrow suppression of thrombopoiesis modulation of endothelial cell by dengue virus destruction of platelets by Anti-NS1 antibodies directed against the virus cross-reacting with the platelets.

However, transfused platelets are as much likely to be destroyed by these antibodies as one's own platelets and hence platelet transfusions have a limited role in the management of dengue.[12]

Mean Platelet Volume in Dengue

Increase in MPV seen in dengue is the result of platelet activation and pseudopod formation. Further, in case of functional marrow, there is release of immature platelets from the bone marrow which are larger in size and could be another reason for increased MPV.

When platelet production is decreased, young platelets become bigger and more active, and MPV levels increase.

Increase in MPV together with a stable platelet count possibly indicates recovery whereas a persistently elevated MPV together with ongoing thrombocytopenia is suggestive of active disease causing platelet destruction with possible need to prepare for platelet transfusions.

Decreased MPV has been noted in patients with hemorrhagic tendencies. Decreased MPV with severe thrombocytopenia (<20,000 platelets/Ul) could be an ominous sign in dengue and could indicate need for red cell transfusion [Figure 2].[13],[14]
Figure 2: Role of mean platelet volume in dengue

Click here to view


Immature platelet fraction in dengue

Increased IPF is suggestive of an active responsive marrow, whereas a low IPF possibly indicates suppressed thrombopoiesis.

In a study by Suman et al., it was observed that in thrombocytopenic patients, a cutoff value of IPF ≥6.25 indicated that there is a 67% chance that there will be a rise in platelet count by 20,000 platelets/UL within 48 hours. A cutoff value of 10.6 or more indicated that there is 100% chance of platelet recovery by 20,000 platelets/UL within 48 hours and hence transfusion decision could be put on hold.[15]

In another study by Dadu et al., it was seen that 93.75% of the patients show platelet recovery within 24–48 h if the IPF was more than 10%.[16]

Plateletcrit, Platelet Distribution Width, and Platelet Large-cell Ratio in Dengue

PCT is directly related to platelet counts, whereas P-LCR is inversely related to platelet count and an increased P-LCR is seen in destructive thrombocytopenia (more likely in dengue). PDW is reported to be higher in dengue fever patients compared to controls. A study by Mukker et al. showed that PDW and PCT values were significantly altered in dengue fever patients with platelet counts below 20,000/ul compared to control group of patients with platelet count more than 1 lakh.[17] Studies have shown that a high PDW >13 Fl is associated with dengue fever, whereas a PDW >15 Fl, a high P-LCR (>42%), and low PCT (<0.15%) are more sensitive for DHF. In conclusion, Low platelet count, low PCT, and high PDW may be used as predictors of severity of dengue infection.[18]


  Summary Top


In dengue:

  1. Increased HCT suggests hemoconcentration and warrants treatment with bolus IV fluids (10–20ml/kg/h)
  2. Decreased HCT in an unstable patient may indicate bleeding and act as a predictor for red cell transfusions, whereas it suggests recovery from disease in a stable patient
  3. Platelet counts have no role in determining need for transfusion in dengue
  4. An increase MPV with falling platelets implies destruction of platelet and signals need for platelet transfusion
  5. A decrease in MPV with low platelets <20,000/ul coupled with hemorrhagic tendency warrant need for red cell transfusions
  6. Low platelet count, low MPV, low PCT, high PDW, and high P-LCR may be used as probable indicators for dengue in endemic area
  7. Low platelet count, low PCT, and high PDW may be used as a predictor of severity of dengue infection
  8. An increased P-LCR is seen in destructive thrombocytopenia (more likely in dengue)
  9. P-LCR is inversely related to platelet count
  10. An increase in IPF suggestive of responsive marrow and platelet transfusions could be possibly put on hold.



  Conclusion Top


Platelet indices (PI) may act as predictive tools in the diagnosis and predicting outcomes in dengue fever. Clinicians and transfusionists need to be sensitized about the utility and limitations of these indices in day-to-day clinical practice. Transfusion decisions based on these indices may also help in rationalizing the need for red cell and platelet transfusions in dengue and thereby allay anxiety of the clinician and improve preparedness of the blood center to provide necessary blood components for transfusion. However, platelet indices are not routinely used in clinical practice, probably because they are not tested for or reported routinely. IPF is one parameter that is being increasingly used to assess the recovery from thrombocytopenia in dengue but can be done only on 5-part differential machines making it difficult for routine implementation in all laboratories/hospitals. Further, platelet indices are not specifc for (or predictive of) any particular pathological condition.[19] Most of these studies are retrospective in small study populations and the cutoff values have not been validated prospectively. Hence, large epidemiological, randomized, control studies are needed to establish utility of these parameters in dengue beyond doubt.[20]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
World Health Organization. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control – New Edition. Special Programme for Research and Training in Tropical Diseases (TDR). World Health Organization; 2009. Available from: http://www.who.int/tdr/publications/documents/dengue-diagnosis.pdf. [Last accessed on 2018 Aug 20].  Back to cited text no. 1
    
2.
Available from: https://www.cdc.gov/dengue/resources/dengue-clinician-guide_508.pdf. [Last accessed on 2018 Aug 20].  Back to cited text no. 2
    
3.
Joshi AA, Divyashree BN, Gayathri BR. The hematocrit spectrum in dengue. Int J Sci Stud 2018;5:1-5. Available from: https://www.ijsssn.com/uploads/2/0/1/5/20153321/ijss_jan_oa08_-_2018.pdf. [Last accessed on 2018 Aug 20].  Back to cited text no. 3
    
4.
Budak YU, Polat M, Huysal K. The use of platelet indices, plateletcrit, mean platelet volume and platelet distribution width in emergency non-traumatic abdominal surgery: A systematic review. Biochem Med (Zagreb) 2016;26:178-93.  Back to cited text no. 4
    
5.
Babu E, Basu D. Platelet large cell ratio in the differential diagnosis of abnormal platelet counts. Indian J Pathol Microbiol 2004;47:202-5.  Back to cited text no. 5
    
6.
Briggs C, Kunka S, Hart D, Oguni S, Machin SJ. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. Br J Haematol 2004;126:93-9.  Back to cited text no. 6
    
7.
Zhang S, Cui YL, Diao MY, Chen DC, Lin ZF. Use of platelet indices for determining illness severity and predicting prognosis in critically ill patients. Chin Med J (Engl) 2015;128:2012-8.  Back to cited text no. 7
    
8.
Ricart MP, Navalon F, Brugues R, Merino A, James G, Escolar G, et al. Stabilization of the mean platelet component (MPC), a parameter related to platelet granularity provided by new generation of blood analyzers. Blood 2006;108:3919. Available from: http://www.bloodjournal.org/content/108/11/3919?sso-checked=true. [Last accessed on 2018 Aug 20].  Back to cited text no. 8
    
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Krishnamurthy V, Rajeshakar R, Doreswamy SM. Thrombocytopenia in dengue illness: Destruction, suppression and composite platelet index: A retrospective study. Ann Pathol Lab Med 2016;3:A465-70. Available from: https://www.pacificejournals.com/journal/index.php/apalm/article/view/apalm966/pdf_248. [Last accessed on 2018 Aug 20].  Back to cited text no. 9
    
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Sachdev R, Tiwari AK, Goel S, Raina V, Sethi M. Establishing biological reference intervals for novel platelet parameters (immature platelet fraction, high immature platelet fraction, platelet distribution width, platelet large cell ratio, platelet-X, plateletcrit, and platelet distribution width) and their correlations among each other. Indian J Pathol Microbiol 2014;57:231-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24943755. [Last accessed on 2018 Aug 20].  Back to cited text no. 10
    
11.
Managoli N, Garg N, Raheja R, Jacob AJ, Atodaria K, Patel F, et al. Limited role of platelet transfusion in dengue management and the value of reticulocyte production index as a measure of clinical improvement. Int J Sci Stud 2017;4:187-91. Available from: https://www.ijss-sn.com/uploads/2/0/1/5/20153321/ijss_mar_oa40_-_2017.pdf. [Last accessed on 2018 Aug 20].  Back to cited text no. 11
    
12.
Funahara Y, Ogawa K, Fujita N, Okuno Y. Three possible triggers to induce thrombocytopenia in dengue virus infection. Southeast Asian J Trop Med Public Health 1987;18:351-5.  Back to cited text no. 12
    
13.
Khaleed JK, Abeer Anwer AA, Maysem Alwash AA. Platelet indices and their relations to platelet count in hypoproductive and hyper-destructive Thrombocytopenia. Karbala J Med 2014;7:1952-8. Available from: https://www.iasj.net/iasj?func= fulltext&aId=98300. [Last accessed on 2018 Aug 20].  Back to cited text no. 13
    
14.
Eldor A, Avitzour M, Or R, Hanna R, Penchas S. Prediction of haemorrhagic diathesis in thrombocytopenia by mean platelet volume. Br Med J (Clin Res Ed) 1982;285:397-400.  Back to cited text no. 14
    
15.
Suman FR, Cruze LD, Rajendiran R, Varadharajan S. Dengue: Platelet and immature platelet dynamics a study done at a tertiary care centre from South India. Int J Recent Trends Sci Technol 2014;12:620-3. Available from: http://www.pathoindia.com/articles/ipf2013.pdf. [Last accessed on 2018 Aug 20].  Back to cited text no. 15
    
16.
Dadu T, Sehgal K, Joshi M, Khodaiji S. Evaluation of the immature platelet fraction as an indicator of platelet recovery in dengue patients. Int J Lab Hematol 2014;36:499-504.  Back to cited text no. 16
    
17.
Mukker P, Kiran S. Platelet indices evaluation in patients with dengue fever. Int J Res Med Sci 2018;6:2054. Available from: http://www.msjonline.org/index.php/ijrms/article/view File/4865/3978. [Last accessed on 2018 Aug 20].  Back to cited text no. 17
    
18.
Nehara HR, Meena SL, Parmar S, Gupta BK. Evaluation of platelet indices in patients with dengue infections. Int J Sci Res 2016;5:78-81. Available from: https://www.worldwidejournals.com/international-journal-of-scientific-research-(IJSR)/file.php?val=July_2016_1467448011__25.pdf. [Last accessed on 2018 Aug 20].  Back to cited text no. 18
    
19.
Lippi G, Pavesi F, Pipitone S. Evaluation of mean platelet volume with four hematological analyzers: Harmonization is still an unresolved issue. Blood Coagul Fibrinolysis 2015;26:235-7.  Back to cited text no. 19
    
20.
Leader A, Pereg D, Lishner M. Are platelet volume indices of clinical use? A multidisciplinary review. Ann Med 2012;44:805-16.  Back to cited text no. 20
    


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