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Original Article

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Blood Res 2023; 58(1):

Published online March 31, 2023

https://doi.org/10.5045/br.2023.2022133

© The Korean Society of Hematology

Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH)

Christopher Chin Keong Liam1,2,3, Jim Yu-Hsiang Tiao1,2, Yee Yee Yap3, Yi Lin Lee4, Jameela Sathar3, Simon McRae5, Amanda Davis6, Jennifer Curnow7, Robert Bird8, Philip Choi9, Pantep Angchaisuksiri10, Sim Leng Tien11, Joyce Ching Mei Lam12, Doyeun Oh13, Jin Seok Kim14, Sung-Soo Yoon15, Raymond Siu-Ming Wong16, Carolyn Lauren17, Eileen Grace Merriman18,19, Anoop Enjeti20, Mark Smith17, Ross Ian Baker1,2

Author Info. +

1Perth Blood Institute, 2Western Australia Centre of Thrombosis and Haemostasis (WACTH), Murdoch University, Perth, Australia, 3Haematology, Hospital Ampang, 4Centre for Clinical Trials, Hospital Ampang, Selangor, Malaysia, 5Haematology, Northern Cancer Service, Tasmania, 6Haematology, The Alfred Hospital, Melbourne, 7Haematology, Westmead Hospital, New South Wales, 8Haematology, Princess Alexandra Hospital, Woolloongabba, Queensland, 9Haematology, The Canberra Hospital, Canberra, Australia, 10Haematology and Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 11Haematology, Singapore General Hospital, 12Haematology, KK Women's and Children's Hospital, Singapore, 13Internal Medicine, Cha Bundang Medical Centre, Cha University, Seongnam, 14Internal Medicine, Yonsei University College of Medicine, 15Internal Medicine, Seoul National University Hospital, Seoul, Korea, 16Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, 17Haematology, Canterbury District Health Board, Christchurch, 18Haematology, North Shore Hospital, 19Haematology, Waitemata District Health Board, Auckland, New Zealand, 20Calvery Mater Hospital Newcastle, Waratah, New South Wales, Australia

Correspondence to : Christopher Chin Keong Liam, M.D.
Hematology Unit, Department of Internal Medicine, Hospital Sultanah Aminah, Jalan Persiaran Abu Bakar Sultan, Johor Bahru, Johor 80100, Malaysia
E-mail: liamck85@hotmail.com

Received: July 11, 2022; Revised: November 11, 2022; Accepted: January 5, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background
The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis.
Methods
Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score.
Results
46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%.
Conclusion
Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

Graphical Abstract

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Keywords: Thrombotic microangiopathy, PLASMIC score, Lactate dehydrogenase (LDH)

Article

Original Article

Blood Res 2023; 58(1): 36-41

Published online March 31, 2023 https://doi.org/10.5045/br.2023.2022133

Copyright © The Korean Society of Hematology.

Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH)

Christopher Chin Keong Liam1,2,3, Jim Yu-Hsiang Tiao1,2, Yee Yee Yap3, Yi Lin Lee4, Jameela Sathar3, Simon McRae5, Amanda Davis6, Jennifer Curnow7, Robert Bird8, Philip Choi9, Pantep Angchaisuksiri10, Sim Leng Tien11, Joyce Ching Mei Lam12, Doyeun Oh13, Jin Seok Kim14, Sung-Soo Yoon15, Raymond Siu-Ming Wong16, Carolyn Lauren17, Eileen Grace Merriman18,19, Anoop Enjeti20, Mark Smith17, Ross Ian Baker1,2

1Perth Blood Institute, 2Western Australia Centre of Thrombosis and Haemostasis (WACTH), Murdoch University, Perth, Australia, 3Haematology, Hospital Ampang, 4Centre for Clinical Trials, Hospital Ampang, Selangor, Malaysia, 5Haematology, Northern Cancer Service, Tasmania, 6Haematology, The Alfred Hospital, Melbourne, 7Haematology, Westmead Hospital, New South Wales, 8Haematology, Princess Alexandra Hospital, Woolloongabba, Queensland, 9Haematology, The Canberra Hospital, Canberra, Australia, 10Haematology and Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 11Haematology, Singapore General Hospital, 12Haematology, KK Women's and Children's Hospital, Singapore, 13Internal Medicine, Cha Bundang Medical Centre, Cha University, Seongnam, 14Internal Medicine, Yonsei University College of Medicine, 15Internal Medicine, Seoul National University Hospital, Seoul, Korea, 16Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, 17Haematology, Canterbury District Health Board, Christchurch, 18Haematology, North Shore Hospital, 19Haematology, Waitemata District Health Board, Auckland, New Zealand, 20Calvery Mater Hospital Newcastle, Waratah, New South Wales, Australia

Correspondence to:Christopher Chin Keong Liam, M.D.
Hematology Unit, Department of Internal Medicine, Hospital Sultanah Aminah, Jalan Persiaran Abu Bakar Sultan, Johor Bahru, Johor 80100, Malaysia
E-mail: liamck85@hotmail.com

Received: July 11, 2022; Revised: November 11, 2022; Accepted: January 5, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background
The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis.
Methods
Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score.
Results
46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%.
Conclusion
Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

Keywords: Thrombotic microangiopathy, PLASMIC score, Lactate dehydrogenase (LDH)

Fig 1.

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Figure 1.Study cohort design outlining the method of patient selection for analysis. The total PLASMIC/ PLASMIC LDH score was calculated with one point designated for each component and subsequently stratified into low risk (0–4 points), intermediate risk (5 points), and high risk (6–7 points).
Blood Research 2023; 58: 36-41https://doi.org/10.5045/br.2023.2022133

Fig 2.

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Figure 2.DeLong’s test for the receiver operator curve (ROC) with a comparison of the area under the curve (AUC) of PLASMIC (black) and PLASMIC-LDH (blue).
Blood Research 2023; 58: 36-41https://doi.org/10.5045/br.2023.2022133

Table 1 . Patient baseline clinical characteristics..

CharacteristicsN (%) (N=46)
Median age (years; interquartile range)50 (35–54)
Sex
Male19 (41.3)
Female27 (58.7)
Racial ethnicity
Southeast Asian (Malaysia, Thailand, Singapore)23 (50.0)
Caucasian (Australia, New Zealand)17 (37.0)
East Asian (Korea, Hong Kong)4 (8.7)
Others2 (4.3)
Clinical presentation
Central nervous system (CNS)33 (71.7)
Renal and genito-urinary system17 (37.0)
Bleeding manifestations12 (26.1)
Gastrointestinal system (GI)11 (23.9)
Cardiovascular system (CVS)8 (17.4)
Investigation Results
ADAMTS13 <10%34 (73.9)
ADAMTS13 inhibitor21 (45.7)
ADAMTS13 ≥10%12 (26.1)
Final TMA Diagnosis
Severe TTP (ADAMTS13 <10%)34 (73.9)
Complement mediated/atypical haemolytic uremic syndrome (aHUS)7 (15.2)
Pregnancy-related TMA2 (4.3)
Transplant related TMAa)1 (2.2)
Malignancy related TMA1 (2.2)
Others (sepsis-related DIC)1 (2.2)

a)One patient had allogeneic stem cell transplantation for acute myeloid leukaemia and was categorised as having transplant-related rather than malignancy-related TMA..

Abbreviations: DIC, disseminated intravascular coagulopathy; IQR, interquartile range; TMA, thrombotic microangiopathy; TTP, thrombotic thrombocytopenic purpura..

Table 2 . Comparison of the PLASMIC variables between TTP (ADAMTS13 <10%) and non-TTP (ADAMTS13 ≥10%)..

Non-TTP, N=12 (%)TTP, N=34 (%)P
1. Stem cell transplantation1 (8.3)0 (0.0)0.261
2. Active malignancy2 (16.7)0 (0.0)0.064
3. MCV <90 fL5 (41.7)17 (50.0)0.619
4. Platelet <30×109/L7 (58.3)32 (94.1)0.009
5. Creatinine <2 mg/dL5 (41.7)33 (97.1)<0.001
6. INR <1.512 (100.0)34 (100.0)NA
7. LDH (>2×ULN)8 (66.7)29 (85.3)0.211
8. Haemolysis markers5 (41.7)21 (61.8)0.227

Positive lysis markers (reticulocyte >2.5%, undetected haptoglobin or indirect bilirubin >2 mg/dL)..

Abbreviations: INR, international normalized ratio; LDH, lactate dehydrogenase; MCV, mean cell volume; ULN, upper limit of normal..

Table 3 . Logistic regression analysis of factors associated with TTP (ADAMTS13 <10%)..

No.VariableCrude OR (95% CI)P
1MCV<90 fL1.40 (0.37, 5.57)0.619
2Platelet <30×109/L11.43 (2.03, 92.48)0.005
3Creatinine <2 mg/dL46.20 (6.45, 968.25)<0.001
4LDH >2 ULN2.90 (0.60, 13.71)0.179
5Haemolysis markers2.26 (0.60, 9.12)0.229

Abbreviations: CI, confidence interval; OR, odds ratio..

Table 4 . Patient risk stratification based on both PLASMIC and PLASMIC-LDH models..

Risk StratificationPLASMIC (N=46)PLASMIC LDH (N=46)
High (6–7 points)28 (60.9%)32 (69.6%)
Intermediate (5 points)10 (21.7%)9 (19.6%)
Low (0–4 points)8 (17.4%)5 (10.8%)

Table 5 . Performance of PLASMIC and PLASMIC-LDH predictive tools..

PLASMICTTP (ADAMTS13 <10%)Non TTP (ADAMTS13 ≥10%)
Intermediate to high (5–7 points)335
Low (0–4 points)17
PLASMIC-LDHTTP (ADAMTS13 <10%)Non TTP (ADAMTS13 ≥10%)
Intermediate to high (5–7 points)338
Low (0–4 points)14

Sensitivity of 97.1%, specificity of 58.3%, 33.3%..

Positive predictive value (PPV) 86.8%, 80.5%, negative predictive value (NPV) 87.5%, 80.0%..
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