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Clinical utility of activated partial thromboplastin time clot waveform analysis and thrombin generation test in the evaluation of bleeding phenotype in Hemophilia A.
Indian J Pathol Microbiol. 2021 Jan-Mar; 64(1):117-122.IJ

Abstract

Context

Hemophilia A is classified as mild, moderate, and severe based on Factor VIII levels (FVIII). Clot-based assays only detect initiation of thrombin generation, hence FVIII levels may not accurately predict the bleeding risk in all hemophilia patients. The entire process of thrombin generation as measured by global hemostasis tests like activated partial thromboplastin time clot waveform analysis (APTT CWA) and thrombin generation test (TGT) may reflect the actual bleeding phenotype.

Aims

To assess the utility of TGT and CWA as a screening tool to identify bleeders and to evaluate the bleeding phenotype in Hemophilia A.

Settings and Design

Prospective, observational study of 147 consecutive patients referred for coagulation workup.

Subjects and Methods

Bleeding assessment tool was used to identify bleeders. Patients were classified as severe and nonsevere bleeders based on clinical criteria. TGT was performed by calibrated automated thrombogram, CWA by photo-optical coagulometer and factor levels by one stage clot-based assays.

Statistical Analysis Used

The Kruskal-Wallis test with post-hoc analysis was done to examine the difference in CWA/TGT parameters amongst hemophilia classified by FVIII levels. Receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic accuracy of CWA and TGT in discriminating between clinically severe vs nonsevere bleeders.

Results

Using ROC derived cut-offs of min1, min2 and peak height of thrombin (PH), the sensitivity (min1:91.67%, min2:91.67%, PH: 97.22%, FVIII: 86.11%) and specificity (min1:100%, min2:100%, PH: 90.91%, FVIII: 90.91%) of CWA/TGT was superior to FVIII to distinguish between clinically severe vs nonsevere bleeders. Phenotypic heterogeneity of bleeding severity was identified in our study population. Clinical severity correlated with CWA/TGT parameters instead of FVIII levels.

Conclusions

CWA and TGT are more effective tools than conventional factor assays to identify clinically severe bleeders and tailor prophylaxis as per bleeding phenotype.

Authors+Show Affiliations

Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, Tamil Nadu, India.Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, Tamil Nadu, India.Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, Tamil Nadu, India.Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, Tamil Nadu, India.Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India.Department of Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, Tamil Nadu, India.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

33433420

Citation

Dave, Rutvi G., et al. "Clinical Utility of Activated Partial Thromboplastin Time Clot Waveform Analysis and Thrombin Generation Test in the Evaluation of Bleeding Phenotype in Hemophilia A." Indian Journal of Pathology & Microbiology, vol. 64, no. 1, 2021, pp. 117-122.
Dave RG, Geevar T, Mammen JJ, et al. Clinical utility of activated partial thromboplastin time clot waveform analysis and thrombin generation test in the evaluation of bleeding phenotype in Hemophilia A. Indian J Pathol Microbiol. 2021;64(1):117-122.
Dave, R. G., Geevar, T., Mammen, J. J., Vijayan, R., Mahasampath, G., & Nair, S. C. (2021). Clinical utility of activated partial thromboplastin time clot waveform analysis and thrombin generation test in the evaluation of bleeding phenotype in Hemophilia A. Indian Journal of Pathology & Microbiology, 64(1), 117-122. https://doi.org/10.4103/IJPM.IJPM_336_19
Dave RG, et al. Clinical Utility of Activated Partial Thromboplastin Time Clot Waveform Analysis and Thrombin Generation Test in the Evaluation of Bleeding Phenotype in Hemophilia A. Indian J Pathol Microbiol. 2021 Jan-Mar;64(1):117-122. PubMed PMID: 33433420.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical utility of activated partial thromboplastin time clot waveform analysis and thrombin generation test in the evaluation of bleeding phenotype in Hemophilia A. AU - Dave,Rutvi G, AU - Geevar,Tulasi, AU - Mammen,Joy J, AU - Vijayan,Ramya, AU - Mahasampath,Gowri, AU - Nair,Sukesh C, PY - 2021/1/12/entrez PY - 2021/1/13/pubmed PY - 2021/7/24/medline KW - Clot waveform analysis KW - Hemophilia A KW - International Society of Thrombosis and Haemostasis-Bleeding Assessment Tool score KW - factor VIII KW - thrombin generation test SP - 117 EP - 122 JF - Indian journal of pathology & microbiology JO - Indian J Pathol Microbiol VL - 64 IS - 1 N2 - Context: Hemophilia A is classified as mild, moderate, and severe based on Factor VIII levels (FVIII). Clot-based assays only detect initiation of thrombin generation, hence FVIII levels may not accurately predict the bleeding risk in all hemophilia patients. The entire process of thrombin generation as measured by global hemostasis tests like activated partial thromboplastin time clot waveform analysis (APTT CWA) and thrombin generation test (TGT) may reflect the actual bleeding phenotype. Aims: To assess the utility of TGT and CWA as a screening tool to identify bleeders and to evaluate the bleeding phenotype in Hemophilia A. Settings and Design: Prospective, observational study of 147 consecutive patients referred for coagulation workup. Subjects and Methods: Bleeding assessment tool was used to identify bleeders. Patients were classified as severe and nonsevere bleeders based on clinical criteria. TGT was performed by calibrated automated thrombogram, CWA by photo-optical coagulometer and factor levels by one stage clot-based assays. Statistical Analysis Used: The Kruskal-Wallis test with post-hoc analysis was done to examine the difference in CWA/TGT parameters amongst hemophilia classified by FVIII levels. Receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic accuracy of CWA and TGT in discriminating between clinically severe vs nonsevere bleeders. Results: Using ROC derived cut-offs of min1, min2 and peak height of thrombin (PH), the sensitivity (min1:91.67%, min2:91.67%, PH: 97.22%, FVIII: 86.11%) and specificity (min1:100%, min2:100%, PH: 90.91%, FVIII: 90.91%) of CWA/TGT was superior to FVIII to distinguish between clinically severe vs nonsevere bleeders. Phenotypic heterogeneity of bleeding severity was identified in our study population. Clinical severity correlated with CWA/TGT parameters instead of FVIII levels. Conclusions: CWA and TGT are more effective tools than conventional factor assays to identify clinically severe bleeders and tailor prophylaxis as per bleeding phenotype. SN - 0974-5130 UR - https://www.unboundmedicine.com/medline/citation/33433420/Clinical_utility_of_activated_partial_thromboplastin_time_clot_waveform_analysis_and_thrombin_generation_test_in_the_evaluation_of_bleeding_phenotype_in_Hemophilia_A_ L2 - http://www.ijpmonline.org/article.asp?issn=0377-4929;year=2021;volume=64;issue=1;spage=117;epage=122;aulast=Dave DB - PRIME DP - Unbound Medicine ER -