PMID- 34597379
OWN - NLM
STAT- MEDLINE
DCOM- 20220422
LR  - 20220422
IS  - 2576-9456 (Print)
IS  - 2475-7241 (Linking)
VI  - 7
IP  - 2
DP  - 2022 Mar 2
TI  - Performance of C-Reactive Protein, Procalcitonin, TAT Complex, and Factor VIII in 
      Addition to D-Dimer in the Exclusion of Venous Thromboembolism in Primary Care 
      Patients.
PG  - 444-455
LID - 10.1093/jalm/jfab094 [doi]
AB  - BACKGROUND: In primary care, D-dimer-combined with a clinical assessment-is 
      recommended for ruling-out venous thromboembolism (VTE). However, D-dimer testing 
      frequently yields false-positive results, notably in the elderly, and the search 
      for novel biomarkers thus continues. We assessed the added diagnostic value of 4 
      promising laboratory tests. METHODS: Plasma samples from 256 primary care 
      patients suspected of VTE were collected. We explored added value (beyond 
      D-dimer) of C-reactive protein (CRP), procalcitonin (PCT), thrombin-antithrombin 
      III complex (TAT-c), and factor VIII (FVIII). Diagnostic performance of these 
      biomarkers was assessed univariably and by estimating their area under the 
      receiver operating curve (AUC). Added diagnostic potential beyond D-dimer testing 
      was assessed using multivariable logistic regression. RESULTS: Plasma samples of 
      237 VTE-suspected patients were available for analysis-36 patients (25%) 
      confirmed deep vein thrombosis, 11 patients (12%) pulmonary embolism. Apart from 
      D-dimer, only CRP, and FVIII levels appeared to be higher in patients with VTE 
      compared to patients without VTE. The AUCs for these 3 markers were 0.76 (95% CI: 
      0.69-0.84) and 0.75 (95% CI: 0.68-0.83), respectively, whereas the AUC for 
      D-dimer was 0.90 (95% CI: 0.86-0.94). Combining these biomarkers in a 
      multivariable logistic model with D-dimer did not improve these AUCs 
      meaningfully. CONCLUSIONS: In our dataset, we were unable to demonstrate any 
      added diagnostic performance beyond D-dimer testing of novel biomarkers in 
      patients suspected of VTE in primary care. As such, D-dimer testing appears to 
      remain the best choice in the exclusion of clinically suspected VTE in this 
      setting. TRIAL REGISTRATION: Netherlands Trial Register NL5974. (METC protocol 
      number: 16-356/M; NL56475.041.16.).
CI  - (c) American Association for Clinical Chemistry 2021.
FAU - Heerink, Jorn S
AU  - Heerink JS
AUID- ORCID: 0000-0002-3802-4302
AD  - Department of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, 
      's-Hertogenbosch, the Netherlands.
AD  - Department of Health Technology and Services Research, Technical Medical Centre, 
      University of Twente, Enschede, the Netherlands.
FAU - Gemen, Eugenie
AU  - Gemen E
AD  - Department of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, 
      's-Hertogenbosch, the Netherlands.
FAU - Oudega, Ruud
AU  - Oudega R
AD  - Department of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, 
      's-Hertogenbosch, the Netherlands.
AD  - Julius Centre for Health Sciences and General Practice, University Medical Centre 
      Utrecht, the Netherlands.
FAU - Geersing, Geert-Jan
AU  - Geersing GJ
AD  - Julius Centre for Health Sciences and General Practice, University Medical Centre 
      Utrecht, the Netherlands.
FAU - Hopstaken, Rogier
AU  - Hopstaken R
AD  - Star-shl Diagnostic Centres, Etten-Leur, the Netherlands.
FAU - Kusters, Ron
AU  - Kusters R
AUID- ORCID: 0000-0003-1279-5448
AD  - Department of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, 
      's-Hertogenbosch, the Netherlands.
AD  - Department of Health Technology and Services Research, Technical Medical Centre, 
      University of Twente, Enschede, the Netherlands.
LA  - eng
SI  - NTR/NL5974
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Appl Lab Med
JT  - The journal of applied laboratory medicine
JID - 101693884
RN  - 0 (Biomarkers)
RN  - 0 (Fibrin Fibrinogen Degradation Products)
RN  - 0 (Procalcitonin)
RN  - 0 (fibrin fragment D)
RN  - 9001-27-8 (Factor VIII)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Aged
MH  - Biomarkers
MH  - C-Reactive Protein
MH  - Factor VIII
MH  - Fibrin Fibrinogen Degradation Products
MH  - Humans
MH  - Primary Health Care
MH  - Procalcitonin
MH  - *Venous Thromboembolism/diagnosis
OTO - NOTNLM
OT  - C-reactive protein
OT  - D-dimer
OT  - TAT complex
OT  - factor VIII
OT  - procalcitonin
OT  - venous thromboembolism
EDAT- 2021/10/02 06:00
MHDA- 2022/04/23 06:00
CRDT- 2021/10/01 17:19
PHST- 2021/04/02 00:00 [received]
PHST- 2021/06/28 00:00 [accepted]
PHST- 2021/10/02 06:00 [pubmed]
PHST- 2022/04/23 06:00 [medline]
PHST- 2021/10/01 17:19 [entrez]
AID - 6379042 [pii]
AID - 10.1093/jalm/jfab094 [doi]
PST - ppublish
SO  - J Appl Lab Med. 2022 Mar 2;7(2):444-455. doi: 10.1093/jalm/jfab094.