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C-Reactive Protein in Primary Antiphospholipid Syndrome

To the Editor:

In their article, Sailer, et al¹ did not find a relationship between the acute phase reactants C-reactive protein (CRP) and fibrinogen with thrombosis in patients with lupus anticoagulants (LAC). To add to this topic we measured CRP (immunoturbidimetry, Beckman, CV < 4%: linear range 0.04-84 mg/dl) in 20 consecutive patients with primary antiphospholipid syndrome (PAPS) (14 women, 6 men, ages 41 ± 15 yrs, mean disease duration 9.8 ± 4.3 yrs; myocardial infarction n = 2, ischemic stroke n = 6, deep vein thrombosis n = 12, smokers n = 6) diagnosed according to established criteria²; in 24 patients with inherited thrombophilia (IT) (16 women, 8 men, ages 55 ± 17 yrs, mean disease duration 8.6 ± 4.4 yrs; myocardial infarction n = 2, ischemic stroke n = 4, deep vein thrombosis n = 18, factor V Leiden heterozygous n = 16, protein C deficiency n = 4, protein S deficiency n = 4, smokers n = 4); and in 30 healthy subjects (15 blood donors, 15 medical personnel, 20 women, 10 men, mean age 48 ± 15 years, smokers n = 8). Occlusive events had been diagnosed by Doppler ultrasound, angio computerized tomography, angio magnetic resonance imaging, and electrocardiogram as indicated. All patients with PAPS and 22 with IT were taking warfarin at the time of CRP measurement, whereas the remaining patients with IT were taking aspirin (75 mg/day). All participants gave informed consent to the study, none self-reported an infection in the previous 4 weeks, and urinary dipstick test for nitrates was negative in all. In the PAPS group, IgG and IgM anticardiolipin antibodies (aCL; enzyme immunoassay, Cambridge Life Sciences, UK) had been detected twice 6 weeks apart at the time of diagnosis and then yearly thereafter. All patients with PAPS had a LAC measurement at diagnosis. Those detected as activated partial thromboplastin time (n = 16) were reconfirmed (n = 16) by comparing a sensitive and an insensitive reagent to the LAC³. In the PAPS group, median IgG aCL was 102 GPL (range 11-479 GPL) and median IgM aCL was 10 MPL (range 2-847 MPL). The PAPS group displayed higher mean CRP than the IT and control groups (Figure 1). Within the PAPS group, higher CRP was noted in patients with arterial rather than venous events (CRP 4.8 ± 3.2 vs 1.9 ± 1.5; p = 0.02, Mann-Whitney t-test) and in patients with multiple (n = 8) rather than single events (n = 12) (4.9 ± 3.3 vs 1.8 ± 1.2 mg/dl; p = 0.02, Mann-Whitney t-test), and a similar pattern was noted in the IT group (3.7 ± 3.1 vs 1.3 ± 0.7 mg/dl; nonsignificant). Moreover, IgG aCL correlated to CRP titer (Figure 2A) and to plasma fibrinogen (Clauss assay; Figure 2B). Having employed an IT control group rather than a LAC-positive thrombosis-negative group, we came to the same conclusion reached by Sailer, et al¹, that of a possible low-grade inflammatory state in PAPS. However, the involvement of CRP in the type and number of occlusive events is being investigated further, as it might represent a worthwhile and inexpensive test to predict persistence of antiphospholipid antibodies⁴ and severity of antiphospholipid related vascular damage⁵.

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Figure 1. Mean CRP in healthy controls (CTR), and patients with inherited thrombophilia (IT) and primary antiphospholipid syndrome (PAPS). *Kruskal-Wallis analysis of variance.

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Figure 2. Pearson's correlation between log-transformed IgG aCL and CRP (A) and fibrinogen (B).

PAUL R.J. AMES, MD, Department of Hematology, Inverclyde Royal Hospital, Greenock, United Kingdom; CATELLO TOMMASINO, MD, Chemical Pathology and Immunology, San Gennaro Hospital;
VINCENZO BRANCACCIO, MD, Haemostasis Unit, Cardarelli Hospital, Naples; ANTONIO CIAMPA, MD, Haemostasis Unit, San Giovanni Moscati Hospital, Avellino, Italy.

Address reprint requests to Dr. P.R.J. Ames, Inverclyde Royal Hospital, Haematology, Larkfield Road, Greenock, PA16 0XN, UK.
E-mail: paxmes@aol.com

REFERENCES

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3. Brancaccio V, Ames PR, Glynn J, Iannaccone L, Mackie IJ. A rapid screen for lupus anticoagulant with good discrimination from oral anticoagulants, congenital factor deficiency and heparin, is provided by comparing a sensitive and an insensitive APTT reagent. Blood Coagul Fibrinolysis 1997;8:155-60.

4. Twito O, Reshef T, Ellis MH. C-reactive protein level as a predictor of transient vs sustained anticardiolipin antibody positivity. Eur J Haematol 2006;76:206-9.

5. Miesbach W, Gokpinar B, Gilzinger A, Claus D, Scharrer I. Predictive role of hs-C-reactive protein in patients with antiphospholipid syndrome. Immunobiology 2005;210:755-60.