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Prevalence of the American College of Rheumatology hematological classification criteria and associations with serological and clinical variables in 460 systemic lupus erythematosus patients

Abstract

Objective:

To study systemic lupus erythematosus in a Brazilian population using the American College of Rheumatology hematological classification criteria and report associations of the disease with serological and clinical profiles.

Methods:

This is a retrospective study of 460 systemic lupus erythematosus patients followed in a single rheumatologic center during the last 10 years. Hematological manifestations considered for this study were hemolysis, leukopenia, lymphocytopenia and thrombocytopenia.

Results:

The cumulative prevalences of leukopenia, thrombocytopenia, lymphocytopenia and hemolytic anemia were 29.8%, 21.08%, 17.7% and 8.4%, respectively. A higher percentage of patients with hemolysis had anticardiolipin IgM (p-value = 0.002). Those with leukopenia had more lymphopenia (p-value = 0.02), psychosis (p-value = 0.01), thrombocy- topenia (p-value <0.0001) and anti-double stranded DNA antibodies (p-value = 0.03). Patients with lymphopenia had more leukopenia (OR = 1.8; 95% CI = 1.01-3.29) and lupus anticoagulant antibodies (OR = 2.2; 95% CI = 1.16-4.39) and those with thrombocytopenia had more leukopenia (OR = 3.1; 95% CI = 1.82-5.44) and antiphospholipid syndrome (OR = 3.1; 95% CI = 1.28-7.87).

Conclusion:

The most common hematological finding was leukopenia and the least common was hemolysis. Associations of low platelet count and hemolysis were found with antiphospholipid syndrome and anticardiolipin IgM positivity, respectively. Leukopenia and lymphocytopenia are correlated and leukopenia is more common in systemic lupus erythe- matosus patients with psychosis, thrombocytopenia and anti-double stranded DNA.

Systemic lupus erythematosus; Hemolytic anemia; Leukopenia; Thrombocytopenia


Introduction

Systemic lupus erythematosus (SLE), a systemic autoimmune disease most common in young females, has a very heterogeneous clinical profile.11. Lutz CA, James JA. Antibodies to spliceosomal components. In: Wallace DJ, Hahn BH, editors. Dubois' lupus erythematosus. Philadelphia: Lippincott, Williams & Wilkins; 2007. p. 500-13. The genetic background of patients affects not only the prevalence of SLE but also the phenotype.22. Boackle SA. Advances in lupus genetics. Curr Opin Rheumatol. 2013;25(5):561-8.

Accordingly ethnic features favor the appearance of autoantibodies and clinical clusters that define the subtypes of the disease.33. Jurencák R, Fritzler M, Tyrrell P, Hiraki L, Benseler S, Silverman E. Autoantibodies in pediatric systemic lupus erythematosus: ethnic grouping, cluster analysis, and clinical correlations. J Rheumatol. 2009;36(2):416-21. , 44. To CH, Petri M. Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus? Arthritis Rheum. 2005;52(12):4003-10. These aspects highlight the need to know lupus clusters as this awareness allows the clinician to predict a future manifestation from one already present. It also highlights the need for local knowledge of disease behavior, particularly in a population such as the Brazilian which is highly mixed from the ethnic point of view.

The classical hematological manifestations in SLE are hemolytic anemia, leukopenia, and thrombocytopenia; these manifestations are part of the 1997 revised American College Classification Criteria for SLE55. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. as well as the new 2012 Systemic Lupus International Collaborating Clinics Classification Criteria.66. Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-86.

According to previous works, thrombocytopenia has a prevalence in the lupus population ranging from 7 to 30%.77. Wang F, Wang CL, Tan CT, Manivasagar M. Systemic lupus erythematosus in Malaysia: a study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups. Lupus. 1997;6(3):248-53.

8. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1.000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine. 1999;78(3):167-75.
- 99. Mok CC, Lee KW, Ho CT, Lau CS, Wong RW. A prospective study of survival and prognostic indicators of systemic lupus erythematosus in a southern Chinese population. Rheumatology (Oxford). 2000;39(4):399-406.

Although thrombocytopenia is not directly associated with end organ damage, it defines a subgroup of patients with higher morbidity and consequently has important prognostic implications.1010. Ziakas P, Giannouli S, Zintzaras E, Tzioufas AG, Voulgarelis M. Lupus thrombocytopenia: clinical implications and prognostic significance. Ann Rheum Dis. 2005;64(9):1366-9.

Leukopenia is a typical feature of SLE and may occur as a result of lymphopenia, neutropenia or both.1111. Hepburn AL, Santosh Narat S, Mason JC. The management of peripheral blood cytopenias in systemic lupus erythematosus. Rheumatology (Oxford). 2010;49(12):2243-54. Neutropenia, which may be mediated by anti-neutrophil antibodies, is common, with a prevalence in the order of 47%.1111. Hepburn AL, Santosh Narat S, Mason JC. The management of peripheral blood cytopenias in systemic lupus erythematosus. Rheumatology (Oxford). 2010;49(12):2243-54. , 1212. Worrall JG, Snaith ML, Batchelor JR, Isenberg DA. SLE: a rheumatological view. Analysis of the clinical features, serology and immunogenetics of 100 SLE patients during long-term follow-up. Q J Med. 1990;74(275):319-30. The prevalence of lymphopenia is variable, ranging from 20 to 81% and correlates with disease activity. Both T and Bclymphocytes are reduced while natural killer (NK) cells are elevated.1111. Hepburn AL, Santosh Narat S, Mason JC. The management of peripheral blood cytopenias in systemic lupus erythematosus. Rheumatology (Oxford). 2010;49(12):2243-54. , 1414. Glinski W, Gershwin ME, Budman DR, Steinberg AD. Study of lymphocyte subpopulations in normal humans and patients with systemic lupus erythematosus by fractionation of peripheral blood lymphocytes on a discontinuous Ficoll gradient. Clin Exp Immunol. 1976;26(2):228-38. Although there are numerous reports of lymphocytotoxic antibodies,1111. Hepburn AL, Santosh Narat S, Mason JC. The management of peripheral blood cytopenias in systemic lupus erythematosus. Rheumatology (Oxford). 2010;49(12):2243-54. , 1515. Winfield JB, Winchester RJ, Kunkel HG. Association of cold-reactive antilymphocyte antibodies with lymphopenia in systemic lupus erythematosus. Arthritis Rheum. 1975;18(6):587-94. their significance in this context remains uncertain. Reduced surface expression of complement regulatory proteins such as CD55 and CD59 has also been implicated in the pathogenesis of lupus lymphopenia, as this deficiency will make cells susceptible to complement-mediated lysis.1111. Hepburn AL, Santosh Narat S, Mason JC. The management of peripheral blood cytopenias in systemic lupus erythematosus. Rheumatology (Oxford). 2010;49(12):2243-54. , 1616. Garcia-Valladares I, Atisha-Fregoso Y, Richaud-Patin Y, Jakez-Ocampo J, Soto-Vega E, Elías-López D, et al. Diminished expression of complement regulatory proteins (CD55 and CD59) in lymphocytes from systemic lupus erythematosus patients with lymphopenia. Lupus. 2006;15(9):600-5.

Autoimmune hemolytic anemia (AIHA) is described in 7-15% of lupus patients and may occur together with immune thrombocytopenia in the Evans syndrome.1717. Quismorio FP Jr. Hematologic and lymphoid abnormalities in systemic lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois' lupus erythematosus. Philadelphia: Lippincott, Williams & Wilkins; 2007. p. 801-28. , 1818. Sultan SM, Begum S, Isenberg DA. Prevalence, patterns of disease and outcome in patients with systemic lupus erythematosus who develop severe haematological problems. Rheumatology (Oxford). 2003;42(2):230-4. It is associated with the presence of warm (predominantly) and cold anti-red blood cell autoantibodies.1717. Quismorio FP Jr. Hematologic and lymphoid abnormalities in systemic lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois' lupus erythematosus. Philadelphia: Lippincott, Williams & Wilkins; 2007. p. 801-28.

The aim of the current study was to assess the prevalence of hematological manifestations in a cohort of Brazilian lupus patients as well as its associations with clinical and autoanti-body profiles.

Methods

This is a retrospective study, approved by the local Research Ethics Committee. The charts of 460 SLE patients seen over the last 10 years in a single tertiary center were reviewed. To be included in this study, patients had to comply with at least four of the 1997 revised American College of Rheumatology classification criteria for SLE.55. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. Patients diagnosed before the age of 16 years and those with incomplete records were excluded. Data on demographic, clinical and serological profile were obtained. The definition of all clinical findings followed those of the ACR classification criteria.55. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. The criteria were cumulatively considered when the patient had no known infections. According to these criteria, hematological manifestations were defined as the presence of hemolytic anemia, leukopenia defined as less than 4 × 103 cells/mL on at least two occasions, lymphopenia defined as less than 1.5 × 103 cells/mL on at least two occasions and thrombocytopenia defined as less than 100 × 103 cells/mL in the absence of an offending drug.55. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.

Antiphospholipid syndrome (APS) was diagnosed according to the 2006 modified APS criteria.1919. Miyakis S, Lockshin MD, Atsumi T, Cranch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306. The complete cell count was performed using an automated analyzer (XE2100D, Sysmex) and the white cell differential count was performed manually using Giemsa stain.

Statistical analysis

All obtained data were collected as frequencies in contingency tables. The Kolmogorov-Smirnov test was used to study data distribution. Groups of patients with one hematological manifestation (hemolyticanemia, leukopenia or thrombocytopenia) were compared with those without this particular manifestation in respect to other clinical manifestations and their autoantibody profile. Central tendency was expressed as median and interquartile range (IQR) when numeric data were nonparametric and mean and standard deviation (SD) when parametric. Association studies were performed by Fisher's exact and chi-square tests for nominal data and with Mann-Whitney and unpaired t-test for numerical data. All variables that had significance with a p-value <0.1 in univariate analysis, were further studied using logistic regression to assess independency. Statistical analyses were made using the Medcalc software version 10.0, and significance was set for an alpha error of 5%.

Results

Analysis of the sample

The sample was comprised of 93.5% females and 6.5% males with ages ranging from 16 to 88 years and median disease duration of 8 years. The clinic and serological profiles are listed in Table 1.

Table 1
Clinical and serological profile of lupus patients.

Study of lupus patients with hemolytic anemia

The comparison data of patients with and without hemolytic anemia (p-value <0.1) are shown in Table 2.

Table 2
Association studies of demographic, clinical and serological variables of lupus patients with hemolytic anemia.

Association studies of hemolytic anemia with disease duration, age at diagnosis, gender, photosensitivity, oral ulcers, malar rash, discoid lesions, arthritis, glomerulonephritis, seizures, psychosis, serositis, lymphopenia, anti-Ro/SS-A, anti-La/SS-B, anti-ribonucleoprotein (anti-RNP), anti-double stranded DNA (anti-dsDNA), rheumatoid factor and APS were not significant.

On further investigating variables with p-values <0.1 in univariate analysis using a logistic regression model, only anticardiolipin IgM remained significant [p-value = 0.002; OR 5.1; 95% confidence interval (CI) = 1.7-14.9].

Association studies with leukopenia

Data of patients with and without leukopenia (p-value <0.1) are listed in Table 3. Comparisons of age, disease duration, age at diagnosis, gender, photosensitivity, oral ulcers, malar rash, discoid lesions, arthritis, glomerulonephritis, serositis, presence of anti-Ro/SS-A; Anti-La/SS-B, anti-RNP, anticardiolipin IgG and IgM, rheumatoid factor and APS were not significant.

Table 3
Comparison of lupus patients with (n = 136) and without (n = 319) leukopenia.

On including the variables with a p-value <0.1 in the univariate analysis in a logistic regression model, lymphopenia (p-value = 0.02; OR = 1.8; 95% CI = 1.06-3.15), psychosis (p-value = 0.01; OR = 3.1; 95% CI = 1.22-8.03); thrombocytopenia (p-value <0.0001; OR = 3.2; 95% CI = 1.93-5.33); and anti-dsDNA (p-value = 0.03; OR = 1.6; 95% CI = 1.02-2.54) were independently associated with leukopenia.

Association studies of thrombocytopenia

Association studies of thrombocytopenia are shown in Table 4. Comparative analysis of associations with age,disease duration, age at diagnosis, gender, oral ulcers,malar rash, discoid lesions, glomerulonephritis, psychosis,serositis, anti-Ro/SS-A, anti-La/SS-B, anti-RNP, anti-SM,anti-dsDNA and rheumatoid factor were found to benon-significant.

Table 4
Comparison of lupus patients with (n = 97) and without (n = 363) thrombocytopenia.

When the variables with p-values <0.1 in univariateanalysis were assessed using logistic regression, arthritisremained inversely associated to thrombocytopenia (OR = 0.3;95% CI = 0.20-0.61) and leukopenia (OR = 3.1; 95% CI = 1.82-5.44)and APS (OR = 3.1; 95% CI = 1.28-7.87) were associated tothrombocytopenia.

Association studies of lymphocytopenia

Associations of variables with lymphocytopenia are shown in Table 5. Analysis of disease duration, gender, photosensitivity, oral ulcers, malar rash, discoid lesions, arthritis, seizures, psychosis, serositis, hemolytic anemia, anti-Ro, anti-dsDNA, anticardiolipin IgG and IgM and rheumatoid factor were non-significant.

Table 5
Comparison of lupus patients with (n = 80) and without (n = 370) lymphopenia.

In the logistic regression study of variables with p-values <0.1 in the univariate analysis, only leukopenia (OR = 1.8; 95% CI = 1.01-3.29) and lupus anticoagulant (OR = 2.2; 95% CI = 1.16-4.39) remained independently significant.

Discussion

Hematological findings in lupus patients are very common and may be the presenting feature of the disease. In the current study hemolytic anemia was the least common manifestation (8%) followed by lymphopenia (18%), thrombocytopenia (21%) and leukopenia (30%).

There was an association between hemolytic anemia and anticardiolipin IgM antibodies; this association has been described in other studies. Lang et al.2020. Lang B, Straub RH, Weber S, Rother E, Fleck M, Peter H-H. Elevated anticardiolipin antibodies in autoimmune haemolytic anaemia irrespective of underlying systemic lupus erythematosus. Lupus. 1997;6(8):652-5. described associations with both anticardiolipin IgG and IgM antibodies. Sultan et al.,1818. Sultan SM, Begum S, Isenberg DA. Prevalence, patterns of disease and outcome in patients with systemic lupus erythematosus who develop severe haematological problems. Rheumatology (Oxford). 2003;42(2):230-4. studying 305 lupus patients from the United Kingdom, found an association with anticardiolipin IgG anti-bodies but Deleze et al.2121. Deleze M, Alarcon-Segovia D, Oria CV, Sánchez-Guerrero J, Fernández-Dominguez L, Gomez-Pacheco L, et al. Hemocytopenia in systemic lupus erythematosus. Relationship to antiphospholipid antibodies. J Rheumatol. 1989;16(7):926-30. studying Spanish lupus patients and Cervera et al.88. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1.000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine. 1999;78(3):167-75. analyzing a Mexican sample reported strong associations with anticardiolipin IgM antibodies similar to the current study.

Leukopenia was the most common hematological finding in this study appearing in almost one in three of the patients. The importance of this finding is highlighted when one notes that infections are a leading cause of death in SLE patients.2222. Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus. 2013;22(12):1286-94. Bacterial infections are the most common, followed by viral and fungal infections.2222. Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus. 2013;22(12):1286-94. In this sample, leukopenia was associated with lymphopenia, psychosis, thrombocytopenia and anti-dsDNA. The correlation between this finding, lymphopenia and ds-DNA has been reported by others.1717. Quismorio FP Jr. Hematologic and lymphoid abnormalities in systemic lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois' lupus erythematosus. Philadelphia: Lippincott, Williams & Wilkins; 2007. p. 801-28. A low lymphocyte count is found to be inde- pendent of (although contributory to) leukopenia1717. Quismorio FP Jr. Hematologic and lymphoid abnormalities in systemic lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois' lupus erythematosus. Philadelphia: Lippincott, Williams & Wilkins; 2007. p. 801-28. and has been associated, in the literature, to higher lupus activity,2323. Vollá LM, Alarcón-Segovia GS, McGwin G Jr, Bastian HJ, Fessler BJ, Reveille JD. Systemic Lupus erythematosus in a multiethnic US cohort. XXXVII: Association of lymphopenia with clinical manifestations, serologic abnormalities, disease activity and damage accrual. Arthritis Rheum. 2006;55(5):799-806. more severe acral damage,2323. Vollá LM, Alarcón-Segovia GS, McGwin G Jr, Bastian HJ, Fessler BJ, Reveille JD. Systemic Lupus erythematosus in a multiethnic US cohort. XXXVII: Association of lymphopenia with clinical manifestations, serologic abnormalities, disease activity and damage accrual. Arthritis Rheum. 2006;55(5):799-806. and some clinical disease characteristics such as neurologic involvement.1717. Quismorio FP Jr. Hematologic and lymphoid abnormalities in systemic lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois' lupus erythematosus. Philadelphia: Lippincott, Williams & Wilkins; 2007. p. 801-28. In the current sample, although lymphopenia was found to be associated with glomerulonephritis, thrombocytopenia, anti-RNP, anti-SM, APS, lupus anticoagulant and leukopenia, only the last two remained significant after logistic regression. Lupus disease activity and cumulative damage were not studied.

SLE thrombocytopenia results from disease activity or from suppression of the bone marrow by an immunosuppressant.24 24. Ktona E, Barbullushi M, Backa T, Idrizi A, Shpata V, Roshi E. Evaluation of thrombocytopenia in systemic lupus erythematosus and correlation with different organs damages. Mater Sociomed. 2014;26(2):122-4.Autoantibodies against platelets, against thrombopoietin and bone marrow abnormalities have been detected in these patients.2424. Ktona E, Barbullushi M, Backa T, Idrizi A, Shpata V, Roshi E. Evaluation of thrombocytopenia in systemic lupus erythematosus and correlation with different organs damages. Mater Sociomed. 2014;26(2):122-4. Although antibodies against platelets are common among thrombocytopenic patients they are not always linked to low platelet counts.2424. Ktona E, Barbullushi M, Backa T, Idrizi A, Shpata V, Roshi E. Evaluation of thrombocytopenia in systemic lupus erythematosus and correlation with different organs damages. Mater Sociomed. 2014;26(2):122-4. Furthermore, anti-thrombopoietin autoantibodies are considered to have a weak effect on platelet counts.2424. Ktona E, Barbullushi M, Backa T, Idrizi A, Shpata V, Roshi E. Evaluation of thrombocytopenia in systemic lupus erythematosus and correlation with different organs damages. Mater Sociomed. 2014;26(2):122-4. In the current study positive associations were found for thrombocytopenia with APS and with leukopenia. The association between APS and thrombocytopenia is well known not only in lupus but in other autoimmune thrombocytopenias.1717. Quismorio FP Jr. Hematologic and lymphoid abnormalities in systemic lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois' lupus erythematosus. Philadelphia: Lippincott, Williams & Wilkins; 2007. p. 801-28.

Conclusion

The most common hematological abnormality of the SLE classification criteria in a cohort of Brazilian SLE patients was leukopenia followed by thrombocytopenia, lymphopenia and hemolytic anemia. Low platelet counts and hemolysis were associated to APS and anticardiolipin IgM, respectively. Leukopenia and lymphocytopenia are correlated and leukopenia is more common in SLE patients with psychosis, thrombocytopenia and anti-dsDNA.

REFERENCES

  • 1
    Lutz CA, James JA. Antibodies to spliceosomal components. In: Wallace DJ, Hahn BH, editors. Dubois' lupus erythematosus. Philadelphia: Lippincott, Williams & Wilkins; 2007. p. 500-13.
  • 2
    Boackle SA. Advances in lupus genetics. Curr Opin Rheumatol. 2013;25(5):561-8.
  • 3
    Jurencák R, Fritzler M, Tyrrell P, Hiraki L, Benseler S, Silverman E. Autoantibodies in pediatric systemic lupus erythematosus: ethnic grouping, cluster analysis, and clinical correlations. J Rheumatol. 2009;36(2):416-21.
  • 4
    To CH, Petri M. Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus? Arthritis Rheum. 2005;52(12):4003-10.
  • 5
    Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.
  • 6
    Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-86.
  • 7
    Wang F, Wang CL, Tan CT, Manivasagar M. Systemic lupus erythematosus in Malaysia: a study of 539 patients and comparison of prevalence and disease expression in different racial and gender groups. Lupus. 1997;6(3):248-53.
  • 8
    Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1.000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine. 1999;78(3):167-75.
  • 9
    Mok CC, Lee KW, Ho CT, Lau CS, Wong RW. A prospective study of survival and prognostic indicators of systemic lupus erythematosus in a southern Chinese population. Rheumatology (Oxford). 2000;39(4):399-406.
  • 10
    Ziakas P, Giannouli S, Zintzaras E, Tzioufas AG, Voulgarelis M. Lupus thrombocytopenia: clinical implications and prognostic significance. Ann Rheum Dis. 2005;64(9):1366-9.
  • 11
    Hepburn AL, Santosh Narat S, Mason JC. The management of peripheral blood cytopenias in systemic lupus erythematosus. Rheumatology (Oxford). 2010;49(12):2243-54.
  • 12
    Worrall JG, Snaith ML, Batchelor JR, Isenberg DA. SLE: a rheumatological view. Analysis of the clinical features, serology and immunogenetics of 100 SLE patients during long-term follow-up. Q J Med. 1990;74(275):319-30.
  • 13
    Nossent JC, Swaak AJ. Prevalence and significance of haematological abnormalities in patients with systemic lupus erythematosus. Q J Med. 1991;80(291):605-12.
  • 14
    Glinski W, Gershwin ME, Budman DR, Steinberg AD. Study of lymphocyte subpopulations in normal humans and patients with systemic lupus erythematosus by fractionation of peripheral blood lymphocytes on a discontinuous Ficoll gradient. Clin Exp Immunol. 1976;26(2):228-38.
  • 15
    Winfield JB, Winchester RJ, Kunkel HG. Association of cold-reactive antilymphocyte antibodies with lymphopenia in systemic lupus erythematosus. Arthritis Rheum. 1975;18(6):587-94.
  • 16
    Garcia-Valladares I, Atisha-Fregoso Y, Richaud-Patin Y, Jakez-Ocampo J, Soto-Vega E, Elías-López D, et al. Diminished expression of complement regulatory proteins (CD55 and CD59) in lymphocytes from systemic lupus erythematosus patients with lymphopenia. Lupus. 2006;15(9):600-5.
  • 17
    Quismorio FP Jr. Hematologic and lymphoid abnormalities in systemic lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois' lupus erythematosus. Philadelphia: Lippincott, Williams & Wilkins; 2007. p. 801-28.
  • 18
    Sultan SM, Begum S, Isenberg DA. Prevalence, patterns of disease and outcome in patients with systemic lupus erythematosus who develop severe haematological problems. Rheumatology (Oxford). 2003;42(2):230-4.
  • 19
    Miyakis S, Lockshin MD, Atsumi T, Cranch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306.
  • 20
    Lang B, Straub RH, Weber S, Rother E, Fleck M, Peter H-H. Elevated anticardiolipin antibodies in autoimmune haemolytic anaemia irrespective of underlying systemic lupus erythematosus. Lupus. 1997;6(8):652-5.
  • 21
    Deleze M, Alarcon-Segovia D, Oria CV, Sánchez-Guerrero J, Fernández-Dominguez L, Gomez-Pacheco L, et al. Hemocytopenia in systemic lupus erythematosus. Relationship to antiphospholipid antibodies. J Rheumatol. 1989;16(7):926-30.
  • 22
    Danza A, Ruiz-Irastorza G. Infection risk in systemic lupus erythematosus patients: susceptibility factors and preventive strategies. Lupus. 2013;22(12):1286-94.
  • 23
    Vollá LM, Alarcón-Segovia GS, McGwin G Jr, Bastian HJ, Fessler BJ, Reveille JD. Systemic Lupus erythematosus in a multiethnic US cohort. XXXVII: Association of lymphopenia with clinical manifestations, serologic abnormalities, disease activity and damage accrual. Arthritis Rheum. 2006;55(5):799-806.
  • 24
    Ktona E, Barbullushi M, Backa T, Idrizi A, Shpata V, Roshi E. Evaluation of thrombocytopenia in systemic lupus erythematosus and correlation with different organs damages. Mater Sociomed. 2014;26(2):122-4.

Publication Dates

  • Publication in this collection
    Mar-Apr 2015

History

  • Received
    10 Nov 2014
  • Accepted
    24 Dec 2014
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