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Int J Endocrinol Metab 2005; 1:33-36

'l. Iso\a­ pressive 1Cer pa­ >2. ttner H, lunosup­ metasta­ la. Sf J Anticoagulant Positivity in With f in vitro 1mbinant erleukin­ Retinal Vascular

), Ashby r1eukin-2 b :olorectal Dash Sa, Dash RJ , Gupta A" !neer Im-

O. Inter­ lffillne re­ Departments of aHaematology, bEndocrinology , and cOphthalmology, Postgraduate Institute lents with of Medical Education and Research, Chandigarh, India 01 1995

. Mueins o investigate whether lupus anticoagu­ set and progression of are poorly lant (LA) positivity, a frequently asso­ n antigen understood. Several risk factors have been :ytotoxic­ ciated factor in a variety of throm­ identified. A number of studies indicate that a -6. T boembolic events, might be relevant to luang IS. the pathogenesis of retinal vascular disease in hypercoagulable state is present in diabetes, induces diabetes mellitus. especially so in type I diabetes with retinopa­ . cell line Materials and Methods: Eighty-five diabetic pa­ lular iron tients (44 type 1 and 41 type 2) were examined thy? Vascular damage and disturbed endo­ Igs. 2002 for total blood counts, screening coagulogram thelial function seem to occur early in the and LA. course of , converting the Results: LA was positive in 20.5% of patients with and in 33.3% with patients endothelial surface from thromboresistant to 4 5 of type 1 diabetes and retinopathy, whereas, LA a thrombogenic surface. • Immunological was positive in only 7.3% of patients with type 2 mechanisms may also play a role through diabetes and in 6.4% of them with retinopathy. deposition of material.6 Conclusion: These findings suggest that LA positivity might be considered as an additional Auto antibodies to endothelial antigens could risk factor in the pathogenesis of microvascular be responsible for initiating vascular injury ,7 disease in type 1 diabetes. and, could thus be a marker for endothelial dysfunction. Key Words: Lupus anticoagulant, Retinopathy, Type 1 diabetes, Lupus anticoagulant (LA) is an anti­ phospholipid antibody frequently associated Introduction with thromboembolic events, e.g. miscar­ Diabetic retinopathy is the most common riage, SLE and diabetic vascular disease such microvascular in diabetes, as nephropathy, and retinal occlusive vascu­ - which can lead to severe visual lossY The lopathies,8-12 mediated by an LA induced en­ 8 9 pathogenetic mechanisms involved in the on- dothelial dysfunction. • Guisti et al,13 found increased incidence of retinopathy, in dia­ betic patients positive for LA suggesting LA, Correspondence:. Sumitra Dash, Depaliment of positivity as an additional risk factor in the Haematology, PGIMER, Chandigarh-160012, India E-mail: [email protected] pathogenesis of microangiopathy in diabetes. 'r~

34 S. Dash e t al.

The present study was designed to examine mmollL buffered citrate solution in a 1:9 whether LA positivity is associated with an propol1ion. After centrifugation at 4000g for T increased prevalence of retinopathy in pa­ 20 minutes at 4°C, platelet-poor plasma was o tients with . used immediately for coagulation assays. The following coagulation tests were used for the Materials and Methods laboratory detection of LA: Kaolin-clotting A total of 85 patients with diabetes mellitus time (KCT), confirmed by dilute Russels Vi­ (DM), 44 with type 1, and 41 with type 2, per Venom time (dRVVT). Normal values classified according to the National Diabetes were obtained from the normal pooled Data Group criteria 14 were studied. They in­ plasma for the day of test. All tests were per­ cluded 64 males (27 with type 1, 37 with type formed on the patient's plasma and normal T' 2) and 21 females (1 7 with type1, 4 with type pool plasma. Mixing studies were evaluated L 2). Those with good glycaemic control by the ratio of clotting time mixture: clotting (HbA I c<7%) and no hypertension (> 140/90), time of normal pool, for KCT index and hypertriglyceridaemia (fasting triglyceride dRVVT index. A positive result was indi­ > 1.9 mmollL), or hypercholesterolaemia (to­ cated by a ratio greater than 1.0 in both KCT tal cholesterol >5.6 mmollL) were included. and dRVVT. po Most patients were on multiple injections of wI subcutaneous (Isophane insulin alone Results po or mixed with soluble insulin 70/30), with or Of the 85 plasma samples, 12 were LA ­ 2 without additional drugs such as , positive (14.1%). LA positivity was higher in pa andlor glitazone. All patients were non­ type I DM (20.5%) than in type 2 (7.3%). oc · smokers and had not taken any drugs known The results are shown in Table 1. tw to affect hemostasis for at least 4 weeks be­ fore the study. Type 1 diabetes me There were 44 patients in this group. Their Retinopathy was assessed by clinical ex­ the amination by a consultant ophthalmologist, age ranged from 7. 5 to 38 years with a me­ qu dian of 17 years. Retinopathy was present in fundus photography and fluorescein an­ (ar 9 cases (20.5%, proliferative in 2 and non­ giography. Diabetic retinopathy was catego­ no proliferative in 7). LA was positive in 3 of rized into proliferative (PDR) and non­ III proliferative (NPDR) types, as per ADA them (33.3%). Of the 35 without retinopathy, ty~ 15 6 were positive for LA (1 7.1 %). Thus in type guidelines. Complete blood counts includ­ em 1 DM, LA was positive in 9 of the 44 cases ing platelet counts were performed in an pia (20.5%). Conversely retinopathy was present automated hematology cell counter. Plasma am in 33.3% of the LA -posiitivee patients, but samples were examined for prothrombin time bOI (PT) and activated pal1ial thromboplastin only in 18.7% of the LA-negative patients. time (APTT). LA was diagnosed according to Oi Type 2 diabetes the criteria of the International Society of I 6 There were 41 patients in this group. Their Hemostasis and Thrombosis.1 ate age ranged from 22 years to 74 years with a dia median of 52 years. Retinopathy was present Detection ofLA ret Blood drawn by clean venipuncture was in 31 (85.5%, proliferative in 15, and non tici collected in plastic tubes containing 105 proliferative in 16). Of these, only 2 were ant

International Journal of and Metabolism LA Positivity in Diabetes with Retinopathy 35

1:9 for Table 1. Lupus anticoagulant (LA) positivity in patients with type 1 and type 2 diabetes with or with­ was out retinopathy The Diabetics Total no. of cases Retinopathy present Retinopathy absent the (%) (%) (%) ting T)/pe I Vi­ 44 (100) 9 (20.5) 35 (7 9.5) LA -positive 9 (20.5) 3 (33.3) 6 (17.1) lues )led Type 2 41 (100) 31 (75.6) 10 (24.4) LA -positive 3 (7.3) 2 (6.4) 1 (10.0) per­ mal Type I versus type 2 (ratio) 1 : I 1 : 3.7 3.2 : 1 5.2 : 1 ated LA positivity in type 1 vs. 2.9 : 1 1.7 : I type 2 ting and ndi­ eCT positive for LA (6.4%). Of the 10 patients group of IgM and IgG against who did not have retinopathy, one was LA­ protein/phospholipid complexes. The lupus positive (10%). Overall LA positivity in type anticoagulant is characterized by a paradoxi­ 2 DM was 3 (7.3%) only. Since only three cal phenomenon of a thrombotic tendency in er m patients were LA positive, no comparison of vivo, despite prolongation of phospholipid 3%). occurrence of retinopathy was considered be­ dependent coagulation assays in vitro. The tween LA-positive and LA-negative cases. LA dependent pathophysiologic mechanisms Though retinopathy was around 4 times causing thrombophilia seem to be multifunc­ more common in type 2 diabetes patients tional including impaired anticoagulant activ­ 'heir than in type I , LA positivity was more fre­ ity of activated . LA also induces me­ quent (around 3 times) in type I, more so endothelial cell dysfunction,8 ,9,17 and in dia­ ;]t in (around 5 times) in type 1 patients with reti­ betes mellitus, there are many reports that ex­ oon­ nopathy. Retinopathy was also more common tensively document the presence of a remark­ of 3 in LA positive type 1, than in LA negative able endothelium-related dysfunction of the tthy, type 1. We did not find any significant differ­ coagulant and anticoagulant pathways. 18,1 9 type ence for gender ratio, duration of diabetes, The present study shows that the presence :ases platelet counts, or degree of retinopathy of LA in type I DM is not infrequent. The :sent among the patients with or without LA in prevalence is even higher in type 1 diabetics . but both type 1 and type 2 cases. who already have retinopathy, although no ;;. comparison could be drawn as to the occur­ Discussion rence of LA between proliferative and non­ Lupus anticoagulant is frequently associ­ proliferative retinopathy as the numbers were - 'heir ated with thromboembolic events including small. Our prevalence of 33.3% is less than ith a 13 , macroangiopathy and the 60% reported by Guisti et a1. This could :sent retinal occlusive vasculopathy.7.ll Lupus an­ be due to the smaller number (20.5%) of type non ticoagulant is a subgroup of antiphospholipid I patients with retinopathy in our study .vere antibodies, and consists of a heterogenous

International Journal of Endocrinology and Metabolism 36 S. Dash et al. group, while retinopathy was documented In ered as an additional risk factor. To clarifY 30% of cases in their study. and support this issue, studies in larger multi­ The precise role played by LA in retinopa­ ethnic patient groups are necessary, not only thy in type 1 diabetes is speculative. In view to reach a better understanding of the patho­ of increasing evidence of immune abnormali­ genesis of diabetic retinopathy but also to ties in the pathogenesis of type 1 diabetes, prevent its onset and/or progression, with ap­ and the possible role of LA in endothelial propriate treatment. dysfunction, LA positivity should be consid-

References l. Klein R, Klein BE, Moss SE, Davis MD, DeMets matosus. Semin Arthritis Rheum. 1999 Apr;28 DL. The Wisconsin epidemiologic study of dia­ (5):326-32. betic retinopathy. III. Prevalence and risk of dia­ 11. Galtier-Dereure F, Biron C, Vies M, Bourgeois V, betic retinopathy when age at .diagnosis is 30 or Schved JF, Bringer J. Vascular complications of more years. Arch Ophthalmol. 1984 Apr; 102 diabetes mellitus: what role for phospholipid­ (4):527-32. binding antibodies? Lupus. 1998;7 (7):469-74. 2. Klein R, Klein BE, Moss SE. Epidemiology of 12. Wiechens B, Schroder JO, Potzsch B, Rochels R. proliferative diabetic retinopathy. Diabetes Care. PrimalY anti phospholipid antibody syndrome and 1992 Dec;15 (12):1875-91. retinal occlusive vasculopathy. Am J Ophthalmol. 3. Fuller JH, Keen H, Jarrett RJ, Omer T, Meade 1997 Jun; 123 (6):848-50. ~ TW, Chakrabarti R, et al. Haemostatic variables 13. Giusti C, Schiaffini R, Bosco D, Ciampalini P, associated with diabetes and its complications. Br Pantaleo A, Vingolo EM, et al. Lupus anticoagu­ MedJ.19790ct20;2(6196):964-6. lant positivity in insulin dependent diabetic pa­ 4. Haefliger [0, Meyer P, Flammer J, Luscher TF. tients: an additional risk factor in the pathogenesis ~ The vascular endothelium as a regulator of the of diabetic retinopathy? Br J Ophthalmol. 2000 \ ocular circulation: a new concept in ophthalmol­ May;84 (5):531-3. ogy? Surv Ophthalmol. 1994 Sep-Oct;39 (2):123­ 14. National Diabetes Data Group. Classification of 32. diabetes mellitus and other categories of

5. Kohner EM, Patel V, Rassam SM. Role of blood intolerance. Diabetes. 1970; 28: 1039-57. t flow and impaired autoregulation in the patho­ 15. American Diabetes Association. Diabetes Care I genesis of diabetic retinopathy. Diabetes. 1995 2000; 23 (suppl). Jun;44 (6):603-7. 16. Brandt JT, Triplett DA, Alving B, Scharrer I. Cri­ 6. Andreani D. Malignant microangiopathy. Diabe­ teria for the diagnosis of lupus anticoagulants: an l tologia. 1980 Mar; 18 (3):255. update. On behalf of the Subcommittee on Lupus 7. Jones DB, Wallace R, Frier BM. Vascular endo­ Anticoagulant/Antiphospholipid Antibody of the ~ thelial cell antibodies in diabetic patients. Scientific and Standardisation Committee of the I Association with diabetic retinopathy. Diabetes ISTH. Thromb Haemost. 1995 Oct; 74 (4): 1185­ Care. 1992 Apr;15 (4):552-5. 90. ( 8. Lechner K, Pabinger-Fasching 1. Lupus anticoagu­ 17. Meroni PL, Papa ND, Beltrami B, Tincani A, \ lants and thrombosis. A study of 25 cases and re­ Balestrieri G, Krilis SA. Modulation of endothe­ view of the literature. Haemostasis. 1985;15 (4): lial cell function by antiphospholipid antibodies. 254-62. Lupus. 1996 Oct;5 (5):448-50. 9. Triplett DA. Obstetrical complications associated 18. Dash S. Alterations in haemorrheological and co­ with antiphospholipid antibodies. In: Coulama agulation parameters in Diabetes. In: Dash RJ, BC, Faulk WP, Mclntyre lA, ed. Immunological editor. New Vistas in type 2 Diabetes; 2000. p.61­ t Obstetrics. New York: WW Norton; 1992. p. 377­ 72. s 403. 19. Lorenzi M, Cagliero E. Pathobiology of endothe­ 10. Montehermoso A, Cervera R, Font J, Ramos­ lial and other vascular cells in diabetes mellitus. Casals M, Garcia-carrasco M, Formiga F, et al. Call for data. Diabetes. 1991 Jun;40 (6):653-9. Association of anti phospholipid antibodies with retinal vascular disease in systemic lupus erythe­ - C ( 1.

International Journal of Endocrinology and Metabolism