Background: Behcet’s disease (BD) has been shown to be associated with increased mortality rate in several studies. A significant portion of this mortality (40%) was related to vascular thrombosis. The basis for the thrombotic tendency in BD is not fully understood and studies on hemostatic parameters have been controversial.

Objectives: To determine the frequency of vascular events in Omani patients with BD and to study various hemostatic variables that might contribute to this vascular risk in BD.

Methods: The study was started after approval by the institutional review board. Blood samples from 34 patients with BD, and 30 healthy controls after an informed consent and were analyzed for several hemostatic parameters including protein C, protein S, AT, factor VIII:C, factor V Leiden, von Willibrand factor antigen, ristocetin and collagen binding activity, Plasminogen, Alpha 2 antiplasmin, tissue plasminogen activator, and Plasminogen activator inhibitor-1. Additionally, anticardiolipin antibodies, anti-B2 glycoprotein antibodies, lupus anticoagulant, homocysteine, ESR, CRP, glucose and lipid profile were also studied.

Results: Eight patients with BD had thrombotic events (26%). Of these, 50% were arterial, 25% were venous and 25% had mixed arterial and venous events. The mean values of factors VIII:C, vWF:Ag, Protein C and ATIII were significantly higher in the patient’s group compared to the controls (P<0.05, Mann-Whitney). (Table) There were no deficiencies in protein C, S, or AT and factor V Leiden was absent in these patients. Six patients had elevated FVIII [>150 iu/ml] [p<0.01;Fisher’s exact test]. There were no differences in anti-cardiolipin antibodies, anti-b2-glycoprotein-1 antibodies, lupus anticoagulant, homocysteine, total cholesterol, triglycerides or blood glucose levels, between patients and controls. We found significant correlations between inflammatory markers [ESR, CRP] and factor VIII:C, Anti-thrombin, vWF:Ag;vWF:CBA, vWF:RiCof in the control group but not in the patient group. Furthermore, the elevated factor VIII levels were normalized on repeat testing after 3 months.

Comparison of hemostatic parameters in BD patients with thrombosis v/s normal controls [Mean ± SD]

Reference RangePatientsControlsP value
Plasma F VIII:C 50–150[iu/ml] 107 ± 48 78 ± 31 0.017 
Functional Protein C Chromogenic 72–154[iu/ml] 125 ± 37 118 ± 25 NS 
Protein C Clotting 80–181[iu/ml] 139 ± 43 126 ± 32 NS 
Protien S Functional 52–118[iu/ml] 101 ± 28 83 ± 27 0.008 
Antithrombin 83–118[iu/ml] 108 ± 12 100 ± 12 0.022 
Plasminogen 73–127[iu/ml] 114 ± 15 114 ± 19 NS 
Alpha 2 Antiplasmin 89–112[iu/ml] 118 ± 15 116 ± 16 NS 
Tissue Plasminogen Activator 1–12[ng/ml] 7 ± 3 7 ± 2 NS 
Plasminogen Activator Inhibitor-1 4–43[ng/ml] 31 ± 21 38 ± 33 NS 
Plasma vWF:Ag 50–158[iu/ml] 102 ± 34 83 ± 25 0.008 
Plasma vWF:RiCof 40–150[iu/ml] 100 ± 46 90 ± 30 NS 
Plasma vWF:CBA 50–400[iu/ml] 101 ± 38 94 ± 37 NS 
Plasma Homocystine 5–15 [mmol/L] 9 ± 2 9 ± 2 NS 
Reference RangePatientsControlsP value
Plasma F VIII:C 50–150[iu/ml] 107 ± 48 78 ± 31 0.017 
Functional Protein C Chromogenic 72–154[iu/ml] 125 ± 37 118 ± 25 NS 
Protein C Clotting 80–181[iu/ml] 139 ± 43 126 ± 32 NS 
Protien S Functional 52–118[iu/ml] 101 ± 28 83 ± 27 0.008 
Antithrombin 83–118[iu/ml] 108 ± 12 100 ± 12 0.022 
Plasminogen 73–127[iu/ml] 114 ± 15 114 ± 19 NS 
Alpha 2 Antiplasmin 89–112[iu/ml] 118 ± 15 116 ± 16 NS 
Tissue Plasminogen Activator 1–12[ng/ml] 7 ± 3 7 ± 2 NS 
Plasminogen Activator Inhibitor-1 4–43[ng/ml] 31 ± 21 38 ± 33 NS 
Plasma vWF:Ag 50–158[iu/ml] 102 ± 34 83 ± 25 0.008 
Plasma vWF:RiCof 40–150[iu/ml] 100 ± 46 90 ± 30 NS 
Plasma vWF:CBA 50–400[iu/ml] 101 ± 38 94 ± 37 NS 
Plasma Homocystine 5–15 [mmol/L] 9 ± 2 9 ± 2 NS 
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Conclusion: The elevated hemostatic parameters are likely to represent an acute phase phenomena as shown by their normalization in the repeat testing after 3 months. Thrombophillic factors do not seem to explain the thrombotic tendency in BD. Further work is needed to elucidate the basis for the thrombotic complication of BD. It is hypothesized that active BD causes endothelial damage and dysfunction leading to the increased propensity for thrombosis.

Topics:
behcet syndrome, hemostatics, thrombosis, von willebrand factor, protein c, thrombus, antibodies, alpha-2 antiplasmin, alteplase, antiphospholipid syndrome

Disclosures: AlKaabi:Sultan Qaboos University Hospital: Research Funding.

Author notes

Corresponding author

2008, The American Society of Hematology
2008
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