Is There a Thrombotic Tendency in Patients with Familial Mediterranean Fever? A Small Case Series and Review of the Literature

Abstract

in spite of its chronic inflammatory nature [2-4]. With regard to this discrepancy, it was suggested that there is a subtle balance between procoagulant and anticoagulant activities during the attack period. Furthermore, it was suggested that if there is an Abstract Objectives: Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by fever, abdominal pain and pleuritic attacks. It is well known that there is a relationship between inflammation and thrombosis. However, there is very limited knowledge about thrombotic tendency in familial Mediterranean fever (FMF). Here we reported two patients with FMF who developed thrombo-embolic events in the presence of acquired thrombophilic factors. We would also like to review five additionally published FMF cases that have developed thromboembolic events, as well as briefly discuss haemostatic mechanisms in FMF patients. Methods: We conducted a comprehensive review of the English literature to analyze data on thrombotic or thromboembolic events in patients with FMF. The PubMed, Web of Science, Proquest, and Ovid databases were searched for articles using the term FMF combined with one of the following terms: thrombosis, thromboembolism, deep venous thrombosis, and pulmonary embolism. Results: In four English articles, we identified five FMF patients, plus our two cases with thrombotic complications. A hereditary or at least one acquired thrombophilic factor was determined in six cases. One patient had not had any thrombophilic factor. M694V mutation was determined in five patients. In six patients, thrombotic events developed under the age of 45 years. Conclusions: Thromboembolic events may rarely develop in FMF patients with the presence of congenital or inherited thrombophilic disorders.

Acute stroke in familial Mediterranean fever: An analysis of 23 new cases and systematic review of the literature

“…Alternative causes of stroke, some of which were also present in our cohort, were reported in FMF and include accompanying vasculitis, [23][24][25] dissection, 12 cardiorenal involvement, 26 paradoxical embolism or thrombophilic conditions. 2,27,28 In our study, some features of acute ischemic stroke in FMF cases were much more frequent than random. Small and distal (third order) artery occlusions were common, and most (twice as much)…”

“…However, our observations do not support that atherosclerosis is a dominant mechanism for stroke in FMF cases, who had a tendency to have less strokes caused by atherosclerotic large arteries ( P = .088, Table 2) in comparison to age‐ and gender‐matched controls. Alternative causes of stroke, some of which were also present in our cohort, were reported in FMF and include accompanying vasculitis, 23–25 dissection, 12 cardiorenal involvement, 26 paradoxical embolism or thrombophilic conditions 2,27,28 …”

Autoinflammatory diseases: a possible cause of thrombosis?

“…One case report is about a child, who in addition to FMF had several prothrombotic defects [ 4 ], the second about a 21 year-old man with nephrotic syndrome complicated by AA amyloidosis, and lupus anticoagulant in low titre [ 5 ], the third about a young patient who suffered of a brain stem infarction during a typical FMF attack [ 6 ]. All of them have genetically proven FMF.…”

“…We found 4 case reports of Budd-Chiari syndrome [ 29 - 31 ] and 1 case of portal, splenic and superior mesenteric vein thrombosis [ 32 ] occurring in patients affected by FMF. There is also another case where a mesenteric thrombosis was suspected but it can not be ascertained because the relatives refused autopsy [ 5 ].…”