Embolized ischemic lesions of toes in an afibrinogenemic patient: possible relevance to in vivo circulating thrombin

被引:80
作者
Dupuy, E
Soria, C
Molho, P
Zini, JM
Rosenstingl, S
Laurian, C
Bruneval, P
Tobelem, G
机构
[1] Hosp Lariboisiere, Dept Hematol, F-75475 Paris, France
[2] Hop Broussais, Pathol Lab, F-75674 Paris, France
[3] Hop St Joseph, Dept Vasc Surg, F-75674 Paris, France
[4] Hosp Cochin, Hemophilia Ctr, F-75679 Paris, France
[5] Hop Lariboisiere, Hematol Lab, F-75475 Paris, France
关键词
afibrinogenemia; arterial stenosis; intimal hyperplasia;
D O I
10.1016/S0049-3848(01)00247-X
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fibrinogen plays a complex role in hemostasis, thrombosis, and vascular disease. Hyperfibrinogenemia is an independent vascular risk factor and dysfibrinogenemia can provoke thrombosis. Afibrinogenemia is usually responsible for hemorrhagic diathesis, and unexpected ischemic lesions are intriguing. We report the case of an afibrinogenemic patient, who at the age of 30 developed ischemic lesions of the feet related to severe stenosis of the iliac and hypogastric arteries. The biopsy of the iliac artery lesion showed an intense myointimal hyperplasia. We performed standard hemostatic analysis and analyzed the activation markers of platelets and coagulation factors and the kinetics of thrombin generation in the patient and in normal control plasmas treated or not with reptilase. Occlusive arterial lesions were attributed to a disruptive hematoma penetrating the vascular lumen. Thrombin concentration after calcium addition increase markedly in the afibrinogenemic patient and in defibrinated normal plasma, as compared to untreated normal plasma. Thrombin-antithrombin complexes (T-AT) were markedly enhanced while F1+2 prothrombin fragments stayed in the normal range. These results suggested activation of coagulation and in vivo circulating thrombin. Thrombin activates the platelets that secrete growth factors for smooth muscle cells and generate the intimal hyperplasia. Recurrent hemorrhage within the vessel wall might induce injury and local thrombin generation. Thrombin not trapped by the clot is available for platelet activation and smooth muscle cell migration and proliferation. The absence of a protective fibrin cap on the intima might account for intima vulnerability and embolization. Afibrinogenemia appears in this paradoxical situation as a vascular risk factor. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:211 / 219
页数:9
相关论文
共 27 条
[1]   CONGENITAL AFIBRINOGENEMIA [J].
ALMONDHIRY, H ;
EHMANN, WC .
AMERICAN JOURNAL OF HEMATOLOGY, 1994, 46 (04) :343-347
[2]   FIBRIN AND ITS DERIVATIVES IN THE NORMAL AND DISEASED VESSEL WALL [J].
BINI, A ;
KUDRYK, BJ .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1992, 667 :112-126
[3]   SEVERE HYPOFIBRINOGENEMIA ASSOCIATED WITH BILATERAL ISCHEMIC NECROSIS OF TOES AND FINGERS [J].
CHAFA, O ;
CHELLALI, T ;
STERNBERG, C ;
REGHIS, A ;
HAMLADJI, RM ;
FISCHER, AM .
BLOOD COAGULATION & FIBRINOLYSIS, 1995, 6 (06) :549-552
[4]   FIBRINOGEN AS A MAJOR RISK FACTOR IN CARDIOVASCULAR-DISEASE [J].
COOK, NS ;
UBBEN, D .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1990, 11 (11) :444-451
[5]   The contribution of thrombosis to the clinical expression of coronary atherosclerosis [J].
Davies, MJ .
THROMBOSIS RESEARCH, 1996, 82 (01) :1-32
[6]   VONWILLEBRAND-FACTOR INTERACTION WITH THE GLYCOPROTEIN-IIB GLYCOPROTEIN-IIIA COMPLEX - ITS ROLE IN PLATELET-FUNCTION AS DEMONSTRATED IN PATIENTS WITH CONGENITAL AFIBRINOGENEMIA [J].
DEMARCO, L ;
GIROLAMI, A ;
ZIMMERMAN, TS ;
RUGGERI, ZM .
JOURNAL OF CLINICAL INVESTIGATION, 1986, 77 (04) :1272-1277
[7]   ASSOCIATION OF CONGENITAL AFIBRINOGENEMIA AND K-DEPENDENT PROTEIN-C DEFICIENCY - A CASE-REPORT [J].
DEMATTIA, D ;
REGINA, G ;
GIORDANO, P ;
DELVECCHIO, GC ;
ALTOMARE, M ;
SCHETTINI, F .
ANGIOLOGY, 1993, 44 (09) :745-749
[8]   MEASURING PLASMA-FIBRINOGEN TO PREDICT STROKE AND MYOCARDIAL-INFARCTION [J].
DIMINNO, G ;
MANCINI, M .
ARTERIOSCLEROSIS, 1990, 10 (01) :1-7
[9]   FIBRINOGEN AS A CARDIOVASCULAR RISK FACTOR - A METAANALYSIS AND REVIEW OF THE LITERATURE [J].
ERNST, E ;
RESCH, KL .
ANNALS OF INTERNAL MEDICINE, 1993, 118 (12) :956-963
[10]   Bilateral vertebral artery dissection in a patient with afibrinogenemia [J].
GarciaMonco, JC ;
Canton, GF ;
Beldarrain, MG .
STROKE, 1996, 27 (12) :2325-2327