Benign intracranial hypertension associated to blood coagulation derangements

Benign Intracranial Hypertension (BIH) may be caused, at least in part, by intracranial sinus thrombosis. Thrombosis is normally due to derangements in blood coagulation cascade which may predispose to abnormal clotting activation or deficiency in natural inhibitors' control. The aim of the study is to examine the strength of the association between risk factors for thrombosis and BIH

The role of d-dimer as first marker of thrombophilia in women affected by sterility: implications in pathophysiology and diagnosis of thrombophilia induced sterility

BACKGROUND: D-dimer is considered a marker of hypercoagulable state and of endogenous fibrinolysis, so increased d-dimer is detectable in patients affected by thrombosis. Yet, several studies showed that also infertility, in particular secondary infertility due to recurrent fetal losses, has been often related to thrombotic events, in particular in women carrying thrombotic risk factors such as inherited thrombophilia (MTHFR(C677T), PTHR(A20210G), Factor V Leiden polimorphisms and/or inhAfter this screening we selected 39erited protein C, protein S, AT III deficiency) or acquired thrombophilia (primary antiphospholipid syndrome, acquired protein C, protein S, AT III deficiency, drugs induced thrombophilia). However, because its high predictive negative value in case of suspected thrombosis, increased d-dimer has been often associated to subclinical thrombophilia. The aim of this study is to investigate the role of d-dimer as first marker of thrombophilia in women affected by unexplained infertility and subsequently to search the cause of increased d-dimer, such as inherited and/or acquired thrombophilia. PATIENTS AND METHODS: We selected 79 patients with unexplained primary or secondary infertility. We excluded 40 patients affected by hydrosalpinx, uterine fibroids, uterine malformations, endocrinological and immunological diseases, luteal insufficiency, cytogenetical alterations. All remaining 39 patients were tested for d-dimer and divided in two groups: the patients of group A (25 patients) showed increased plasma d-dimer, in group B were included 14 patients with normal plasma level of d-dimer. After this step all 39 patients were screened for MTHFR(C677T), PTHR(A20210G), Factor V Leiden polimorphisms, protein C, protein S, AT III, anticardiolipin IgM and IgG, lupus anticoagulant. In the control group were included 15 age matched women without sterility problems referred to our outpatient's section of vascular medicine for suspected deep venous thrombosis. Statistical analysis was based on χ(2 )test, differences were considered to be significant if p < 0.05. RESULTS: D-dimer was increased in 25/39 and 20/25 showed inherited/acquired thrombophilia while patients with normal d-dimer showed inherited/acquired thrombophilia in 7/14 (p: < 0.05, s). DISCUSSION: D-dimer is a well known marker of hypercoagulable state, in particular its high predictive negative value in case of suspected thrombosis has been recognised by several reports. Yet, increased d-dimer has been identified also for subclinical thrombophilia besides for vascular thrombosis. Our data, in fact, for the first time suggest an interesting role of d-dimer to identify women affected by unexplained primary or secondary infertility and thrombophilia. So, probably there is a role for d-dimer in these subjects for its predictive positive value. Of course, further data on large based population are needed to confirm our results, because these findings may speed up a diagnostic screening in these patients also for a good cost/effectiveness of this test

Thromboembolic events and haematological diseases: a case of stroke as clinical onset of a paroxysmal nocturnal haemoglobinuria

Some haematological diseases are associated to an increased risk of thromboembolic events. We report a case of paroxysmal nocturnal haemoglobinuria (PNH) in which a cerebrovascular event represented the first clinical manifestation of disease. PNH is associated to thromboembolic events, generally of venous districts often involving unusual locations such as mesenteric vessels, sagittal veins, inferior vena cava and renal veins. To our knowledge arterial thrombotic episodes are rare and the involvement of arterial cerebral vessels is exceptional. Then, our case points out the importance of investigating about haematological disorders in all patients presenting with a stroke, in which the common predisposing conditions are excluded

Different outcome of six homozygotes for prothrombin A20210A gene variant

Prothrombin G20210A gene variant (FII G20210A) is a risk factor for venous thrombotic disease while conflicting results have been reported for the risk of arterial thrombotic events. However, vascular episodes were absent in up to 40% of the 67 homozygotes for the G20210A described so far, which indicates that the clinical expression depends on additional risk/trigger factors. We describe six homozygotes for the G20210A variant, among which the first pair of siblings (cases n. 3 and 4) reported so far that displayed a strongly heterogeneous clinical outcome. Case 1, a female of 27 years, developed a full thrombosis of common femoral, superficial and popliteal veins. She assumed oral contraceptives in the last two years. Case n. 2, 34 years old, suffered of recurrent pregnancy loss in absence of any causative alteration. Cases n. 3 and n. 5 experienced arterial thrombotic disease, i.e., juvenile myocardial infarction (40 years old) and stroke (48 years old), respectively, in absence of other risk factors. Finally, cases n. 4 and 6 identified as homozygotes for the FII G20210A variant being consanguineous of symptomatic subjects bearing the variant, did not experience any episode of venous nor arterial disease. Both of them have chronic liver disease with an impairement of the prothrombin time INR. Thus, homozygotes for the G20210A are at risk for arterial (in addition to venous) thromobotic events; chronic liver disease might modulate this risk

ATHEROSCLEROSIS AND RHEUMATOID ARTHRITIS: EVALUATION OF INTIMA-MEDIA THICKNESS AND CORRELATION WITH INFLAMMATORY AND ATHEROGENIC MARKERS

Background: Recent studies have focused on the role of inflammation in the development of atherosclerosis (AT), there are some similarities in the inflammatory/immunologic response observed in AT and rheumatoid arthritis (RA), the prototype of autoimmune disease. Molecular and cellular mediators of inflammation in RA may be the key to development of atherosclerotic lesions in these patients (1,2). Objectives: To investigate whether the intima-media thickness (IMT) of the common carotid arteries is greater in RA patients than healthy subjects, and to investigate the presence of inflammation and atherogenic lipoprotein markers and their possible correlation with IMT. Methods: We studied 21 patients (15 F, 6 M; age 48-62 median 55) with RA according to the criteria established by the American College of Rheumatology, and 10 controls (6 F, 4 M; age 44-66, median 52). The healthy subjects were compared with RA patients with regard to risk factors for AT, including age, sex, smoking, blood pressure, body mass index and postmenopausal status. Clinical variables reflecting RA were measured: patient's global assessment, physician's global assessment, patient's assessment of pain, physical disability score (HAQ), acute-phase reactant level, numbers of tender and swollen joints, duration of morning stiffness, disease activity score (DAS 28). Laboratory variables relevant to RA: activity erythrocyte sedimentation rate, C-reactive protein level and rheumatoid factor positivity were measured. Laboratory variables relevant dyslipidemic status: serum total cholesterol, trygliceridies, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprtein AI (Apo AI), apolipoprotein B (Apo B) were determined. IMT and plaques were measured in the left and right common carotid arteries (CCA). Three measurements of ITM were made in common carotid arteries and were averaged to determine the mean IMT (3). Mann-Wythney test was used to compare mean value between two groups. Results: The mean ± SD IMT of the left and right CCA was significantly greater in 21 RA patients than in 10 control subjects (1.09±0.3 vs. 0.68±0.3; p=0.0029). Total plasma levels of cholesterol (173±26.2 vs. 182.6±44.6), HDL-cholesterol (58.5±20.3 vs. 60.2±26), LDL-cholesterol (95.3±28.6 vs. 100.1±32.8), were in the normal range in RA patients and were similar to those in the controls; the concentration of triglycerides (122.1±55.6 vs. 154.5±51.8; p=0.8), ApoAI (167.4±52.2 vs. 213.3±68.3; p=0.9) and ApoB (117.8±46.8 vs. 146±33.1; p=0.9) levels were lower in the RA patients than in controls, but this was not statistical significant. In the RA group, IMT did not correlate with inflammatory variables, atherogenic markers, and parameters of activity of RA. Conclusion: In the present study, we demonstrated that the IMT of the common carotid was significantly higher in RA patients than in controls. Our study may contribute to explain the increase in cardiovascular death reported in RA and will allow physicians early stratification of patients with vascular disease.1. Pasceri V, Yeh ET. A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation 1999; 100:2124-6.; 2. Manzi S, Wasko MC. Inflammation-mediated rheumatic diseases and atherosclerosis. Ann Rheum Dis 2000; 59:321-5.; 3. Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Inimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation 1986; 74, 1399-406

Benign intracranial hypertension associated to blood coagulation derangements

Abstract Background Benign Intracranial Hypertension (BIH) may be caused, at least in part, by intracranial sinus thrombosis. Thrombosis is normally due to derangements in blood coagulation cascade which may predispose to abnormal clotting activation or deficiency in natural inhibitors' control. The aim of the study is to examine the strength of the association between risk factors for thrombosis and BIH. Patients and methods The incidence of prothrombotic abnormalities among a randomly investigated cohort of 17 patients with BIH, was compared with 51 healthy subjects matched for sex, age, body mass index, height and social background. Results The number of subjects with protein C deficiency was significantly higher in patients than in controls (3 vs 1, p Increased plasma levels of prothrombin fragment 1+2, fibrinopeptide A (FPA), and PAI-1 were demonstrated in patients group (5.7 ± 1.15 nM vs 0.45 ± 0.35 nM; 8.7 ± 2.5 ng/mL vs 2.2 ± 1.25 ng/mL; 45.7 ± 12.5 ng/mL vs 8.5 ± 6.7 ng/mL, respectively; p Discussion In agreement with other authors our data suggest a state of hypercoagulability in BIH associated with gene polymorphisms. Our findings also showed that mutations in cardiovascular genes significantly discriminate subjects with a BIH history. The association between coagulation and gene derangements, usually regarded to as cryptogenic, may suggest a possible pathogenetic mechanism in BIH. So, a prothrombotic tendency may exist that would, at least in part, explain some cases of BIH. Although based on a small population, these findings raise the exciting possibility of using these haemostatic factors as markers for selecting high-risk subjects in BIH disease.</p