Thrombophilic Risk Factors Research Articles

Thrombophilic risk factors for placental stillbirth

Objectives To define the characteristics of placental stillbirth and the possible contribution of thrombophilic risk factors. Study design A prospective cohort study was performed. Women diagnosed with antenatal stillbirth (>20 weeks) of singleton pregnancies between 2006 and 2008 were referred postpartum for evaluation. Maternal risk factors, fetal, placental and cord abnormalities, and a detailed thrombophilia screening, including inherited and acquired thrombophilia, were evaluated. Fetal autopsy and placental pathology were encouraged. Placental stillbirth was defined as death of a normally-formed fetus with evidence of intrauterine fetal growth restriction, oligohydramnios, placental abruption and/or histological evidence of placental contribution to fetal death. Pregnancy characteristics and thrombophilia profiles were compared between placental and non-placental stillbirth cases. Results Sixty-seven women with stillbirth comprised the study group. Placental stillbirth was evident in 33/67 (49.3%). Significantly more women with placental stillbirth were nulliparous, when compared with non-placental stillbirth women (21/33 vs. 9/34, p = 0.002). Mean gestational age was lower for placental, compared with non-placental stillbirth (31.1 ± 6.1 weeks vs. 33.9 ± 4.8 weeks, p = 0.04), as was birth weight. Thirty-six of the 67 women (53.7%) tested positive for at least one thrombophilia. The prevalence of maternal thrombophilia was higher for placental stillbirth women (63.6%), and even higher (69.6%) for women after preterm (<37 weeks) placental stillbirth. Factor V Leiden and/or prothrombin G20210A mutation were much more prevalent in placental versus non-placental stillbirth women (OR 3.06, 95% CI 1.07–8.7). Conclusions Placental stillbirth comprises a unique subgroup with specific maternal characteristics. Maternal thrombophilia is highly prevalent, especially in preterm placental stillbirth. This may have implications for the management strategy in future pregnancies in this subgroup.

Lungenembolie als Ursache einer Leistungsminderung bei Ausdauersportlern – 2 Kasuistiken

Two trained long-distance runners, aged 53 and 58 years, respectively, presented (independently) at our outpatient department because of an acute reduction in physical performance after considerable exertion. Neither had specific clinical symptoms, particularly no dyspnea. Neither patient had abnormal findings on physical examination, such as signs for deep venous thrombosis. The electrocardiogram and echocardiography were normal. Exercise tests revealed a significant limitation in physical performance and, in one patient, a reduction in arterial blood oxygen and elevated d-dimers as the only abnormal laboratory test result. The diagnosis of pulmonary embolism was made by computed tomography, which showed the typical changes. In both patients venous phlebography revealed deep vein thrombosis and signs of post-thrombotic changes. Laboratory tests were unremarkable, with normal blood coagulation and no factor II mutations. Anticoagulants were administered to each patient and they slowly resumed their training program. At a subsequent examination physical performance had improved, but there was still a reduction in arterial oxygen during exercise. Even endurance-trained sportspersons without thrombophilic risk factors may develop deep vein thrombosis. Even when there are no symptoms, pulmonary embolism should always be included in the differential diagnosis of a sudden and significant reduction in physical performance.

Role of the M2 haplotype within the annexin A5 gene in the occurrence of pregnancy-related venous thromboembolism

Knowledge about risk factors for venous thromboembolism (VTE) is still limited. A recently found haplotype within the natural anticoagulant protein annexin A5 (ANXA5) exerts an important modulating effect on gene expression. Eighty-three nonanticoagulated patients with a documented pregnancy-related VTE and 195 controls were investigated. The presence of the ANXA5 haplotypes was determined. Twenty-seven patients (32.5%) carried the M2 haplotype. Among them, 17 (63.0%) had a history of VTE in puerperium and 10 (37.0%) during pregnancy. The prevalence of the M2 haplotype was different as compared with that recorded among controls (odds ratio, 2.7; 95% confidence interval, 1.5-4.9, P < .001). A logistic regression analysis, correcting for potential confounders (age at which the thrombotic event occurred, factor V Leiden, and factor IIA20210 variants) showed a significant increase (odds ratio, 3.4; 95% confidence interval, 1.7-6.7) of the occurrence of VTE in carriers of the M2 haplotype as compared with noncarriers. The M2 haplotype within the ANXA5 gene may represent a new thrombophilic risk factor for pregnancy-related VTE.

Factor V Leiden in Chioggia: a prevalence study in patients with venous thrombosis, their blood relatives and the general population.

Factor V Leiden (FVL) is the most common genetic polymorphism known to predispose to episodes of venous thromboembolism (VTE) in western countries; heterozygosity for FVL occurs in 3–8%, and the rate of homozygosity is around 1/5,000 in the general population in Italy1. As previously reported, we observed a very high prevalence of FVL carriers in patients with deep venous thrombosis in Chioggia. Among 292 consecutive patients attending our Laboratory for investigation of thrombophilic risk factors after an episode of venous thrombosis we observed 168 (57.5%) normal subjects and 124 (42.5%) FVL carriers: 13 (4.5%) of whom were homozygous for the polymorphism and 111 (38.0%) heterozygous2,3. The high prevalence of FVL carriers among patients with venous thrombosis should be due to case selection but may also reflect a high diffusion of this particular mutation in Chioggia. The aim of this study was to establish the correct prevalence of FVL carriers in our area by evaluating patients, their blood relatives and the general population.

Thrombophilic factors in idiopathic intracranial hypertension: a report of 51 patients and a meta-analysis

Several studies have suggested that thrombophilic risk factors are more prevalent in individuals with idiopathic intracranial hypertension (IIH), and that a prothrombic state may be involved in the etiopathogenesis of this disease. We examine thrombophilic factors in a group of patients with IIH in relation to obesity. In addition, we reviewed the relevant literature and performed a meta-analysis. Thrombophilia work-up was performed on 51 patients with IIH at least 1 month following their first episode. Samples for the analysis of factor V Leiden (FVL), prothrombin gene variant (PGV) G20210A and methylenetetrahydrofolate reductase (MTHFR) were available in an additional 30 patients, that is 81 patients in all. Meta-analysis was performed. Of the 51 patients 40 were obese. Increased concentrations of fibrinogen, D-Dimer, factor VIII, factor IX and factor XI were found in 15, 7, 7, 6 and 2 patients, respectively, all obese. The circulating anticoagulant, measured by dilute Russell's viper venom time (dRVVT assay), found mainly in obese. All 51 patients were negative for the anticardiolipin antibody (IgG immunoglobulin G) and IgG anti-beta2 glycoprotein I. In the meta-analysis antiphospholipid antibodies were significantly associated with IIH [odds ratio (OR) of 4.25 (1.68-12.60)], similar to the association with high factor VIII [OR = 16.17 (2.87-91.01)], higher plasminogen activator inhibitor-1 (PAI-1) levels [OR = 6.91 (2.28-20.91)], and high lipoprotein (a) [LP(a)] [OR = 3.54 (1.54-8.70)]. Obesity often observed in IIH patients is frequently linked with thrombophilic factors. Thus, we believe that dysmetabolism could be the thrombophilic target for treatment in patients with IIH.

Hereditary thrombophilic risk factors for recurrent pregnancy loss

This review summarizes current knowledge about the role of hereditary hypercoagulation factors predisposing to thrombophilia-associated recurrent fetal loss. Thrombophilias are a major cause of adverse pregnancy outcome, playing a role in the etiology of up to 40% of cases worldwide. Hereditary thrombophilic predispositions to recurrent pregnancy wastage include genetic lesions in blood coagulation factors II and V as well as natural anticoagulants antithrombin, protein C, and protein S. Furthermore, methylenetetrahydrofolate reductase gene variants conferring higher thrombophilia risk in combination with these mutations and the newly described annexin A5 gene M2 promoter allele are associated with repeated fetal loss. The review gives a concise description of the molecular defects arising from the genetic changes, of the role these factors play in the timing and definition of fetal loss, and risk estimates from available studies and meta-analysis. This knowledge is instrumental for a more precise assessment of individual risks for repeated fetal loss and should guide therapeutic strategies, where relevant. Since the average childbearing age increases in Western societies, the importance of a timely diagnosis of fetal loss predisposition is increasing.

A study on thrombophilic factors in Italian Behcet's patients

Background Behcet's disease (BD) may complicate with arterial and venous thrombosis. The purpose of this work is to evaluate in an Italian group of BD patients with thrombotic events a large panel of inherited and acquired thrombophilic factors. Methods Thirty BD patients, of which nine with previously arterial or venous thrombosis and 21 without, underwent the following investigations: plasma antithrombin activity, protein C activity, free protein S level, sensitivity to APC, total plasma homocysteine concentration, serum folate level, determination of anti-phospholipid antibodies, serum Lp(a) levels, tests for gene polymorphisms of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase genes. Tests for the gene polymorphisms were also performed in a group of healthy control subjects. Results All the six patients with arterial or deep venous thrombosis showed thrombophilic conditions such as protein C or protein S deficiency (one case each), hyperhomocysteinemia (two cases), positivity of anti-phospholipid antibodies associated with APC resistance or hyperhomocysteinemia (one case each). Among three subjects with superficial thrombophlebitis only one showed a mild hyperhomocysteinemia. No differences were found between BD patients and control subjects concerning polymorphisms of the genes considered. Among BD patients the Factor V H1299R mutation showed a weak association with venous thrombosis ( P = 0.048). Conclusion In BD patients different concomitant significant thrombophilic risk factors may contribute to the development of thrombotic events. Patients affected by vasculo-Behcet should be evaluated for the presence of coexisting major thrombophilic conditions.

Hereditary and acquired thrombophilic disorders complicating vascular access in haemodialysis: O. Sarkar et al.

A 65-year-old male pre-dialysis Turkish patient with diabetic nephropathy received a Cimino fistula of the left lower arm, which occluded before use within the following weeks after the operation. A polytetrafluorethylene (PTFE) loop was created at the left forearm. The first sessions of dialysis were successful; however, 2 weeks after starting dialysis using unfractionated heparin, the loop occluded. Platelet count dropped at this time, but not significantly. As thrombectomy of the loop was unsuccessful, a new PTFE loop at the left upper arm was created. After 2 months without any complications, the PTFE loop occluded again. A loop thrombectomy with revision of the protheto-venous anastomosis was performed initially and after 5 days, as the loop failed again. During both revisions, intraoperative angiography showed no stenosis of the central venous system draining of the left upper limb, and blood flow was well >600 mL/min. As there was no personal or family history of former thrombotic events, no examination for thrombophilic disorders was conducted at this time. Since the loop failed again after 8 days, a brachiocephalic fistula at the right arm was built. As recurrent clotting complications of the Shaldon catheters were recognized during dialysis, a tunnelled-cuffed catheter on the left side was applied to provide dialysis access until complete maturation of the fistula. In the further course, the tunnelled cuffed catheter had to be changed two times due to clotting complications and remained open only after blocking with urokinase. Platelet count did not drop significantly during each event (Figure 1). Laboratory testing for thrombophilia risk factors was performed (Table 1). Abnormal findings included heterozygosity for the prothrombin G20210A mutation, an increased level of von Willebrand factor (vWF) (ristocetin cofactor activity: 289%; vWF antigen: 348%) and elevated plasma factor VIII coagulant activity (273%). A test for lupus anticoagulants was only weakly positive, and cardiolipin antibodies could not be detected. As there was no significant drop in platelet count and the diagnosed thrombophilias were sufficient to explain the recurrent thromboembolic events, no investigation for heparin induced thrombocytopenia antibodies (HIT antibodies) was conducted, and an anticoagulation with phenprocoumon was started. Overlapping, a full anticoagulation with certoparin adapted to body weight was given, until a stable international normalized ratio (INR) within the range of 2–3 was achieved. Dialysis was conducted with unfractionated heparin. Despite sufficient anticoagulation, recurrent clotting complications, especially recurrent thrombotic occlusion of the dialysis machine lines and dialyser, occurred during dialysis. Hence, we conducted a heparin-induced platelet aggregation assay (HIPA), which detected a heparin-dependent activation of donor platelets. Further dialysis was performed with danaparoid (initial dose of 3750 units). Further dosing had to be adapted according to the anti-Xa level. No more thrombotic events occurred from that point, and the fistula was successfully used after 8-week maturation period.

Combined thrombophilic factors increase the risk of recurrent thrombotic events in Behcet’s disease

This retrospective study aims to seek a relationship between the number of thrombotic events and presence of thrombophilic factors in Behcet's disease (BD). Any patient with a vascular problem evaluated for at least one thrombophilic factor was deemed eligible for the present study. Upon an evaluation of their medical records, 96 (23.9%) of the 402 patients diagnosed with BD were determined to have a history of thrombosis. Of these 96 patients, 72 (75%) had only one thrombotic attack, while the remaining 24 (25%) had two or more thrombotic attacks. Thrombophilic parameters were evaluated in only 36 of the 72 patients (50%) who had one thrombotic event (Group I) and in 18 of the 24 patients (75%) who had more than one thrombotic event (Group II). The patients with recurrent thrombotic events had a significantly higher incidence of combined thrombophilias than those patients with only one thrombotic event (8/18, 44%; 4/36, 11%; p < 0.01). The number of the patients free from thrombophilic risk factors was significantly higher in Group I than in Group II (21/36, 58%; 4/18, 22%; p < 0.02). Group II had an increased frequency of combined thrombophilic risk factors (OR 6.4; 95% CI 1.5-25.8) when compared to Group I. No significant differences were found between Groups I and II with respect to clinical features of BD. In conclusion, combined thrombophilias in patients with BD may have a role in the development of recurrent thrombotic events.

Bilateral renal vein thrombosis secondary to methylene tetrahydrofolate reductase mutation: a rare case

Bilateral renal vein thrombosis secondary to methylene tetrahydrofolate reductase mutation: a rare case

Antiphospholipid syndrome and the brain in pediatric and adult patients

The most common neurological manifestations of antiphospholipid syndrome (APS) in all age-groups include stroke and transient ischemic attacks due to arterial thromboses and cerebral ischemia. Antiphospholipid antibodies may cause additional non-criteria neurological impairments through vascular, neuroinflammatory and direct neuronal effects. Anti-aggregant or anticoagulant therapies are indicated for APS-related ischemic strokes. Treatment regimens for asymptomatic antibody-positive patients and those with refractory or recurrent disease remain controversial. There is scant literature on the epidemiology and therapy of neurological APS manifestations in pediatric patients. Assessments of modifiable cardiovascular and inherited thrombophilia risk factors are essential in patients with APS. There may be a role for novel neuroimaging modalities in quantifying APS-related microstructural brain damage. The clinical utility of statins, antimalarials, angiotensin-converting enzyme inhibitors, and thrombin inhibitors warrant further research.

Clinical guidelines for testing for heritable thrombophilia

Trevor Baglin, Elaine Gray, Mike Greaves, Beverley J. Hunt, David Keeling, Sam Machin, Ian Mackie, Mike Makris, Tim Nokes, David Perry, R. C. Tait, Isobel Walker and Henry Watson Addenbrooke’s Hospital, Cambridge, NIBSC, South Mimms, University of Aberdeen, Aberdeen, Guy’s and St Thomas’, London, Churchill Hospital, Oxford, University College Hospital, London, Royal Hallamshire Hospital, Sheffield, Derriford Hospital, Plymouth, Glasgow Royal Infirmary, Glasgow and Aberdeen Royal Infirmary, UK

The C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene Is Associated with Idiopathic Ischemic Stroke in the Young Mexican-Mestizo Population

Background and Purpose: Previous studies have demonstrated that a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with an increased risk for stroke. However, this relation remains controversial. Our aim was to investigate the possible association between the C677T polymorphism in the MTHFR gene and idiopathic ischemic stroke in the young Mexican-Mestizo population. Methods: One hundred seventy-eight patients <45 years with idiopathic ischemic stroke and 183 controls were tested for the C677T polymorphism in the MTHFR gene. Causes of primary thrombophilia as well as classical risk factors for atherothrombotic disease were also evaluated. Results: There was a significant difference in the genotype distribution between patients and controls (p = 0.01), but the allele frequency was similar in both groups (p = 0.09). The univariate analysis identified the T allele as a risk factor for ischemic stroke (TT and CT carriers), as compared with homozygous for C allele (p = 0.01). Hypertension and smoking prevalences were significantly higher in the group of patients. Also the T allele was significantly associated with large-vessel ischemic stroke. The postoral methionine load homocysteine levels were higher in patients with ischemic stroke versus controls (p < 0.001). There was a low prevalence of primary thrombophilia markers. Conclusions: The T allele from the C677T polymorphism of the MTHFR gene represents an independent risk factor for idiopathic ischemic stroke at young age in the Mexican-Mestizo population. Also, hypertension and smoking were independent risk factors in our study population. Primary thrombophilic risk factors were not associated with ischemic stroke in our population.

Thrombophilic risk factors in the pathogenesis of non-arteritic anterior ischemic optic neuropathy patients

Non-arteritic anterior ischemic optic neuropathy (N-AION) is caused by acute ischemic infarction of the optic nerve head, supplied by the posterior ciliary arteries. Thrombophilia is the tendency/predisposition to vascular thromboses of arteries and veins, and the existence of thrombophilic risk factors leads to blood hypercoagulability and potentially increased risk for thromboses. To investigate whether there is an association between N-AION and a wide spectrum of thrombophilic risk factors. Seventy-seven consecutive cases of confirmed N-AION and 60 age- and sex-matched consecutive controls constituted the study group. Fibrinogen levels, deficiency of proteins C, S, ATIII, lupus anticoagulant, activated protein C resistance, factor V Leiden, factor V H1299R, factor II G20210A, MTHFR C677T, MTHFR A1298C, GPIIIa A1/A2, and ACE I/D polymorphisms were analysed. Statistical analysis of the plasma proteins in our study demonstrated that the only significant difference was the one concerning protein S levels. In particular, the mean value for N-AION patients was 78.8% +/- 21.2, and for the control group the mean value was 88% +/- 21.2 (p = 0.013). Despite the above-mentioned result, there was not any statistical difference between the two subgroups regarding actual protein S deficiency, as 9/77 (11.7%) patients and 4/60 (6.7%) controls had protein S levels below 60% (p = 0.32). In our study sample, homozygosity for MTHFR C677T polymorphism in the study group as a whole, and the presence of at least one A2 allele of GPIIIa in the subgroup of male patients as compared to healthy male controls, proved to be the most significant thrombophilic risk factors, with odds ratios of 16.78 (95% C.I 0.96-294.42, p = 0.054) and 4.6 (95% C.I 1.52-13.88, p = 0.007) respectively. Screening for these polymorphisms would probably constitute a valuable procedure in N-AION patients, as they may have an important contribution to the pathogenesis of the disease.

Thrombophilia and abdominal vessel thrombosis in a Greek University hospital: A five year experience

Thrombophilia, either congenital or acquired, has foremost consequences in the abdominal vessels. We review here the cases of patients admitted with abdominal vessel thrombosis over a five-year period. Our data focused on gender and age at diagnosis, site of thrombosis, previous thromboembolic events, underlying conditions, and family history. Investigations included measurement of protein C, protein S, activated PC resistance, and antithrombin, and screening for factor V Leiden, prothrombin G20210A, the C677T variant of the methylenetetrahydrofolate reductase gene, and V617F JAK2 mutation, r lupus anticoagulant, antiphospholipid antibodies and paroxysmal nocturnal hemospherinouria, and also serum folate, vitamin 12, and total homocysteine concentrations. Twenty-nine patients were admitted and 18 of their family members also underwent the same thrombophilia investigations. Eighteen patients (62.1%) presented with portal vein thrombosis (PVT), five patients (17.2%) with mesenteric vein thrombosis (MVT), four patients (13.8%) with splenic vein thrombosis (SVT), and two (6.9%) patients with hepatic vein thrombosis (HVT). There was a high incidence of congenital thrombophilia (37.9%), acquired thrombophilic conditions (27.6%), or both (20.7%). Sixteen of 18 patients with PVT, four of five patients with MVT, all four patients with SVT, and one of two patients with HVT had one or more thrombophilic risk factors. In 13.8% of the patients no underlying condition was identified. We concluded that thrombophilia may have major implications in the pathogenesis of abdominal vessel thrombosis in adult life, and a thorough thrombophilia investigation should be performed in all these patients.

Thrombophilic risk factors and peripheral arterial disease severity

Few data are available on thrombophilic risk factors and progression of atherosclerotic peripheral arterial disease (PAD). Thrombophilic alterations can be an aggravating factor when arterial stenoses are present. In a cross-sectional study, we evaluated the presence of the thrombophilic factors fibrinogen, homocysteine, factor (F)VIII, lupus anticoagulant (LAC), FII G20210A, and FV R506Q mutations in 181 patients with PAD at Fontaine's stage II (claudication), in 110 patients with critical limb ischaemia (CLI), and in 210 controls. Fibrinogen was higher in patients with CLI vs. those with claudication and controls (427.9 +/- 10.5 vs. 373.1 +/- 5.2 vs. 348.9 +/- 7.0 p=0.001, respectively). Homocysteine and FVIII were higher in patients with PAD than in controls, but were similar in patients with CLI and claudication. The prevalence of LAC increased in patients with CLI vs. those with claudication and controls (21.4% vs. 7.8% vs. 5.2% p<0.001, respectively). The prevalence of FII 20210A allele was higher in patients with CLI vs. those with claudication and controls. Using a logistic model, FII G20210A mutation (odds ratio [OR] 19.8, confidence interval [CI] 4.5-87.1, p=0.001), LAC (OR 2.7, CI1.1-6.5, p=0.032), and fibrinogen (OR 1.01, CI 1.00-1.01, p=0.001) were associated with CLI, whereas homocysteine, FVIII, and FV R506Q mutation were not. CLI risk increased according to the number of thrombophilic alterations. In conclusion, altered levels of some important thrombophilic risk factors are independently associated with PAD severity. These data suggest that the presence of two or more thrombophilic risk factors raise the likelihood of PAD being more severe, justifying the need for larger longitudinal studies.

Hyperhomocysteinemia and thrombophilia

It is now widely accepted that hyperhomocysteinemia (HHC) is a risk factor for thrombophilia. HHC is the result of either impaired enzyme function or a deficiency of vitamin B (folate, B₆, B₁₂), or both, and can be treated with vitamin supplements. Measuring plasma total homocysteine (tHcy) is included in the routine thrombophilia panel in many laboratories, despite having a limited value to the clinician. Many methods are available for tHcy measurements. High-pressure liquid chromatography (HPLC) with fluorescence detection is a widely used method, but is being replaced by more convenient immuno- or enzyme assays. In this paper a general overview on homocysteine is given, with an emphasis on laboratory methods.

Prevalence of common thrombophilia markers and risk factors in Indian patients with primary venous thrombosis.

venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. this was a cross-sectional study carried out in Mumbai. samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). the popliteal vein was the most commonly involved site. Forty-four samples (56%) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9% each), followed by low protein S (16.6%). this study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.

Coagulation disorders and the risk of retinal vein occlusion

Over the past years, there has been a dramatic increase in the number of identifiable causes of thrombophilia. However, to date, there are no large, prospective studies to assess an optimal, cost-effective approach with regard to screening and case finding for thrombophilic risk factors in patients presenting with retinal vessel occlusion. Two hundred twenty-eight patients with retinal vein occlusion (RVO) and 130 age-matched healthy controls were prospectively screened for thrombophilic risk factors. Both cohorts were divided into three subgroups, depending on the patients' age at the time of the RVO or a previous thromboembolic event. Patient age < or =45 years was associated with a high prevalence of coagulation disorders (p<0.0001). Among patients < or =45 years and >45 to < or =60 years, a family history of thromboembolism was strongly associated with the presence of thrombophilic disorders. The absence of cardiovascular risk factors was found to be a strong predictor for the presence of coagulation disorders in all patient groups (< or =45 years, p=0.003; >45 to < or =60 years, p=0.0008; >60 years, p=0.001). Multivariate analysis revealed the presence of resistance to activated protein C (p=0.014), antiphospholipid antibodies (p=0.022), and deficiency of the anticoagulant proteins (p=0.05) as independent risk factors for the development of RVO among patients < or =45 years. Our results indicate that thrombophilic disorders are associated with the development of retinal vein occlusion in patients < or =45 years by the time of the RVO or a previous thromboembolic event, in patients with a family history of thromboembolism, or in patients without cardiovascular risk factors.

Thrombophilic Risk Factors in Patients With Inflammatory Bowel Disease.

BackgroundInflammatory bowel disease (IBD) patients have an increased risk for thromboembolism. The aim of this study was to assess the presence of thrombophilic risk factors in IBD patients and to assess the associations of these factors with disease activity.MethodsForty-eight patients with IBD (24 ulcerative colitis, 24 Crohn’s disease) and 40 matched healthy control individuals were enrolled. In addition to routine biochemical analysis, fasting blood samples were studied for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, protein-C, protein-S, antithrombin III, factor VII, factor VIII, D-dimer, vitamin B12, folic acid and homocysteine.ResultsLevels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, D-dimer and the number of platelets were significantly higher in patients with IBD. When compared to control group, in patients with Crohn’s disease serum homocystein levels were significantly higher (p = 0.025) while serum folic acid levels were significantly lower (p < 0.019). Levels of fibrinogen, D-dimer, protein C, factor VIII, total homocystein and the number of platelets were found to be significantly higher in Crohn’s disease patients who were in active period of the disease.ConclusionsThrombophilic defects are multifactorial and might be frequently seen in IBD patients. They might contribute to thrombotic complications of this disease.