Contribution of recurrent venous thrombosis and inherited thrombophilia to the pathogenesis of postthrombotic syndrome.

Postthrombotic syndrome (PTS) is a common complication of deep vein thrombosis. This study aims to assess the role of recurrent venous thrombosis and inherited thrombophilia in the pathogenesis of PTS. A series of 206 patients diagnosed with lower extremity venous thrombosis were retrospectively reviewed. The PTS was observed in 30.58% of the patients. Recurrent venous thrombosis was identified in 3.4% of the patients without PTS and in 33.3% of patients with PTS (P < .001). Inherited thrombophilia alone or in association with recurrent venous thrombosis was more commonly detected when PTS was moderate to severe (P = .04 and <.001) or severe (P < .001). Recurrent venous thrombosis increases the incidence of PTS significantly. The severity of PTS raises when an underlying thrombophilia is present either alone or in association with recurrent venous thrombosis.

Influence of acquired and genetic risk factors on the prevention, management, and treatment of thromboembolic disease.

Prevention, management, and treatment of venous thromboembolism requires understanding of the epidemiology and associated risk factors, particularly in recognizing populations warranting prophylaxis, in evaluating patients with high risk situations, and in determining the duration of anticoagulation required to minimize recurrent thrombosis and to avoid postthrombotic syndrome. The present paper reviews recent advances concerning acquired and genetic risk factors for venous thrombosis, analyses individual risks related to age, and focuses on thrombotic genetic risk factors and the synergistic gene-environment and gene-gene interactions and their importance in the management and treatment of venous thromboembolic disease.

Factor V-Leiden Mutation: A Common Risk Factor for Venous Thrombosis among Lebanese Patients.

Aim. Lebanon exhibits one of the highest prevalences of factor V-Leiden (FVL) in the world (14.4%). The aim of this study is to evaluate the incidence of FVL mutation among Lebanese patients with lower extremity venous thrombosis. Material and Methods. From January 2003 to January 2011, 283 consecutive Lebanese patients, diagnosed with deep venous thrombosis (DVT) by duplex scan, were retrospectively reviewed. FVL mutation was tested among patients with conditions highly suggestive of hypercoagulation states (65 patients). Results. FVL mutation was detected among 56.9% of patients, 68.6% of patients younger than 50 years, and 43.4% of patients older than 50 years (P = 0.041). FVL mutation was commonly reported in young adults, in patients with pregnancy, estrogen drugs, recurrent DVT, and resistance to anticoagulation. Conclusion. The high rate of FVL mutation observed among Lebanese patients with venous thrombosis is related to the high prevalence of this mutation in the Lebanese population. Thrombophilia screening should be tailored to accommodate a population's risk factor. In countries with high prevalence of FVL, this mutation should be screened among patients younger than 50 years and patients with situations highly suggestive of hypercoagulation states.

Acquired and genetic risk factors for deep vein thrombosis of lower extremities among Lebanese patients.

AIM: Venous thrombosis results from the interaction of environmental and genetic risk factors. These factors vary according to the ethnic and geographic distribution of the populations. The aim of this study is to define the role of acquired and genetic risk factors for venous thrombosis of lower extremities among Lebanese patients assessed in a university hospital and to discuss them according to the international literature. MATERIAL AND METHODS: From January 2005 to January 2010, 166 patients (72 males and 94 females) were diagnosed with lower extremity deep vein thrombosis. Mean age was 67 years (range: 25 to 96 years). RESULTS: The most frequently reported acquired risk factors for venous thrombosis in this study were advanced age, obesity, history of venous thromboembolism, immobilization, surgery, varicose veins and malignancy. Screening for prothrombotic genetic abnormalities was requested in patients with conditions highly suggestive of hypercoagulation state such as young patients, patients with spontaneous, recurrent or extensive venous thrombosis, patients with family history, oral contraceptives, air travel and pregnancy. All the 45 patients (27.1%) tested for thrombophilia were positive and were carriers for factors V-Leiden (17.4%), MTHFR C 677 T (16.8%), MTHFR A 1298 C (4.8%), II G 20210 A (1.8%) and V H 1299 R (1.2%) mutation. Twelve patients (7.2%) had increased homocysteine level. CONCLUSION: Advanced age is the most common risk factor for venous thrombosis in these series. Thrombophilia is the second most frequently observed risk factor and is related to the high prevalence of factor V-Leiden and MTHFR C 677 T mutation among the Lebanese population.

Lower extremity venous thrombosis in patients younger than 50 years of age.

AIM: Lower extremity deep venous thrombosis in the young adult is uncommon and has not been well studied in the literature. The aim of this study is to define risk factors for deep venous thrombosis among patients younger than 50 years of age, to compare them with a control group, and to suggest recommendations for the management and treatment of venous thrombosis in this particular group of patients. METHODS: From January 2003 to January 2011, 66 consecutive Lebanese patients (29 males and 37 females) younger than 50 years, diagnosed in an academic tertiary-care center with lower extremity deep venous thrombosis by color flow duplex scan, were retrospectively reviewed. Their age varied between 21 and 50 years (mean 38.7 years). The control group included 217 patients (86 males and 131 females) older than 50 years (range: 50-96 years; mean 72.9 years). RESULTS: The most commonly reported risk factors in the younger age group were inherited thrombophilia (46.9% compared with 13.8% in the control group; P < 0.001), pregnancy (18.2% compared with 0.5%; P < 0.001), treatment with estrogen drugs (13.6% compared with 2.3%; P = 0.001), and family history of venous thromboembolism (9.1% compared with 3.8%; P = 0.084). CONCLUSION: Inherited thrombophilia is the most commonly observed risk factor among patients younger than 50 years, with a prevalence of three times more than the control group. Young adults should be screened for thrombophilia even in the presence of transient acquired risk factors. Pregnancy and treatment with estrogen drugs essentially when associated with inherited thrombophilia represent a frequent cause of venous thrombosis among young female patients. Inferior vena cava abnormalities should be excluded in young patients with spontaneous proximal venous thrombosis especially when recurrent venous thrombosis or resistance to anticoagulation are observed.

Value of venous color flow duplex scan as initial screening test for geriatric inpatients with clinically suspected pulmonary embolism.

AIM: The contribution of lower extremity venous duplex scan to the diagnostic strategy for pulmonary embolism has been demonstrated by many authors. However, the positive diagnostic value of this noninvasive test in clinically suspected pulmonary embolism is not very high (10% - 18%). Since thromboembolic risks increase considerably in hospitalized patients with advanced age, this study aims to determine the importance of lower extremity venous color flow duplex scan in this particular subgroup of patients with clinically suspected pulmonary embolism. The effects of clinical presentation and risk factors on the results of duplex scan have been also studied. METHODS: Between July 2007 and January 2010, 95 consecutive Lebanese geriatric (≥ 60 years of age) inpatients with clinically suspected pulmonary embolism assessed in an academic tertiary-care center for complete lower extremity venous color flow duplex scan were retrospectively reviewed. Age varied between 60 and 96 years (mean, 79.9 years). Forty patients were males and 55 females. Absence of compressibility was the most important criteria for detecting acute venous thrombosis. RESULTS: Out of 95 patients, 33 patients (34.7%) were diagnosed with recent deep venous thrombosis of lower extremities (14 proximal and 19 distal) using complete venous ultrasound. Nine of these 33 patients (27.2%) had a history of venous thromboembolism and eleven (33.3%) presented with edema of lower extremities. A total of 28 patients (84.8%) with positive duplex scan had associated risk factors for venous thromboembolism. CONCLUSION: Lower extremity venous color flow duplex scan appears to be a reasonable initial screening test in the diagnostic algorithm of pulmonary embolism in geriatric inpatients with clinically suspected pulmonary embolism. This is particularly true in patients with a history of venous thromboembolism, in patients with a clinical presentation suggesting venous thrombosis, in uremic patients and in patients with altered general and mental status who are not candidates for chest computed tomography.

Livedoid vasculopathy associated with combined prothrombin G20210A and factor V (Leiden) heterozygosity and MTHFR C677T homozygosity.

Livedoid vasculopathy (LV) is an occlusive thrombotic disease of lower extremities. A 34-year-old woman presented with 4-year history of recurrent necrotic and painful lesions with violaceous and purpuric border on both legs. Initial treatment with hydroxychloroquine, dapsone and prednisone were unsuccessful. Skin biopsy showed inflammatory infiltrate with epidermal necrosis. Prothrombin G20210A and factor V-Leiden heterozygosity, and MTHFR C677T homozygosity with hyperhomocysteinemia were confirmed. LV diagnosis was made; acetylsalicylic acid, folic acid, vitamin B12, and prednisone treatement resulted in complete healing. This is the first report on coexistence of prothrombin G20210A, factor V-Leiden, and homozygous MTHFR C677T with hyperhomocysteinemia in LV.

Mycotic aneurysm of the tibioperoneal trunk. An extremely rare localization with pseudo-phlebitis clinical presentation.

Since antibiotics have been widely used in the treatment of bacterial endocarditis, mycotic aneurysms caused by septic emboli have become extremely rare. We report the case of a 66-year-old male patient who presented mycotic aneurysm of the right tibioperoneal trunk two weeks after aortic and mitral valve replacement due to Enterococcus fecalis endocarditis. The clinical presentation simulated thrombophlebitis of the deep veins of right calf. A pulsating mass was diagnosed clinically and duplex ultrasound confirmed the diagnosis of a mycotic aneurysm of the tibioperoneal trunk. Surgical treatment included the closure of the orifice of the aneurysm and excision of the aneurysmal sac. Arterial reconstruction was not required. Postoperative course was uneventful. No complication was observed at long-term follow-up. This observation represents the seventh case reported in the literature of mycotic aneurysm at this localization.

Distinct association of factor V-Leiden and prothrombin G20210A mutations with deep venous thrombosis in Tunisia and Lebanon.

Factor V G1691A (FV-Leiden) and prothrombin (PRT) G20210A single nucleotide polymorphisms (SNPs) were associated with venous thrombosis among Caucasians. We assessed the contribution of both SNPs to the genetic susceptibility of deep venous thrombosis (DVT) among Lebanese and Tunisian patients. Subjects comprised 198 DVT patients and 540 healthy controls from Lebanon and 126 Tunisian DVT patients and 197 control subjects; FV-Leiden (MnlI) and PRT G20210A (HindIII) genotyping was done by PCR-RFLP. While the prevalence of FV-Leiden mutant A allele and the G/A and A/A genotypes were significantly higher among DVT patients from Lebanon and Tunisia, the association of PRT G20210A with DVT was pronounced among Lebanese but not Tunisian patients. The prevalence of PRT G20210A mutant A allele (P < 0.001 vs. P = 181) and G/A genotype (P < 0.001 vs. P = 0.994) was significantly higher among Lebanese but not Tunisians, respectively. While FV-Leiden was a common genetic risk factor for DVT in both communities, the contribution of PRT G20210A to the genetic susceptibility of DVT differed among Lebanese and Tunisians, which underscores the need to determine prothrombotic gene polymorphisms associated with DVT among Arab and Mediterranean basin communities.

A case control study on the contribution of factor V-Leiden, prothrombin G20210A, and MTHFR C677T mutations to the genetic susceptibility of deep venous thrombosis.

BACKGROUND: Insofar as the inherited prothrombotic single nucleotide polymorphisms (SNPs) factor V G1691A (FV-Leiden), prothrombin (PRT) G20210A, and methylenetetrahydrofolate reductase (MTHFR), C677T are inherited risk factors of venous thromboembolism (VTE), the aim of this study was to determine the prevalence of single and combined SNPs in 198 patients with documented deep venous thrombosis (DVT), and 697 control subjects, and to estimate the associated risks. METHODS: Factor V-Leiden, PRT G20210A, and MTHFR C677T were analyzed by PCR and restriction fragment length polymorphism (RFLP). RESULTS: The prevalence of the heterozygote and homozygous variants for FV-Leiden (52.02 vs. 14.78%, RR 6.28), PRT G20210A (19.2 vs. 3.6%; RR 6.38), and to a lesser extent the T/T genotype of MTHFR C677T (20.71 vs. 11.0%; RR 1.49) were higher among DVT patients vs. controls, respectively. Two or more SNPs were detected in 90 of 198 patients (45.5%) and in 60 of 697 controls (8.6%), with odds ratios of 16.754 for joint occurrence of FV-Leiden and PRT G20210A, 10.471 for FV-Leiden and MTHFR C677T, and 6.283 for PRT G20210A SNPs and MTHFR 677T/T. Logistic regression analysis showed a further increased odds for FV-Leiden in combination with PRT G20210A (85.198) or homozygous MTHFR C677T (81.133), and to a lesser extent for PRT G20210A in combination with homozygous MTHFR C677T (20.812). CONCLUSIONS: This indicates that FV-Leiden and PRT G20210A, more than MTHFR C677T, are important risk factors for DVT, and that the presence of more than one prothrombotic SNPs was associated with a significant risk of DVT.

Acute limb ischemia secondary to heparin-induced thrombocytopenia after cardiac surgery.

UNLABELLED: Heparin-induced thrombocytopenia is an important and sometimes life-threatening immunological drug reaction. About 2.5% of patients receiving heparin develop immune-mediated (type II) heparin-induced thrombocytopenia that may be complicated by a paradoxical thrombotic syndrome either arterial or venous. This severe syndrome carries relevant rates of mortality and morbidity secondary to cerebral, myocardial and limb infarction. OBJECTIVE: To report two cases of successfully treated severe limb acute ischemia secondary to heparin-induced thrombocytopenia after cardiac surgery. METHODS: Seven days after aorto-coronary bypass and heparin exposure, a 75-year-old female patient developed acute ischemia of the left hand and a 60-year-old female patient presented a severe ischemia of the left lower extremity. Platelet count level decreased to 12000/mm3 in the first case and to 11000/mm3 in the second case. RESULTS: The first patient underwent emergent fasciotomy of the left hand and forearm and the second one had urgent thrombectomy of the left deep femoral, popliteal and posterior tibial arteries with venous patch angioplasty. Heparin was discontinued and warfarin started few days later. The patients had an uneventful course and they completely recovered. CONCLUSION: Early recognition of heparin-induced thrombocytopenia syndrome has allowed for significant advances in therapy leading to marked reduction in mortality and morbidity. Recently, available thrombin inhibitor drugs have dramatically changed outcomes for patients having this severe syndrome.