Venous thromboembolism (VTE) is a multifactorial disease that results from a conjunction of several risk factors, both inherited and acquired. The younger the person, the more risk factors are required to cause the disease. Since 1937, when the term thrombophilia was coined by Nygaard and Brown, and 1965 when it was used for the first time by Egeberg, a substantial increase in the percentage of patients with VTE and underlying thrombophilia has been reported, particularly after the discovery of the most common thrombophilic mutations, FV Leiden and FII G20210A. Presence of thrombophilia could be detected in as many as 50% of all patients with VTE. Thrombophilia testing has increased lately not only in patients with thromboses but also for other indications, however, whether the results will help in the clinical management of the patients is still unclear. Thrombo philia testing is most commonly performed in young patients with VTE, patients with recurrent episodes of VTE or with thromboses at unusual sites and in persons with positive family history. Whether the presence of thrombophilia influences the clinical management of the patient remains controversial. Patients with VTE and the recognized risk factors such are surgery, trauma, immobilization, pregnancy and the puerperium are at very low risk for recurrence, but prediction of the recurrence of VTE based on the presence of thrombophilia has not been sufficiently explored. Presence of clinical risk factors should be integrated in the strategy of VTE risk assessment. Since many risk factors, such as obesity, hypertension, dyslipidemia, diabetes and smoking are common for both arterial and venous thromboses, it has been suggested that VTE should be considered as part of a pancardiovascular syndrome, along with coronary artery disease, peripheral artery disease and cerebrovascular disease. Positive family history for VTE in a first-degree relative increases the risk for VTE occurrence by 2-fold, regardless of the presence of inherited thrombophilia. Pregnancy-related risk of VTE is sixfold in creased compared to nonpregnant age-matched women. Women with thrombophilia have been shown to be at an increased risk not only of pregnancy-associated thromboembolism, but also of other vascular complications, including recurrent fetal loss and intrauterine fetal death. Risk for antepartal pregnancy-related VTE is considerably increased in obese women confined to bed for longer than one week, in women who underwent assisted reproduction, in multiple pregnancies, gestational diabetes and maternal age over 35 years. Postpartal risk factors differ, with eclampsia, emergency cesarian section and placenta praevia being the most important. Testing for thrombophilia generally does not alter the management of a patient with VTE, except for selected groups of patients. Women of fertile age with positive family history and presence of thrombophilia may benefit from thromboprophylaxis implementation during pregnancy, or can make the decision not to use oral contraceptives. In the future, the use of global coagulation tests that could detect a hypercoagulable state, along with other clinical risk factors, might improve VTE risk assessment and optimize the duration of treatment of VTE disease.
Iva Salatić, Katarina Kiralj, Gorana Mitić, Igor Veselinović and Dušan Vapa
FV Leiden Mutation and Deep Venous Thrombosis in Vojvodina: A Case-Control Study
Between September 2007 and February 2010, the occurrence of symptomatic deep venous thrombosis (DVT) was investigated in a cohort of 79 consecutive patients. A case-control study inclu ded 71 healthy controls matched with cases for sex and age. The prevalence of factor V G1691A mutation genotype was analyzed. Eighteen cases (22.79%; 95% confidence interval (CI) 13.53% to 32.03%) and four controls (5.63%; 95% CI 0.27% to 10.99%) were heterozygous carriers of FV Leiden (p= 0.025). The odds ratio for DVT was 4.94 (95% CI 1.58 to 15.42) and the relative risk 4.04 (95% CI 1.44-11.38) compared with FV 1691G carriers. Four cases were homozygous carriers of FV Leiden, giving a prevalence of 5.06% (95% CI 0.23 to 9.89%) and no controls, therefore OR and RR calculation was based on the prevalence of homozygotes in the general Caucasian population. The OR for DVT was 47.28 (95% CI 0.04 - 52167.3) and the RR 45.57 (95% CI 0.04 to 49540.77; p=0.025) compared with FV 1691 G carriers. Our study confirms that factor V Leiden carriers in Vojvodina, as in similar studies previously carried out in other populations, have an increased risk of developing DVT. The evaluated risk of DVT in heterozygous carriers of the mutation is four- to five-fold higher, whereas for homozygous carriers it is 45- to 48-fold higher than in non-carriers. These results confirm that patients with DVT and their relatives should undergo screening for FV Leiden mutation.
In Serbia, the first isolates of C. difficile were isolated in the Public Health Institute (PHI), Center for Microbiology in Niš, at the end of 2005.
The National Reference Laboratory for Anaerobic Infections (NRLA) in PHI Niš confirmed the toxigenic strains that caused the first three registered hospital epidemics in Serbia, in 2006 at the Clinic of Neurology, Clinical Center Niš, in 2007 at the Clinical Center of Vojvodina in Novi Sad, and in 2009 in the General Hospital in Požarevac.
In 2014, C. difficile species were isolated for the first time from 175 environment samples in the research studies which were conducted in NRLA of PHI Niš. In the samples of soil taken from the ground within the Clinical Center Niš, those taken from the parks at the territory of the Municipality of Niš, samples of mud and sand around the illegal sewage systems at the territory of the Municipality of Niška Banja, a small number of bacteria C. difficile producing the toxins (A+B+) as well as non-toxigenic isolates (A−B−) were found.
Results of the first epidemiological investigations of cases of diarrhea associated with prior antibiotic treatment applied in hospitalized patients in a number of health centers in our country, microbiological investigations done in the Public Health Institute, valuable discussions at professional and scientific meetings influenced the general attitude that isolation and identification of C. difficile and/or detection of toxin produced by this bacteria should be part of the routine work in the Serbian microbiological laboratories.