Position Paper on the Management of Pregnancy-Associated Superficial Venous Thrombosis. Balkan Working Group for Prevention and Treatment of Venous Thromboembolism.

Venous thromboembolism (VTE) is a multifactorial disease that can possibly affect any part of venous circulation. The risk of VTE increases by about 2 fold in pregnant women and VTE is one of the major causes of maternal morbidity and mortality. For decades superficial vein thrombosis (SVT) has been considered as benign, self-limiting condition, primarily local event consequently being out of scope of well conducted epidemiological and clinical studies. Recently, the approach on SVT has significantly changed considering that prevalence of lower limb SVT is twice higher than both deep vein thrombosis (DVT) and pulmonary embolism (PE). The clinical severity of SVT largely depends on the localization of thrombosis, when it concerns the major superficial vein vessels of the lower limb and particularly the great saphenous vein. If untreated or inadequately treated, SVT can potentially cause DVT or PE. The purpose of this review is to discuss the complex interconnection between SVT and risk factors in pregnancy and to provide evidence-based considerations, suggestions, and recommendations for the diagnosis and treatment of this precarious and delicate clinical entity.

Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Arterial stiffness as a measure of cardiovascular risk in obese adolescents and adolescents with diabetes type 1.

Background Cardiovascular disease (CVD) is the end result of vascular aging and atherosclerosis, having its origins in childhood. The aim of our study was to compare arterial stiffness (AS) and intima-media thickness (IMT) as markers of an early vascular damage between obese adolescents, adolescents with diabetes type 1 (T1D) and lean control subjects. Methods We analyzed AS and IMT in 68 obese adolescents (13.27±2.31 years), 42 adolescents with T1D (14.95±2.35 years) lasting over 5 years and 38 controls (15.02±1.94 years). AS (measured by pulse wave velocity [PWV], arterial compliance [AC] and ß-stiffness) and IMT were assessed using an e-tracking ultrasound method. Results A significant difference between the groups was found for AC (p=0.022) and PWV (p=0.010), with the lowest compliance and higher velocities in T1D patients. When corrected for age, the difference in AC among the groups did not reach a statistical difference (p=0.059). Correlation analysis in the obese adolescents showed lower AC in females (p=0.041), with higher systolic blood pressure (SBP) (p=0.032). In T1D adolescents, disease duration was the strongest determinant of AS (AC p=0.028, ß p=0.029 and PWV p=0.003), followed by body mass index (BMI; PWV p=0.008; ß p=0.033), SBP (AC p<0.001; PWV p=0.023), diastolic BP (AC p=0.049; PWV p=0.048) and HbA1c (PWV p=0.048). No significant correlations were found for AS measures or IMT with sex, age, BMI, Tanner stage or BP levels in controls. Conclusions Early vascular damage is more pronounced in T1D adolescents than in obese or lean adolescents, which may emphasize the impact of hyperglycemia as a major threat for cardiovascular health.

Rosuvastatin-Induced Rhabdomyolysis - Possible Role of Ticagrelor and Patients' Pharmacogenetic Profile.

Up to the beginning of 2018, a total of eight cases describing rare but clinically important drug interactions between rosuvastatin and ticagrelor which resulted in rhabdomyolysis have been noted in the Global World Health Organization (WHO) adverse drug reaction (ADR) database (VigiBase) as well as in available literature. There are several possible factors which could contribute to the onset of rhabdomyolysis: old age, initially excessive rosuvastatin dose, drug-drug interactions (DDI) on metabolic enzymes (CYPs and UGTs) and drug transporter levels (ABCB1, ABCG2, OATP1B1) and pharmacogenetic predisposition. We reviewed all available cases plus the case of an 87-year-old female Croatian/Caucasian patient who developed rhabdomyolysis following concomitant treatment with rosuvastatin and ticagrelor. The results of the pharmacogenetic analysis indicated that the patient was a carrier of inactivating alleles CYP2C9*1/*3, CYP3A4*1/*22, CYP3A5*3/*3, CYP2D6*1/*4, UGT1A1*28/*28, UGT2B7 -161C/T, ABCB1 3435C/T and ABCB1 1237C/T which could have added to the interactions not only between ticagrelor and rosuvastatin but also other concomitantly prescribed medicines, such as amiodarone and proton pump inhibitors. In this case report, the possible multifactorial causes for rhabdomyolysis following concomitant use of rosuvastatin and ticagrelor such as old age, polypharmacy, renal impairment, along with pharmacogenetics will be discussed.

Familial antiphospholipid syndrome presenting as bivessel arterial occlusion in a 17-year-old girl.

This article presents a case of a 17-year-old girl with primary antiphospholipid syndrome developing subacute signs of hand and leg ischaemia caused by radiologically verified radial and popliteal artery occlusion. She is successfully treated with a thrombolytic agent (alteplase) and recovers completely. Her laboratory results came positive for all three subtypes of antiphospholipid antibodies. This kind of antiphospholipid syndrome presentation is a very rare entity in itself. Shortly afterwards her mother is diagnosed with primary antiphospholipid syndrome as well. A familial form of antiphospholipid syndrome is suspected. Combination of a familial antiphospholipid syndrome presenting as bivessel arterial thrombosis is a unique case, to the best of our knowledge, never described in the literature before.

Correlation of femoral intima-media thickness and the severity of coronary artery disease.

The carotid artery intima-media thickness (IMT) is an established surrogate marker of vascular risk. We assessed the common femoral artery IMT and its correlation with coronary artery disease (CAD). We also assessed the influence of vascular risk factors on the femoral IMT. Patients (n = 180; mean age 60.4 ± 10.5 years) who had undergone coronary angiography due to symptoms of CAD were enrolled in this study. We found significantly higher values of femoral IMT in patients with CAD than in those without CAD (P = .0000). A strong positive correlation between femoral IMT and the severity of CAD expressed by the Gensini Score (P = .0000) was observed. There was a positive correlation between femoral IMT and levels of triglycerides (P = .017), body mass index (BMI; P = .036), male gender (P = .0000), and smoking (P = .028). There was a negative correlation between femoral IMT and the level of high-density lipoprotein-cholesterol (P = .001). Femoral IMT could be a novel cardiovascular risk marker.

Interactions of MinK and e-NOS gene polymorphisms appear to be inconsistent predictors of atrial fibrillation propensity, but long alleles of ESR1 promoter TA repeat may be a promising marker.

Interactions of MinK and e-NOS Gene Polymorphisms Appear to Be Inconsistent Predictors of Atrial Fibrillation Propensity, but Long Alleles of ESR1 Promoter TA Repeat May Be a Promising Marker. We analyzed minK, e-NOS and ESR1 gene polymorphisms in 40 patients with atrial fibrillation (AF) without major structural heart disease compared to 35 healthy controls. A missense polymorphism in the minK gene with A/G substitution at nucleotide 112 causing serine (S) to glycine (G) change, 786 T/C polymorphism in the 5' flanking region of e-NOS gene and TA polymorphism in the regulatory region of estrogen receptor ESR1 gene with long (> or = 19 TA repeats) and short alleles were examined. Only a slight increase in minK G allele frequency, but with marked excess in AG/TT combination of minK and e-NOS polymorphisms was found in the AF group. The interpretation remains tentative due to small groups precluding statistical significance of differences, possible lab flaws and inconsistencies with earlier data. However, ESR1 long allele homozygotes were strikingly more frequent in the AF than in control group, reaching statistical significance surprisingly in males (p < 0.02). Functional activity of estrogen receptors may be more critical in males than in females with abundance of circulating estrogen. Contrasting the intricate complexity of genetic polymorphisms influencing cardiac rhythm with our modest research, we would limit the conclusion to the plea for further research of ESR1 role in AF.

Access site complications following cardiac catheterization assessed by duplex ultrasonography.

Access site complications are major source of morbidity following cardiac catheterization. Their incidence varies in the literature because of multiple definitions and methods of determining the presence of particular complication. The aim of this prospective study was to determine the incidence of access site complications following cardiac catheterization using arterial duplex ultrasonography. A total of 319 consecutive patients, who had cardiac catheterization underwent femoral artery duplex study 24 to 48 hours following manual hemostasis. Diagnostic angiogram had 232 (71.8%) while 87 (28.2%) had percutaneous coronary intervention (PCI). Femoral artery duplex ultrasound was normal in 247 (77.4%). Haematoma was found in 48 (15.1%), pseudoaneurysm in 17 (5.3%), AV fistula in 2 (0.6%) and dissection of the femoral artery in 5 (1.6%) patients. Baseline demografic characteristics were similar in group with normal duplex study and group with detected complication. Pseudoaneurysm and AV fistula were more commonly observed in patients following PCI than diagnostic angiogram (9.2% vs. 4.7%, p<0.001). Patients with documented complications more frequently had concomitant administration of antiplatelet and anticoagulant medication compared to the patients without complications (p=0.003). Hemodynamic disturbances (hypotension and bradycardia) during manual compression were more frequent in patients with complication (11% vs. 4.5%, p=0.047). Low threshold for use of duplex ultrasound should be exercised in patients following cardiac catheterization to establish the presence of access site complications. Special attention is needed in the setting of aggressive antiplatelet and anticoagulant therapy, interventional procedures and hemodynamic disturbances during manual hemostas.

Treatment of extensive subacute portal, mesenteric and ileocolic vein thrombosis with recombinant tissue plasminogen activator.

Portal or/and mesenteric vein thrombosis is a rare condition with high mortality in an acute form. Therapy of thrombosis is not well defined, although there are some general guidelines that differ according to disease onset and clinical presentation. In acute thrombosis with bowel infarction, surgical resection with possible thrombolysis is advised. The best therapy for the subacute form is not known and the approach differs between centers. For chronic disease, prolonged anticoagulant therapy is recommended. Thrombolysis is well recognized in the treatment of acute ischemic coronary or cerebral diseases. Success of treatment is better if therapy is introduced within a few hours after symptoms have begun. We describe a 25-year-old patient with the subacute form of extensive portal, mesenteric and ileocolic vein thrombosis in the setting of underlying liver cirrhosis due to autoimmune disease. An aggressive therapeutic approach is advised, especially in patients who will eventually undergo liver transplantation, since portal and/or mesenteric vein thrombosis is relative contraindication for liver transplantation in the majority of transplant centers.

Primary cardiac lymphoma presenting as atrial flutter and total heart block.

Primary cardiac lymphoma is extremely rare. We present the case of a 70-year-old man with primary cardiac lymphoma involving interatrial septum, presenting as atrial flutter and total heart block. The diagnosis was obtained by echocardiography-guided transvenous endocardial biopsy which revealed diffuse large B-cell non-Hodgkin's lymphoma, CD 20+. After six courses of immunochemotherapy the patient achieved complete remission. After 2 months he developed a series of epileptic attacks. Intracerebral lymphoma extension was diagnosed. Two cycles of high-dose methotrexate and cranial irradiation were applied, resulting in a second complete remission.

Obliteration of a left main coronary artery aneurysm with a PTFE-coated stent.

The successful percutaneous obliteration of a left main coronary artery aneurysm using a covered stent (JOMED) is described. The immediate angiographic result was excellent and the early post-procedural period was uneventful. Six-month follow-up angiography revealed no changes.

[Venous thrombosis at the beginning of the new millennium]. / Venska tromboza--na pocetku novog milenija.

The author presents new theories related to the etiopathogenesis, diagnostic procedures and therapy of the deep vein thrombosis, according to latest publication data. Dilemmas related to the diagnosis and therapeutic strategies in hospital as well as the possibilities of treatment on the outpatient basis will be discussed. The intention was to cut the costs of therapy in favour of low molecular weight heparin treatment on the outpatient basis, as the cornerstone of the new therapeutic possibilities besides the importance of fibrinolytic therapy. Hereditary and acquired thrombophilia and venous thrombosis related to pregnancy will be discussed.