Antithrombotic treatment for retinal vein occlusion: a systematic review and meta-analysis.

BACKGROUND: Retinal vein occlusion (RVO) represents a common thrombotic disorder. OBJECTIVES: In this meta-analysis, we evaluated the efficacy and safety of anticoagulant and antiplatelet therapy in RVO. METHODS: MEDLINE and EMBASE were searched up to December 2021 for observational studies and randomized controlled trials including patients with RVO. Efficacy outcomes were best-corrected visual acuity improvement, recurrent RVO, fluorescein angiography improvement, cardiovascular events, and safety outcomes were major bleeding and intraocular bleeding. RESULTS: A total of 1422 patients (15 studies) were included. Antiplatelet therapy was administered to 477 patients (13 studies), anticoagulant therapy to 312 patients (12 studies), and 609 (7 studies) patients received no antithrombotic treatment. The treatment duration ranged between 0.5 and 3 months. The median follow-up duration was 12 months. Best-corrected visual acuity improvement was reported in 58% of the patients (95% confidence interval [CI], 45%-69%) overall, 64% (95% CI, 58%-71%) in those on anticoagulant therapy, and 33% (95% CI, 21%-47%) in those on antiplatelet therapy. The rates of recurrent RVO was 11% (95% CI, 7%-17%), 7% (95% CI, 2%-19%), and 15% (95% CI, 8%-28%), respectively. The rate of recurrent RVO in untreated patients was 9% (95% CI, 6%-14%). The rate of major bleeding was 5% (95% CI, 3%-9%) overall, 4% (95% CI, 2%-9%) in those on anticoagulant therapy, and 7% (95% CI, 2%-23%) in those on antiplatelet therapy. CONCLUSION: Anticoagulant therapy was associated with higher visual acuity improvement and fewer recurrent RVO events than antiplatelet therapy, at the cost of an acceptable proportion of bleeding complications.

Antithrombotic treatment of retinal vein occlusion: a position statement from the Italian Society on Thrombosis and Haemostasis (SISET).

Retinal vein occlusion (RVO) represents a common cause of visual impairment and blindness. RVO may be associated with both local (e.g., hyperopia, glaucoma) and systemic (e.g., hypertension, diabetes, smoking, obesity, and dyslipidaemia) risk factors. The association with thrombophilia remains controversial. Data on the use of antithrombotic therapy for RVO are poor and inconsistent with most of the information being derived from observational studies. Here we provide a position statement from the Italian Society on Thrombosis and Haemostasis (SISET) to guide the clinical and therapeutic management of patients with RVO based on the available evidence and expert opinion.

Vitamin B12 levels in patients with retinal vein occlusion and their relation with clinical outcome: a retrospective study.

Retinal vein occlusion (RVO) is the second most common retinal vascular disorder, after diabetic retinopathy. Most patients suffering RVO develop some degree of visual loss consequent to retinal complications such as edema and microhemorrhages. Even if some risk factors for RVO have been identified, the clinical outcome of RVO remains highly unpredictable because studies investigating potential prognostic markers for visual improvement are lacking. Cyanocobalamin belongs to the group of B vitamins and plays a role in homocysteine metabolism; however, cyanocobalamin deficiency associates with an increase of some toxic bioproducts involved in endothelial injury and platelet activation independent of homocysteine levels. We retrospectively evaluated the levels of vitamin B12 at diagnosis in 203 patients with RVO, and in a parallel cohort of 120 age- and sex-matched patients without RVO from an internal medicine ward, and correlated them with visual outcome at follow-up (median time 150 days, IQR 30-210). In patients with RVO, vitamin B12 levels at diagnosis were significantly lower than in controls and independently predicted worse clinical outcome at multivariate analysis (OR 3.2; CIs 1.2-8.2; p = 0.015). Our data suggest the opportunity to prospectively evaluate the effect on visual outcome of cyanocobalamin supplementation in RVO patients.

Role of Increased Lipoprotein (a) in Retinal Vein Occlusion: A Systematic Review and Meta-analysis.

Background Increased lipoprotein (a) [Lp(a)] has been associated with enhanced risk of cardiovascular events and more recently with venous thromboembolism. However, there is inconclusive data on the association between enhanced Lp(a) and retinal vein occlusion (RVO). We aimed to assess the role of Lp(a) in RVO. Methods We performed a systematic review and meta-analysis of the studies addressing the role of Lp(a) in RVO. A systematic literature search was performed to identify all published papers reporting Lp(a) levels. Main outcome measures consisted of Lp(a) levels in patients with (cases) or without (controls) RVO. Results We included 13 studies for a total of 1,040 cases and 16,648 controls. Lp(a) levels above normal limits were associated with RVO (OR 2.38, 95% CI 1.7-3.34) and patients with RVO had higher Lp(a) levels than controls (weighted mean difference: 13.4 mg/dL, 95% CI 8.2-18.6). Conclusion Increased Lp(a) levels associate with RVO and should be included among diagnostic and prognostic indexes for this unusual-site vein thrombosis. Therapeutic interventions aimed to lower Lp(a) should be tested in RVO patients.

Long-term treatment with thalidomide for severe recurrent hemorrhage from intestinal angiodysplasia in Glanzmann Thrombasthenia.

Gastrointestinal angiodysplasia (GIA) is the most common cause of occult gastrointestinal bleeding (GIB) requiring often hospitalization and transfusions, especially in patients with hemorrhagic disorders. Thalidomide, impairing neo-angiogenesis, has been successfully used in the management of bleeding in patients with GIA and in particular in patients with inherited bleeding disorders. Only one case of short-term treatment with thalidomide in a patient with Glanzmann thrombasthenia (GT) and recurrent GIB due to GIA has been reported so far.We report the case of a woman with GT developing high frequency recurrent GIB due to GIA requiring repeated blood and platelet transfusions, who was treated with thalidomide obtaining a striking and stable reduction of GIB and of the requirement of platelet and blood transfusions for over 5 years. Moreover, we raise the suspicion that the association between GT and GIA may not be fortuitous.

Association of Neutrophil Activation, More Than Platelet Activation, With Thrombotic Complications in Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection is associated with hypercoagulability, which predisposes to venous thromboembolism (VTE). We analyzed platelet and neutrophil activation in patients with coronavirus disease 2019 (COVID-19) and their association with VTE. METHODS: Hospitalized patients with COVID-19 and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase 9, a neutrophil-released enzyme, were measured. Four patients were restudied after recovery. The activating effect of plasma from patients with COVID-19 on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied. RESULTS: A total of 36 patients with COVID-19 and 31 healthy controls were studied; VTE developed in 8 of 36 patients with COVID-19 (22.2%). Platelets and neutrophils were activated in patients with COVID-19. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic matrix metalloproteinase 9 was significantly increased in patients with COVID-19. Platelet and neutrophil activation markers, but less so NETs, normalized after recovery. In vitro, plasma from patients with COVID-19 triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic-dose low-molecular-weight heparin, but not by aspirin or dypiridamole. CONCLUSIONS: Platelet and neutrophil activation are key features of patients with COVID-19. NET biomarkers may help to predict clinical worsening and VTE and may guide low-molecular-weight heparin treatment.

Eltrombopag to allow chemotherapy in a patient with MYH9-related inherited thrombocytopenia and pancreatic cancer.

Chemotherapy is the mainstay of treatment for advanced pancreatic cancer however, due to possible myelotoxicity, it is used with caution in patients with thrombocytopenia, especially when severe. TPO-receptor agonists have been employed for chemotherapy-induced thrombocytopenia, however treatment with TPO-receptor agonists to allow chemotherapy in patients with inherited thrombocytopenia has not been reported so far. We report the first successful use of eltrombopag to prevent chemotherapy-induced thrombocytopenia in a patient with MHY9-related disorder and pancreatic cancer. Treatment with eltrombopag allowed to attain a safe and stable platelet count for several months sufficient to permit chemotherapy and to allow the patient to undergo endoscopic placement of a biliary stent with no bleeding complications.

Antithrombotic treatment of asymptomatic carotid atherosclerosis: a medical dilemma.

Carotid artery atherosclerosis (CAAS) is a common finding in asymptomatic subjects evaluated for cardiovascular (CV)-risk stratification. Besides the careful control of CV-risk factors, antithrombotic agents, and in particular aspirin, may be considered for primary prevention in patients at CV-risk. However, there is strong controversy on the use of aspirin in primary prevention. Even if several studies confirmed the association between CAAS and CV-events, CAAS is not universally recognized as an independent risk factor and the choice to use aspirin as primary prevention in these patients remains a medical dilemma. Here we review the available evidence on the prognostic value of asymptomatic CAAS for major CV-events and on the utility of antithrombotic agents in this population. We conclude that the detection of asymptomatic CAAS can not be considered as a direct indication to carry out primary prophylaxis with antithrombotic drugs, and the choice to use aspirin should be made only after the careful estimate of the individual's CV-and hemorrhagic risk.

Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study.

Major surgery is associated with an increased risk of venous thromboembolism (VTE), thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of VTE in patients with inherited platelet disorders (IPD) undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes in IPD patients undergoing surgery at VTE-risk participating in the multicenter SPATA study. We evaluated 210 surgical procedures carried out in 155 patients with well-defined forms of IPD (VTE-risk: 31% high, 28.6% intermediate, 25.2% low, 15.2% very low). The use of thromboprophylaxis was low (23.3% of procedures), with higher prevalence in orthopedic and gynecological surgeries, and was related to VTE-risk. The most frequently employed thromboprophylaxis was mechanical and appeared to be effective, as no patients developed thrombosis, including patients belonging to the highest VTE-risk classes. Low-molecular-weight-heparin use was low (10.5%) and it did not influence the incidence of post-surgical bleeding or of antihemorrhagic prohemostatic interventions use. Two thromboembolic events were registered, both occurring after high VTE-risk procedures in patients who did not receive thromboprophylaxis (4.7%). Our findings suggest that VTE incidence is low in patients with IPD undergoing surgery at VTE-risk and that it is predicted by the Caprini score. Mechanical thromboprophylaxis may be of benefit in patients with IPD undergoing invasive procedures at VTE-risk and low-molecular-weight-heparin should be considered for major surgery.

PCSK9 in Haemostasis and Thrombosis: Possible Pleiotropic Effects of PCSK9 Inhibitors in Cardiovascular Prevention.

Since increased cholesterol levels are crucial in determining the development of atheroma, their reduction represents a mainstay in primary and secondary cardiovascular prevention. The most recent spectacular advancement in cholesterol-lowering therapy is represented by proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors. Although their benefit over currently available treatments has been ascribed primarily to their strong low-density lipoprotein (LDL)-cholesterol reducing action, several clues suggest that PCSK9 inhibitors may also influence platelet function and blood coagulation. PCSK9 knockout mice develop less venous and arterial thrombosis and show reduced in vivo platelet activation upon arterial injury. In patients with acute coronary syndromes (ACSs) treated with P2Y12 inhibitors, a direct association between PCSK9 serum levels and residual platelet reactivity was found. A direct correlation between urinary excretion of 11-dehydro-thromboxane-B2, a marker of in vivo platelet activation, and circulating PCSK9 levels was reported in patients with atrial fibrillation. Moreover, recombinant human PCSK9 added in vitro to human platelets potentiated activation induced by weak agonists. Finally, blood clotting factor VIII (FVIII), which is associated with stroke and ACS risk, is cleared from the circulation by members of the LDL receptor (LDLR) family. Given that PCSK9 degrades LDLR, it is conceivable that PCSK9 inhibitors by enhancing the expression of LDLR may slightly decrease circulating FVIII, in this way contributing to the prevention of cardiovascular events. This review aims to discuss the possible and hypothetical interactions between PCSK9 and the haemostatic system and to examine the possible pleiotropic effects of PCSK9 inhibitors in cardiovascular prevention.