A 10-year Australian experience of rare intraabdominal venous thrombosis with comparison to deep vein thrombosis and pulmonary embolism.

OBJECTIVE: Intra-abdominal venous thromboembolism is rare with heterogeneous management. We aim to evaluate these thrombosis and compare them to deep vein thrombosis and/or pulmonary embolism. METHOD: A 10-year retrospective evaluation of consecutive venous thromboembolism presentations (January 2011-December 2020) at Northern Health, Australia, was conducted. A subanalysis of intraabdominal venous thrombosis involving splanchnic, renal and ovarian veins was performed. RESULTS: There were 3343 episodes including 113 cases of intraabdominal venous thrombosis (3.4%) - 99 splanchnic vein thrombosis, 10 renal vein thrombosis and 4 ovarian vein thrombosis. Of the splanchnic vein thrombosis presentations, 34 patients (35 cases) had known cirrhosis. Patients with cirrhosis were numerically less likely to be anticoagulated compared to noncirrhotic patients (21/35 vs. 47/64, P  = 0.17). Noncirrhotic patients ( n  = 64) were more likely to have malignancy compared to those with deep vein thrombosis and/or pulmonary embolism (24/64 vs. 543/3230, P  < 0.001), including 10 patients diagnosed at time of splanchnic vein thrombosis presentation. Cirrhotic patients reported more recurrent thrombosis/clot progression (6/34) compared to noncirrhotic patients (3/64) (15.6 vs. 2.3 events/100-person-years; hazard ratio 4.7 (95% confidence interval 1.2-18.9), P  = 0.030) and other venous thromboembolism patients (2.6/100-person-years; hazard ratio 4.7, 95% confidence interval 2.1-10.7; P  < 0.001) with comparable major bleeding rates. All renal vein thrombosis were provoked including five malignant-related cases while three ovarian vein thrombosis occurred postpartum. No recurrent thrombotic or bleeding complications were reported in renal vein thrombosis and ovarian vein thrombosis. CONCLUSION: These rare intraabdominal venous thromboses are often provoked. Splanchnic vein thrombosis (SVT) patients with cirrhosis have a higher rate of thrombotic complications, while SVT without cirrhosis was associated with more malignancy. Given the concurrent comorbidities, careful assessment and individualized anticoagulation decision is needed.

Age, sex and racial differences in fibrin formation and fibrinolysis within the healthy population.

Increased fibrin generation and reduced fibrinolytic potential have been detected using global coagulation assays in several hypercoagulable states including cardiovascular disease and venous thromboembolism. We aimed in this study to define the impact of age, sex and race on fibrin generation and lysis using the Overall Haemostatic Potential (OHP) assay in a group of stringently defined healthy adults. Healthy adult patients not receiving anticoagulation and without a history of thrombotic disease were prospectively recruited. Iindividuals with cardiovascular risk factors (e.g. hypertension, diabetes, smoking), receiving hormonal therapy, antiplatelet agents or with abnormal routine blood tests were also excluded. Platelet-poor plasma was obtained and the OHP assay, which evaluates fibrin formation with and without tissue plasminogen activator, was performed on all plasma samples. 144 healthy subjects (34.7% male) with median age 42 years (interquartile range 20, 77) were recruited. After multivariate analysis, age at least 50 years and female sex were associated with significantly increased fibrin generation parameters (overall coagulation potential, OHP, maximum optical density, fibrin) as well as reduced markers of fibrinolysis (overall fibrinolytic potential and time-to-50% lysis). There were no significant differences in OHP parameters between whites, East Asians and South Asians after accounting for age and sex. This study defines age, sex and racial differences of fibrin generation and fibrinolysis as measured by the OHP assay in a sample of healthy subjects. Further studies are warranted in diseased populations, where there is growing awareness of the role of global coagulation assay in defining prothrombotic and hypofibrinolytic states.

An evaluation of global coagulation assays in myeloproliferative neoplasm.

: Myeloproliferative neoplasms (MPN) are independent risks for thrombotic events. Routine laboratory tests are inadequate to evaluate the underlying procoagulant state. Global coagulation assays such as thromboelastography, thrombin and fibrin generation may provide better assessment of coagulation activation and thereby of thrombosis risk. Participants with MPN were recruited. Thromboelastography was performed on citrated whole blood while thrombin generation using calibrated automated thrombogram, fibrin generation using overall haemostatic potential assays and P-selectin were quantified on platelet-poor plasma. Thirty-eight MPN patients (median age: 65 years) were recruited. There were 26 patients with essential thrombocythemia (68.4%), eight polycythemia vera (20.5%), three primary myelofibrosis and one MPN, unclassifiable. Compared with normal controls, there was no difference in maximum amplitude although lysis time (LY30) was significantly higher (2.9 vs. 0.6%, adjusted P < 0.01) using thromboelastography. Calibrated automated thrombogram showed higher thrombin peak (260.8 vs. 222.6 nmol/l; P < 0.01) and velocity index (91.1 vs. 65.0 nmol/l/min; P < 0.01) with comparable endogenous thrombin potential. Fibrin generation parameters were significantly reduced with preserved overall fibrinolytic potential, whereas P-selectin was markedly increased (108.9 vs. 49.3 ng/ml, P < 0.01). This study demonstrated unique differences between MPN population and normal controls using a combination of global coagulation assays. The presence of high lysis time (LY30) and reduced fibrin generation in MPN patients were contradictory to the prothrombotic nature and may represent a compensatory effort to achieve equilibrium within the Virchow's triad. Both markers may be important prognostic indicators of thrombosis in MPN and further prospective studies to confirm these findings are proposed.

Venous thromboembolism management in Northeast Melbourne: how does it compare to international guidelines and data?

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality with significant heterogeneity in its management, both within our local practice and in international guidelines. AIMS: To provide a holistic evaluation of 'real-world' Australian experience in the warfarin era, including how we compare to international guidelines. METHODS: Retrospective evaluation of VTE from July 2011 to December 2012 at two major hospitals in Melbourne, Australia. These results were compared to recommendations in the international guidelines. RESULTS: A total of 752 episodes involving 742 patients was identified. Contrary to international guidelines, an unwarranted heritable thrombophilia screen was performed in 22.0% of patients, amounting to a cost of AU$29 000. The duration of anticoagulation was longer compared to international recommendations, although the overall recurrence (3.2/100 person-years) and clinically significant bleeding rates (2.4/100 person-years) were comparable to 'real-world' data. Unprovoked VTE (hazard ratio 2.06; P = 0.01) was a risk factor for recurrence, and there was no difference in recurrence between major VTE (proximal deep vein thrombosis (DVT) and/or pulmonary embolism) and isolated distal DVT (3.02 vs 3.94/100 person-years; P = 0.25). Fourteen patients were subsequently diagnosed with malignancy, and patients with recurrent VTE had increased risk of prospective cancer diagnosis (relative risk 6.68; P < 0.001). CONCLUSIONS: While our 'real-world' VTE experience during the warfarin era largely correlates with international guidelines, there remains heterogeneity in the management strategies, including excessive thrombophilia screening and longer duration of anticoagulation. This audit highlights the need for national VTE guidelines, as well as prospective auditing of VTE management, in the direct oral anticoagulant era for future comparison.

Retrospective review on isolated distal deep vein thrombosis (IDDVT) - A benign entity or not?

INTRODUCTION: Isolated distal deep venous thrombosis (IDDVT) is traditionally associated with less severe clinical sequelae, with ongoing debate on multiple aspects of its management. Despite numerous studies evaluating its acute management, there remains a paucity of data evaluating long-term complications such as recurrence and subsequent malignancy. We aim to evaluate the characteristics of IDDVT in institutions that routinely perform whole leg ultrasonography, and the risks of recurrence and complications in comparison to major venous thromboembolism (major VTE; defined as above-knee or proximal DVT and pulmonary embolism (PE)). METHODS: Retrospective evaluation of consecutive IDDVT and major VTE from July 2011 to December 2012 in a hospital network in Melbourne, Australia. Patients were followed up for a minimum of 24months. Patients with active malignancy were excluded. RESULTS: Of 1024 VTE cases, there were 164 non-cancer patients (92 males, 72 females, median age of 61years) with IDDVT. Compared to major VTE, IDDVT was more likely to be provoked (73% vs 59%, p<0.01), has shorter duration of anticoagulation (median 3.5months vs 6.0months, p<0.01) and less clinically significant bleeding (2.4% vs 6.7%, p=0.05), independent of duration of therapy. Recurrence was non-inferior compared to major VTE (10% vs 7%, p=0.36) and 60% recurred with major VTE. Three (1.8%) were subsequently diagnosed with cancer (vs 1.9% in major VTE, p=0.97). CONCLUSIONS: IDDVT has non-inferior rates of recurrence and subsequent cancer detection compared to major VTE and hence, its clinical significance should not differ from major VTE. Further studies are required to determine the adequate length of anticoagulation.

Cytomegalovirus retinitis after treatment with lenalidomide for multiple myeloma.

PURPOSE: To describe a case of cytomegalovirus retinitis in a patient after treatment with lenalidomide, a novel therapy in the treatment of multiple myeloma. METHODS: Descriptive case report of a 67-year-old man on Lenalidomide maintenance therapy for multiple myeloma, who presented with unilateral painless blurring of vision because of retinitis. RESULTS: Polymerase chain reaction of the vitreous sampling confirmed cytomegalovirus retinitis, although the patient's serum polymerase chain reaction was negative for cytomegalovirus. The patient was treated with ganciclovir with good effect. CONCLUSION: Cytomegalovirus retinitis is rare in immunocompetent patients and not commonly reported in myeloma patients. Given the increasing use of novel therapies such as Lenalidomide, unusual infections such as cytomegalovirus retinitis should be considered in patients with visual symptoms, even if they are considered to be immune competent at presentation.