Direct oral anticoagulant use and risk of perioperative bleeding:Evidence of absence or absence of evidence?

Clinical epidemiolog

Infections, inflammation and venous thrombosis; an epidemiological perspective

Alledaagse, relatief onschuldige ontstekingsklachten zoals luchtweginfecties, diarree of een grieperig gevoel, brengen een verhoogde kans op trombose met zich mee. Hierdoor vergroot het risico op een longembolie of een trombosebeen. Dat blijkt uit onderzoek van promovendus Vladimir Tichelaar. Ook andere ziekten, zoals chronische infecties en auto-immuunziekten, zorgen voor een verhoogd risico op trombose, zo stelt Tichelaar vast in analyse van studies die de afgelopen vijftien jaar werden verricht. De ziekte van Crohn en colitis ulcerosa zijn hier voorbeelden van. Tijdens een opvlamming van een chronische darmziekte is het risico op veneuze trombose tot acht maal verhoogd. Verder laat Tichelaar zien dat patiënten met een HIV-infectie een hoog risico hebben op veneuze en arteriële trombose, zoals een hartinfarct of een beroerte, en dat een infectie met cytomegalovirus bij deze patiënten een extra verstoring van de stollingsfactoren in het bloed veroorzaakt. Bij patiënten met een acute veneuze trombose bestaat er een relatie tussen het bloedglucose en de trombose, zo ontdekte Tichelaar. Hoe hoger de glucosewaarden, hoe groter de waarschijnlijkheid dat er een veneuze trombose gevonden wordt. Dokters moeten alert zijn op het gebruik van nieuwe antistollingsmedicijnen, waaronder Rivaroxaban, stelt Tichelaar ten slotte vast. Gebruik van dit medicijn blijkt de meting van onder andere factor VIII te beïnvloeden. Inflammation and coagulation share many pathways. In this thesis we showed that infections increase the risk of venous thrombosis about 2.5-fold. These include (upper) airway, gastro-intestinal and malaise symptoms. Chronic inflammatory and infectious diseases increase also the risk of venous thrombosis as high as 8-fold when having a flare-up of chronic inflammatory bowel disease. We showed that patients with HIV-infection have an increased risk of venous and arterial thrombosis and that a super infection with cytomegalovirus disturbs the coagulation hemostasis even more, tipping the balanc towards a pro-coagulant state. Also, a high glucose level was associated with an increased risk of venous thrombosis, but conclusions about causality cannot be drawn from our studies. This is also true of high factor VIII levels. About 66% of high factor VIII levels at presentation remained high during and after treatment. An association with the acute phase was found, which was not found in previous studies. The highest levels of factor VIII were the least affected by the acute phase reaction. It might be that these patients with an increased risk of a recidive venous thrombosis can be identified early (at presentation). Finally, we found that factor VIII:C levels, determined by one stage clotting assays and chromogenic assays, were falsely lowered by Rivaroxaban, a new anti-Xa oral anticoagulant. Physicians should be aware of this interference.

Acute infection as a trigger for incident venous thromboembolism: Results from a population- based case- crossover study

Background: A bidirectional relation exists between acute infection and immobilization, and both are triggers for venous thromboembolism (VTE). To what extent the association between infection and VTE‐risk is explained by immobilization is unknown. Aims: To investigate the impact of hospitalization with acute infection on the VTE‐risk in patients with and without concomitant immobilization, and to explore the differential impact of respiratory‐ (RTI) and urinary‐ (UTI) tract infections on the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods: We conducted a case‐crossover study of VTE‐patients (n = 707) recruited from a general population. Hospitalizations and VTE‐triggers were registered during the 90 days before a VTE (hazard period) and in four preceding 90‐day control periods. Conditional logistic regression was used to estimate odds ratios (ORs) for VTE according to triggers. Results: Acute infection was registered in 267 (37.8%) of the hazard periods and in 107 (3.8%) of the control periods, corresponding to a high VTE‐risk after infection (OR 24.2, 95% CI 17.2‐34.0), that was attenuated to 15‐fold increased after adjustment for immobilization. The risk was 20‐fold increased after infection without concomitant immobilization, 73‐fold increased after immobilization without infection, and 141‐fold increased with the two combined. The risk of PE was apparently higher after RTIs (OR 48.3, 95% CI 19.4‐120.0) than UTIs (OR 12.6, 95% CI 6.4‐24.7), but diminished in sensitivity analyses excluding uncertain RTI diagnoses. Conclusions: Our findings suggest that hospitalization with infection is a strong VTE‐trigger also in non‐immobilized patients. Infection and immobilization had a synergistic effect on the VTE‐risk

Risk of Recurrent Venous Thromboembolism in Autoimmune Diseases: A Systematic Review of the Literature

Despite an abundance of literature on the risk of a first venous thromboembolic event (VTE) in autoimmune diseases, specific recommendations about managing VTE in autoimmune diseases are lacking. This article aimed to collect evidence on the risk of recurrent VTE in patients with autoimmune diseases. The authors searched PubMed/Embase for studies including patients with VTE and autoimmune diseases as an exposure or studies including patients with autoimmune diseases in which recurrent VTE was one of the outcomes. Eleven articles were selected from 4,739 unique abstracts. Of the 11 studies, 3 reported time-dependent rates. Two studies collected rates of recurrence in Behcet's disease, reporting a 5-year recurrence risk between 35 and 40%. However, the 5-year recurrence risk was lower than 10% in patients treated with immunosuppressant medication, while two studies suggested frequent recurrence in patients on only anticoagulant therapy. The other study reporting time-dependent incidence concerned patients with inflammatory bowel disease and index VTE. The 5-year risk of recurrent VTE was 33.4%, yielding a hazard ratio of 1.7 versus controls. All studies were retrospective and therefore risk may overestimate recurrence risk in comparison with known prospective cohort studies. There are insufficient data to make confident recommendations about the management of recurrent VTE prevention in patients with autoimmune diseases in general. The overall VTE risk profile, lower effectiveness of anticoagulants, and the observation that immunosuppression lowered risk of recurrence in patients with Behcet's disease seem to warrant immunosuppressant therapy over anticoagulation as a first consideration when preventing VTE recurrence in these patients