Reevaluating Thrombocytosis as a Risk Factor in Free Flap Surgery: Does Timing Matter?

INTRODUCTION: Thrombocytosis, defined as a platelet count >400,000, has been implicated as a risk factor in free flap failure. Despite proposed mechanisms of pedicle thrombosis, recent studies have suggested that thrombocytosis has no effect on free tissue transfer viability. Risk factors that may compromise successful free tissue transfer should be understood and elucidated, with particular attention to thrombocytosis and its conflicting evidence in the literature. We hypothesize that thrombocytosis has no bearing on free flap success or the rates of pedicle thrombosis. METHODS: Our institution performed a retrospective chart review on all patients who underwent free flap reconstruction over the past 6 years. Patient demographics, medical history, type and location of free tissue transfer, preoperative platelets, postoperative platelets, and flap outcomes and complications (wound dehiscence, infection, hematoma, seroma, and need for blood transfusion) were recorded. Independent t test, Mann-Whitney U tests, χ2 test, and Fisher exact tests were used to determine P values to compare flap outcomes in patients with thrombocytosis (platelet count >400,000) and those with platelet counts less than 400,000. RESULTS: In our 502-patient cohort, 71 were found to have a platelet count >400,000 (35 preoperatively and 36 postoperatively) and 431 patients had platelet counts <400,000. There were 42 reconstructive failures (flap success rate of 91.6%) and 111 returns to the operating room (OR). For patients with postoperative thrombocytosis, 24 flaps returned to the OR (44.4%), whereas in patients without thrombocytosis, 87 flaps returned to the OR (19.4%; P < 0.001). In patients with postoperative thrombocytosis, 10 OR returns were due to pedicle venous thrombosis (18.5%), in comparison to 10 returns for venous thrombosis in those with normal platelets (2.2%; P < 0.001). There was a small difference in free flap success rates between those with postoperative thrombocytosis and normal platelets, 88.7% versus 92.11%; however, this was not statistically significant ( P = 0.71). The thrombocytosis group had a higher incidence of overall postoperative complications ( P = 0.002). CONCLUSIONS: Thrombocytosis has historically been cited as a risk factor for free flap reconstruction failure with recent conflicting evidence in the literature. In patients with postoperative thrombocytosis, we found an increased risk of venous thrombosis; however, this did not result in increased flap failure. There was an increase in postoperative complications, which corresponds with National Surgical Quality Improvement Program data reported in the literature. We suspect that thrombocytosis is not a harbinger of free flap failure but rather a marker for overall inflammation, which may confer a higher rate of venous thrombosis requiring reoperation and postoperative complications.

ß-carotene improves fecal dysbiosis and intestinal dysfunctions in a mouse model of vitamin A deficiency.

Vitamin A deficiency (VAD) results in intestinal inflammation, increased redox stress and reactive oxygen species (ROS) levels, imbalanced inflammatory and immunomodulatory cytokines, compromised barrier function, and perturbations of the gut microbiome. To combat VAD dietary interventions with ß-carotene, the most abundant precursor of vitamin A, are recommended. However, the impact of ß-carotene on intestinal health during VAD has not been fully clarified, especially regarding the VAD-associated intestinal dysbiosis. Here we addressed this question by using Lrat-/-Rbp-/- (vitamin A deficient) mice deprived of dietary preformed vitamin A and supplemented with ß-carotene as the sole source of the vitamin, alongside with WT (vitamin A sufficient) mice. We found that dietary ß-carotene impacted intestinal vitamin A status, barrier integrity and inflammation in both WT and Lrat-/-Rbp-/- (vitamin A deficient) mice on the vitamin A-free diet. However, it did so to a greater extent under overt VAD. Dietary ß-carotene also modified the taxonomic profile of the fecal microbiome, but only under VAD. Given the similarity of the VAD-associated intestinal phenotypes with those of several other disorders of the gut, collectively known as Inflammatory Bowel Disease (IBD) Syndrome, these findings are broadly relevant to the effort of developing diet-based intervention strategies to ameliorate intestinal pathological conditions.

Impact of vitamin A transport and storage on intestinal retinoid homeostasis and functions.

Lecithin:retinol acyltransferase and retinol-binding protein enable vitamin A (VA) storage and transport, respectively, maintaining tissue homeostasis of retinoids (VA derivatives). The precarious VA status of the lecithin:retinol acyltransferase-deficient (Lrat-/-) retinol-binding protein-deficient (Rbp-/-) mice rapidly deteriorates upon dietary VA restriction, leading to signs of severe vitamin A deficiency (VAD). As retinoids impact gut morphology and functions, VAD is often linked to intestinal pathological conditions and microbial dysbiosis. Thus, we investigated the contribution of VA storage and transport to intestinal retinoid homeostasis and functionalities. We showed the occurrence of intestinal VAD in Lrat-/-Rbp-/- mice, demonstrating the critical role of both pathways in preserving gut retinoid homeostasis. Moreover, in the mutant colon, VAD resulted in a compromised intestinal barrier as manifested by reduced mucins and antimicrobial defense, leaky gut, increased inflammation and oxidative stress, and altered mucosal immunocytokine profiles. These perturbations were accompanied by fecal dysbiosis, revealing that the VA status (sufficient vs. deficient), rather than the amount of dietary VA per se, is likely a major initial discriminant of the intestinal microbiome. Our data also pointed to a specific fecal taxonomic profile and distinct microbial functionalities associated with VAD. Overall, our findings revealed the suitability of the Lrat-/-Rbp-/- mice as a model to study intestinal dysfunctions and dysbiosis promoted by changes in tissue retinoid homeostasis induced by the host VA status and/or intake.