Red blood cells (RBCs) influence rheology, and release ADP, ATP, and nitric oxide, suggesting a role for RBCs in hemostasis and thrombosis. Here, we provide evidence for a significant contribution of RBCs to thrombus formation. Anemic mice showed enhanced occlusion times upon injury of the carotid artery. A small population of RBCs was located to platelet thrombi and enhanced platelet activation by a direct cell contact via the FasL/FasR (CD95) pathway known to induce apoptosis. Activation of platelets in the presence of RBCs led to platelet FasL exposure that activated FasR on RBCs responsible for externalization of phosphatidylserine (PS) on the RBC membrane. Inhibition or genetic deletion of either FasL or FasR resulted in reduced PS exposure of RBCs and platelets, decreased thrombin generation, and reduced thrombus formation in vitro and protection against arterial thrombosis in vivo. Direct cell contacts between platelets and RBCs via FasL/FasR were shown after ligation of the inferior vena cava (IVC) and in surgical specimens of patients after thrombectomy. In a flow restriction model of the IVC, reduced thrombus formation was observed in FasL^–/– mice. Taken together, our data reveal a significant contribution of RBCs to thrombosis by the FasL/FasR pathway.

Acute ischemia of an extremity occurs in several stages, a lack of oxygen being the primary contributor of the event. Although underlying patho-mechanisms are similar, it is important to determine whether it is an acute or chronic event. Healthy tissue does not contain enlarged collaterals, which are formed in chronically malperfused tissue and can maintain a minimum supply despite occlusion. The underlying processes for enhanced collateral blood flow are sprouting vessels from pre-existing vessels (via angiogenesis) and a lumen extension of arterioles (via arteriogenesis). While disturbed flow patterns with associated local low shear stress upregulate angiogenesis promoting genes, elevated shear stress may trigger arteriogenesis due to increased blood volume. In case of an acute ischemia, especially during the reperfusion phase, fluid transfer occurs into the tissue while the vascular bed is simultaneously reduced and no longer reacts to vaso-relaxing factors such as nitric oxide. This process results in an exacerbative cycle, in which increased peripheral resistance leads to an additional lack of oxygen. This whole process is accompanied by an inundation of inflammatory cells, which amplify the inflammatory response by cytokine release. However, an extremity is an individual-specific composition of different tissues, so these processes may vary dramatically between patients. The image is more uniform when broken down to the single cell stage. Because each cell is dependent on energy produced from aerobic respiration, an event of acute hypoxia can be a life-threatening situation. Aerobic processes responsible for yielding adenosine triphosphate (ATP), such as the electron transport chain and oxidative phosphorylation in the mitochondria, suffer first, thus disrupting the integrity of cellular respiration. One consequence of this is irreparable damage of the cell membrane due to an imbalance of electrolytes. The eventual increase in net fluid influx associated with a decrease in intracellular pH is considered an end-stage event. Due to the lack of ATP, individual cell organelles can no longer sustain their activity, thus initiating the cascade pathways of apoptosis via the release of cytokines such as the BCL2 associated X protein (BAX). As ischemia may lead to direct necrosis, inflammatory processes are further aggravated. In the case of reperfusion, the flow of nascent oxygen will cause additional damage to the cell, further initiating apoptosis in additional surrounding cells. In particular, free oxygen radicals are formed, causing severe damage to cell membranes and desoxyribonucleic acid (DNA). However, the increased tissue stress caused by this process may be transient, as radical scavengers may attenuate the damage. Taking the above into final consideration, it is clearly elucidated that acute ischemia and subsequent reperfusion is a process that leads to acute tissue damage combined with end-organ loss of function, a condition that is difficult to counteract.

Median arcuate ligament syndrome is a rare condition with abdominal symptoms. Accepted treatment options are open release of median arcuate ligament, laparoscopic release of edian arcuate ligament, robot-assisted release of median arcuate ligament and open vascular treatment. Here we aimed to evaluate the central priority of open vascular therapy in the treatment of median arcuate ligament syndrome. We conducted a monocentric retrospective study between January 1996 and June 2016. Thirty-one patients with median arcuate ligament syndrome underwent open vascular surgery, including division of median arcuate ligament in 17 cases, and vascular reconstruction of the celiac artery in 14 cases. In a 20-year period, 31 patients (n = 26 women, n = 5 men) were treated with division of median arcuate ligament (n = 17) or vascular reconstruction in combination with division of median arcuate ligament (n = 14). The mean age of patients was 44.8 ± 15.13 years. The complication rate was 16.1% (n = 5). Revisions were performed in 4 cases. The 30-day mortality rate was 0%. The mean in-hospital stay was 10.7 days. Follow-up data were obtained for 30 patients. The mean follow-up period was 52.2 months (range 2–149 months). Patients were grouped into a decompression group (n = 17) and revascularisation group (n = 13). The estimated Freedom From Symptoms rates were 93.3, 77.8, and 69.1% for the decompression group and 100, 83.3, and 83.3% for the revascularisation group after 12, 24 and 60 months respectively. We found no significant difference in the Freedom From Re-Intervention CA rates of the decompression (100% at 12, 24 and 60 months post-surgery) and revascularisation (100% at 12 months, and 91.7% at 24 and 60 months post-surgery) groups during follow-up (p = 0.26). Open vascular treatment of median arcuate ligament syndrome is a safe, low mortality-risk procedure, with low morbidity rate. Treatment choice depends on the clinical and morphological situation of each patient.

Congenital absence of the inferior vena cava (AIVC) is a rare malformation which may be associated with an increased risk for deep vein thrombosis (DVT). However, the role of thrombophilia in AIVC and DVT is unknown. Between 1982 and 2013 41 patients (12 female, 29 male, mean age 28 S.D. 11 years) were detected at the University of Düsseldorf, Germany, with AIVC. Based on medical history, clinical examination, imaging and coagulation studies, we performed on this collective a risk characterisation. Extensive literature research added further 123 published cases during 1993 and 2013. AIVC-patients were compared with iliocaval DVT-patients without AIVC (n = 168) treated during the same period in our clinic (90 female, 78 male, mean age 38 S.D. 17 years). In contrast to classical DVT younger men were more often affected. Factor-V-Leiden-mutation, 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and hyperhomocysteinemia individually are associated with an increased risk of DVT in patients with AIVC. Aplasia/hypoplasia of the right or left kidney is also associated with IVCA. AIVC should be considered in young patients who present with DVT involving the vena cava. Analysis of publications with AIVC and our patients yielded a typical spectrum of AIVC-associated DVT characteristics: AIVC occurs in young male adults, is revealed by proximal DVT, not necessarily accused by precipitating factors like immobilisation, and is mostly located bilateral. Hereditary coagulation abnormalities seem to be more often a contributing factor for DVT in AIVC.