Respiratory failure is presumptively caused by microvascular thrombosis in some patients with coronavirus disease 2019 (COV-ID-19) requiring therapeutic anticoagulation. Anticoagulation treatment may cause life-threatening bleeding complications such as retroperitoneal hemorrhage. To the best of our knowledge, we report first case of a COVID-19 patient treated with therapeutic anticoagulation resulting in psoas hematoma due to lumbar artery bleeding. A 69-year-old patient presented with fever, malaise and progressive shortness of breath to our hospital. He was diagnosed with COVID-19 by RT-PCR. Due to an abnormal coagulation profile, the patient was started on enoxaparin. Over the course of hospitalization, the patient was found to have hypotension with worsening hemoglobin levels. Computed tomography scan of the abdomen and pelvis revealed a large psoas hematoma. Arteriogram revealed lumbar artery bleeding which was treated with embolization. Anticoagulation therapy, while indicated in COVID-19 patients, has its own challenges and guidelines describing dosages and indications in this disease are lacking. Rare bleeding complications such as psoas hematoma should be kept in mind in patients who become hemodynamically unstable, warranting prompt imaging for diagnosis and treatment with arterial embolization, thus eliminating need of surgical intervention.

Summary Background Laminin is the most abundant non-collagenous protein in the basement membrane. Recent studies have shown that laminin supports platelet adhesion, activation and aggregation under flow conditions, highlighting a possible role for laminin in hemostasis. Objective To investigate the ability of laminin to promote coagulation and support thrombus formation under shear. Results and methods Soluble laminin accelerated factor (F) XII activation in a purified system, and shortened the clotting time of recalcified plasma in a FXI- and FXII-dependent manner. Laminin promoted phosphatidylserine exposure on platelets and supported platelet adhesion and fibrin formation in recalcified blood under shear flow conditions. Fibrin formation in laminin-coated capillaries was abrogated by an antibody that interferes with FXI activation by activated FXII, or an antibody that blocks activated FXI activation of FIX. Conclusion This study identifies a role for laminin in the initiation of coagulation and the formation of platelet-rich thrombi under shear conditions in a FXII-dependent manner.

Several studies have implicated the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in inhibition of normal platelet function, suggesting a role for platelets in EPA- and DHA-mediated cardioprotection. However, it is unclear whether the cardioprotective mechanisms arise from alterations to platelet-platelet, platelet-matrix, or platelet-coagulation factor interactions. Our previous results led us to hypothesize that EPA and DHA alter the ability of platelets to catalyze the generation of thrombin. We tested this hypothesis by exogenously modifying platelet membranes with EPA and DHA, which resulted in compositional changes analogous to increased dietary EPA and DHA intake. Platelets treated with EPA and DHA showed reductions in the rate of thrombin generation and exposure of platelet phosphatidylserine. In addition, treatment of platelets with EPA and DHA decreased thrombus formation and altered the processing of thrombin precursor proteins. Furthermore, treatment of whole blood with EPA and DHA resulted in increased occlusion time and a sharply reduced accumulation of fibrin under flow conditions. These results demonstrate that EPA and DHA inhibit, but do not eliminate, the ability of platelets to catalyze thrombin generation in vitro. The ability of EPA and DHA to reduce the procoagulant function of platelets provides a possible mechanism behind the cardioprotective phenotype in individuals consuming high levels of EPA and DHA.

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The routine observation of tumor emboli in the peripheral blood of patients with carcinomas raises questions about the clinical relevance of these circulating tumor cells. Thrombosis is a common clinical manifestation of cancer and circulating tumor cells may play a pathogenetic role in this process. The presence of coagulation-associated molecules on cancer cells has been described, but the mechanisms by which circulating tumor cells augment or alter coagulation remains unclear. In this study we utilized suspensions of a metastatic adenocarcinoma cell line, MDA-MB-231, and a non-metastatic breast epithelial cell line, MCF-10A, as models of circulating tumor cells to determine the thromobogenic activity of these blood-foreign cells. In human plasma, both metastatic MDA-MB-231 cells and non-metastatic MCF-10A cells significantly enhanced clotting kinetics. The effect of MDA-MB-231 and MCF-10A cells on clotting times was cell number-dependent and inhibited by a neutralizing antibody to tissue factor (TF) as well as inhibitors of activated factor X and thrombin. Using fluorescence microscopy, we found that both MDA-MB-231 and MCF-10A cells supported the binding of fluorescently-labeled thrombin. Furthermore, in a model of thrombus formation under pressure-driven flow, MDA-MB-231 and MCF-10A cells significantly decreased the time to occlusion. Our findings indicate that the presence of breast epithelial cells in blood can stimulate coagulation in a TF-dependent manner, suggesting that tumor cells that enter the circulation may promote the formation of occlusive thrombi under shear flow conditions.

BackgroundRecombinant T cell receptor ligands (RTLs) are bio-engineered molecules that may serve as novel therapeutic agents for the treatment of neuroinflammatory conditions such as multiple sclerosis (MS). RTLs contain membrane distal α1 plus β1 domains of class II major histocompatibility complex linked covalently to specific peptides that can be used to regulate T cell responses and inhibit experimental autoimmune encephalomyelitis (EAE). The mechanisms by which RTLs impede local recruitment and retention of inflammatory cells in the CNS, however, are not completely understood.MethodsWe have recently shown that RTLs bind strongly to B cells, macrophages, and dendritic cells, but not to T cells, in an antigenic-independent manner, raising the question whether peripheral blood cells express a distinct RTL-receptor. Our study was designed to characterize the molecular mechanisms by which RTLs bind human blood platelets, and the ability of RTL to modulate platelet function.ResultsOur data demonstrate that human blood platelets support binding of RTL. Immobilized RTL initiated platelet intracellular calcium mobilization and lamellipodia formation through a pathway dependent upon Src and PI3 kinases signaling. The presence of RTL in solution reduced platelet aggregation by collagen, while treatment of whole blood with RTL prolonged occlusive thrombus formation on collagen.ConclusionsPlatelets, well-known regulators of hemostasis and thrombosis, have been implicated in playing a major role in inflammation and immunity. This study provides the first evidence that blood platelets express a functional RTL-receptor with a putative role in modulating pathways of neuroinflammation.

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The underlying pathogenesis of cardiovascular disease is the formation of occlusive thrombi. While many well-defined animal models recapitulate the process of intravascular thrombosis, there is a need for validated ex vivo models of occlusive thrombus formation. Using the force of gravity to provide a constant pressure gradient, we designed and validated an ex vivo model of thrombosis. Times to occlusion on a collagen matrix in our model were within the range of occlusion times observed in murine thrombosis models. Prolongation of time to occlusion in the presence of platelet a IIb b 3 antagonists or inhibitors to thrombin or activated factor X is in agreement with established mechanisms of thrombus formation. The use of this model may be expanded to characterize the mechanisms of thrombosis and to determine the efficacy of pharmacological agents designed to prevent occlusive thrombus formation.