The platelet aIIbβIII integrin has no role in thrombosis in myeloproliferative neoplasm

We present a patient with congenital Glanzmann Thrombasthenia, who developed recurrent venous thrombosis. Over time, she developed the clinical picture of a myeloproliferative neoplasm, being JAK2 positive. This case clearly indicates that the platelet aIIbβIII integrin (lacking in Glanzmann thrombasthenia) does not have a role in thrombosis in MPN

Venous Thromboembolism

Venous thromboembolism, which involves venous thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality in hospitalized patients and is being seen with increasing frequency in outpatients. This chapter discusses the risk factors, etiology, classification, pathophysiology, natural history, prognosis, diagnosis (including venous thrombosis, recurrent venous thrombosis, and pulmonary embolism), prophylaxis, and treatment of venous thromboembolism (including the pharmacology of antithrombotic agents), as well as venous thromboembolism in pregnancy and miscellaneous thromboembolic disorders (including thrombosis of unusual sites). This review contains 8 figures, 16 tables, and 79 references. Keywords: Venous thromboembolism, pulmonary embolism, deep vein thrombosis, embolectomy, thrombolysis, hypercoagulability, duplex ultrasonography, D-dimer, anticoagulation

Venous Thromboembolism

Venous thromboembolism, which involves venous thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality in hospitalized patients and is being seen with increasing frequency in outpatients. This chapter discusses the risk factors, etiology, classification, pathophysiology, natural history, prognosis, diagnosis (including venous thrombosis, recurrent venous thrombosis, and pulmonary embolism), prophylaxis, and treatment of venous thromboembolism (including the pharmacology of antithrombotic agents), as well as venous thromboembolism in pregnancy and miscellaneous thromboembolic disorders (including thrombosis of unusual sites). This review contains 8 figures, 16 tables, and 79 references. Keywords: Venous thromboembolism, pulmonary embolism, deep vein thrombosis, embolectomy, thrombolysis, hypercoagulability, duplex ultrasonography, D-dimer, anticoagulation

Venous Thromboembolism

Venous thromboembolism, which involves venous thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality in hospitalized patients and is being seen with increasing frequency in outpatients. This chapter discusses the risk factors, etiology, classification, pathophysiology, natural history, prognosis, diagnosis (including venous thrombosis, recurrent venous thrombosis, and pulmonary embolism), prophylaxis, and treatment of venous thromboembolism (including the pharmacology of antithrombotic agents), as well as venous thromboembolism in pregnancy and miscellaneous thromboembolic disorders (including thrombosis of unusual sites). This review contains 8 figures, 16 tables, and 79 references. Keywords: Venous thromboembolism, pulmonary embolism, deep vein thrombosis, embolectomy, thrombolysis, hypercoagulability, duplex ultrasonography, D-dimer, anticoagulation

Venous Thromboembolism

Venous thromboembolism, which involves venous thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality in hospitalized patients and is being seen with increasing frequency in outpatients. This chapter discusses the risk factors, etiology, classification, pathophysiology, natural history, prognosis, diagnosis (including venous thrombosis, recurrent venous thrombosis, and pulmonary embolism), prophylaxis, and treatment of venous thromboembolism (including the pharmacology of antithrombotic agents), as well as venous thromboembolism in pregnancy and miscellaneous thromboembolic disorders (including thrombosis of unusual sites). This review contains 8 figures, 16 tables, and 79 references. Keywords: Venous thromboembolism, pulmonary embolism, deep vein thrombosis, embolectomy, thrombolysis, hypercoagulability, duplex ultrasonography, D-dimer, anticoagulation

Recurrent Superior Vena Cava Syndrome in a Patient with Sarcoidosis and Pancreatic Adenocarcinoma: A Case Report and Literature Review

Background: Superior vena cava (SVC) syndrome may result from extravascular compression or intravascular obstruction such as thrombosis. Recurrent venous thrombosis is typically associated with a hypercoagulable state such as malignancy, and inheritable or acquired coagulopathy. Sarcoidosis is a derangement of the immune system, and it has been associated with malignant diseases and hypercoagulation. The association of pancreatic cancer and sarcoidosis with SVC syndrome has not been reported previously. Here, we present a case of recurrent venous thrombosis causing SVC syndrome in a patient with pancreatic ductal adenocarcinoma and underlying thoracic sarcoidosis. Methods: The patient’s electronic health record was retrospectively analyzed. Results: A 66-year-old woman with pancreatic adenocarcinoma was treated with neoadjuvant chemotherapy followed by Whipple procedure, before developing tumor recurrence in the liver. Her treatment course was complicated with repeated incidents of venous thrombosis in the presence of a central venous catheter leading to recurrent SVC syndrome, which resolved with anti-coagulation. Conclusions: This case raises a plausible inter-relationship between sarcoidosis, pancreatic cancer, and hypercoagulable state. We suggest that patients with multiple risk factors for developing venous thrombosis should be carefully monitored for any thrombotic event, and they may benefit from prophylactic anti-coagulation.

Thr90Ser Mutation in Antithrombin is Associated with Recurrent Thrombosis in a Heterozygous Carrier

Antithrombin (AT) is a serine protease inhibitor that regulates the activity of coagulation proteases of both intrinsic and extrinsic pathways. We identified an AT-deficient patient with a heterozygous Thr90Ser (T90S) mutation who experiences recurrent venous thrombosis. To understand the molecular basis of the clotting defect, we expressed AT-T90S in mammalian cells, purified it to homogeneity, and characterized its properties in established kinetics, binding, and coagulation assays. The possible effect of mutation on the AT structure was also evaluated by molecular modeling. Results demonstrate the inhibitory activity of AT-T90S toward thrombin and factor Xa has been impaired three- to fivefold in both the absence and presence of heparin. The affinity of heparin for AT-T90S has been decreased by four- to fivefold. Kinetic analysis revealed the stoichiometry of AT-T90S inhibition of both thrombin and factor Xa has been elevated by three- to fourfold in both the absence and presence of heparin, suggesting that the reactivity of coagulation proteases with AT-T90S has been elevated in the substrate pathway. The anticoagulant activity of AT-T90S has been significantly impaired as analyzed in the AT-deficient plasma supplemented with AT-T90S. The anti-inflammatory effect of AT-T90S was also decreased. Structural analysis predicts the shorter side-chain of Ser in AT-T90S has a destabilizing effect on the structure of AT and/or the AT-protease complex, possibly increasing the size of an internal cavity and altering a hydrogen-bonding network that modulates conformations of the allosterically linked heparin-binding site and reactive center loop of the serpin. This mutational effect increases the reactivity of AT-T90S with coagulation proteases in the substrate pathway.