Acquired Prothrombotic Conditions

Classic Acquired Prothrombotic Conditions

Although there is a growing number of known established thrombophilias with an underlying genetic basis, the majority of venous thromboembolism events are provoked in the context of an acquired hypercoagulability state, leading to venous thrombosis. These acquired cases can be associated with clinical events, such as surgery, malignancy, pregnancy, drugs, kidney disease, infection, and inflammatory states. The most classic acquired conditions include hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura, antiphospholipid syndrome (APS), disseminated intravascular coagulopathy (DIC), and heparin-induced thrombocytopenia and are discussed in further detail in other chapters (see Table 155.1 ). A full assessment may be indicated in patients with recurrent thrombotic events and may begin with platelet count, fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time, reptilase time, activated protein C, immunological and functional ATIII, protein C, and protein S.

Cancer, especially in metastasis is a prothrombotic state. Particularly certain hematologic malignancies are strongly prothrombotic such as paroxysmal nocturnal hemoglobinuria (PNH), polycythemia vera, and essential thrombocythemia and may present with thrombosis as a first clinical sign. Evaluation for these disorders is usually triggered by abnormal complete blood count results. PNH is an extremely rare acquired hematopoietic stem cell disorder. It arises because of mutations in phosphatidylinositol glycan A, resulting in deficiency of proteins anchored to the cell membrane via glycophosphatidylinositol (GPI). This defect in turn leads to complement-induced hemolysis and a prothrombotic state. Flow cytometry assessing for the presence of GPI-linked proteins on neutrophils, monocytes, and red blood cells is the test modality of choice for PNH investigation.

Role of Inflammation in Acquired Prothrombotic Conditions

Although it has been well accepted that inflammation is associated with a prothrombotic state, its exact pathogenesis continues to be complicated. By inducing endothelial damage, inflammation could increase procoagulant factors, yet at the same time inhibit anticoagulation pathways and fibrinolysis. Systemic inflammatory disease that could induce prothrombotic states includes rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Many questions remain in defining the complex relationship between proinflammatory states and hemostasis. As such, there are no clear guidelines of how to assess thrombosis in the setting of chronic and active/transient inflammation. For example, C-reactive protein (CRP) is an acute-phase reactant, which acts as a marker for underlying systemic inflammation. As with D-dimer, CRP may be a negative predictor of thrombosis, but its clinical utility has neither been clearly evaluated nor have any guidelines been set in its interpretation in the context of other laboratory testing.