No abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement‐mediated intravascular hemolysis and thrombosis. The increased incidence of PNH‐driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement‐mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients. Based on previously described links between changes in fibrin clot structure and thrombosis in other disorders, our aim was to investigate clot structure as a possible mechanism of thrombosis in patients with PNH and the anti‐thrombotic effects of eculizumab treatment on clot structure. Clot structure, fibrinogen levels and thrombin generation were examined in plasma samples from 82 patients from the National PNH Service in Leeds, UK. Untreated PNH patients were found to have increased levels of fibrinogen and thrombin generation, with subsequent prothrombotic changes in clot structure. No link was found between increasing disease severity and fibrinogen levels, thrombin generation, clot formation or structure. However, eculizumab treated patients showed decreased fibrinogen levels, thrombin generation and clot density, with increasing time spent on treatment augmenting these antithrombotic effects. These data suggest that PNH patients have a prothrombotic clot phenotype due to increased fibrinogen levels and thrombin generation, and that the antithrombotic effects of eculizumab are, in‐part, due to reductions in fibrinogen and thrombin generation with downstream effects on clot structure.

We present the case of a 56-year-old female brought to the Emergency Department via routine ambulance transport with complaints of blurred vision and malaise. She was screened by ambulance crew using the facial arm speech time (FAST) tool and a basic top-to-toe assessment as per current routine. The examining practitioner performed a thorough assessment of the patient, revisiting the initial examination findings, and establishing new clinical features of visual field deficit and pan-systolic murmur. The likely diagnosis of septic emboli or stroke with infective endocarditis was identified through the power of rigorous history taking and examination. These were then supported by investigation with blood tests and imaging. This prompted discussion with a tertiary centre and subsequent transfer for further investigation and management. The patient’s journey shows that there may indeed be a role for a more comprehensive (but not exhaustive) initial screening from ambulance services in order to help appropriately stream specific patients to hospital in a timelier manner (to meet the thrombolysis window). This case supports the addition of V (visual fields) to the FAST screening tool.