Genetic and Molecular Testing in Thrombosis and Hemostasis: Informing Surveillance, Treatment, and Prognosis.

The understanding of molecular mechanisms brought about by the rapid expansion of gene sequencing has helped to characterize molecular interactions underpinning normal hemostasis and identify inherited and acquired risks for thrombosis and hemorrhage. The widespread availability of molecular testing may serve to replace some currently available investigations with more precise diagnostic tools and add to phenotypic tests. Molecular studies will increasingly enable prenatal diagnosis, confirm difficult diagnostic challenges, early intervention, and assist in prognostication. This approach facilitates specific individualization of treatment options, with personally targeted therapy expected to increase. There remain many challenges, however, in the clinic. Prior to any test there should be consideration of how the results may influence treatment, and also how they may affect the patient within their familial and social environments. Massive parallel sequencing has the capacity to produce results that create uncertainty that needs to be considered prior to testing. In this context, the potential benefits of adding phenotypic and genotypic personal data to large databases should be discussed with patients. There is a paradox in that personalized medicine is dependent on large datasets to interpret the significance of genetic variation. This review will provide an outline of specific current and emerging roles for molecular testing for the personalization of care in the practice of thrombosis and hemostasis and highlight principles that can be implemented as new opportunities inevitably arise with the rapid expansion of knowledge from genomics.

A Wolf in Sheep's clothing: A case report series of oral manifestations of multiple myeloma.

Multiple myeloma is the most common haematological malignancy accounting for 10 % of all haematological cancers. Treatment of myeloma has evolved in recent years leading to improved survival. Lesions related to myeloma are frequently observed within the oral cavity and jawbone. In addition, many of the therapeutic agents have side effects with implications for provision of dental treatment. This case series aims to highlight some of these presentations to remind dental practitioners to be vigilant. Observation of suspicious lesions within the oral cavity or jawbone might warrant further investigation.

Successful treatment of central nervous system myeloma manifesting as cauda equina nodules with intrathecal chemotherapy, lenalidomide and dexamethasone.

We report a case of central nervous system myeloma manifesting as cauda equina nodules, successfully treated with triple intrathecal (IT) chemotherapy, lenalidomide and dexamethasone. After presenting with multiple plasmacytomas which led to a diagnosis of non-secretory myeloma at age 56, the patient underwent multiple episodes of treatment for relapsing myeloma over a 7-year period. In March 2017, he presented with declining gait over a month with bilateral hip flexion weakness, absent lower limb reflexes and dorsal column loss. MRI of the spine revealed multiple enhancing cauda equina nodules at L1-L3. Cerebrospinal fluid (CSF) examination confirmed a clonal plasma cell population and disease was not found elsewhere. He was treated with radiotherapy, IT and intravenous methotrexate and cytarabine. However, repeat lumbar puncture revealed persistent disease. Clearance of CSF plasma cells was achieved with two times a week IT cytarabine, methotrexate and dexamethasone. He was started on lenalidomide and dexamethasone with no evidence of disease progression at 12 months.

Granulicatella adiacens subacute bacterial endocarditis as the underlying cause of type II mixed cryoglobulinaemia.

A 57-year-old man with type II mixed cryoglobulinaemia presented to the emergency department with a history of worsening lethargy, malaise and non-drenching night sweats in a relapsing-remitting pattern. He was diagnosed with type II mixed cryoglobulinaemia 7 months ago following episodes of fever, night sweats, lethargy and malaise associated with a non-blanching, purpuric, raised erythematous rash that responded partially to immunosuppressive therapy and short courses of oral antibiotics. A single blood culture then yielded Granulicatella adiacens which was reported as a possible contaminant and therefore, not pursued. Despite numerous other investigations, the underlying cause of his type II cryoglobulinaemia remained undetermined. On his current presentation, the physical examination revealed signs of infective endocarditis. Two further blood cultures grew G. adiacens. The diagnosis of infective endocarditis was established on a transoesophageal echocardiography, and the subsequent antibiotic and surgical therapy resulted in complete remission of his type II mixed cryoglobulinaemia.