Hereditary proximal spinal muscular atrophy (SMA) is caused by survival motor neuron (SMN) protein deficiency due to homozygous loss of SMN1 gene function. Residual SMN protein levels are produced by the SMN2 gene and SMN protein is expressed ubiquitously. Its deficiency causes alpha motor neuron loss.
Observations in animal models suggest other tissues, for example heart, peripheral vascular system, liver and pancreas, may also require SMN protein above specific threshold levels. This is further supported by case reports of severely affected patients but it remains to be established whether multisystem pathology is actually part of the patient phenotype. This is even more relevant now that SMN-augmenting therapies have become available.
The authors here report a systematic characterisation of coagulation in patients with SMA, which they studied for several reasons. First, they observed abnormal coagulation screening results frequently during the course of clinical trials and nusinersen treatment. Second, local thrombotic small vessel occlusions and peripheral vascular dysfunction have been suggested to play a role in causing some of the observed non-neuromuscular pathology. Third, relatively high levels of SMN protein are found in platelets.2
Here, the researchers find activated partial thromboplastin time (APTT) to be significantly and consistently prolonged in patients with SMA. Prothrombin time, platelet count, von Willebrand Factor (vWF) antigen and activity also differ significantly from reference values. These findings represent a common functional defect outside the nervous system in patients with SMA.
