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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.1
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.2 3 This is even more relevant now that SMN-augmenting therapies have become available.
We here report a systematic characterisation of coagulation in patients with SMA, which we studied for several reasons. First, we 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, we 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.
We enrolled patients with SMA types 1–4 and analysed blood samples to …
Contributors CAW, AH, RW, REGS and W-LvdP were involved in the study concept and design. CAW, AH, RIW, IC, MS, KMJH-P, EJNG, REGS and W-LvdP were involved in acquisition, analysis and interpretation of data. CAW, AH, EJNG and W-LvdP were involved in drafting a significant portion of the manuscript and figures. All authors were involved in revising the manuscript for intellectual content and have approved its final version.
Funding Our work was financially supported by the Prinses Beatrix Spierfonds (WAR 14-26) and stichting Spieren voor Spieren.
Competing interests The competing interests statement reads 'nothing to report'. This option was chosen as none of the conflicts are relevant financial activities/relevant interests to the submitted work. Full details are provided in the ICMJE forms that were uploaded to the journal.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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