A previously heathy 4-year-old boy presented with hemorrhagic symptoms (ISTH-BAT:4) including gum bleeding, petechiae, subperiosteal hemorrhages, positive tourniquet test indicating capillary fragility, and pseudoparalysis (refusal to walk due to pain). Based on the diagnosis of malnutrition-induced scurvy (patient's diet was completely free from fruits or vegetables) with vitamin C levels <0.5 mg/L (normal range: 5–15 mg/L), oral substitution of ascorbic acid was started with prompt improvement of bleeding manifestations.

At the peak of symptoms, coagulation studies showed normal international normalized ratio (INR), slightly decreased activated partial thromboplastin time (aPTT), elevated D-dimers, and mild thrombocytosis (platelet count: 720 × 109/L) with a mean platelet volume (MPV) of 9 fL (normal range: 9–13 fL). The patient also displayed a mild microcytic anemia (Hb: 8.5 g/dL; mean corpuscular volume [MCV]: 68.9 fL) due to concomitant iron deficiency. White blood cell count was normal. Upon treatment, platelet count (334 × 109/L, MPV: 11 fL), hemoglobin concentration (13.5 g/dL), and MCV (75 fL) normalized.

By light microscopy, platelet morphology was normal ([Fig. 1A]), whereas by immunofluorescence microscopy,[1] a defect of the platelet cytoskeleton was apparent with peculiar disarrangement of α-tubulin in 60% of the platelets ([Fig. 1B, C]), while other cytoskeletal proteins (filamin A, nonmuscular myosin IIA, β1-tubulin, [Fig. 1D–F]) appeared normal.

Interaction between ascorbic acid and cytoskeletal physiology have been reported. In 1987, Nath and colleagues showed that vitamin C influenced tubulin tyrosination and promoted microtubule assembly in granulocytes.[2] In 2016, Parker et al demonstrated ascorbic acid improved endothelial tightness by enhancing the microtubule network via specific stabilization of α-tubulin.[3] More recently, the role of vitamin C in cytoskeletal organization was corroborated by experiments on porcine oocytes.[4]

Here, we show that also a cytoskeletal platelet defect is associated with vitamin C deficiency. α-Tubulin is not expressed in the typical ring form but appears tangled or twisted within the platelets. These changes are compatible with the predicted major role of α-tubulin in cytoskeleton stabilization exerted by vitamin C.[3] Re-assessment after >12 months of supplementation (vitamin C level: 9.8 mg/L) showed a remarkable normalization of the α-tubulin structure ([Fig. 1G, H]).

α-Tubulin is a component of microtubule cytoskeleton, which plays a major role at different stages of platelet function. Cytoskeletal defects also impair clot retraction, thus making blood clots more prone to fibrinolysis.[5] The resulting bleeding tendency is usually mild, but can worsen the symptoms in the presence of a concomitant hemostatic defect. Our findings suggest that the alteration of the platelet cytoskeleton likely contributes to the bleeding alongside the scurvy-related impairment of collagen synthesis.