Decreased platelet number in multiple sclerosis during alemtuzumab infusion: a common, transient and clinically silent phenomenon

Abstract

BackgroundThe cause and clinical significance of the transient decrease in platelet (PLT) count observed in relapsing remitting multiple sclerosis (RRMS) during alemtuzumab administration remain undefined. The aim of this study was to analyse the kinetics and clinical relevance of early onset thrombocytopaenia in alemtuzumab-treated RRMS.MethodsA total of 26 patients with RRMS were included in a longitudinal study. Blood samples were collected immediately before the first alemtuzumab infusion (D0), and after 3 days (D3), 28 days (D28) and 49 days (D49). PLT, red blood cell (RC), leucocyte and lymphocyte counts, haemoglobin (Hb) concentration and haematocrit (Htc) were measured. Patients with MS were clinically evaluated every day of drug infusion and then at D28 and D49 to verify the presence of signs or symptoms suggestive of thrombocytopaenia.ResultsPLT number significantly decreased at D3 (p < 0.005) and was associated with a decrease in RC count (r: 0.53, p < 0.01), Hb (r: 0.42, p = 0.05) and Htc (r: 0.53, p < 0.01). A progressive reversion of PLT number to normal values was observed at D28 and D49. A mild thrombocytopaenia was observed in 12 patients (46.2%), 8 of which (66.6%) had PLT nadir values at D3, and 4 (33.3%) at D28. No sign or symptom suggestive of thrombocytopaenia was observed. A strong correlation between pretreatment and nadir PTL counts (r: 0.59, p < 0.005) was observed; indeed, mild thrombocytopaenia was observed more frequently in these patients with a baseline PTL count lower than 230 × 109/L (83.3% versus 42.9%, p < 0.05).ConclusionsThe early PLT decrease in alemtuzumab-treated patients is transient, mild, not associated with clinically relevant events and is probably related to the cytokine-released syndrome. Notwithstanding this, our findings suggest the opportunity for PLT monitoring during infusion and in the following 2 months, since a decrease in PLT count may occur.

Alemtuzumab induced hemodynamic change in relapsing multiple sclerosis occurs independent of corticosteroid premedication – a retrospective multicentre study

“…In three patients, the criteria of mild thrombocytopenia were met. However, platelet decrease was a common transient and mild phenomenon and did not correlate with an increased risk of severe events (Puthenparampil et al, 2018). It was hypothesized that there is an association with a cytokine-release syndrome induced by ATZ infusion.…”

Alemtuzumab in multiple sclerosis: A retrospective analysis of occult hemorrhagic magnetic resonance imaging lesions and risk factors

“…In the present cohort, a mild reduction of thrombocyte levels occurred during one of the administration courses (N = 20), but absolute thrombocyte counts remained within the normal range in all patients. Alternatively, the observed reduction might be artefactually caused by platelet-toendothelium-adhesion [11]. Furthermore, platelet dysfunction, coagulation defects (such as acquired hemophilia) and damage or dysfunction of the epithelium by toxicity or by alemtuzumab-related cytokine release might also contribute to bleeding or vascular events [4,7,9,10,12].…”

Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis

“…Recent meta-analyses and cohort studies concluded that MS is declared to be associated with cardiovascular disease (CVD) due to both thrombin upregulation and blood platelet pro-thrombotic over-activity [ 9 , 10 , 11 ]. Nevertheless, the vast majority of studies that confirmed the platelet abnormalities in MS patients referred only to the initial phase, that is RR MS [ 12 , 13 , 14 ]. The chronic activation of blood platelets in SP MS, as expressed by high levels of activation markers, altered mitochondrial function, and increased platelet reactivity, has been proven in our previous studies to focus exclusively on the progressive stage of MS, characterized with an especially high risk of CVD [ 15 , 16 , 17 ].…”