Relapsing thrombotic thrombocytopenic purpura with low ADAMTS13 antigen levels: An indication for splenectomy?

With more recent modalities of immunosuppression, splenectomy is now rarely considered in refractory/relapsed thrombotic thrombocytopenic purpura (TTP). However, the surgical approach had shown convincing evidences of high efficacy in the pre-rituximab era and therefore may still represent a lifesaving option in selected challenging cases. To define the characteristics of subjects who may benefit from splenectomy may ease clinical decision making. In this paper we describe the clinical and laboratory data of 2 multiple relapsing TTP cases who successfully underwent splenectomy in the pre-rituximab era. Whereas high anti-ADAMTS13 antibody titre and low ADAMTS13 activity never correlated with remission and relapse, a drop in the ADAMTS13 antigen level was always associated with the acute phase, whereas levels consistently returned to normal following splenectomy, heralding long term remission. Splenectomy may therefore be considered in refractory TTP cases associated with increased ADAMTS13 antigen clearance, irrespective of persistence of inhibitory antibodies

Decreased VLDL-Apo B 100 fractional synthesis rate despite hypertriglyceridemia in subjects with type 2 diabetes and nephropathy

Subjects with Type 2 Diabetes Mellitus (T2DM) and diabetic nephropathy (DN) often exhibit hypertriglyceridemia. The mechanism(s) of such an increase are poorly known. OBJECTIVE: We investigated VLDL-Apo B 100 kinetics in T2DM subjects with and without DN, and in healthy controls. DESIGN: Stable isotope 13C-leucine infusion, and modelling analysis of tracer-to-tracee ratio dynamics in the protein product pool in the 6-8 hr period following tracer infusion, were employed. SETTING: Male subjects affected by T2DM, either with (n=9) or without (n=5) DN, and healthy male controls (n=6), were studied under spontaneous glycemic levels in the post-absorptive state. RESULTS: In the T2DM patients with DN, plasma triglyceride (TG) (2.2\ub10.8 mmol/L, Mean\ub1SD) and VLDL-Apo B 100 (17.4\ub110.4 mg/dl) concentrations, and VLDL-Apo B 100 pool (0.56\ub10.29 g), were 3e60-80% greater (p<0.05 or less) than those of the T2DM subjects without DN (TG: 1.4\ub10.5 mmol/L; VLDL-Apo B 100: 9.9\ub12.5 mg/dl; VLDL-Apo B 100 pool: 0.36\ub10.09 g), and 3e80-110% greater (p<0.04 or less) than those of nondiabetic controls (TG: 1.2\ub10.4 mmol/L; VLDL-Apo B 100: 8.2\ub11.7 mg/dl; VLDL-Apo B 100: 0.32\ub10.09 g). In sharp contrast however, in the subjects with T2DM and DN, VLDL-Apo B 100 FSR was 6550% lower (4.8\ub12.2 pools/day) than that of either the T2DM subjects without DN (9.9\ub14.3 pools/day, p<0.025) or the control subjects (12.5\ub19.1 pools/day, p<0.04). CONCLUSIONS: The hypertriglyceridemia of T2DM patients with DN is not due to hepatic VLDL-Apo B 100 overproduction, which is decreased, but it should be attributed to decreased apolipoprotein removal

Spectrum of 5’UTR mutations in ANKRD26 gene in patients with inherited thrombocytopenia: c.-140C>G mutation is more frequent than expected

none8noneFerrari, Silvia; Lombardi, Anna Maria; Putti, Maria Caterina; Bertomoro, Antonella; Cortella, Irene; Barzon, Isabella; Girolami, Antonio; Fabris, FabrizioFerrari, Silvia; Lombardi, ANNA-MARIA; Putti, Maria Caterina; Bertomoro, Antonella; Cortella, Irene; Barzon, Isabella; Girolami, Antonio; Fabris, Fabrizi

Correlation between ADAMTS13 activity and neurological impairment in acute thrombotic microangiopathy patients

Differential diagnosis between thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies (TMA) is usually difficult because of frequently overlapping clinical presentations. Severely depressed ADAMTS13 activity (<10\ua0%) seems distinctive for TTP because of its pathogenetic role. However a long debate exists in the literature about its sensibility and specificity. Our aim was to search for clinical differences between TMA patients referred to our laboratory, comparing them for protease activity\ua0<10 versus\ua0 6510\ua0%. ADAMTS13 activity\ua0 6510\ua0% patients (n\ua0=\ua073) showed a higher prevalence of drug- (p\ua0=\ua00.005) and cancer-associated (p\ua0<\ua00.001) TMA. Mean platelet count and renal dysfunction prevalence was lower (p\ua0<\ua00.001), while neurological impairment was more frequent (p\ua0=\ua00.001) in the\ua0<10\ua0% ADAMTS13 activity group (n\ua0=\ua0109), confirming previous literature findings. When taken neurological manifestations singularly, epilepsy (p\ua0=\ua00.04), focal motor deficit (p\ua0<\ua00.001) and cranial nerve palsy (p\ua0=\ua00.007) were more frequent in the\ua0<10\ua0% activity group. In our case series, a\ua0<10\ua0% ADAMTS13 activity depicts a group of patients with clinical features similar to TTP patients. Focal motor impairment or epileptic manifestations could further address toward a TTP diagnosis. Studies about treatment efficacy and follow-up are advised to determine whether laboratory findings can guide therapeutic decisions