Contributions
Abstract: EP1098
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Clinical
Background
Acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder that resembles inherited von Willebrand disease. AvWS may be associated with myeloproliferative neoplasms (MPN), due to the adsorption of von Willebrand Factor (vWF) on platelets (PLT), and enhanced cleavage of vWF multimers. Current guidelines recommend to test VWF activity in MPN with PLT above 1000 x109/L. However, there is no convincing evidence that correlates PLT count, VWF activity and risk of bleeding.
Aims
We aimed to describe vWF parameters, in terms of antigen and functional activity, and correlate the frequency of AvWS with risk of bleeding in MPN patients with extreme thrombocytosis, considering different PLT thresholds and different severity of AvWS. Moreover, we analysed the impact of patients’ genotype.
Methods
We interrogated our MPN database to identify patients affected with essential thrombocythemia and polycythemia vera and extreme thrombocytosis (PLT higher than 1.000 x109/L) and identified 58 patients (15 at diagnosis, 43 during follow-up), as reported in table. vWF testing included vWF antigen (vWF: ag) and vWF ristocetin cofactor activity (vWF:RCo). AvWS was diagnosed when vWF:RCo was below the normal range (50-200%), vWF:RCo / vWF: ag was below 0.7 and in the absence of a familial history. Analyses were performed in 3 clusters of PLT count (1000-1200, 1200-1400, >1400 x109/L, defined as mild, intermediate ad severe thrombocytosis respectively). Severe AvWS was diagnosed for vWF:RCo below 30%.
Results
We found an inverse relationship between PLT count and vWF:RCo (Spearman’s Rho=-0.4 P 0.002). VWF:RCo was significantly different (P 0.022) in the 3 clusters of thrombocytosis, with a median of 44.4% (IQR 35.7-65.6) in mild thrombocytosis, 32.6% (IQR 26.9-38.2) in intermediate and 35.2% (IQR 29.8-44.9) in severe. Frequency of AvWS was higher among JAK2 mutated patients (26/30, 86.7%) as compared to CALR mutated ones (5/24, 62.5%, P 0.056). Also median vWF:RCo was different according to genotypes (P 0.004), being 35.9% (IQR 27.9-44.4) in JAK2 mutated patients, 44.2% (IQR 32.4-63.9) in CALR mutated patients, and 68.5% (IQR 67.4-76.6) in triple-negative ones. In a ROC analysis we found PLT ≥ 1211 x109/L and PLT ≥ 1153 x109/L as the better cut-offs to identify AvWS and severe AvWS, respectively. In bivariable logistic model, AvWS was associated with PLT ≥ 1211 x109/L (OR=16.8 P 0.012), adjusting for mutational profile (presence versus absence of JAK2 mutation, OR=7.4 P 0.005). Similarly, severe AvWS was associated with PLT ≥ 1153 x109/L (OR=12 P 0.004), after adjusting for diagnosis (TE vs PV, OR=0.25 p=0.091). Of 58 patients, 23 (39.7%) experienced bleeding events (all mild and muco-cutaneous). We did not find association between bleeding and vWF level (P 0.632), also after adjusting for antiplatelet treatment (P 0.640). This result might be influenced by the introduction of cytoreduction (32 patients, 55.2%), that was coincident with vWF assessment (n= 10) or prescribed shortly after (n= 22). Accordingly, number of patients experiencing bleedings significantly decreased after starting cytoreduction: 35% (12/32) before compared to 6.3% (2/32) after therapy (P=0.002).
Conclusion
vWF:RCo reduction is associated with PLT count and mutational profile. Extreme thrombocytosis is associated with muco-cutaneous bleedings, as expected in primary haemostasis defects. The introduction of cytoreduction significantly reduces the number of bleeding events.
Keyword(s): Bleeding, Myeloproliferative disorder, Thrombocytosis, Von Willebrand's disease
Abstract: EP1098
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Clinical
Background
Acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder that resembles inherited von Willebrand disease. AvWS may be associated with myeloproliferative neoplasms (MPN), due to the adsorption of von Willebrand Factor (vWF) on platelets (PLT), and enhanced cleavage of vWF multimers. Current guidelines recommend to test VWF activity in MPN with PLT above 1000 x109/L. However, there is no convincing evidence that correlates PLT count, VWF activity and risk of bleeding.
Aims
We aimed to describe vWF parameters, in terms of antigen and functional activity, and correlate the frequency of AvWS with risk of bleeding in MPN patients with extreme thrombocytosis, considering different PLT thresholds and different severity of AvWS. Moreover, we analysed the impact of patients’ genotype.
Methods
We interrogated our MPN database to identify patients affected with essential thrombocythemia and polycythemia vera and extreme thrombocytosis (PLT higher than 1.000 x109/L) and identified 58 patients (15 at diagnosis, 43 during follow-up), as reported in table. vWF testing included vWF antigen (vWF: ag) and vWF ristocetin cofactor activity (vWF:RCo). AvWS was diagnosed when vWF:RCo was below the normal range (50-200%), vWF:RCo / vWF: ag was below 0.7 and in the absence of a familial history. Analyses were performed in 3 clusters of PLT count (1000-1200, 1200-1400, >1400 x109/L, defined as mild, intermediate ad severe thrombocytosis respectively). Severe AvWS was diagnosed for vWF:RCo below 30%.
Results
We found an inverse relationship between PLT count and vWF:RCo (Spearman’s Rho=-0.4 P 0.002). VWF:RCo was significantly different (P 0.022) in the 3 clusters of thrombocytosis, with a median of 44.4% (IQR 35.7-65.6) in mild thrombocytosis, 32.6% (IQR 26.9-38.2) in intermediate and 35.2% (IQR 29.8-44.9) in severe. Frequency of AvWS was higher among JAK2 mutated patients (26/30, 86.7%) as compared to CALR mutated ones (5/24, 62.5%, P 0.056). Also median vWF:RCo was different according to genotypes (P 0.004), being 35.9% (IQR 27.9-44.4) in JAK2 mutated patients, 44.2% (IQR 32.4-63.9) in CALR mutated patients, and 68.5% (IQR 67.4-76.6) in triple-negative ones. In a ROC analysis we found PLT ≥ 1211 x109/L and PLT ≥ 1153 x109/L as the better cut-offs to identify AvWS and severe AvWS, respectively. In bivariable logistic model, AvWS was associated with PLT ≥ 1211 x109/L (OR=16.8 P 0.012), adjusting for mutational profile (presence versus absence of JAK2 mutation, OR=7.4 P 0.005). Similarly, severe AvWS was associated with PLT ≥ 1153 x109/L (OR=12 P 0.004), after adjusting for diagnosis (TE vs PV, OR=0.25 p=0.091). Of 58 patients, 23 (39.7%) experienced bleeding events (all mild and muco-cutaneous). We did not find association between bleeding and vWF level (P 0.632), also after adjusting for antiplatelet treatment (P 0.640). This result might be influenced by the introduction of cytoreduction (32 patients, 55.2%), that was coincident with vWF assessment (n= 10) or prescribed shortly after (n= 22). Accordingly, number of patients experiencing bleedings significantly decreased after starting cytoreduction: 35% (12/32) before compared to 6.3% (2/32) after therapy (P=0.002).
Conclusion
vWF:RCo reduction is associated with PLT count and mutational profile. Extreme thrombocytosis is associated with muco-cutaneous bleedings, as expected in primary haemostasis defects. The introduction of cytoreduction significantly reduces the number of bleeding events.
Keyword(s): Bleeding, Myeloproliferative disorder, Thrombocytosis, Von Willebrand's disease