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Fostamatinib demonstrated efficacy in phase 3 trials of adults with immune thrombocytopenia (ITP). Post hoc analysis compared patients who received fostamatinib as second‐line therapy (after steroids ± immunoglobulins) versus third‐or‐later‐line therapy (after ≥2 prior lines of therapy including a second‐line agent). Platelet responses ≥50 000/µl were observed in 25/32 (78%) second‐line and 54/113 (48%) third‐or‐later‐line patients. Bleeding events were less frequent in second‐line (28%) versus third‐or‐later‐line (45%) patients. Responses once achieved tended to be durable in both groups. The safety profile was similar in both groups. In this post hoc analysis, fostamatinib was more effective as second‐line than third‐or‐later‐line therapy for ITP.

It is not known whether the synergistic effect of genetic markers, increasing the risk of venous thrombosis (VT), and combined oral contraceptives (COC) use varies between different types of progestogens in these preparations. We investigated the joint effect of genetic risk factor, that is, F5 rs6025, F2 rs1799963, and FGG rs2066865 mutations, and different progestogens on the risk of VT. The constrained maximum likelihood estimation (CMLE) method was used to calculate joint effects, expressed as odds ratio (OR) with 95% confidence intervals [CI]. As the dose of estrogen is known to be a risk factor for VT, analyses were restricted to COC with 30 mu g estrogen and each progestogen. Overall, the joint effect of COC and genetic variants was lowest for COC containing the progestogen levonorgestrel, albeit CIs were wide. The OR (95% CI) of the four different analyses (i.e. joint effect with F5 rs6025, F2 rs1799963, F5 rs6025 or F2 rs1799963 and FGG rs2066865) ranged between 7 center dot 4 (5 center dot 4-10 center dot 2) and 24 center dot 8 (12 center dot 3-50 center dot 0) for levonorgestrel. For gestodene the joint effect ranged between 11 center dot 7 (7 center dot 2-19 center dot 1) and 30 center dot 9 (10 center dot 6-89 center dot 9). Desogestrel and cyproterone acetate had the highest risk estimates: 14 center dot 6 (9 center dot 7-21 center dot 9) and 32 center dot 6 (13 center dot 2-80 center dot 6) and 15 center dot 5 (9 center dot 7-24 center dot 9) and 44 center dot 4 (16 center dot 9-116 center dot 3) respectively. In women with inherited thrombophilia, COC containing levonorgestrel were associated with the lowest risk of VT, albeit the CIs were wide.

We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non-rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8 center dot 75 min (95% CI -13 center dot 8 to -3 center dot 72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (-0 center dot 05 U/ml; 95% CI -0 center dot 07 to -0 center dot 02 and -4 center dot 77%; 95% CI -6 center dot 81 to -2 center dot 73, respectively). PAI-1 levels did not change and fibrinogen levels were 0 center dot 17 g/l (95% CI 0 center dot 04-0 center dot 29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non-statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE.

Summary Antibodies to first‐generation recombinant thrombopoietin (TPO) neutralized endogenous TPO and caused thrombocytopenia in some healthy subjects and chemotherapy patients. The second‐generation TPO receptor agonist romiplostim, having no sequence homology to TPO, was developed to avoid immunogenicity. This analysis examined development of binding and neutralising antibodies to romiplostim or TPO among adults with immune thrombocytopenia (ITP) in 13 clinical trials and a global postmarketing registry. 60/961 (6·2%) patients from clinical trials developed anti‐romiplostim‐binding antibodies post‐baseline. The first positive binding antibody was detected 14 weeks (median) after starting romiplostim, at median romiplostim dose of 2 µg/kg and median platelet count of 29.5 × 109/l; most subjects had ≥98·5% of platelet assessments showing response. Neutralising antibodies to romiplostim developed in 0·4% of patients, but were unrelated to romiplostim dose and did not affect platelet count. Thirty‐three patients (3·4%) developed anti‐TPO‐binding antibodies; none developed anti‐TPO‐neutralising antibodies. In the global postmarketing registry, 9/184 (4·9%) patients with spontaneously submitted samples had binding antibodies. One patient with loss of response had anti‐romiplostim‐neutralising antibodies (negative at follow‐up). Collectively, anti‐romiplostim‐binding antibodies developed infrequently. In the few patients who developed neutralising antibodies to romiplostim, there was no cross‐reactivity with TPO and no associated loss of platelet response.