Disparities in the consensus for treatment of chemotherapy-induced thrombocytopenia.

Introduction: Chemotherapy-induced thrombocytopenia (CIT) is an arduous complication of chemotherapy to be dealt with, and there are many unmet needs in this field to be addressed on the global front. We have conducted this study to contribute to the understanding of existing knowledge gaps of CIT management and highlight the direction to focus future investigations. Methods: This was an academic single-institution report on a cross-sectional study evaluating CIT management practices using platelet (PLT) transfusions by haematologists and oncologists in Armenia. Results: Physicians' opinions differed significantly when it came to defining thrombocytopenia by PLT levels. 13.2% of those surveyed considered thrombocytopenia to be when PLT counts fall below 180 × 109/L, 42.1% defined thrombocytopenia to have a PLT threshold of 150 × 109/L, 15.8% and 21.0% specialists setting their thresholds at 140 × 109/L and 100 × 109/L, respectively.All physicians managed CIT by performing PLT transfusions for prophylactic purposes (i.e., when PLT count falls below a certain threshold) with none of them transfusing PLTs only on-demand to address active bleeding. 73.3% haematologists (adult), 57.1% medical oncologists, and 50% paediatricians deemed 10 × 109/L as the threshold PLT count for transfusing afebrile patients with haematologic malignancies (besides acute promyelocytic leukaemia (APL)) and solid tumours.PLT products availability varied among the respondents, with only 53% of them responding that they had 24/7 access. Conclusion: CIT is a complication of interest to physicians worldwide and has not been resolved yet. This is the first conducted survey regarding CIT and the initial step for further research.

Drug-induced antiphospholipid syndrome: Analysis of the WHO international database.

OBJECTIVE: As with drug-induced lupus, some drugs may induce an antiphospholipid syndrome (APS). With the always growing numbers of new molecules, the list of the liable treatments evolves rapidly. We herein analyzed VigiBase, the international pharmacovigilance database, to identify drugs suspected of inducing APS. METHODS: All the reported cases associated with "anti-phospholipid syndrome" using the preferred term level of medDRA (dictionary of regulated drug activity) when associated with anti-phospholipid antibodies in VigiBase were analyzed. For each treatment, a Bayesian disproportionality indicator (i.e. information component, IC) was calculated. A drug was significantly associated with APS if the 95% lower-end of the IC credibility interval was positive (IC025 > 0). Drugs with potential protopathic bias were excluded. RESULTS: From 01/11/2000 to 25/07/2021, 790 reports of suspected drug-induced APS were found in VigiBase. After excluding drugs reported by a single country and drugs with protopathic bias, fourteen drugs (n = 359 reports) were associated with APS with an IC0 25 > 0. These drugs were hormons: ethinylestradiol-etonogestrel and drospirenone-ethynilestradiol; platelet growth factors: eltrombopag, romiplostim; vaccines: Human Papillomavirus vaccine, hepatitis A and B vaccines and typhoid vaccine; antibiotics: minocycline; nonstreroidal anti-inflammatory: rofecoxib; biotherapy: interferon beta-1-a, etanercept; anti-hypertensive drug: hydralazine; bisphosphonates: alendronic acid and antipsychotic: olanzapine. The mean age at diagnosis of drug-induced APS was 39.2 years [29.3;47.9] and there were 63.5% of female patients. The mean delay from first exposition to drug-induced APS was 19.7 months [4.5; 38.8]. Drug-induced APS was reported as a severe side effect in 66.3% of cases: 8.4% with a life-threatening event and 2.5% of death (n = 9). A third (n = 118, 32.9%) pulmonary embolism events were reported and 4.2% (15) cerebral infarctions. 14.8% (53) cases were associated with a systemic lupus, a sub-analysis without lupus cases showed the same severity of cases. CONCLUSION: This study identified 14 drugs potentially associated with drug-induced APS that may prove useful in the investigational work-up in any new diagnosis of APS. TRIAL REGISTRATION NUMBER: NCT03994302.

Subcutaneous engineered factor VIIa marzeptacog alfa (activated) in hemophilia with inhibitors: Phase 2 trial of pharmacokinetics, pharmacodynamics, efficacy, and safety.

BACKGROUND: Marzeptacog alfa (activated) (MarzAA), a novel recombinant activated human factor VII (FVIIa) variant, was developed to provide increased procoagulant activity, subcutaneous (SC) administration, and longer duration of action in people with hemophilia. OBJECTIVES: To investigate if daily SC administration of MarzAA in subjects with inhibitors can provide effective prophylaxis. METHODS: This multicenter, open-label phase 2 trial (NCT03407651) enrolled men with severe congenital hemophilia with an inhibitor. All subjects had a baseline annualized bleeding rate (ABR) of ≥12 events/year. Subjects received a single 18 µg/kg intravenous dose of MarzAA to measure 24-hour pharmacokinetics (PK) and pharmacodynamics (PD), single 30 µg/kg SC dose to measure 48-hour PK/PD, then daily SC 30 µg/kg MarzAA for 50 days. If spontaneous bleeding occurred, the dose was sequentially escalated to 60, 90, or 120 µg/kg, with 50 days at the final effective dose without spontaneous bleeding to proceed to a 30-day follow-up. The primary end point was reduction in ABR. Secondary end points were safety, tolerability, and antidrug antibody (ADA) formation. RESULTS: In the 11 subjects, the mean ABR significantly reduced from 19.8 to 1.6, and the mean proportion of days with bleeding significantly reduced from 12.3% to 0.8%. Of a total of 517 SC doses, six injection site reactions in two subjects were reported. No ADAs were detected. One fatal unrelated serious adverse event occurred: intracerebral hemorrhage due to untreated hypertension. CONCLUSIONS: The data demonstrated that MarzAA was highly efficacious for prophylactic treatment in patients with inhibitors by significantly decreasing bleed frequency and duration of bleeding episodes.