In March and April 2018, more than 150 patients presented to hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians and public health organizations identified an association between coagulopathy and synthetic cannabinoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant.

Introduction: A recombinant porcine factor VIII B‐domain‐deleted product (rpFVIII; OBIZUR, Baxalta Incorporated, Deerfield, IL 60015, USA) was recently approved for treatment of bleeding episodes in adults with acquired haemophilia A (AHA) in the United States. To date, no clinical experience outside the registration study has been reported.Aim: To describe early clinical experience using rpFVIII for AHA.Methods: A retrospective chart review of seven patients with AHA treated with rpFVIII at four institutions from November 2014 to October 2015.Results: The time to diagnosis of AHA ranged from 5 days to 6 weeks. Six major and one other bleed were treated with rpFVIII following unsatisfactory bypassing agent (BPA) therapy. Good haemostatic efficacy was seen in five of seven cases. rpFVIII loading doses of 100 (n = 6) or 200 U kg⁻¹ (n = 1) increased FVIII activity from <1 to 9% at baseline to 109–650% within 0.25–7 h in six of seven cases. Subsequent median doses ranged from 30 to 100 U kg⁻¹ for 3–26 days. No rpFVIII‐related adverse events were reported. Three patients survived with inhibitor eradication, one with persistent inhibitor, two died with inhibitors present and one was discharged and later died from unrelated causes.Conclusions: rpFVIII showed good haemostatic efficacy with no recurrences in most cases, with consumption substantially less than in the registration study. Treatment decisions were based on FVIII activity levels and clinical assessment. The ability to titrate rpFVIII dose using FVIII activity was considered advantageous compared with BPA therapy. Notable delays in diagnosis were observed.

The rollout of the SARS-CoV-2 vaccine is underway, and millions have already been vaccinated. At least 25 reports of “immune thrombocytopenia” (ITP) or “thrombocytopenia” following the Moderna or Pfizer vaccine have been added to the Vaccine Adverse Event Reporting System (VAERS) in the US. ITP is a rare but known complication of several vaccinations. SARS-CoV-2 vaccine is new, with a novel mechanism of action, and understanding the epidemiology, clinical manifestations, treatment success and natural history of post-vaccination thrombocytopenia is evolving. We report a 74-year-old man who developed refractory thrombocytopenia within one day of receiving the Moderna SARS-CoV-2 vaccine. Several hours after vaccination, he developed significant epistaxis and cutaneous purpura. Severe thrombocytopenia was documented the following day, and he developed extremity weakness and encephalopathy with facial muscle weakness. Over a 14-day period, thrombocytopenia was treated first with high dose dexamethasone, intravenous immunoglobulin, platelet transfusions, rituximab, plasma exchange (for presumed acute inflammatory demyelinating polyneuropathy (AIDP)), and four daily doses of the thrombopoietin receptor agonist (TPO-RA) eltrombopag (Promacta™), without a platelet response. Three days later, he received the TPO-RA romiplostim (Nplate™). Five days later, his platelet count began to rise and by post-vaccination day 25, his platelet count was in the normal range. Thrombocytopenia was refractory to frontline and second-line treatment. The eventual rise in his platelet count suggests that one or both TPO-RAs may have impacted platelet recovery. Possibly, but less likely given the temporality, the drug-induced thrombocytopenia was subsiding. The aggressive use of immunosuppressive treatment may jeopardize the intended purpose of the SARS-CoV-2 vaccine, and earlier use of non-immunosuppressive second-line treatment for vaccine-related severe thrombocytopenia, such as with TPO-RAs, should be considered. While it is imperative to continue the global vaccination program, vigilance to the occurrence of post-vaccination severe thrombocytopenia is warranted.

Solder joints in electronic assemblies are typically subjected to thermal cycling, either in actual application or in accelerated life testing used for qualification. Mismatches in the thermal expansion coefficients of the assembly materials leads to the solder joints being subjected to cyclic (positive/negative) mechanical strains and stresses. This cyclic loading leads to thermomechanical fatigue damage that involves damage accumulation, crack initiation, crack propagation, and failure. While the effects of isothermal aging on solder constitutive behavior (stress-strain and creep) have been examined in some detail, there have been few prior studies on the effects of aging on solder failure and fatigue behavior. Aging leads to both grain and phase coarsening, and can cause recrystallization at Sn grain boundaries. Such changes are closely tied to the damage that occurs during cyclic mechanical loading. In this investigation, we have examined the effects of aging on the cyclic stress-strain and fatigue behaviors of lead free solders. Solder test specimens (SAC105 and SAC305) have been prepared and subjected to cyclic stress/strain loading at different aging conditions. Both uniaxial specimens subjected to cyclic tension/compression and Iosipescu lap shear samples subjected to cyclic positive/negative shear have been studied. A four-parameter hyperbolic tangent empirical model has been used to fit the entire cyclic stress-strain curve and the hysteresis loop size (area) was calculated using definite integration for a given strain limit. This area represents the energy dissipated per cycle, which is correlated to the damage accumulation in the joint. Samples were subjected to cyclic loading over a particular strain range until fatigue failure occurred, and then various popular empirical failure criteria such as the Coffin-Manson model and the Morrow model have been used to estimate the fatigue life. Fatigue failure was defined to occur when there was a 50% peak load drop during mechanical cycling. Prior to testing, the specimens were aged (preconditioned) at 125 C for various aging times, and then the samples were subjected to cyclic loading at room temperature (25 C). It has been observed that prior aging dramatically decreases the mechanical fatigue life. It was also found that degradations in the fatigue/failure behavior of the lead free solders with aging are highly accelerated for lower silver content alloys (e.g., SAC105). Comparisons have been made between the fatigue lives under both uniaxial tension/compression and shear loadings, and good agreement was found. A microstructural adaptive fatigue model including aging effects has been proposed, and shown to accurately predict the measured fatigue data for all aging conditions.

Summary: Von Willebrand disease (VWD) is considered the most common inherited bleeding disorder and may also be the most difficult to diagnose. Clinical symptoms of VWD include predominantly mild mucosal bleeding; surgical bleeding may occur with specific challenges and joint bleeding can occur in the most severe forms. A family history either of diagnosed VWD or of bleeding symptoms is typically present. Laboratory diagnosis requires a series of assays of von Willebrand factor (VWF) quantity and function, and factor VIII activity, with no single straightforward diagnostic test available to either confirm or exclude the diagnosis. Newer assays of VWF function are becoming more available and useful in determining the laboratory diagnosis of VWD.

Introduction: To address the need for a patient‐reported outcome that can measure clinically and personally meaningful change in people with haemophilia (PwH) on prophylaxis, an approach based on Goal Attainment Scaling (GAS) was developed: the GAS‐Hēm.Aim: To establish real‐world feasibility of GAS‐Hēm in PwH.Methods: Patients aged 5‐65 years were enroled from four North American centres for a 12‐week study. The primary outcome was the proportion of participants who completed GAS‐Hēm interviews at baseline, 6 and 12 weeks. GAS‐Hēm scores were obtained by subject‐ and clinician‐rated goal attainment at Weeks 6 and 12, and compared with quality of life (QoL) measures and annualized bleed rate (ABR) for construct validity. Goals were evaluated qualitatively for content validity. Responsiveness was calculated using standardized response means (SRM).Results: Forty‐two participants set 63 goals. Participants preferred to define (37/63) their own goals or further individualize (23/63) from the GAS‐Hēm menu. Thirty of the 37 self‐defined goals were matched to goals on the GAS‐Hēm menu. The most common goal areas were: weight, exercise and nutrition (n = 17); leisure activities (n = 8); and joint problems (n = 7). Both participant‐ and clinician‐rated GAS‐Hēm scores at 6 weeks (n = 40) and 12 weeks (n = 41) demonstrated satisfactory goal attainment (SRM [subject‐rated] at 12 weeks for adult and paediatric groups was 1.25 and 1.16, respectively). Correlations of GAS‐Hēm scores with QoL measures and ABR were uniformly small.Conclusion: GAS‐Hēm was feasible and tapped constructs not captured by ABR or QoL measures.