Repeated successful use of eltrombopag in chronic primary immune thrombocytopenia: description of an intriguing case.

Thrombopoietin receptor agonists (TPO-RAs) are used as effective alternative treatments in ITP patients unresponsive to first-/second-line therapies. TPO- RAs can also be used to normalize platelet count to safely perform invasive pro- cedures and chemotherapy, in case of malignancies. In few responsive patients, TPO-RAs can be suspended maintaining a sustained respons

Right elbow arthropathy in a patient with severe haemophilia A

A 56‐year‐old male had been diagnosed with severe haemophilia A at the age of one year (missense mutation, exon 10, variant NM_000132.3c.1537+1G). He had been treated on demand with plasma‐derived factor VIII (pdFVIII) concentrate for most of his life; he was not compliant with prophylaxis and attended the clinic only when he thought it was strictly necessary. In April 2017 he underwent an orthopaedic assessment, which showed severe arthropathy of both elbows, knees and ankles. In August 2017, he attended the clinic with a major haemarthrosis of the right elbow, which had not resolved with self‐medication. On physical examination, the right elbow was deformed with multidirectional laxity; paradoxically the range of motion was preserved. An X‐ray of the right elbow showed severe arthropathy with complete joint dislocation (upper images). There were also widespread areas of erosion and absorption of the articular surfaces; these were confirmed on computed tomography (CT) scanning (lower left image). The patient was treated for six days with pdFVIII concentrate at a dosage of 50 U/kg/day, and then the frequency of infusions was decreased to every other day. After the acute phase, he continued with pdFVIII 40 U/kg every other day with continued clinical improvement. A peripherally inserted central catheter was used to improve compliance with intravenous infusions. In April 2018 a switch was made to extended half‐life FVIII concentrate (recombinant FVIII‐Fc fusion protein, rFVIII‐Fc, efmoroctocog alpha) to reduce the frequency of infusions. Thereafter the patient accepted prophylaxis with rFVIII‐Fc, at a dosage of 50 U/kg every 96 h, with a FVIII trough level of approximately 10% and stable joint status. Such severe joint damage is now uncommon in patients with haemophilia A. Our patient is a reminder of the possible consequences if prophylaxis is either unavailable or is not accepted by the patient

Immune thrombocytopenia management during COVID-19 pandemic: An Italian monocentric experience

Over the last 2 years, different cases of immune thrombocytopenia (ITP) in patients affected by SARS-CoV2 have been reported. The management of SARS-CoV2 in subjects with simultaneous or previous ITP can be challenging because of the great involvement of the haemostatic system in this viral infection. In this report,wedescribe themanagement and outcome of patients with newly diagnosed (ND), chronic and previous ITP, infected by COVID-19, referred to the Haematology Institute of University HospitalPoliclinicoUmberto I inRome. Steroids+immunoglobulins forNDor relapsed ITP and continuation of home therapy for chronic ITP are advised, although further knowledge is required

Direct oral anticoagulants for the treatment of Mondor's disease not responding to low-molecular weight heparin

Mondor's disease is a rare condition and usually treated with low-molecular weight heparin and non-steroidal anti-inflammatory drugs. Because of paucity of cases and for the usually spontaneous resolution, there is not a standard treatment strategy and the use of oral anticoagulation in controversial. We reported the efficacy of direct oral anticoagulants in the recurrent Mondor's disease refractory to standard therapy

Oral anticoagulant therapy in Italian patients 80 yr of age or older with atrial fibrillation: a pilot study of low vs. standard PT/INR targets.

BACKGROUND: Oral anticoagulation therapy (OAT), which aims to prevent thromboembolism in patients with atrial fibrillation (AF), is underused in subjects who are over the age of 80 yr because of the associated bleeding risk. The aim of this study was to evaluate the efficacy and safety of OAT with low (2.0) vs. standard (2.5) PT/international normalised ratio (INR) targets in patients over the age of 80. MATERIALS AND METHODS: Of 233 patients aged 80 yr or older with AF on OAT, 58 had unstable PT/INR values and achieved reduced targets. These patients were enrolled as a group (A) in a case-control study and were treated with a low (2.0) PT/INR target. They were compared with a second group (B) of 58 additional patients who were matched for age and CHADS scores and treated with a standard (2.5) PT/INR target. Group A OAT parameters were also compared before and after the PT/INR reduction. The time in the therapeutic range (TTR%), PT/INR values >5, haemorrhages and strokes were prospectively evaluated in the two groups after 2 yr of follow-up. RESULTS: Of the 116 enrolled patients, 55 group A and 57 group B patients were evaluated. The TTR was 72.59% in group A and 64.43% in group B (P 5 was 0.68% for group A and 1.42% for group B (P 5 (1.72% vs. 0.68%; P < 0.001). CONCLUSIONS: A low PT/INR target seems effective and safe in Italian patients with AF over the age of 80. Further trials are needed to confirm the hypothesis generated by this study

Safety of Switching Factor VIII Products in the Era of Evolving Concentrates: Myths and Facts

Recent advances in the development of factor VIII (FVIII) concentrates offer patients with hemophilia the opportunity to switch to products considered safer or with improved properties. In some cases, product switch occurs due to side effects, convenience issues, or economic reasons affecting clinical choices. Reluctance to change FVIII concentrates is shown by patients and also by their physicians, because of concerns in particular about the risk of inhibitor development. A literature review was performed to retrieve the best evidence regarding safety issues of switching FVIII concentrate in patients with severe hemophilia A. Product switch was not associated with an increased inhibitor risk in four studies in patients during the first 50 to 75 exposure days, or in three studies reporting national switches in Canada and United Kingdom. The latter, the only available study comparing switcher and nonswitcher patients, showed an inhibitor incidence similar to that historically reported in the United Kingdom. In 16 phase III clinical trials and 6 postmarketing studies of FVIII concentrates, few de novo inhibitors were detected in previously treated patients, mostly transient and low-titer, with some additional recurrent inhibitors in patients with previous positive testing. On the whole, although rigorous controlled studies are lacking, literature data do not support increased risk of inhibitor development or other safety issues related to product switch. Therefore, in the presence of clinical needs, the advantages of switching FVIII products should not be missed because of perceived more than evidence-based challenges, in particular in this era of products with improved properties recently introduced or available in few years. Caution, however, is suggested in patients with high inhibitor risk, including in those in concomitance with surgery or intensive treatment. A careful inhibitor testing prior to and after product switch is always needed, to identify real de novo inhibitors and to gather further information in the current evolving scenario, in particular comparing switch and nonswitch patients

Severe Thrombotic Complications in Congenital Afibrinogenemia: A Pathophysiological and Management Dilemma

Congenital afibrinogenemia (CA) is a disease characterized by a complex pathophysiology, involving both the procoagulant and fibrinolytic systems, as well as platelet activity. Although hemorrhagic diathesis represents the most frequent clinical presentation of this disorder, severe thrombotic events can occur. It is not yet clear if these events are strictly related to the disease itself or to the fibrinogen replacement therapy. Different hypotheses on the pathophysiological mechanisms have been proposed. It is well known that fibrinogen/fibrin has a role in the downregulation of thrombin generation in plasma. In the absence of circulating fibrinogen, this "antithrombin" activity is missing and plasma thrombin levels rise; this excess of thrombin could promote clotting of the infused fibrinogen, initiating the thrombotic process. Furthermore, the observation of impaired plasmin generation in the plasma of CA patients has raised the hypothesis of a fibrinolytic system deficiency. We report the case of a CA male patient who at the age of 36 years experienced an arterial thrombosis in his left lower limb. Despite an aggressive medical treatment with low-molecular-weight heparin, fibrinolytic and antiplatelet agents, the arterial thrombosis progressed to the obstruction of the whole left arterial district and the patient underwent the amputation of the left lower limb. This case demonstrates the complexity of pathophysiology and clinical management of a "so-called" bleeding disorder as CA

Plasma Vitamin K1 Levels in Italian Patients Receiving Oral Anticoagulant Therapy for Mechanical Heart Prosthesis: A Case–Control Study

Background Oral anticoagulant therapy (OAT) with a vitamin K antagonist (VKA) is the choice of treatment for preventing thromboembolism in patients with mechanical heart valve prosthesis (MHP). The percentage of time in the therapeutic range (TTR%) expresses the OAT quality. We planned a case-control study in order to determine vitamin K1 plasmatic concentrations in MHP patients and to correlate these with TTR%. Materials and Methods Of 756 MHP patients receiving OAT, 125 patients (61 younger than 65 years, and 64 older than 65 years) and 120 healthy blood donors, matched for sex and age, were enrolled in the study. All subjects completed a living questionnaire regarding diet, and underwent blood collection. Vegetable and fruit intake was categorized as optimal or suboptimal, and the high-performance liquid chromatography method was used to determine vitamin K1 levels. Results Neither the patients nor controls had been taking vitamin supplements prior to the start of the study. The median vitamin K1 level was 290 pg/L in 72 controls with optimal intake, and 274 pg/L in 48 controls with suboptimal intake, while the median vitamin K1 level in MHP patients with optimal intake was 409 pg/L, significantly higher (p &lt; 0.001) than the 133.5 pg/L in patients with suboptimal intake. Vitamin K1 concentration in MHP patients appears to be linked to an agerelated threshold: in patients younger than 65 years of age, the median vitamin K1 level was 431 pg/L, significantly higher (p &lt; 0.05) than the 290 pg/L in patients older than 65 years of age. No clear relation was found between vitamin K1 levels and TTR% (Pearson = 0.14). However, patients with vitamin K1 &gt; 160 pg/L showed a TTR% &gt; 60 %. Among patients younger than 65 years, subjects with vitamin K1 &gt; 160 pg/L showed a median TTR of 66 %, this being significantly higher (p &lt; 0.001) than the 46 % level shown by patients with vitamin K1 &gt; 160 pg/L. Conclusions Vitamin K1 concentrations in MHP patients seem to be related to both diet and age. © Springer International Publishing Switzerland 2016

Satisfaction, quality of life and therapy adherence assessment in real life patients transitioning from vitamin K antagonists to direct oral anticoagulants

Anticoagulant therapy has undergone a significant change since direct oral anticoagulants (DOACs) introduction. Their obvious advantages including the fixed dose, the few interactions and less frequent controls, have made them the first choice anticoagulant therapy. More and more patients have therefore switched from therapy with vitamin K antagonists (VKAs) to DOACs. Aim of our study was to assess the satisfaction, quality of life (QoL) and therapy adherence of patients who switched from VKA to DOACs therapy. This single center study evaluated satisfaction and QoL of 107 patients who switched from VKA to DOACs therapy through Anti-Clot Treatment Scale and SF-36 respectively. The questionnaires were administered before therapy change, after 3&nbsp;months of DOACs therapy and then annually. We also evaluated DOACs therapy adherence with a questionnaire administered each visit and through the measures of DOACs plasma levels. Patients' satisfaction and QoL were high during VKA therapy, but with DOACs we observed an improvement after the first 3&nbsp;months and then maintained over the time of DOACs therapy. DOACs adherence was excellent, also confirmed by DOACs plasma levels