Key Points• This study is the first to assess prognostic factors in patients with AHA treated according to a uniform immunosuppressive regimen.• Residual factor VIII activity and inhibitor concentration at baseline are potentially useful predictors of remission.Acquired hemophilia A (AHA) is caused by autoantibodies against factor VIII (FVIII).Immunosuppressive treatment (IST) results in remission of disease in 60% to 80% of patients over a period of days to months. IST is associated with frequent adverse events, including infections as a leading cause of death. Predictors of time to remission could help guide IST intensity but have not been established. We analyzed prognostic factors in 102 prospectively enrolled patients treated with a uniform IST protocol. Partial remission (PR; defined as no active bleeding, FVIII restored >50 IU/dL, hemostatic treatment stopped >24 hours) was achieved by 83% of patients after a median of 31 days (range 7-362).Patients with baseline FVIII <1 IU/dL achieved PR less often and later (77%, 43 days) than patients with ‡1 IU/dL (89%, 24 days). After adjustment for other baseline characteristics, low FVIII remained associated with a lower rate of PR (hazard ratio 0.52, 95% confidence interval 0.33-0.81, P < .01). In contrast, PR achieved on steroids alone within £21 days was more common in patients with FVIII ‡1 IU/dL and inhibitor concentration <20 BU/mL (odds ratio 11.2, P < .0001). Low FVIII was also associated with a lower rate of complete remission and decreased survival. In conclusion, presenting FVIII and inhibitor concentration are potentially useful to tailor IST in AHA. (Blood. 2015;125(7):1091-1097

There are no evidence-based guidelines on pain management in people with haemophilia (PWH), who may suffer acute, disabling pain from haemarthroses and chronic arthropathic pain. To review evidence and to investigate current clinical practice in pain assessment and management in PWH the European Haemophilia Therapy Standardisation Board undertook a literature review and a survey in 22 Haemophilia Treatment Centres (HTC), using a questionnaire and seven clinical scenarios. Consensus was sought on pain assessment and management in PWH. Few clinical studies on pain management in PWH were identified. The HTCs care for 1678 children (47% severe haemophilia, 84% on prophylaxis, 17% with arthropathy and 8% with chronic pain) and 5103 adults (44% severe haemophilia, 40% on prophylaxis, 67% with arthropathy and 35% with chronic pain). Analgesics are prescribed by HTCs in 80% of cases (median; range 0-100%) and in 10% (median; range 0-80%) are bought over the counter. Pain and analgesic use are assessed when reported by patients and at check-ups. Only eight centres use a specific pain scale and/or have specific pain guidelines. Two HTCs arrange regular consultations with pain specialists. For acute pain, the preferred first-line drug is paracetamol for children, and paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for adults. Children with chronic pain are treated with paracetamol or NSAIDs, whereas adults usually receive Cox-2 inhibitors. Second-line therapy is heterogeneous. There is little published evidence to guide pain assessment and management in PWH, and clinical practice varies considerably across Europe. General and specific recommendations are needed.

Haemarthroses cause major morbidity in patients with haemophilia. Blood has devastating effects on all joint components, resulting in synovitis, osteochondral degeneration and ultimately end‐stage haemophilic arthropathy. Key players in this process are iron and inflammation. Preventing joint bleeds is of utmost importance to maintain joint health as targeted therapies directed against blood‐induced inflammation and iron‐mediated processes are lacking. Joint bleeds result in acute pain as well as chronic pain due to synovitis or arthropathy. Acute pain originates from nociceptors activated by tissue damage. In chronic inflammation, central and peripheral sensitization of nociceptors might occur resulting in chronic pain. This also triggers a series of brain disorders such as emotional fear, anxiety, mood depression and impairment of cognitive functions. Treatment of haemophilia‐related pain not only consists of analgesics, but also of exercise, education and in selected cases antidepressants and anticonvulsants. For objective assessment of joint structural outcome and detecting earlier changes of haemophilic arthropathy, both ultrasound (US) and magnetic resonance (MR) imaging have shown valuable. Both can be considered equally able to reveal signs of disease activity. MR imaging is able to visualize haemosiderin deposition and is more comprehensive in depicting osteochondral changes. Disadvantages of MR imaging are the duration of the examination, evaluation of a single joint at a time, costs and may require sedation, and it may need intraarticular contrast injection to depict initial osteochondral changes with accuracy. As such, US is a more useful screening tool and can be used for repeated follow‐up examinations.

Acquired hemophilia A (AHA) is due to autoantibodies against coagulation factor VIII (FVIII) and most often presents with unexpected bleeding. In contrast to congenital hemophilia, the patient's residual FVIII activity does not seem to correlate with the risk of bleeding as suggested from previous studies. Risk factors for bleeding have not been described. We used data from the prospective GTH-AH 01/2010 study to assess the risk of bleeding and the efficacy of hemostatic therapy. FVIII activity was measured at baseline and weekly thereafter. Bleeding events were assessed by treating physicians. A total of 289 bleeds was recorded in 102 patients. 141 new bleeds starting after day 1 were observed in 59% of the patients, with a mean rate of 0.13 bleeds per patient-week in weeks 1 to 12, or 0.27 bleeds per patient-week before achieving partial remission. Weekly measured FVIII activity was significantly associated with the bleeding rate, but only achieving FVIII ≥50% abolished the risk of bleeding. A good WHO performance status assessed at baseline (score 0 vs. higher) was associated with a lower bleeding rate. Hemostatic treatment was reported to be effective in 96% of bleeds. In conclusion, the risk of new bleeds after a first diagnosis of AHA remains high until partial remission is achieved, and weekly measured FVIII activity may help to assess the individual risk of bleeding. These results will help to define future strategies for prophylaxis of bleeding in AHA.

Tissue factor (TF) expressed on sub-cellular membrane vesicles, so-called plasma microparticles (MPs), has recently emerged as a potential key player in intravascular coagulation activation in various disease states. In this report, we demonstrate significantly increased levels of TF-specific procoagulant activity (PCA) of plasma MPs in five patients presenting with overt disseminated intravascular coagulation (DIC) due to an underlying malignancy, including non-small-cell lung cancer (n = 1), melanoma (n = 1), prostate cancer (n = 2), and acute promyelocytic leukemia (n = 1). Clotting experiments on available tumor cell samples suggested that cancer cells were a potential source of circulating TF-positive MPs at least in three of the five patients. Furthermore, follow-up plasma samples from two surviving patients revealed that response of their malignancies to specific anti-cancer therapy was paralleled by resolution of overt DIC and a significant decline in MP-associated TF PCA. Levels of plasma TF antigen, as assessed by an enzyme-linked immunosorbent assay, were also increased at presentation albeit to a lesser extent compared to MP-associated TF PCA, likely due to insufficient solubilization of the phospholipid-incorporated full-length TF molecule by the detergent. In summary, our findings suggest that MP-associated TF PCA may play an important pathogenic role in the evolution of overt DIC in various types of malignancy.