A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study)

Summary. Background: Prevention of arthropathy is a major goal of hemophilia treatment. While studies in adults have demonstrated an impact of prophylaxis on the incidence of joint bleeds and patients’ well‐being in terms of improved quality of life (QoL), it is unclear whether or not prophylaxis influences the outcome and perception of well‐ of children with hemophilia. Objective: This randomized controlled study compared the efficacy of prophylaxis with episodic therapy in preventing hemarthroses and image‐proven joint damage in children with severe hemophilia A (factor VIII <1%) over a 10‐year time period. Methods: Forty‐five children with severe hemophilia A, aged 1–7 years (median 4), with negative clinical‐radiologic joint score at entry and at least one bleed during the previous 6 months, were consecutively randomized to prophylaxis with recombinant factor VIII (25 IU kg^?1 3 × week) or episodic therapy with ≥25 IU kg^?1 every 12–24 h until complete clinical bleeding resolution. Safety, feasibility, direct costs and QoL were also evaluated. Results: Twenty‐one children were assigned to prophylaxis, 19 to episodic treatment. Children on prophylaxis had fewer hemarthroses than children on episodic therapy: 0.20 vs. 0.52 events per patient per month (P < 0.02). Plain‐film radiology showed signs of arthropathy in six patients on prophylaxis (29%) vs. 14 on episodic treatment (74%) (P < 0.05). Prophylaxis was more effective when started early (≤36 months), with patients having fewer joint bleeds (0.12 joint bleeds per patient per month) and no radiologic signs of arthropathy. Conclusion: This randomized trial confirms the efficacy of prophylaxis in preventing bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life.     

Rheumatological presentations of anticoagulation related hemorrhages

Background: Joint, back and muscle pain are common in patients referred to a rheumatology unit. Acute pain due to hemorrhage may be difficult to distinguish from more common causes of pain in these patients. This article describes a small case‐series of patients who presented acutely with hemarthroses, spinal hemorrhage or muscle hematomas while receiving anticoagulant treatment. Methods: Case notes of nine patients were reviewed retrospectively. The demographic characteristics, indication for anticoagulation, international normalized ratio, and management were evaluated. Results: The majority of hemorrhages occurred when the INR was within the therapeutic range. Anticoagulation was held in all cases. Joint aspiration was performed in all cases of hemarthrosis. Surgical intervention was required in management of the spinal epidural bleed and also in one case of muscle hematoma. Conclusion: Cases described represent major hemorrhages in anticoagulated patients. There is little literature on specific treatment and prognosis, particularly with respect to hemarthrosis, and further studies are needed.     

Embolization of the Geniculate Arteries Is an Effective Treatment of Recurrent Hemarthrosis Following Total Knee Arthroplasty That Can Be Safely Repeated

Background

Recurrent hemarthrosis is a late complication in up to 1.6% of patients following total knee arthroplasty (TKA). In the absence of intrinsic coagulopathy, one etiology is bleeding of hypertrophic vascular synovium. The aim of this study is to evaluate the clinical outcome of patients referred to our center for angiographic embolization of geniculate arteries for recurrent hemarthrosis following TKA.

Magnetic resonance angiography in the management of recurrent hemarthrosis after total knee arthroplasty

Spontaneous hemarthrosis is an infrequent but disabling complication after total knee arthroplasty. The purpose of this case series is to demonstrate the utility of magnetic resonance angiography (MRA) in the evaluation of hemarthrosis after total knee arthroplasty. Patients presenting with hemarthrosis unexplained by trauma, anticoagulation, or a bleeding diathesis were retrospectively identified. Eighteen patients were referred for MRA to evaluate recurrent hemarthrosis after failing conservative therapy (n = 16) or synovectomy (n = 2). Despite artifact caused by the metallic components, diagnostic evaluation of regional vessels was made. In 12 of 13 cases that underwent embolization or synovectomy, a hypertrophic feeding artery (or arteries) was visualized on MRA. One case of negative MRA did not have subsequent surgery, and we are unable to comment on the rate of false-positives because all patients in this case series had evidence of bleeding. By characterizing the vascular anatomy and identifying a dominant artery (or arteries) supplying the hypervascular synovium, MRA can serve as a guide for subsequent embolization or synovectomy, as indicated.     

Hemarthrosis due to a rare cause of hemorrhagic diathesis: Ehlers-Danlos syndrome

The authors report a case of hemarthrosis complicated by severe anemia related to a congenital connective tissue disease: Ehlers-Danlos syndrome. A boy fell down and suffered tumefaction of both knees with bilateral rupture of the rotula tendon. He underwent surgical reinsertion of each tendon on the rotula. He later showed an unexpected ongoing hematic effusion, with severe anemia. He was screened for coagulation disorders with no results. On taking a more detailed history and investigating the patient's phenotypical features, the authors diagnosed Ehlers-Danlos syndrome, hypermobile variant. The hemarthrosis and anemia were thus concluded to be consequences of excessive tissue fragility due to a congenital connective tissue disease.     

Molecular Response of Rabbit Menisci to Surgically Induced Hemarthrosis and a Single Intra‐Articular Dexamethasone Treatment

Anterior cruciate ligament reconstructive surgery can restore biomechanical stability, however, such surgery cannot reliably prevent the onset of post‐traumatic osteoarthritis. The aim of this study was to elucidate the molecular response that occurs within the menisci following a surgical injury that allows bleeding into the joint space, and then to investigate the effect of dexamethasone (DEX) on this molecular response. Cell viability studies following acute controlled exposure to blood and blood plus DEX were also conducted. Forty‐eight New Zealand white rabbits were randomly allocated into control, sham, surgical, and surgical + DEX groups (each group n = 6). Animals were sacrificed at 48 h and 9 weeks, and menisci were harvested. The messenger RNA (mRNA) expression levels for key inflammatory, and degradative proteins, as well as mRNA levels for autophagy pathway molecules were quantified, and statistically significant changes were described. Meniscal cell viability was calculated by incubating groups of medial and lateral menisci in autologous blood, or autologous blood plus DEX for 48 h (each group n = 4; total of eight medial and eight lateral menisci), and then conducting a histological live/dead assay. Results indicated a significant reduction in only medial meniscal cell viability when the tissue was exposed to blood in combination with DEX. A single administration of DEX following surgery significantly suppresses the elevated molecular expression for key inflammatory and degradative markers within menisci at 48 h and 9 weeks post‐surgery. In vitro, autologous blood did not affect cell viability, but addition of DEX uniquely impacted the medial menisci. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2043–2052, 2019