Tranexamic Acid Use in Knee and Shoulder Arthroscopy Leads to Improved Outcomes and Fewer Hemarthrosis-Related Complications: A Systematic Review of Level I and II Studies.

PURPOSE: To systematically review the literature to compare the efficacy and safety of tranexamic acid (TXA) as a means to minimize hemarthrosis-related complications after arthroscopic procedures of the knee, hip, and shoulder. METHODS: A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed by searching PubMed, Cochrane Library, and Embase databases to locate randomized controlled trials comparing the clinical outcomes and postoperative complications of patients undergoing arthroscopy with and without TXA. Search terms used were "tranexamic acid," "arthroscopy," "knee," "hip," and "shoulder." Patients were evaluated based on early (<6 weeks) postoperative signs of hemarthrosis using the Coupens and Yates classification, postoperative complications (myocardial infarction, stroke, venous thromboembolism events), range of motion (ROM), and patient-reported outcome scores (Visual analog scale, Subjective International Knee Documentation Committee, Lysholm, and Tegner activity scores). RESULTS: Five studies (2 level I and 3 level II) met inclusion criteria, including a total of 299 patients undergoing arthroscopy with TXA and 299 patients without TXA. The average follow-up duration for all patients was 43.9 days. Procedures performed were partial meniscectomy, anterior cruciate ligament reconstruction, and rotator cuff repair. No studies evaluating TXA use in hip arthroscopy were identified. Coupens-Yates hemarthrosis grades significantly improved in the TXA groups across all studies. Three studies found TXA patients to experience significantly less postoperative pain at latest follow-up, 1 study found TXA patients to have significantly better postoperative Lysholm scores, and 1 study found TXA patients to have significantly more ROM at latest follow-up compared with non-TXA patients (P < .05). CONCLUSION: Patients undergoing arthroscopy, particularly arthroscopic meniscectomy, arthroscopic-assisted anterior cruciate ligament reconstruction, and arthroscopic rotator cuff repair, with TXA can be expected to experience improved outcomes and less hemarthrosis-related complications in the early postoperative period compared with non-TXA patients. LEVEL OF EVIDENCE: II, systematic review of level I and II studies.

Blood in the joint: effects of hemarthrosis on meniscus health and repair techniques.

Injury to the meniscus is common and frequently leads to the development of post-traumatic osteoarthritis (PTOA). Many times meniscus injuries occur coincident with anterior cruciate ligament (ACL) injuries and lead to a bloody joint effusion. Hemarthrosis, or bleeding into the joint, has been implicated in degeneration of joint tissues. The goal of this review paper is to understand the pathophysiology of blood-induced joint damage, the possible effects of blood on meniscus tissue, and the implications for current meniscus repair techniques that involve the introduction of blood-derived products into the joint. In this review, we illustrate the similarities in the pathophysiology of joint damage due to hemophilic arthropathy (HA) and osteoarthritis (OA). Although numerous studies have revealed the harmful effects of blood on cartilage and synovium, there is currently a gap in knowledge regarding the effects of hemarthrosis on meniscus tissue homeostasis, healing, and the development of PTOA following meniscus injury. Given that many meniscus repair techniques utilize blood-derived and marrow-derived products, it is essential to understand the effects of these factors on meniscus tissue and the whole joint organ to develop improved strategies to promote meniscus tissue repair and prevent PTOA development.

Magnetic Resonance Imaging of Hemophilic Joints: Correlations with the Bleeding Phenotype and Physical Examination.

INTRODUCTION: Blood-induced joint damage as a hallmark of haemophilia continues to occur despite the widespread prophylaxis. Pre-cise assessment and follow-up of joint status are crucial for tailoring their treatment. AIM: To study the correlation between the bleeding phenotype, the functional joint status, and the magnetic resonance imaging score in pediatric patients with haemophilia. MATERIALS AND METHODS: Eighty-six joints (ankles, knees, and elbows) in patients aged 10.7±0.5 (range 4 - 20) years with severe/moderate haemophilia A, severe haemophilia B and haemophilia A with inhibitors were included in the study. The joints were assessed by Haemophilia Joint Health Score 2.1 (HJHS2.1) one month after the last hemarthrosis in a non-bleeding state. The magnetic reso-nance imaging was performed on 40 (46.5%) of the examined hemophilic joints (16 ankles, 11 knees and 13 elbows). RESULTS: Joint bleeds were present in 37 (38.9%) of the joints with ankles being the most commonly affected. Sixty joints (69.8%) had normal HJHS2.1 score. Only the loss of flexion score differed significantly between the joints and the ankles had highest score. The cumulative number of hemarthrosis in the joint correlated moderately with hemosiderin deposition and strongly with the formation of subchondral cysts on magnetic resonance imaging. The magnetic resonance imaging scores for soft tissue and osteochondral domains correlated moderately with the cumulative number of hemarthrosis in the joint and only with the presence of pain and crepitus of mo-tion from the physical examination. CONCLUSIONS: Magnetic resonance imaging is more sensitive than the bleeding phenotype and physical examination in detecting early signs of haemophilic arthropathy.

Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII-deficient mice.

BACKGROUND: Vascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood. OBJECTIVES: To explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypocoagulable mice. METHODS: Factor VIII (FVIII)-deficient mice +/- FVIII treatment and hypocoagulable wild-type mice (Hypo BALB/c) were subjected to subpatellar puncture. Hypo BALB/c mice were treated with warfarin and anti-FVIII before injury, after which warfarin was continued for 2 weeks or reversed +/- continuous anti-FVIII until harvest. Synovial vascularity was analyzed at baseline and 2 to 4 weeks post injury by histology, musculoskeletal ultrasound with power Doppler (microvascular flow), and Evans blue extravasation (vascular permeability). Synovial gene expression and systemic markers of vascular collagen turnover were studied in FVIII-deficient mice by RNA sequencing and enzyme-linked immunosorbent assay. RESULTS: Vascular changes occurred in FVIII-deficient and Hypo BALB/c mice after injury with minimal effect of hemostasis correction. Increased vascular permeability was only significant in FVIII-deficient mice, who exhibited more pronounced vascular remodeling than Hypo BALB/c mice despite similar bleed volumes. FVIII-deficient mice exhibited a strong transcriptional response in synovium that was only partially affected by FVIII treatment and involved genes relating to angiogenesis and extracellular matrix remodeling, with vascular collagen turnover markers detected systemically. CONCLUSIONS: Intact hemostasis at the time of hemarthrosis and during healing are both critical to prevent vascular remodeling, which appears worse with severe and prolonged FVIII deficiency. Unbiased RNA sequencing revealed potential targets for intervention and biomarker development to improve management of HA.

Sinoviortesis con radioisótopos en hemofilia: Experiencia de un centro en Chile / Radionuclide synoviorthesis in hemophilia: experience in 107 patients

Background: In patients with hemophilia, radionuclide synoviorthesis, or the intra-articular injection of a radionuclide to decrease the synovial hypertrophy tissue, aims to decrease or avoid hemarthrosis. Aim: To evaluate the effectiveness of radionuclide synoviorthesis in hemophilia. Material and Methods: Observational retrospective study of the evolution of 107 male patients aged 3 to 54 years who were subjected to radionuclide synoviorthesis between 2007 and 2015. Results: Of 164 treated joints, in 65% treatment was successful, (defined as zero to two hemarthroses and absence of synovitis during the follow up period), in 17% it was partially successful (defined as two or less hemarthroses, but persistence of the synovitis) and failed in 18% of the procedures. No important complications were recorded. Conclusions: Radionuclide synoviorthesis has an overall 82% success rate, is minimally invasive, can be used at any age and is inexpensive We recommend its implementation in Chilean hemophilia treatment centers.

Rapid inflammation and early degeneration of bone and cartilage revealed in a time-course study of induced haemarthrosis in haemophilic rats.

OBJECTIVES: Detailed knowledge of the sequential cell and tissue responses following haemarthrosis is important for a deep understanding of the pathological process initiated upon extensive bleeding into the joint causing haemophilic arthropathy (HA). The underlying pathobiology driving haemarthrosis towards HA has been difficult to establish in detail, although animal models have shed light on some processes. Previous studies have focused on a single or a few distant time points and often only characterizing one tissue type of the joint. The objective of this study was, therefore, to carefully map early onset of synovitis and HA following induced haemarthrosis. METHODS: One hundred and thirty haemophilia A rats were subjected to induced haemarthrosis or a sham procedure in full anaesthesia and euthanized from 30 min to 7 days after the procedure. Pathological changes of the joints were visualized using micro-computed tomography, histology and immunohistochemistry. RESULTS: Synovitis developed within 24 h and was dominated by myeloid cell infiltrations. Cartilage and bone pathology were evident as early as 48-96 h after haemarthrosis, and the pathology rapidly progressed with extensive periosteal bone formation and formation of subchondral cysts. CONCLUSION: Fast, extensive and simultaneous cartilage and bone degeneration developed shortly after haemarthrosis, as shown by the detailed mapping of the early pathogenesis of HA. The almost immediate loss of cartilage and the pathological bone turnover suggest a direct influence of blood on these processes and are unlikely to be attributed simply to an indirect effect of inflammation.

Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterize synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty acutely painful joints in patients with haemophilia (PWH) were imaged by musculoskeletal ultrasound with Power Doppler (MSKUS/PD) to detect vascular abnormalities and bloody effusions. Nineteen out of 30 painful joint episodes in PWH were associated with haemarthrosis, and abnormal vascular perfusion was unique to bleeding joints. A model of induced haemarthrosis in factor VIII (FVIII)-deficient mice was used for histological assessment of vascular remodelling (α-smooth muscle actin [αSMA] expression), and monitoring of in vivo vascular perfusion and permeability by MSKUS/PD and albumin extravasation, respectively. Inflammatory (M1) and reparative (M2) macrophage markers were quantified in murine synovium over a 10-week time course by real-time polymerase chain reaction. The abnormal vascular perfusion observed in PWH was recapitulated in FVIII-deficient mice after induced haemarthrosis. Neovascularization and increased vessel permeability were apparent 2 weeks post-bleed in FVIII-deficient mice, after a transient elevation of inflammatory macrophage M1 markers. These vascular changes subsided by week 4, while vascular remodelling, evidenced by architectural changes and pronounced αSMA expression, persisted alongside a reparative macrophage M2 response. In conclusion, haemarthrosis leads to transient inflammation coupled with neovascularization and associated vascular permeability, while subsequent tissue repair mechanisms coincide with vascular remodelling. Together, these vascular changes may promote re-bleeding and HA progression.

Arthroscopic knee debridement can delay total knee replacement in painful moderate haemophilic arthropathy of the knee in adult patients.

The role of arthroscopic debridement of the knee in haemophilia is controversial in the literature. The purpose of this study is to describe the results of arthroscopic knee debridement (AKD), with the aim of determining whether it is possible to delay total knee replacement (TKR) for painful moderate haemophilic arthropathy of the knee in adult patients. In a 14-year period (1998-2011), AKD was performed for moderate haemophilic arthropathy of the knee in 27 patients with haemophilia A. Their average age at operation was 28.6 years (range 26-39 years). Indications for surgery were as follows: more than 90° of knee flexion, flexion deformity less than 30°, good axial alignment of the knee, good patellar alignment, and pain above >60 points in a visual analogue scale [0 (no pain) to 100 points]. Secondary haematological prophylaxis and rehabilitation (physiotherapy) was given for at least 3 months after surgery. Follow-up was for an average of 7.5 years (range 2-14 years). We assessed the clinical outcome before surgery and at the time of latest follow-up using the Knee Society pain and function scores, the range of motion, and the radiological score of the World Federation of Haemophilia. Knee Society pain scores improved from 39 preoperatively to 66 postoperatively, and function scores improved from 36 to 52. Range of motion improved on an average from -15° of extension and 90° of flexion before surgery, to -5° of extension and 110° of flexion at the last follow-up. A radiological deterioration of 2.8 points on average was found. There were two (7.4%) postoperative complications (haemarthroses resolved by joint aspiration). One patient (3.7%) required a TKR 12.5 years later. AKD should be considered in painful moderate haemophilic arthropathy of the knee in adult patients to delay TKR.

Joint haemorrhage partly accelerated immobilization-induced synovial adhesions and capsular shortening in rats.

PURPOSE: To elucidate the effects of intra-articular haemorrhage on the joint capsule of immobilized knees in rats. METHODS: The unilateral knee joints were immobilized using a plastic plate and screws. Sham operated rats had only screws inserted. A single injection of fresh autologous blood was given postoperatively into the knee joints of the immobilized blood injection (Im-B) and the Sham blood injection (Sm-B) groups. Normal saline was administered for the immobilized-saline injection (Im-S) group. Sagittal sections were prepared from the medial midcondylar region of the knee and assessed with histological, histomorphometric, and immunohistochemical methods. The range of motion (ROM) was measured, and the mechanical property of the capsule was assessed by scanning acoustic microscope. RESULTS: Absorption of the injected blood was delayed and made severe adhesions in the Im-B group. The length of the synovial membrane in the Im-B group was significantly shorter than that of the other groups. The ROM was significantly restricted in the Im-B group compared with the other groups. The elasticity of the posterior capsule in the Im-B group was significantly lower than that in the Sm-B group. Iron deposition was observed in the Im-B and Sm-B groups. Strong immunoreactivities of CD68, TGF-ß1, and α-SMA were observed in the adhesion area of the Im-B group. Joint immobilization with blood injection caused severe capsular adhesion and limited range of motion. Immunostaining related to fibrosis increased with joint haemorrhage. CONCLUSION: Intra-articular haemorrhage with joint immobilization might be an accelerated risk factor for joint contracture. It is likely that leaving a haematoma inside an immobilized joint should be avoided.

Total knee replacement in patients with haemophilia: the Scottish experience.

INTRODUCTION: Patients with haemophilia commonly develop arthropathy secondary to recurrent haemarthroses. Although modern treatment with replacement coagulation factors has reduced the prevalence of end-stage arthropathy, total joint replacement is still required in a small group of patients. These patients may be at higher risk of complications and the outcome of surgery may not be comparable to reports of outcomes of total joint replacement in the general population. The purpose of this study was to describe the change in function in patients undergoing total knee replacement for haemophilic arthropathy. PATIENTS AND METHODS: Patients undergoing total knee arthroplasty in a tertiary centre had prospective evaluations of patient reported outcome measures and range of movement. Their post-operative function was evaluated in a combined orthopaedic-haematology clinic. Eight male patients underwent 13 total knee replacements from 1999 to 2007 and were followed up for a median of 78 months (range 17-116). RESULTS: The median Oxford knee score improved from 45.5 pre-operatively to 28 (p = 0.049). There was a similar improvement in SF-12 physical (p = 0.017) and Knee Society scores (objective p = 0.001; function p = 0.002). Four total knee replacements were performed in patients with inhibitor antibodies and were treated with recombinant activated factor VIIa. These patients had reduced range of movement (p = 0.047). No patients suffered deep infection. CONCLUSIONS: Total knee replacement in patients with haemophiliac arthropathy resulted in improvement in range of movement and function. The presence of factor VIII inhibitors resulted in reduced range of movement, but similar patient reported outcome measures.

Intra-articular injections of hyaluronic acid induce positive clinical effects in knees of patients affected by haemophilic arthropathy.

INTRODUCTION: Haemophilic arthropathy is the most common clinical manifestation of haemophilia, secondary to recurrent haemarthrosis and chronic synovitis, and the knee represents the main target joint. Modern bleeding prevention has significatively limited the incidence of severe arthropathy, and primary approach is usually conservative. Viscosupplementation is felt as one of the most efficient treatments for the early stages of knee haemophilic arthropathy, based on short-term follow-up studies. The aim of this prospective case series study is to assess the clinical effectiveness of intra-articular administration of hyaluronic acid in the knee, evaluating long-term results, and focusing on the necessity of further treatments after viscosupplementation. METHODS: Twenty-seven haemophilic patients with knee arthropathy underwent at least two cycles of injections of hyaluronians between 2003 and 2009. They were evaluated with VAS, SF-36, WFH, Pettersson score, and WOMAC, with a seven-year follow-up. RESULTS: All patients showed improvement in pain relief and functional recovery without any complications. Considering the severity of arthropathy in haemophilic patients, only a limited number of subjects (five) underwent total knee arthroplasty for persistent pain or functional limitation. CONCLUSIONS: Viscosupplementation is a safe and effective therapeutic strategy in knee haemophilic arthropathy, with no complications, persisting good clinical results, and determining in most cases a delay of surgery.

[Recurrent intra-articular bleeding episodes in haemophiliacs. Treatment outcomes in the patients at the university hospital motol in 1985-2005]. / Efekt lécby recidivujícího nitrokloubního krvácení v souboru hemofiliku lécených ve FN v Motole v letech 1985-2005.

PURPOSE OF THE STUDY: Chronic synovitis is a common finding in people with haemophilia. It regularly appears after recurrent episodes of intra-articular bleeding. The bleeding originates from the subsynovial venous plexus underlying the capsule where a lack of thromboplastic activity has been demonstrated. Therefore, the changed synovium appears to be a treatment target. There are several methods which can be used to remove the synovial layer from the joint. The aim of our study was to asses the efficacy of different treatment approaches used in a group of haemophiliacs between 1985 and 2005 in our hospital. MATERIAL AND METHODS: A group of 30 patients with bleeding disorders was evaluated in the study. There were 29 men with haemophilia and one woman with von Wilebrandt factor deficiency. Their age ranged from 6 to 18 (median 13) years. They underwent a total of 68 interventions including surgical synovectomy (n=28), radionuclide synovectomy (n=33) and corticosteroid instillation (n=7). The necessity of a repeat intervention was used as a criterion of successful treatment. RESULTS: In the group of surgical synovectomies, 22% of the patients required repeat operations, in the group of radiation synovectomy, this was 9% and, in the group treated with corticosteroids, this was 43%. The average hospitalisation time was 50 days for surgical procedures (19-133 days) and 7 days for radiation synovectomy procedures (4-13 days). DISCUSSION: In 1994 Merchan presented seven excellent or good results in a group of 10 knees evaluated 1 year after treatment with methylprednisolone. Six years later he reported that "five years after completion of treatment, all results of the observed patients were poor". Generally, corticosteroids will reduce synovitis in the majority of patients but the effect is temporary. A complete remission is a very rare situation under corticosteroid treatment. The experience with surgical synovectomies is not recent and this method is described as carrying a high risk of complications and requiring a high amount of coagulating factor consumption. There are several recent reports on the application of Yttrium-90: in Madrid they evaluated treated joints (knees, ankles and elbows, n = 66) in 44 patients aged from 9 to 39 years. The results were good in less than half of the knees and ankles. The treatment of elbows was more successful. It was recommended to perform synoviorthesis at the early stages of synovitis. In Israel, they reported that a decrease in the number of bleeding episodes was achieved in 80% of 115 patients treated with Yttrium-90; in 15% of them, bleeding in the treated joints stopped completely. In Izmir, Yttrium was used in the treatment of knees, elbows, ankles and also shoulders in children and young adults (3-25 years). The method was found to be safe and effective. Brazilian authors have experience with the treatment of knees, ankles, elbows and shoulders too; they have concluded that this method represents an important resource for the treatment of chronic haemophilic synovitis and markedly reduces joint bleeding frequency and pain, irrespective of the radiographic stage and inhibitor status. While the European Association of Nuclear Medicine (EANM) recommend using 186Re-sulfide for treatment in medium-sized joints, Chinese authors have published a study comparing the effect of using three different doses of 186Re-sulfide in the treatment of chronic synovitis in knees. Their patients have received an amount of radionuclide according to the thickness of their synovial layer measured on MRI, with the result that 22 patients exhibited significant reduction in synovial thickness. A reduction in the number of bleeding episodes was reached in 71% of the patients within an 18-month period. No significant differences were found among the groups receiving different radioactivity doses. In Turkey, 35 elbows, 26 ankles and two shoulders in 49 patients aged between 3 and 30 years were treated with 186Re. The patients were followed up from 6 months to 3 years. At 6 months after the procedure, 81% of the elbows and 86% of the ankles with grade II synovitis were free from bleeding, as well as 53% and 44% of the elbows and ankles with grade III synovitis, respectively. CONCLUSIONS: Radiation synovectomy appears to be the method of choice in the treatment of recurrent bleeding in the joint cavity in people with haemophilia. The efficacy of surgical synovectomy is lower in comparison with radiation synovectomy. Risks associated with surgery and anaesthesia, the need of hospitalisation and a prolonged period of rehabilitation are bothering. On the contrary, the application of corticosteroids cannot be recommended as a good method to treat recurrent haemarthroses.

Musculoskeletal care of the hemophiliac patient.

Hemophilia is caused by a deficiency of clotting factor VIII or IX and is inherited by a sex-linked recessive pattern. von Willebrand disease, a common, moderate bleeding disorder, is caused by a quantitative or qualitative protein deficiency of von Willebrand factor and is inherited in an autosomal dominant or recessive manner. The most important clinical strategy for the management of patients with hemophilia is the avoidance of recurrent hemarthrosis by continuous, intravenous hematologic prophylaxis. Early hemarthrosis should be aggressively managed with aspiration and clotting factor concentrate until the joint examination is normal. Starting prophylactic factor replacement in infancy may prevent chronic synovitis and arthropathy. The natural history of poorly controlled disease is polyarticular hemophilic arthropathy; functional prognosis is poor. Patients with chronic synovitis may be treated effectively with radiosynovectomy; those who develop joint surface erosions may require realignment osteotomies, joint arthroplasty, and treatment of pseudotumors. Reconstructive surgery for hemophilic arthropathy, especially in patients with factor inhibitor, requires careful hematologic management by an experienced, multidisciplinary team.

Coagulation aggravates blood-induced joint damage in dogs.

OBJECTIVE: Joint bleeding due to trauma, major joint surgery, or hemophilia leads to joint damage. It is unclear if there are differences between coagulating blood and anticoagulated blood with respect to joint degeneration, especially in vivo. Therefore, we undertook this study to evaluate in a canine in vivo model whether intraarticular exposure to coagulating blood is more destructive than exposure to anticoagulated blood, and whether inflammation plays a role in the cartilage- damaging process. METHODS: In 7 dogs the left knees were injected with coagulating blood 4 times a week during weeks 1 and 4, and the right knees were injected with saline. In 7 other dogs, anticoagulated heparinized blood was injected, and heparinized saline was used as control. Ten weeks after the last injection, cartilage matrix turnover and synovial inflammation were analyzed. To study inflammation-independent cartilage damage, explants of cartilage from at least 6 human donors per group were exposed in vitro to coagulating and anticoagulated blood, plasma, and serum for 4 days. Cartilage matrix turnover was determined after a recovery period of 12 days. RESULTS: Canine knees injected with coagulating blood showed more disturbed proteoglycan turnover than knees injected with anticoagulated blood. Synovial inflammation was present only after intraarticular injections with coagulating blood. In in vitro experiments, exposure of human cartilage explants to coagulating blood resulted in more damage than did exposure to anticoagulated blood, while exposure to plasma and serum did not alter cartilage matrix turnover. CONCLUSION: This study shows that coagulating blood causes more long-lasting in vivo joint damage than anticoagulated blood, thereby suggesting that along with joint bleeding in hemophilia, exposure to intraarticular blood should also be avoided during surgery and trauma to prevent joint damage.

Rituximab and intravenous immunoglobulin (IVIG) for the management of acquired factor VIII inhibitor in multiple myeloma: case report and review of literature.

Acquired factor VIII inhibitor (AFI) is a rare disorder and is even more uncommon in multiple myeloma patients, with only five cases reported in literature. Solid and hematologic malignancies, autoimmune conditions, drugs, and infections are the conditions commonly associated with the development of this condition, with mucocutaneous bleeding being the most common presenting sign. Diagnosis is usually made with the laboratory finding of an elevated partial thromboplastin time aPTT that cannot be corrected by plasma mixing, and further confirmed by low factor VIII activity/antigen levels along with elevated factor VIII inhibitor levels using the Bethesda assay. Treatment is usually based on the clinical picture with factor VIII inhibitor bypass activity (FEIBA) and recombinant factor VIIa (rFVIIa) employed to control acute bleeding; steroids and cyclophosphamide to suppress the inhibitor with Rituximab, in combination with other immunosuppressants in cases not suitable for steroids, and finally wherever possible, to remove the offending drug or control the underlying pathology that might predispose to the development of this condition. This case report highlights the successful management of a myeloma patient who presented with life-threatening hemorrhagic pericardial effusion and hemarthrosis. The patient was treated with FEIBA to control the acute bleeding and then received Rituximab in combination with intravenous immunoglobulin to suppress the AFI.

In-patient rehabilitation in haemophilic subjects with total knee arthroplasty.

Total knee arthroplasty (TKA) is a major orthopaedic surgery intervention, indicated for severe haemophilic arthropathy. The aim of our study was to analyse rehabilitation outcome in haemophilic patients after TKA. A consecutive series of 21 patients (23 knees) was retrospectively evaluated. The mean age was 37 ± 8 years (range 22-55). Physiotherapy treatment was performed twice a day for 5 days week⁻¹, for 3 h day⁻¹. Assessment included knee range of motion (ROM), Visual Analogue Scale (VAS) for pain evaluation, Western Ontario and McMaster University (WOMAC) Score for functional outcome, Medical Research Council Scale (MRC) for quadriceps muscle strength evaluation, incidence of adverse events and a self-reported questionnaire. The patients'data were recorded before surgery (t0), at Rehabilitation Unit admission (t1), before discharge (t2) and at follow-up (t3), 11-48 months after rehabilitation. Western Ontario and McMaster University Score (ref. score: 0-96) was 56.7 ± 12 at t0 and 6.2 ± 6 at t3 (t3 vs. t0: P < 0.001). Visual Analogue Scale (ref. score: 0-10) decreased from 5.0 ± 2 at t1 to 2.1 ± 2 at t2 (t2 vs. t1: P < 0.05) and to 0.1 ± 0 at t3 (t3 vs. t2: P < 0.05). Flexion degrees increased from 43.4 ± 21° at t1 to 80.2 ± 15° at t2 (t2 vs. t1: P < 0.001) and to 95.0 ± 15° at t3 (t3 vs t2: P < 0.05). According to MRC (ref. score: 0-5), quadriceps muscle strength increased from 2.3 ± 0.6 at t1 to 3.6 ± 0.5 at t2 (t2 vs. t1: P < 0.05). Adverse events were found in four patients. Patients' satisfaction on their outcome at follow-up was referred as good by 72% of patients or excellent by 28% of patients. Postsurgical intensive rehabilitation in haemophilic patients resulted effective, safe and feasible.

Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease in southern Iran.

The objective of the present study was to compare old and new bleeding scores in patients with type-3 von Willebrand disease (vWD), obligatory carriers and normal controls, and to compare the ability of bleeding scores vs. clinical and laboratory data to predict bleeding after surgery. We identified 15 patients from 12 families who had type 3 vWD. Normal controls were matched to carriers by sex and age. Two physician-administered standardized questionnaires were used to evaluate old and new bleeding symptoms. Scores for old symptoms were the same in carriers and control participants (median score 0.00 vs. 0.00, P < 0.001), and patients with vWD had a significantly higher bleeding score than carriers (median 10.00 vs. 0.00, P < 0.001). Scores for new symptoms were higher in carriers than in control participants (median score -1.00 vs. -2.00, P < 0.001), and patients had a significantly higher bleeding score than carriers (median 14.00 vs. -1.00, P < 0.001). The clinical situations associated with increased bleeding risk (old symptoms) in patients with type 3 vWD compared to obligatory carriers were epistaxis [odds ratio (OR) = 175.5; 95% confidence interval (CI) 14.55-2116.69; P < 0.001], cutaneous symptoms (OR = 108; 95% CI 10.16-1147.39; P < 0.001) and hemarthrosis (OR = 19.5%; 95% CI 4.32-156.46; P < 0.001). The clinical situations associated with increased bleeding risk according to scores for new symptoms in patients with type 3 vWD compared to obligatory carriers were epistaxis (OR = 175.5; 95% CI 14.55-2116.69; P < 0.001), cutaneous symptoms (OR = 52; 95% CI 7.65-353.09; P < 0.001) and bleeding from minor wounds (OR = 74.25; 95% CI 7.43-741.118; P < 0.001). The three groups differed significantly in the severity of epistaxis and cutaneous bleeding according to scores for new and old symptoms. The new bleeding score was more reliable than the old bleeding score in predicting bleeding after invasive procedure.

Neoangiogenesis contributes to the development of hemophilic synovitis.

Joint arthropathy secondary to recurrent hemarthroses remains a debilitating complication of hemophilia despite the use of prophylactic factor concentrates. Increased vascularity and neoangiogenesis have been implicated in the progression of musculoskeletal disorders and tumor growth. We hypothesized that de novo blood vessel formation could play a major role in the pathogenesis of hemophilic joint disease (HJD). We observed a 4-fold elevation in proangiogenic factors (vascular endothelial growth factor-A [VEGF-A], stromal cell-derived factor-1, and matrix metalloprotease-9) and proangiogenic macrophage/monocyte cells (VEGF(+)/CD68(+) and VEGFR1(+)/CD11b(+)) in the synovium and peripheral blood of HJD subjects along with significantly increased numbers of VEGFR2(+)/AC133(+) endothelial progenitor cells and CD34(+)/VEGFR1(+) hematopoietic progenitor cells. Sera from HJD subjects induced an angiogenic response in endothelial cells that was abrogated by blocking VEGF, whereas peripheral blood mononuclear cells from HJD subjects stimulated synovial cell proliferation, which was blocked by a humanized anti-VEGF antibody (bevacizumab). Human synovial cells, when incubated with HJD sera, could elicit up-regulation of HIF-1α mRNA with HIF-1α expression in the synovium of HJD subjects, implicating hypoxia in the neoangiogenesis process. Our results provide evidence of local and systemic angiogenic response in hemophilic subjects with recurrent hemarthroses suggesting a potential to develop surrogate biologic markers to identify the onset and progression of hemophilic synovitis.

Orthopedic approach of haemophiliacs. A single center experience in Romania.

Clinical expression of inadequately treated haemophilia is dominated by orthopedic complications, requiring invasive or non-invasive interventions. OBJECTIVE: In Romania, with under dosed and late introduced "on demand" substitution, we aimed at highlighting the experience of orthopedic treatment and its outcome. PATIENTS, METHODS: Single center retrospective analysis regarding orthopedic interventions and their outcomes was conducted on 59 hemophilia A, B, and von Willebrand disease patients, between 2002 and 2007. RESULTS: The majority of interventions, invasive (60.71%) and non-invasive (39.28%), were elective, only two being emergencies. Postoperative functional evolution after synovectomies was good in 68.28%, fair in 24.39%, satisfactory in 7.31%. Results of 33 non-invasive (extensive releases) procedures were very good in 27.27%, good in 63.63%, poor in 9.09%. DISCUSSION, CONCLUSIONS: The important number and complexity of orthopedic interventions are proving the precarious musculoskeletal state in persons with hemophilia, demonstrating the need of improving substitution, at least with discontinue prophylaxis in patients with severe forms.