A Case of Anterior Cruciate Ligament (ACL) Injury in a Beta Thalassemia Female Adolescent

Introduction:

Primary care is a challenging yet fascinating scope as evidenced by the myriads of cases that come through the doors on a typical Monday morning. Primary care physicians are the first to encounter the initial complaint of a patient, be it medical, surgical or an injury based problem. A thorough history is then taken followed by a physical examination. At this stage, it is usual that a differential diagnosis is postulated. Sports Medicine, however, is a whole new ball game. If it’s fair to say, it is a multidisciplinary practice which ties together medicine, exercise and injury management.

In this paper, emphasis is placed put on a female patient who is physically active in sports with poor nutritional status presenting with a knee injury. In this day and age, female athletes face multiple challenges. Pressure from coaches or society, and  the drive to improve their performance can cause female athletes to adopt a low body weight(1). Many athletes hide their low pathogenic weight in fear of reprisal from coaches or clinicians(1). Chapman et al. states in his paper that in this modern era there is a cultural bias  amongst female athletes to carry on training despite being injured due to the pressure from external parties and on oneself(2). The notion of certain sports presenting a higher risk of specific musculoskeletal injuries, e.g., sudden change in direction on a hard playing surface as seen in netball will be discussed later in this paper(2).

Case Discussion:

The case that we are discussing is a young 19 years old female of Indian origin who presented herself to an Urgent Care Clinic with a left knee injury. She sustained her knee injury during an amateur league netball game where she made a jump to get the ball and landed on her left foot in a standing position. She developed immediate pain in her left knee and was unable to carry on playing. Her knee swelled up within ten minutes. She struggled to bear weight on the affected knee. There was no history of knee dislocation nor were there any previous injuries to her left knee. Her past medical history was fairly unremarkable. She was not taking any regular medications. She was a vegetarian and a strict teetotaller. On examination, she had an antalgic gait. Her Body Mass Index (BMI) was around 20. She was unable to fully weight bear. She had a moderate sized effusion on her left knee and her range of motion was significantly limited. Examination of her cruciate ligaments was difficult due to the acute presentation. Her collateral ligaments felt intact at initial presentation. The distal extremity neurovascular status was intact. An X-ray of her left knee revealed an effusion but no fractures were found. She was given some analgesia and put into a Zimmer splint with her knee in extension. She was referred to the Sports Clinic for further assessment within 48 hours. She ended up getting an MRI which showed a complete anterior cruciate ligament (ACL) rupture with associated medical meniscus tear. She underwent ACL rehabilitation under the sports physicians for a few months and was eventually referred to orthopaedics for an ACL reconstruction. As part of a full work up, a baseline blood test was also carried out which revealed microcytic hypochromic anaemia. Interestingly, on further query about her menstrual cycle she confirmed having irregular and infrequent periods for the last few years. All of these issues will be discussed separately in this paper.

Anterior Cruciate Ligament(ACL) injury:

The ACL is a connective tissue structure that runs from the anterior tibial spine to the femoral condyle(3). It plays a role in knee stability by preventing anterior tibial translation and resisting rotational forces(3). ACL injuries are reported to be higher in women than in men who play the same sport(4). There is a higher rate of ACL injury in younger female adolescents(5). Certain sports such as basketball and handball carry a much higher risk of ACL injury(5). Risk factors for ACL injury can be categorized as either extrinsic and intrinsic.

Intrinsic risk factors for female athletes suffering ACL injury include(5):

1. being in the ovulatory phase of the menstrual cycle compared with the follicular or luteal phase;
2. having decreased intercondylar notch width on plain radiography; and
3. developing increased knee abduction moment (a valgus intersegmental torque) during impact on landing.

Further elaborating on hormonal influences, higher ACL injuries are sustained during the ovulatory phase as compared to luteal or follicular phase. This can be attributed to the fact that the estrogen levels are at its peak just before ovulation. Estrogen might work on the receptors allocated on the ACL ligament which affects collagen breakdown which in turn affects ligament laxity(4, 5). Other hormones such as progesterone and relaxin should not be overlooked(4). These hormones not only have a direct effect on ligaments but also affect neuromuscular function and  coordination(4). Interestingly, Wojtys et al.  states in his paper that oral contraceptives diminish the rates of ACL injury as compared to their counterparts not on oral contraceptives(4). Females also have smaller tibia condyles. Sonnery-Cottet et al. suggests in his paper that an increased posterior tibial slope and a narrow tibial notch width increases the risk of an ACL injury. Valgus collapse positions leads to ACL shortening(6). This position can be mimicked with the knee in 30 degrees flexion, internally rotating the hip and external tibial rotation, thus putting the knee at high risk of ACL injury(6). Knee adduction moment is at its highest when landing from a jump position(4). Emphasis should be placed on the importance of dynamic loading of the knee joint through proprioception and neuromuscular training(5). Techniques of landing softly on both the forefoot then rolling backward with involvement of both knee and hip flexion(5). As stated above, it is important to avoid excessive valgus loading of the knee. An often advised technique would be the “knee over toe position” when making sudden cutting or change in position(5).

There are also extrinsic risk factors that could play a part in higher rates of ACL injury.  The paper by Paterson K.L. et al. studied the barefoot landing of a small number of women versus stability of using shoes (7). The result  showed that stability with  appropriate footwear improved knee biomechanics and reduced the chances of an ACL injury(7).  The paper suggested that stable footwear should be made readily available to the general population as a simple injury prevention strategy(7). In another study done by Renstrom P. et al. argues that although increasing the coefficient between the playing surface and sports shoe may improve traction contact and enhance performance, it has several ramifications, i.e. higher risk of ACL injury(5). Intuitively sports athletes prefer higher shoe-surface traction interface.  As discussed above, the down side of this is the higher risk of ACL injuries, especially with a foot planted on the ground. The force that go through the knee joint is multifaceted. The high levels of rotational traction or torque presents the athlete a higher risk of an ACL injury(8). A meta-analysis by Thomson A. et al. presented three prospective studies looking at shoe-surface traction and ACL injuries(8).  One of the studies looked at male American footballers and hence, the results may not be applicable to the other variables such as females, and other sports e.g. netball(8). Therefore, as seen in our netball playing patient , subtle changes in playing surface area requires appropriate foot wear due to the changes in friction coefficient playing surface(8). Interestingly , meteorological conditions is also a factor in risk of sustaining ACL injury(5).  Low rain fall and the subsequent evaporation increase the risk of non-contact ACL injury by  increasing the shoe-surface traction coefficient(5). Implementation of programmes that will educate players on these matters  may reduce the likelihood of ACL injuries in the future(8). Nevertheless, this will require the collaboration and joint efforts  of several parties  amongst other, the physicians, coaches, governing bodies, and the athletes themselves(5).

A paper published in the American Journal of Sports Medicine by Failla M.J. and colleagues exhibits that preoperative rehabilitation of ACL improved postoperative outcomes at least in the short term(9). Six weeks of neuromuscular training and strengthening pre operatively revealed better results at three months post op(9).  Although this paper does not achieve an outcome of a specific programme in terms of neuromuscular training or progressive strengthening, it does go to show that any form of additional rehab beyond a quiet knee helped improve outcomes at two years postop(9). Currently, the standard care of ACL injury treatment or norm amongst primary care physicians in New Zealand is an early referral to orthopedic surgery. Patients are missing out on the crucial intensive progressive quadriceps strengthening and knee proprioception. Progressive preoperative ACL rehab should be considered in addition to the standard ACL reconstruction to help achieve better outcomes post operatively(9). Having said that, recent studies have shown similar rates of return to sport following both surgical and conservative management(10).  Keays S.L. and co-authors showed in their paper that almost 90% of ACL deficient individuals treated conservatively led an active sporting life, with one third returning to pivoting sports(10). Frobell R.B. and his colleagues published a randomized controlled trial on young adults with acute ACL injury(11). The result of the study showed no difference between rehabilitation plus early ACL reconstruction compared to structured rehabilitation plus optional delayed ACL reconstruction for knee instability(11).

Female Athlete Triad:

The old school of thought of the Female Athlete Triad was made up of disordered eating, irregularities in menstrual cycle, leading to low endogenous estrogen levels which led to low bone mineral density(12). Relative Energy Deficiency in Sports (RED-S) is a complex syndrome which refers to energy imbalance(12). Energy deficiency is caused by relative energy intake to energy expenditure required for physiological function, activities of daily living, sports and growth(12). Being an athlete that falls in the adolescent age group requires sufficient energy availability to allow for normal physiological cellular function. Energy Availability(EA) is Energy Intake(EI) less Exercise Energy Expenditure(EEE)(12). A person requires at least 30 kcal/kg of fat free mass(FFM) for normal muscle protein synthesis per day(12). Adequate energy availability is essential for normal ovulatory cycle and menstruation to occur. It is plausible that bone health is affected by the availability of sufficient energy. Estrogen helps with the uptake of calcium into the blood circulation and subsequent deposition into bone whereas progesterone facilitates this function through a few complex mechanisms(12). Ergo, any imbalance in estrogen/progesterone will affect bone health. For females, peak bone mineral density is achieved around 19 years of age. Our patient falls around the same age bracket where reaching peak bone mass is essential for the prevention of future bone adverse health problems such as osteoporosis. Nutritional status aside, there are other important factors affecting bone mineral density are; the type of exercise e.g. impact versus non-impact, smoking, alcohol intake and genetics. It is equally  important to find out the competitiveness of the sport, amount and type of exercise per week, pressure on athlete and athlete’s opinion(12). Due to health reasons, there is a clinical realm to educate athletes and get other parties involved such as sports physicians, nutritionist and physiotherapist(12).

Nutrition:

Adolescence is a period of psychological and physiological development(13). Usually there is an increased need of nutrient and energy intake during adolescence to be able to meet healthy bone growth and development(13). Balanced nutrient and fluid intake allows the maximization of exercise performance and recovery process(13). On blood testing, our patient had low haemoglobin (Hb) and Mean Cell Volume (MCV).  Anaemia is a medical problem that usually arises from nutrient deficiency albeit once other causes have been ruled out.  It is more common in females due to the loss of blood in monthly menstruation cycle. Having low haemoglobin can affect oxygen transportation, eventually impairing physical performance during exercise and leading to fatigue(13). Folate and vitamin B12 are also common factors for anaemia. Our case patient also had low vitamin B12 levels. It is not uncommon to see low vitamin B12 and folate levels in vegetarians(13). The blood picture seen in this group is usually macrocytic anaemia. This usually can be offset with concurrent iron deficiency microcytic picture with the MCV being within or close to normal range.  The World Health Organisation (WHO) recommendation of daily folate and B12 intake is still not met by most adolescent athletes and remains below recommended levels(13). The case patient is a strict vegetarian which would explain her higher risk of iron and B12 deficiency. She was eventually prescribed five B12 injections over a period of three months. Close attention was also given to other micronutrients. Her liver function tests showed raised ALP which could be attributable to low Vitamin D levels. She was treated with monthly Colecalciferol. Her risk factors for vitamin D deficiency are dark skin complexion and lack of sunlight exposure, i.e. indoor netball. Although, the majority of Vitamin D is obtained via UV rays, the recommended calcium intake per day is 1500 mg and 1500 IU per day of vitamin D(12).

Anaemia and Thalassemia:

Our patient’s haemoglobin count was 104 g/L with a Mean Cell Volume (MCV) of 73. She had a previous blood result with similar microcytic anaemic picture. Thalassemia prevalence is highest in Middle Eastern, Mediterranean and Asian population(14). Given the Indian ethnicity of our patient, further investigations were requested to clinch the diagnosis of thalassemia. Thalassemia is a common cause of microcytic anaemia(14). It involves reduction in the globin chain synthesis. Heamoglobinopathies electrophoresis testing suggested beta thalassemia minor.  Thalassemia minor patients are  usually asymptomatic and only require genetic counselling as compared to the counterpart thalassemia major in which iron transfusions might be required(14). Borderline low haemoglobin (Hb), increased red cell distribution width (RDW) and low mean cell volume (MCV) usually pathognomonic on haematological testing(14). Dilemma usually arises when there is a suspicion of low iron levels. Iron study added showed low serum iron, ferritin and transferrin saturation. Subsequently, the results of a soluble transferrin receptor (sTfR) which was also carried out came back elevated suggesting iron deficiency. sTfR is a marker of iron status and a reliable parameter in diagnosing iron deficiency due to its poor correlation with inflammation(15). She was prescribed Ferrogradumet 325 mg which contains 100 mg of elemental iron. She was advised to take iron supplementation for at least six months. A repeat full blood count was suggested to the patient, to be done after a three month course of iron replacement.

Observation of low iron is perpetual in female endurance athletes who are vegetarian. A daily requirement of iron is usually 18 mg per day(13). Our patient was advised to have it with orange juice or vitamin C as it promotes iron absorption in the gut and avoid taking iron tablets with food, coffee, tea or milk. Some of the side effects of iron tablet were also discussed such as gastrointestinal upset, nausea or constipation. She was recommended and advised to keep a food diary which included type of food and frequency of meals throughout the day. Unfortunately, being a vegetarian due to religious practices, it was a futile attempt to recommend red meat, fish or eggs in her diet. Instead, she was advised to have a larger intake of broccoli, spinach, nuts, salads, bean curd, beans and lentils in her diet. Iron deficiency can have deleterious effects on exercise especially endurance(16). Current research shows that moderate to high intensity exercise of 30 minutes to two hours plays a role in up regulating circulating hepcidin levels(16). Hepcidin is derived by hepatocytes which plays a role in inhibiting iron transport and leads to degradation of it and thus reduces iron bioavailability(16).  Hepcidin levels can remain elevated for up to six hours and peaks at around three hours post exercise(16).  Therefore, the timing of a meal is important to allow absorption of iron from the gut system. Given our patient is a vegetarian, small details like this is crucial in helping her maintain a normal iron level. 

Menstrual Cycle:

A normal menstrual cycle usually lasts for approximately 28 days. It involves the follicular and luteal phase. Ovulation usually occurs mid cycle. On the other hand, oligomenorrhoea is defined as irregular menstrual cycle lasting for 36 days to three months(1).  Due to the erratic period cycle, ovarian follicle fail to achieve maturity as a result of hypoestrogenism(1). It is important to rule out other medical causes such as pregnancy, hypothyroidism, pituitary tumour (releasing prolactin) or polycystic ovarian syndrome (PCOS)(1). Blood test investigations such as prolactin, estrogen, progesterone, luteinising hormone (LH), follicular stimulating hormone(FSH), testosterone, and thyroid function should be done. As for our patient, her hormonal study came back normal but her thyroid stimulating hormone (TSH) came back borderline raised. She was advised to repeat her TSH level in three months as she did not have any subclinical hypothyroidism symptoms. The cause of her irregular menstrual cycle was eventually narrowed down to iron deficiency. It would have been interesting to find out her menstrual cycle day in relation to her injury, albeit this was not asked.

In conclusion, our patient presented herself to an urgent care clinic with a knee injury. With the knowledge imbibed in sports medicine, the ability to inter-connect other health issues such as irregular menstrual cycle and poor nutritional status helps a clinician to address the patient holistically. Medicine is not a merely a single presenting complaint but also encompasses other important health and social issues which are usually intermingled. Besides addressing the patient’s ACL injury, it is important to take into account her nutritional status and re-establishing her menstrual cycle regularity to prevent future bone insufficiency issues. A multidisciplinary approach was used and she was eventually referred to a dietitian to maximize her nutritional status and to the sports medicine clinic.