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15. HEMOPHILIA IN CHILDREN
Osmonova Gulnaaz Zh
Muskan Kumawat
Krushna Theng
Deepak Yadav
Sahil Ravindra Akare
Fahad
(1, Teacher, Department Of pediatric, International Medical Faculty, Osh State University, Osh, Kyrgyzstan.
2,6, Medical Student, International Medical Faculty, Osh State University, Osh, Kyrgyzstan.)
ABSTRACT
Deficits or malfunctions in clotting factors VIII (hemophilia A) or IX (hemophilia B) cause hemophilia, a genetic X-linked recessive bleeding condition. It mainly affects boys and shows up as sudden or protracted bleeding, especially into the muscles and joints, after minor surgery or trauma. Preventing consequences including persistent hemarthrosis, arthropathy, and potentially fatal bleeding requires early identification in children.
A coagulation factor deficit is usually confirmed by laboratory assessment, which shows a prolonged activated partial thromboplastin time (aPTT) with normal platelet count and prothrombin time (PT). In addition to preventative measures to preserve hemostasis and avoid joint injury, treatment focuses on replacement therapy employing recombinant or plasma-derived clotting factors. Extended half-life factor concentrates, gene therapy, and non-factor medicines like emicizumab are recent developments that provide better results and a higher standard of living. For the best illness control and disability prevention, comprehensive treatment comprising hematologists, physiotherapists, and patient education is essential.
Keywords: Coagulation, Thromboplastin, Hemostasis, Malfunction, Bleeding, Hemarthrosis, Muscle , Trauma , Platelet, Clotting factor.
I. INTRODUCTION
A lack or malfunction of certain clotting factors, most frequently factor VIII (hemophilia A) or factor IX (hemophilia B), is the hallmark of hemophilia, a genetic bleeding illness. Males are the main victims of this X-linked recessive genetic disorder, whereas females often carry it asymptomatically. Prolonged bleeding following an accident, surgery, or in extreme situations, spontaneous bleeding, is caused by the disorder's decreased capacity to form stable blood clots.
Hemophilia frequently manifests in the first few months or years of a child's life as the kid gets more active and experiences spontaneous bruising, profuse bleeding from small wounds, or joint swelling (hemarthrosis). If left untreated, repeated joint bleeding can result in muscle contractures, chronic arthropathy, and permanent disability. Hemophilia A affects around 1 in 5,000 male births worldwide, and hemophilia B affects roughly 1 in 25,000 male births. To avoid problems and enhance prognosis, early detection and timely treatment are crucial. Coagulation studies with extended activated partial thromboplastin time (aPTT) and specific factor assays that identify the missing factor and its activity level are necessary for diagnostic confirmation.
With the advent of recombinant clotting factors, longer half-life products, and preventative treatment plans, which have dramatically decreased morbidity and mortality, the therapy of hemophilia in children has made remarkable strides in recent decades.
Additionally, new treatments like gene therapy and bispecific antibodies (emicizumab) are changing the therapeutic landscape by providing the possibility of long-term repair of the underlying problem.
Symptoms of Hemophilia:
1. Bleeding: This is defined as bleeding that persists longer than usual following small wounds,traumas, or surgical operations (such as tooth extractions or circumcisions).
• Justification: Hours after injury, prolonged oozing or rebleeding occurs because the blood clotting process is delayed due to a lack of clotting factors.
2. Unplanned Bleeding Incidents
• Take place in cases of severe hemophilia (factor activity <1%), particularly when there is no visible damage.
• Soft tissues, muscles, and joints are typical locations. These episodes frequently start as soon as the youngster can move (walk or crawl).
3. Hemarthrosis, or bleeding in the joints; The most typical sign of moderate to severe hemophilia, it frequently affects the elbows, knees, and ankles. Recurrent hemarthroses can result in chronic synovitis and hemophilic arthropathy, which can cause lifelong joint abnormalities and impairment. Symptoms include joint discomfort, swelling, warmth, and restricted mobility.
4. Hemorrhage in the Muscles Large hematomas may compress blood vessels or nerves, resulting in neuropathy or compartment syndrome; they may also cause swelling, discomfort, and restricted movement of the afflicted limb; and they may bleed into muscles like the calf, thigh, or forearm.
5. Easy Bruising (Ecchymosis): Even with minor damage, children may have big, deep bruises that can sometimes go undiagnosed. These bruises might form on the back, trunk, or limbs.
6. Mucosal Surface Bleeding
• Consists of gum bleeding, recurrent nosebleeds (epistaxis), and bleeding during tooth eruption or dental procedures. Severe instances may result in genitourinary or gastrointestinal hemorrhage.
7. Bleeding After Medical Procedures In infants, prolonged or delayed bleeding following a venipuncture, injection, or circumcision may be the first sign of a medical condition. Massive hematomas might result from injections into the muscle.
8. Intracerebral hemorrhage, or ICH
• A potentially lethal outcome, especially in infants or after head trauma. Symptoms include a protruding fontanelle, fatigue, convulsions, agitation, nausea, and unconsciousness. • Requires immediate medical attention and factor replacement.
9. Hematuria: Pain in the abdomen or flanks may occur when there is blood in the urine due to bleeding in the urinary system.
10. Delayed Wound Healing: Bleeding into wounds can cause clots to develop later and take longer to heal.
2. TYPES OF HEMOPHILIA:
A lack or malfunction of certain clotting factors is the hallmark of hemophilia, a genetic bleeding condition that causes prolonged bleeding following trauma or even spontaneous hemorrhages. Based on whether coagulation factor is lacking, the disorder is primarily divided into three types: hemophilia A, hemophilia B, and hemophilia C.
1. Hemophilia A: About 80–85% of all instances are of hemophilia A, commonly known as classic hemophilia, which is the most prevalent kind. It is caused by mutations in the F8 gene on the X chromosome (Xq28), which leads to a lack or malfunction of Factor VIII (antihemophilic factor). Due to the disorder's X-linked recessive inheritance pattern, females are often carriers whereas men are mostly affected. The remaining factor activity determines the severity of hemophilia A: mild instances (6–40%) only bleed after major damage or surgery, moderate cases (1–5%) bleed after minor trauma, and severe cases (<1% activity) manifest with spontaneous joint and muscle bleeding.
2. Hemophilia B: Christmas illness, or hemophilia B, is brought on by mutations in the F9 gene on the X chromosome (Xq27.1–q27.2), which results in a lack of Factor IX (Christmas factor). Similar to hemophilia A, it is X-linked recessive and clinically identical; specific factor testing are needed for diagnosis in order to distinguish between the two. Hemophilia B makes up between 10–15% of all instances of hemophilia, and the degree of factor IX activity in plasma also affects how severe disease is.
3. Hemophilia C: Hemophilia C, also known as Rosenthal syndrome, is a considerably less common variant of the condition that results from mutations in the F11 gene on chromosome 4 (4q35) that induce a lack of Factor XI. Males and females may be equally afflicted by hemophilia C since it has an autosomal recessive inheritance pattern, in contrast to types A and B. It is most frequently observed in people who are Ashkenazi Jews. In terms of clinical presentation, hemophilia C is often less severe than hemophilia A or B, and bleeding usually happens after trauma or surgery.
II. RESEARCH METHODOLOGY
1. Introduction: Understanding the genetic, clinical, and therapeutic aspects of hemophilia—an hereditary bleeding condition brought on by clotting factor deficiencies—requires a well-structured research process. In individuals with hemophilia A, B, and c, a suitable methodological framework aids in determining the prevalence, molecular basis, clinical symptoms, and results of different treatment modalities.
2. Research problem
Due to a lack of knowledge, expensive treatment costs, and a lack of diagnostic facilities, hemophilia is still a major health concern, especially in poor nations. In order to enhance early diagnosis and maximize therapy, the research challenge centers on evaluating the clinical patterns, genetic differences, and management results of individuals with hemophilia.
3. Objectives of the study: Goals of the Research
• To ascertain the patients' hemophilia types (A, B, or C) and prevalence.
• To assess the severity and clinical symptoms according to factor activity levels.
• To examine the genetic alterations that cause the illness.
• To evaluate the efficacy of various treatment techniques, such as factor replacement therapy.
• To detect side effects include joint abnormalities, inhibitor development, and infections linked to transfusions.
4. Research design
Usually, this study uses an analytical and descriptive research approach.
• Descriptive: To outline the patients' demographic profiles and clinical characteristics.
• Analytical: To examine relationships among illness severity, factor levels, and genetic abnormalities.
A cross-sectional, retrospective, or prospective cohort design may be used, depending on the goal.
5. Study population
All individuals with hemophilia who visit the pediatric or hematology departments of hospitals and diagnostic facilities are included in the target population.
Hemophilia A, B, or C cases verified by factor tests are the requirements for inclusion.
Patients with acquired bleeding problems or those with insufficient medical information are excluded.
6. Sampling method
When choosing patients from treatment facilities or registries, a purposive or convenience sample technique is frequently employed. To guarantee representation of all hemophilia types and severity levels, stratified random sampling may be used in bigger research.
7. Data collection method
Both primary and secondary sources are used to get data: • Primary data: Clinical examinations, patient interviews, and laboratory tests (PT, aPTT, factor VIII, IX, and XI assays). • Secondary data: Examining published works, registries, and medical records.
To find the causing gene abnormalities, genetic investigations may use PCR-based mutation analysis and DNA extraction.
8. Analyzing Data
Software for statistical analysis (like SPSS or R) is used to examine the collected data. While descriptive statistics provide an overview of clinical and demographic factors, inferential tests (such as regression analysis, chi-square, and t-test) identify correlations between illness severity, factor levels, and mutation type. It is possible to do a theme analysis of qualitative data, such as patient experiences.
III RESULT AND DISCUSSION
An estimated 400,000 people worldwide are thought to have hemophilia. In China, there are an estimated 109,426 total hemophilia patients. In Pakistan, an estimated 20,000 children were thought to have hemophilia in 2012, though this is a rough estimate and probably not complete. Many nations lack complete registries, particularly for children, so data is not complete across regions.
By WHO, we found that, India has a substantial hemophilia burden, with the greatest number of cases reported occurring in Uttar Pradesh. However, underreporting and uneven data collection make it difficult to get thorough state-specific prevalence figures. The prevalence is estimated to be 0.9 per 100,000 people nationwide, which raises the possibility that there are more cases than that.
And in Kyrgyzstan ,we found that it has at least 425 hemophiliac patients recorded as of June 2023, including about 187 children under the age of 16. This indicates that around 44% of all hemophiliac patients in the nation are youngsters.
Enhancing care and treatment access for hemophiliacs has been a priority for the Kyrgyz Hemophilia Society and the World Federation of Hemophilia (WFH). Over 37 million international units (IUs) of clotting factor have been delivered to Kyrgyzstan under the WFH Humanitarian Aid Program since 2015; in 2024 alone, more than 5 million IUs were given. Due to these efforts, patients' quality of life has significantly improved. For example, joint replacement operations have been introduced, and home rehabilitation and preventative treatment have become more common.Even with these improvements, there are still issues because of few resources and the requirement for more all-encompassing care. Even though the government still spends money on antihemophilic factor purchases, demand frequently outpaces supply.
You can get in touch with the Kyrgyz Hemophilia Society or speak with medical experts at the National Centre of Hematology in Bishkek for more specific information or help.
Management of alopecia:
1. Replacement therapy (replacement of the factor)
When bleeding episodes occur, factor replacement is administered
. • Prophylactic therapy: Consistent infusion to keep clotting factor levels above a certain point in order to stop bleeding on its own. For kids with severe hemophilia, this is advised.
• Setting up the factor: Human plasma is the source of plasma-derived components, which are checked for viruses.
• Recombinant factors: produced in laboratories; reduced susceptibility to infections
. • Extended half-life factors: Improve adherence by requiring fewer infusions.
• Dosage: Relies on the kind of hemophilia, place, degree of bleeding, and severity of the deficit.
• Objective: Sustain factor levels high enough to halt bleeding, shield joints, and permit safe exercise.
2. Management of bleeding episodes: Moderate- With moderate factor supplementation, rest, ice, compression, and elevation (RICE) may be enough
. • Moderate to severe bleeding: In the case of cerebral, muscular, or joint bleeding, immediate factor replacement is necessary.
• Emergency care: Children who experience gastrointestinal or cerebral bleeding need to be hospitalized right away and have their factors replaced aggressively.
3. Treatment of complication
• Replacement of early factors for joint bleeding
. • Physiotherapy to preserve muscular strength and joint mobility.
• Joint replacement or synovectomy as a surgical treatment for persistent arthropathy.
• Inhibitor development: Antibodies against injected clotting factors can form in certain kids.
• Immuno tolerance induction (ITI) or the use of bypassing drugs (such as recombinant factor VIIa or activated prothrombin complex concentrates) are two possible management options.
4. Treatments Without Factors
• Emicizumab: A subcutaneously given bispecific monoclonal antibody that imitates factor VIII action.
• Additional new agents are being studied, including concizumab and fitusiran.
• Benefits: Less frequent infusions, simpler at-home treatment, and a decreased chance of inhibitor-related problems.
5. Assistance with Care
• Physiotherapy: Prevents muscle atrophy and tight joints. Occupational therapy assists kids in preserving their independence and engaging in everyday activities in a safe manner.
• Pain management: Acetaminophen is recommended over non-steroidal anti-inflammatory medications (NSAIDs).
6. Vaccination: Immunizations and Diseases to lower the risk of muscle bleeding, children should have regular vaccines, ideally subcutaneously. It's crucial to screen for HIV, hepatitis B, and C, particularly if they've been around plasma-derived products.
COMPLICATIONS
1. Musculoskeletal complications :
a. Hemarthrosis, or bleeding in the joints
• Constant bleeding into joints, especially the ankles, elbows, and knees.
• Symptoms include warmth, pain, edema, and limited mobility.
• Complication: Hemophilic arthropathy, which results from chronic hemarthrosis, can cause joint abnormalities, restricted mobility, and disability.
b. Hematomas in the muscles
• Flowing into the muscles (forearm, calf, thigh, etc.).
• May result in neuropathy or compartment syndrome by compressing blood vessels or nerves.
• If left untreated, it might result in contractures or muscular fibrosis.
2. Internal Hemorrhage
Hematemesis or melena, anemia, and persistent tiredness can all result from gastrointestinal bleeding.
Urinary Tract Bleeding Hematuria can be brought on by bleeding in the bladder or kidneys.
Hemorrhage within the brain (ICH)
• A potentially fatal consequence, particularly in newborns or following trauma.
• Symptoms include fatigue, irritability, vomiting, seizures, and a protruding fontanelle
• Necessitates hospitalization and emergency factor replacement.
3. Development of Inhibitors • Antibodies (inhibitors) against infused clotting factors can develop in certain people. • Reduces the effectiveness of therapy, resulting in poor joint results and repeated bleeding. • Controlled with bypassing drugs or immunological tolerance induction (ITI).
4. Complications Associated with Treatment
a. Viral Infections: Previously, plasma-derived factors might spread HIV, hepatitis B, or hepatitis C, but this danger has been decreased with current screening.
b. Allergic Reactions: Children who receive recombinant factors are more susceptible to mild to severe hypersensitivity to clotting factor concentrates.
5. Chronic Anemia: Children who have frequent bleeding may develop iron-deficiency anemia, weariness, and stunted growth.
CONCLUSION
Deficit or malfunction of clotting factor VIII (hemophilia A) or factor IX (hemophilia B) results in hemophilia, a hereditary, X-linked recessive bleeding condition that mostly affects men. It is categorized as mild, moderate, or severe according to the amount of clotting factor that is still present. Bleeding from mucosal surfaces, joint and muscle hemorrhages (hemarthrosis and hematomas), spontaneous bleeding episodes, and persistent bleeding following small traumas are frequent symptoms of hemophilia in children. Severe instances may have life-threatening side effects such hematuria, gastrointestinal bleeding, or cerebral hemorrhage, which need to be identified and treated very once.
Childhood hemophilia must be diagnosed early in order to avoid irreparable effects. Prolonged activated partial thromboplastin time (aPTT) with normal platelet counts and prothrombin time (PT) are commonly observed in laboratory evaluations, and certain factor assays validate the kind and degree of the deficit. Early identification makes it possible to start preventive or on-demand factor replacement therapy on time, which has been demonstrated to lower the frequency of bleeding, avoid joint injury, and enhance general quality of life.
Even with major progress, a number of obstacles still exist. These include the emergence of inhibitors that oppose factor replacement therapy, the difficulty in obtaining clotting factor concentrates and high-quality care in low-resource environments, and the long-term psychological and financial strain of maintaining a persistent bleeding problem. International programs, like the World Federation of Hemophilia Humanitarian Aid Program, seek to lower the illness burden in children and provide access to treatment, especially in impoverished nations.
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