Hemophilia is an X-linked recessive bleeding disorder caused by the deficiency of coagulation factors VIII, IX, or XI. Hemophilia A (Factor VIII deficiency) and Hemophilia B (Factor IX deficiency) are the commonest and the serious ones and their clinical presentation mostly overlap. Factor XI deficiency is commonly known as Hemophilia C. It is the milder variant and mostly seen in Ashkenazi Jews.

Deficiency of Factor VIII or Factor IX leads to a defective intrinsic coagulation pathway (decreased and delayed generation of thrombin, defective clot formation, and hemorrhagic diathesis). Being an X- linked recessive disorder, males are affected and females are asymptomatic or mildly affected carriers.

Epidemiology: In 2018, there was a 204% increase in the number of people with bleeding disorders identified since 1999 globally [Figure 1]. World Federation of Hemophilia (WFH) report on the annual global survey 2018, which included 125 national member organizations (NMOs), identified nearly 210,454 hemophilia patients. Out of the global total, nearly, 173,711(82.54%) had hemophilia A while 34,289 (16%) had hemophilia B. 78,547 were identified to have VWD. The total number of people with hemophilia A with clinically identified inhibitors was 6,929. A number of people with hemophilia B with clinically identified inhibitors was only 394 [1].

Figure-1: Identified patients over time – all bleeding disorders

Source: Report on the Annual Global Survey 2018 is published by the World Federation of Hemophilia.

In the year 2018, nearly 20,778 people were suffering from Hemophilia in India, out of the which, 17,606(84.73%) had Hemophilia A while 2,715(13.06%) had Hemophilia B.

Data Collection Procedure: This retrospective study involved patients who were admitted to the Pediatric emergency Ward, Department of Pediatrics, S.N. Medical College, Agra for the purpose of factor transfusion. Ethical clearance was taken from an ethical society. Parents or guardians were informed about the purpose of the study. For each patient, a detailed history was taken from the mother or the attendant. After taking a brief history preliminary selection was done, and the purpose of the study was explained in detail to its subject. After taking consent from the parents, data was collected, which included sex, age at presentation, age at diagnosis and clinical symptoms at presentation. A thorough physical examination was done in each patient.

Ethical Consideration and Permission: The study was conducted in the Department of Pediatrics, S.N. Medical College, Agra after obtaining ethical clearance from the Ethical Committee of S.N. Medical College, Agra.

Out of the total 93 pediatric hemophilia patients, the majority 61% (57/93) belonged to 11 to 18 years of age group. 2.1% (2/93) were< 1 year of age. 17.2% (16/93) were in 1-5 years of age group. 19.35% were in 6-10 years of age group (Table-1).

Table-1: Epidemiological profile of hemophilia patients.

Out of a total of 98.92% (92/93) were males while only 1.07% (1/93) were female (Table-1). 52 children out of 93 were from above the poverty line while 41/93 were from low socioeconomic status. 63/93 belonged to the urban area while 30 came from rural areas in the current study population (Table-1). Type A hemophilia was observed in 87.09% (81/93) patients while Type B hemophilia was present in only 12.9% (12/93) patients (Table

ankle, shoulder, and wrist. In those on prophylaxis, the ankle is commonly involved. Occasionally, mucosal bleeds (epistaxis, gums, gastrointestinal, genitourinary) might be the presenting features. Central nervous system (CNS) bleed may occur at any age, insidiously or following mild trauma. A suspected intracranial bleed in a diagnosed hemophilia patient must be first treated with factor concentrates even before confirmation by neuroimaging.

The bleeding phenotype differs based on the factor level and accordingly, hemophilia is classified into mild (>5%), moderate (1-5%) and severe (<1%) [4]. Severe hemophilia presents with spontaneous bleeds, especially from CNS, muscle, joints, etc. Nearly 50% of patients with severe hemophilia manifest by 6-8 months of age (with an increase in physical activity). Moderate hemophilia has heterogeneous manifestations. People with mild hemophilia usually bleed only after major surgery or trauma. Female carriers of hemophilia too can present with bleeding in the form of menorrhagia, skin bruising and postsurgical or peripartum hemorrhage [5].

Initial screening blood investigations (with reference ranges) for any child with the suspected bleeding disorder include platelet count (150-450 × 10³/µL); prothrombin time (PT) (11-15 seconds), and activated partial thromboplastin time (aPTT) (29-35 seconds). In hemophilia, screening tests reveal a prolonged aPTT with a normal PT and platelet count [6]. The other inherited conditions with similar screening results include von Willebrand disease (certain types), factors XI, XII, high molecular weight kininogen and prekallikrein deficiencies.

Mixing study is a simple test performed by mixing plasma from the patient with pooled normal plasma in 1:1 proportion and repeating aPTT after incubating for 30-60 minutes. Correction of aPTT after mixing suggests a deficiency in any of the factors in the intrinsic pathway. Prolonged aPTT may not get corrected with mixing study in case of the presence of antibodies to factor VIII or IX, lupus anticoagulant or heparinized sample [6]. Specific factor assays for factor VIII or IX should be done for specific diagnosis and ascertaining its severity. All-female carriers in the family should get their factor level tested as they can have levels ranging from normal to borderline (40-60%). Those with borderline levels can have increased bleeding tendency, especially during pregnancy, invasive procedures and trauma [5].

Young age and the reason for the first infusion along with the intensity of treatment could be important risk factors for the development of inhibitors.

Factor replacement is the mainstay of treatment for hemophilia. Minor bleeds in a joint, soft tissue or muscle can be slowed by using First Aid. The steps of this First Aid to slow bleeding are called RICE which stands for Rest, Ice, Compression, and Elevation. It is a common treatment used for many types of injuries, including those suffered by professional athletes.

Rest: While the joint is bleeding, it should be rested. In the event of an ankle or knee bleed, they should keep off their feet as much as possible and not do any physical activities. They should keep a set of crutches at home to use when a bleed starts. In hemophilia care, the “R” in RICE can also mean “Replacement of clotting factor”.

Ice: To help control swelling and reduce the pain they should apply ice. They can use crushed ice in a plastic bag or a bag of frozen vegetables, wrapped in a towel. It is very important not to apply the ice for too long. Ten or fifteen minutes at a time, every 2 hours, is long enough. The “I” in RICE can also mean “Immobilization”. The joint is held still (immobilized). When there is a lot of swelling, and if the movement is difficult and painful, the joint should be immobilized by a half-cast or a splint for short periods only, about 2 or 3 days. If the joint is kept immobilized for longer periods, the joint can become stiff and the muscles can become weak, making the joint more prone to re-injury.

Compression: They should apply pressure on the area that is bleeding to help ‘pinch off’ the blood vessels and slow down the bleeding. Compression of a joint or muscle bleed is done by using an elastic bandage (tensor). They should wrap the injured part in a figure-eight pattern. It is important that they watch carefully for coolness, numbness or a change in color in fingers or toes. If any of these symptoms occur, they should remove the bandage and re-wrap it less tightly. An alternative is a Tubigrip® sleeve. If the injury is very sore, they may find compression increases the pain. If this happens, they should rewrap the injury less tightly, or remove the bandage altogether.

Elevation: Placing the injured limb at a level higher than the heart helps decrease the pressure in the blood vessels and helps to slow the bleeding. They can rest their injured arm or leg on pillows.

The current study is conducted to evaluate the clinical-epidemiological profile of Hemophilia patients in the pediatric age group.

Such studies are pivotal to establish an early diagnosis of patients as well as to prevent complications such as joint swelling, deformity and fatal bleeding in registered patients by active and timely intervention.

Nonresponse to treatment likely suggests the development of inhibitors and thus these researches are a must-have insight into basic pathology and subsequent treatment with available resources.

Dr. Madhu Singh: Concept, study design, Dr. L.K. Gupta: Study design, Dr. G.K. Aneja: Data compilation, Prof (Dr). R. Dayal: Statistical analysis, Prof (Dr). Neeraj Kumar: Statistical analysis, Dr. Sheo Pratap Singh: Manuscript review, Dr. Madhu Nayak: Data analysis, Dr. Ram Kshitiz Sharma: Manuscript preparation

The authors sincerely thank Professor Dr. G.K Aneja, (Dean, S.N. Medical College, Agra) and Professor Dr. R. Dayal (Head, Department of Pediatrics, S.N.MedicalCollege, Agra) for continuous encouragement and inspiration to complete the work. The authors especially would like to thank Prof (Dr). Neeraj Kumar, and Dr. L.K. Gupta who have guided the work. Authors would also like to thank their colleagues for valuable suggestions and encouragement throughout the research work.