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Case ReportKepada Yth.Non-Infection Unit

HEMOPHILIA A IN AN ADOLESCENT BOY

Presenter: Johanes Sandro Timanta Sembiring (100100400)Day/Date: Thursday/ April 3rd 2014 Supervisor: dr. Fera Wahyuni, M.Ked(Ped), Sp.A

INTRODUCTIONHemophilia is the oldest known hereditary bleeding disorder. The transmission of hemophilia from mothers to sons was first described in the early 19th century in the United States. The word hemophilia first appeared in a description of a bleeding disorder condition at the University of Zurich in 1928. Hemophilia has often been called the Royal Disease caused Queen Victoria of England was a carrier of the hemophilia gene and subsequently passed the disease on to several royal families.1 There are two the most common types of hemophilia, hemophilia A (Classic Hemophilia) is caused by a lack or decrease of clotting factor VIII and hemophilia B (Christmas Disease) is caused by a lack or decrease of clotting factor IX. Hemophilia A is about four times as common as hemophilia B, and about half of those affected have the severe form.2In the United States, hemophilia affects 1 in 5,000 male births. About 400 babies are born with hemophilia each year. Currently, the number of people with hemophilia in the United States is estimated to be about 20,000, based on expected births and deaths since 1994.3 In Indonesia, prevalence of hemophilia reached about 4,1/1.000.000 population. This count is very small compared to prediction epidemiologically that is should be about 21.000 populations. At North Sumatra, particularly in Medan, prevalence of hemophilia reached about 34,8/1.000.000 population. This number was higher than prevalence of hemophilia at North Sumatera that was reached about 12,8/1.000.000 population. As a result, we can conclude that was so many undiagnosed hemophilia population in Medan.4The severity of hemophilia is related to the amount of the clotting factor in the blood. About 70% of hemophilia patients have less than one percent of the normal amount and, thus, have severe hemophilia. A small increase in the blood level of the clotting factor, up to five percent of normal, results in mild hemophilia with rare bleeding except after injuries or surgery.5

The aim of this paper is to report the case of hemophilia A in an adolescent boy

CASEName: BTAge: 13 yearsSex: MaleDate of Admission: March, 19th 2014

Main Complaint: Swelling on the left ankleHistory: It has been experienced by the patient for one week caused by trauma. The patients also got bruising on leg for two days. He has a history of amputated left hand finger in 2007 caused by trauma, and there is prolonged bleeding time when that injury was occured. In 2013, patient came with symptoms bleeding from a wound on the left thumb leg and swelling. Beside that, he had symptoms such as arthralgia, bleeding gum, melena and hematoma. His parents deny that there is family members experience the same thing. Fever (-), history of fever (-), nausea (-), vomiting (-), cough (-), influenza (-), urinary (+) normal, feces (+) normal. He has been diagnosed with Hemophilia A since 2007 and routinely got Koate.

History of previous illness: Hemophilia AHistory of previous medications: koateHistory of labor : normal delivery, handled by midwife, no cried as soon as baby was born, no cyanosis, the patient is 3rd child.History of feeding: breast milk until 2 years oldHistory of immunization: no history of immunization

Presens statusSensorium : compos mentisBlood Pressure : 90/60 mmHgTemperature: 37CWeight : 52 kgHeart Rate: 92 bpmHeight : 138 cmRespiratory Rate : 20 x/minutePhysical examinationThe patient consciousness is compos mentis, Weight: 52 kilograms (Weight/Age : 113%), Height: 138 cm (Height/Age: 88,5%), Weight based on Height: 162,5%, Temperature: 37C. General condition was moderate, disease condition was moderate and nutritional was good. There is no pale, dyspnoe, icteric, and cyanosis, but there is an edema.Head: Light reflexes (+/+), pupile were isochoric, conjunctivae palpebra inferior pale (-/-) Ear, mouth, and nose were normalNeck: Lymph node enlargement (-)Chest : Symmetrical fusiform, retraction (-) HR : 92 bpm, regular, murmur (-) RR : 20 x/minute, regular, crackles (-/-)Abdomen : Soepel, peristaltic was normal, liver and spleen were no palpableGenitalia : , anomalies (-)Extremities :Pulse 92 bpm, regular, tone/volume was adequate, CRT < 3, bruising (+), Left ankle oedem (+), pain (+), warm (-), redness (-), BP = 90/60 mmHg

Differential DiagnosesHemarthrosis et causa Hemophilia A Hemophilia B Von Willebrand Disease

Working DiagnosisHemarthrosis et causa Hemophilia A

Treatment Koate injection 30 IU/ kgBW/q12hRegular diet 2140 kcal with 104 gr proteinLaboratory findings on 4th January 2013Complete Blood Count

HematologyUnitResultReference

Hemoglobin (HGB)g%9.712.0-14.4

Erythrocyte (RBC)106/mm34.474.75-4.85

Leucocyte (WBC)103/mm320.014.5-11.0

Hematocrite%30.0036-42

Thrombocyte (PLT)103/mm320.014.5-11.0

MCVFl67.1075-87

MCHPg21.7025-31

MCHCg%32.3033-35

RDW%18.1011.6-14.8

MPVFl10.307.0-10.2

PCT%0.58

PDWFl11.70

Difftel Count

Neutrophil%87.3037-80

Lymphocyte%9.620-40

Monocyte%2.82-8

Eosinophil%0.21-6

Basophil%0.10-1

Neutrophil Absolute103/L17.442.7-6.5

Lymphocyte Absolute103/L1.931.5-3.7

Monocyte Absolute103/L0.560.2-0.4

Eosinophil Absolute103/L0.050-0.1

Basophil Absolute103/L0.030-0.1

Faal Hemostatic

PT+INR

Protrombin Time

ControlSeconds13.00

PatientSeconds15.00

INR1.17

APTT

ControlSeconds30.9

PatientSeconds50.3

Trombin Time

ControlSeconds18.2

PatientSeconds21.6

Faal Hemostatic

UnitResultReference

Factor VIII%3.255-150

Factor IX%143.070-140

Follow up 20th March 2014 S: bruising (+), swelling on the left ankle (+)O: Sensorium : compos mentis ; Temperature: 36,8C ; Weight : 52 kg Head : Eyes : Light reflexes (+/+), pupil were isochoric, conjunctivae palpebrae inferior pale (-/-) Ears, mouth, and nose were normalNeck : Lymph node enlargement (-)Chest : Symmetrical fusiform, retraction (-) HR 86 bpm, regular, murmur (-) RR 18 x/minute, regular, crackles (-/-)Abdomen : Soepel, peristaltic was normal, liver and spleen were not palpableGenitalia : , anomalies (-)Extremities : Pulse 86 bpm, regular, tone/volume was adequate,CRT < 3, bruising (+) Left ankle oedem (+)decreased , pain (-), warm (-), redness (-)A: Hemarthrosis et causa Hemophilia AP: Koate injection 30 IU/ kgBW/q12h Regular diet 2140 kcal with 104 gr protein

Follow up 21st March 2014 S: bruising (+), swelling on the left ankle (+)O: Sensorium : compos mentis ; Temperature: 36,9C ; Weight : 52 kg Head : Eyes : Light reflexes (+/+), pupil were isochoric, conjunctivae palpebrae inferior pale (-/-) Ear, mouth, and nose were normalNeck : Lymph node enlargement (-)Chest : Symmetrical fusiform, retraction (-) HR 96 bpm, regular, murmur (-) RR 20 x/minute, regular, crackles (-/-)Abdomen : Soepel, peristaltic was normal, liver and spleen were not palpableGenitalia : , anomalies (-)Extremities : pulse 96 bpm, regular, tone/volume was adequate,CRT < 3, bruise (+) Left ankle oedem (+)decreased , pain (-), warm (-), redness (-)A: Hemarthrosis et causa Hemophilia AP: Koate injection 30 IU/ kgBW/q12h Regular diet 2140 kcal with 104 gr protein

Follow up 22nd March 2014S: bruising (+), swelling on the left ankle (+)O: Sensorium compos mentis, Temperature 37C, Weight: 52 kg Head: Eyes : Light reflexes (+/+), pupil were isochoric, conjunctivae palpebrae inferior pale (-/-)Ear, mouth, and nose were normalNeck:Lymph node enlargement (-)Chest:Symmetrical fusiform, retraction (-) HR 88 bpm, regular, murmur (-) RR 18 x/minute, regular, crackles (-/-)Abdomen :Soepel, peristaltic was normal, liver and spleen were not palpableGenitalia :, anomalies (-)Extremities :pulse 88 bpm, regular, tone/volume was adequate,CRT < 3, bruising (+) Left ankle oedem (+)decreased , pain (-), warm (-), redness (-)A: Hemarthrosis et causa Hemophilia AP: Regular diet 2140 kcal with 104 gr protein

On 22nd March 2014 Patient was discharge and control to outpatient clinic

DiscussionHemophilia is an X-linked congenital bleeding disorder caused by a deficiency of coagulation factor VIII (in hemophilia A) and factor IX (in hemophilia B). Hemophilia generally affect males, while females are carriers. Most carriers are asymptomatic.6 In this case, the patient is a male. It is suitable with a theory that males more affect with hemophilia, but based on anamnesis his parent deny that families had a history of hemophilia. Hemophilia should be suspected in a patient with a history of easy bruising in early childhood, spontaneous bleeding particularly into joints, muscles, and soft tissues, excessive bleeding following trauma or surgery, epistaxis, gum bleeding, hematuria, and intracranial hemorrhage that can be life threatening.6 In this case, the patient had a history of amputated left hand finger caused by trauma with prolonged bleeding time. And now the patient got bruising on legs for two days and swelling on the left ankle for one week. From this clinical manifestation, we can suspected him with hemophilia.Three mechanisms work together to facilitate healing when a blood vessel is injured .First, the blood vessel constricts to limit the volume of blood that is lost. Second, circulating platelets form a plug at the site of injury. Finally, the blood undergoes coagulation.. This process allows the platelet plug to be stabilised by a fibrin matrix that is formed over its surface, thereby ensuring that the vessel wall can heal.7

Figure 1. Coagulation Cascade Model8The point of integration between the intrinsic and extrinsic pathways in this model occurs with factor IX activation. HMWK, high molecular weight kininogen.

The following tests may be used to screen a patient suspected to have a bleeding disorder are platelet count, BT, PT, and APTT.6Table 1. Interpretation of Screening Tests6Possible conditionPTAPTTBTPlatelet count

Hemophilia A or BNormalProlongedNormalNormal

VWDNormalNormal or PrololongedNormal or ProlongedNormal or reduced

Platelet defectNormalNormalNormal or prolongedNormal or reduced

A definitive diagnosis depends on factor assay to demonstrate deficiency of factor VIII or factor IX. The normal values of clotting factor VIII/IX is 0,5-1,5 U/dl (50-150%) The value of factor VIII on laboratory findings is 3,2%. Based on Leg classification, we could classified the patient in moderate hemophilia (1-5% of normal). Moderate hemophilia usually causes bleeding after minimal trauma.6,9Table 2. Classification of hemophilia based on severity9MildModerateSevere

Percentage of clotting factor5-30% of normal1-5 % of normal< 1%

Frequency Hemophilia A15%15%70%

Frequency Hemophilia B20%30%50%

Onset of age>2 years1-2 years 1 years

Signs in neonatusnever post circumcisional bleeding ; very rare Intracranial HemorrhageFrequent post circumcisional bleeding; rare Intracranial hemorrhageFrequent post circumcisionla bleeding; Intracranial hemorrhage

Bleeding in muscles/jointsSevere injuryMild injuryWithout injury / sponaneous

Bleeding in CNSRareModerate riskHigh risk

Bleeding post operationMayor surgicalNeed a bandageFrequent and fatal

Oral bleeding (trauma, dental extraction)RareCan occurFrequently occur

The aim of treatment patient with hemophilia is to prevent bleeding. There are some types of treatment, such as : factor concentrate (plasma-derived factor concentrate, recombinant factor concentrate), desmopressin acetate (for factor VIII deficiency), antifibrinolytic (for both factor VIII and IX deficiency). Non-drug treatments should be used when a patient with mild or moderate hemophilia has a bleed. These tratments are Rest, Ice, Compression, and Elevation (RICE).15In this case, the patient got Koate injection since 2007. Koate is antihemophilia factor concentrate/factor VIII concentrate for classic hemophilia therapy. Koate must be administered intravenously. Koate should be given after dissolved or in three hours after dissolved maximally. Dosage of koate in mild hemorrhage and prophylaxis is a single dose of 10 IU/kg; moderate hemorrhage is 15-25 IU/kg, if reqiured repeated doses of 10-15 IU/kg every 8-12 hours; severe hemorrhage initially 40-50 IU/kg with maintenance dose 20-25 IU/kg 8-12 hourly. The patient got Koate with doses 30 IU/kg every 12 hours. There are two form of Koate injection : 250 IU and 500 IU. Adverse drug reactions of Koate are allergic reactions, tingling in the arm, ear and face, blurred vision, headache, nausea, stomachache and jittery feeling.10,11Complications of hemophlia related to excessive or frequent blood loss. The complications are musculoskeletal complications (hemarthrosis, muscles athrophy, pain, joint deformity, synovitis, pseudotumours, and fracture)6, severe anemia from blood loss, hematuria, bleeding in digestive system, and compartement syndrome.12The outcome is usually good with treatment. Patients with hemophilia shouldestablish regular care with a hematologist, especially one who is associated with a hemophilia treatment center.13The prospects for youngster with hemophilia are excellent. Only a few decades ago, children with hemophilia had a significantly reduced life expectancy. Many recent studies have documented a greatly increased life expectancy among people suffering from hemophilia in developed countries over the last few decades.14

SummaryPatient BT came to Adam Malik caused by swelling on left ankle for one week with bruising for 2 days. The patient had a history of prolonged bleeding time caused by trauma in his hand finger on 2007. The doctor was diagnosed him with hemophilia A from faal hemostatic examination of factor VIII. The count was 3,2%. From this result, we could classified this patient with moderate hemophlia A. The patient had typical clinical manifestation of hemophilia A, such as swelling on the ankle which called hemarthrosis. Joints and muscles of extremities is the most common manifestation of bleeding. In acute condition, we can do Rest, Ice, Compression, Elevation (RICE) in site of bleeding.9The patient is treated with Koate which is antihemophilia factor concentrate/factor VIII concentrate. The patient got koate with dose 30 IU/kgBW/12 hours. After three days treated with Koate, swelling on the ankle was diminished and patient was permitted to go home and come back to control if clinical manifestation of bleeding recurrent.

References1. National Hemophilia Foundation. History of Bleeding Disorders. 2014. Available fromhttp://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=178&contentid=62. Centers for Disease Control and Prevention. Types of Hemophilia. 2014. Available from http://www.cdc.gov/ncbddd/hemophilia/facts.html3. Center for Disease Control and Prevention. Data and Statistic of Hemophilia in the United States. 2014. Available from http://www.cdc.gov/ncbddd/hemophilia/data.html).4. Koesoema Adi. Penyakit Hemofilia di Indonesia: Masalah Diagnostik dan Pemberian Komponen Darah. 2006.p 3-4 5. National Heart, Lung, and Blood Institute. Hemophilia. 2014. Available from http://www.nhlbi.nih.gov/health/public/blood/other/hemophel.htm6. World Federation of Hemophilia. Guidelines for The Management of Hemophilia. 2005. p 3-197. Vidlex V. Haemophilia: Pathophysiology and Management. In : Waugh A, Grant A, editors. Ross and Wilsons Anatomy and Physiology in Health and Illness. Edinburgh: Churcill Livingstone; 2003.p 30-318. James, Bradley, Christine, David. Theories of Blood Coagulation. In: Hoffman, R., Benz, J., Edward, J., Shattil, S. J., Furie, B., Cohen,H. J., et al., editors. Hematology: Basic principles and practice. Philadelphia: Elsevier, 2007. p 125-1279.Linda. Hemophilia A and B. In: Aru, Bambang, Idrus, Marcellus, Siti, editors. Textbook of Internal Medicine Chapter II 5th ed. Jakarta: Interna Publishing; 2009. p.1307-1210.Indonesian Hemophilia Society. The Golden Standard Therapy for Hemophilia A. 2014. Available from http://www.hemofilia.or.id/koate.php11.MIMS Indonesia. Koate-DVI. 2014. Available from http://www.mims.com/indonesia/drug/info/Koate-DVI/12.Brian, Thompson. Complications of Hemophilia. 2011. Available from http://www.webmd.com/a-to-z-guides/complications-of-hemophilia13.Kessler CM. Hemorrhagic disorders: coagulation factor deficiencies. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 180.14.WHO, Genes and Human Disease. 2014. Available from http://www.who.int/genomics/public/geneticdiseases/en/index2.html15. Carcao M. Mild and Moderate Hemophilia Chapter 7. p.5-9