History

Fact Explanation
Gender Hereditary factor IX deficiency (Christmas disease or Hemophilia B) is a X-linked inherited bleeding disorder[4][8], usually manifested in males while females are silent carriers [8]. Haemophilia B has a prevalence of around 1 in 30,000 male live births [1].
Age Age is very important in the history as evaluation will depend on the age of the patient (eg:- bruising will be common when the child starts moving) and there can be changes in the factor level in various stages of the life. [9] Newborns without hemophilia have reduced levels of Factor IX (approximately 40%) while premature babies have much lower levels due to the immaturity of the liver. Then the level gradually increases in the first year into the low-normal adult range. Also there is a puberty-related (testosterone induced) rise in Factor IX levels during the adolescent period.
Easy bruising[8] There is a bleeding tendency following factor IX deficiency as it is a major component in common clotting pathway. Factor IX is a vitamin K–dependent single-chain glycoprotein, which is synthesized by the hepatocyte as a precursor protein. Common features are: multiple bruising marks following delivery, easy bruising with mild/ unnoticed trauma especially when the child starts to walk and bruising following sports.
Bleeding tendency[4][8] : prolonged bleeding with skin damage, delayed bleeding, bleeding from mucous membranes[8] The following features may be seen in the history: prolonged bleeding from the umbilical cord cutting, prolonged bleeding from minor surgeries like circumcision or prolonged bleeding following minor trauma. Delayed bleeding (bleeding occurs several hours to days after) with trauma, surgery or dental extractions. This is characteristic feature of hemophiliacs. Patients can present with spontaneous mucosal bleeding or this can be induced by alcohol or NSAIDs.
Haematoma formation[8] in soft tissues[6], body cavities Excessive bleeding in to soft tissue plains causes formation of haematomas. Features that can be seen are: scalp swelling following labour suggestive of cephalohematoma this is mostly associated with instrumentation/ vacuum extraction, haematoma following Vk IM injection at birth or following other intramuscular injections during giving vaccination and development of acute pain and swellings in the body following minor trauma/ contact sports. When soft tissue hematomas disseminate through fascial planes it can compromise vital organs. If they extend into the retroperitoneal space may leads to severe blood loss. If haematomas form in limited spaces like the femoral canal it can compress nerve leading to weakness and nerve palsy. Haematoma formation inside compartments (eg; limbs, abdomen) can cause symptoms of compartment syndrome (severe intractable pain, which will severe on passive movements, limiting functions).
History of fits, sudden onset loss of consciousness, paralysis and other neurological complications[11] If they bleed into the brain or spinal cord, a haematoma forms in central nervous system[5] neurological symptoms or sudden death can occur. There may be progressive neurological symptoms with expanding haematoma. Blood can irritate the meningeal layers causing headache, stiff neck, vomiting, lethargy and irritability.
Bleeding into joints[7][8] (Haemarthrosis) Joint bleeds develop as physical activity increases.The most common joint affected is the knee joint while elbow, ankle, hip, shoulder and wrist can also be affected. Sudden onset severe pain and swelling in the joint limiting/preventing the movements following trauma. Patients usually present with affecting the same joint repeatedly (target joint). Repeated bleeding can damage the intra articular cartilage(synovial proliferation can destroy by fibrosis and the release of proteolytic enzymes within the joint) and adjacent bones causing gradual destruction of joint function.
Family history of bleeding disorder[10] Family history of bleeding should be sought as this is a X-linked recessive disorder[1], 1/3 of persons with hemophilia does not have family history of bleeding). A history of bleeding disorders, early unexpected sudden deaths in previous generations of maternal side, females relatives with menorrhagia or excessive bleeding after trauma (carriers with Factor IX < 30% can have a clinically evident bleeding disorder).
Dietary history This is important in a patient with history of recurrent/ excessive bleeding as it can cause iron deficiency anaemia[12]. Overall nutritional condition should be improved in such patients.
References
  1. LIN HF, MAEDA N, SMITHIES O, STRAIGHT DL, STAFFORD DW. A coagulation factor IX-deficient mouse model for human hemophilia B. Blood [online] 1997 Nov 15, 90(10):3962-6 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9354664
  2. CAMPOS-DE-MAGALHãES M, EDUARDO BRANDãO-MELLO C, LúCIA ELIAS PIRES M, CECíLIA DA FONSECA SALGADO M, BARCELO DE BRITO S, JOSé DE ALMEIDA A. Factor VIII and IX deficiencies related to acquired inhibitors in a patient with chronic hepatitis C virus infection receiving treatment with pegylated interferon plus ribavirin. Hematology [online] 2011 Mar, 16(2):80-5 [viewed 10 August 2014] Available from: doi:10.1179/102453311X12902908412156
  3. FIGLER TJ, KESHAVARZIAN A, NAND S, DEMOS TC. Retroperitoneal amyloidosis, factor IX and X deficiency,and gastrointestinal bleeding. Abdom Imaging [online] 1996 May-Jun, 21(3):266-8 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8661563
  4. OSTERUD B, RAPAPORT SI. Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc Natl Acad Sci U S A [online] 1977 Dec, 74(12):5260-5264 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC431674
  5. BORKAR SA, PRASAD GL, SATYARTHEE GD, MAHAPATRA AK. Spontaneous spinal extradural hematoma in a child with hemophilia B, surgery or medical management - A dilemma? J Pediatr Neurosci [online] 2011, 6(2):131-133 [viewed 10 August 2014] Available from: doi:10.4103/1817-1745.92837
  6. JAHNS M, FRIESS D, DEMARMELS BIASIUTTI F, KREMER HOVINGA JA, ALBERIO L, OLDENBURG J, LäMMLE B, COLUCCI G. Massive muscle haematoma three months after starting vitamin K antagonist therapy for deep-vein thrombosis in an antithrombin deficient patient: another case of factor IX propeptide mutation. Thromb Haemost [online] 2011 Aug, 106(2):381-2 [viewed 10 August 2014] Available from: doi:10.1160/TH11-03-0191
  7. SIMPSON ML, VALENTINO LA. Management of joint bleeding in hemophilia. Expert Rev Hematol [online] 2012 Aug, 5(4):459-68 [viewed 10 August 2014] Available from: doi:10.1586/ehm.12.27
  8. PHILIP J, SARKAR RS, KUMAR S, PRATHIP BR, PATHAK A. Factor IX deficiency (Christmas disease) Med J Armed Forces India [online] 2012 Oct, 68(4):379-380 [viewed 10 August 2014] Available from: doi:10.1016/j.mjafi.2011.12.007
  9. BJöRKMAN S, SHAPIRO AD, BERNTORP E. Pharmacokinetics of recombinant factor IX in relation to age of the patient: implications for dosing in prophylaxis. Haemophilia [online] 2001 Mar, 7(2):133-9 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11260271
  10. MISHRA KL. Hereditary bleeding disorder, factor ix deficiency in females: a case series Cases J [online] :8940 [viewed 10 August 2014] Available from: doi:10.4076/1757-1626-2-8940
  11. STRBIAN D, MICHEL P, SEIFFGE DJ, SAVER JL, NUMMINEN H, MERETOJA A, MURAO K, WEDER B, FORSS N, PARKKILA AK, ESKANDARI A, CORDONNIER C, DAVIS SM, ENGELTER ST, TATLISUMAK T. Symptomatic intracranial hemorrhage after stroke thrombolysis: comparison of prediction scores. Stroke [online] 2014 Mar, 45(3):752-8 [viewed 10 August 2014] Available from: doi:10.1161/STROKEAHA.113.003806
  12. GHOSH S. Investigating iron deficiency anemia without clinical evidence of gastrointestinal blood loss Can J Gastroenterol [online] 2012 Oct, 26(10):686 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472905
  13. KöITER J, VAN GENDEREN FR, BRONS PP, NIJHUIS-VAN DER SANDEN MW. Participation and risk-taking behaviour in sports in children with haemophilia. Haemophilia [online] 2009 May, 15(3):686-94 [viewed 10 August 2014] Available from: doi:10.1111/j.1365-2516.2009.02006.x
  14. LINDVALL K, COLSTRUP L, WOLLTER IM, KLEMENZ G, LOOGNA K, GRöNHAUG S, THYKJAER H. Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia. Haemophilia [online] 2006 Jan, 12(1):47-51 [viewed 10 August 2014] Available from: doi:10.1111/j.1365-2516.2006.01192.x
  15. CHOWDARY P, DASANI H, JONES JA, LORAN CM, ELDRIDGE A, HUGHES S, COLLINS PW. Recombinant factor IX (BeneFix) by adjusted continuous infusion: a study of stability, sterility and clinical experience. Haemophilia [online] 2001 Mar, 7(2):140-5 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11260272
  16. KIRTAVA A, SOUCIE M, EVATT B, MDIVINISHVILI M, ABASHIDZE M, IOSAVA G. National haemophilia programme development in the Republic of Georgia. Haemophilia [online] 2005 Sep, 11(5):529-34 [viewed 10 August 2014] Available from: doi:10.1111/j.1365-2516.2005.01127.x
  17. TOBIAN AA, SAVAGE WJ, TISCH DJ, THOMAN S, KING KE, NESS PM. Prevention of allergic transfusion reactions to platelets and red blood cells through plasma reduction. Transfusion [online] 2011 Aug, 51(8):1676-83 [viewed 10 August 2014] Available from: doi:10.1111/j.1537-2995.2010.03008.x

Examination

Fact Explanation
Evidence of clotting defect[3] : bruising marks, excessive bleeding( blood in urine, blood in stools) and haematoma formation If a patient presents with a fresh wound/ following surgery/ cannulation excessive bleeding can be seen with difficulty in stopping. Urine and stool examination also helpful in haematuria and malena[2]. Haematoma can be identified as a painful soft tissue swelling. Large encapsulated haematoma with progressive cystic swelling (Haemophilic pseudo tumours) can be seen in facial and muscle planes, large muscle groups, long bones, pelvis and cranium.
Joint examination for: haemarthrosis[3], joint deformity On joint examination an acute haemarthrosis will be seen as a swelling(fullness) around joint, severe tenderness on touching, bogginess around the involved joint due to an inflamed synovium, presence of blood inside and fluid and limitation of joint mobility causing pseudo paralysis. Long term follow up and joint examination for deformity and destruction should be assessed.
Neurological examination[4]: neck stiffness, motor and sensory deficits Neck stiffness, seizures, motor and sensory deficit will be examination findings in a patient with haemorrhage into the central nervous system or a CNS haematoma formation.
References
  1. CAMPOS-DE-MAGALHãES M, EDUARDO BRANDãO-MELLO C, LúCIA ELIAS PIRES M, CECíLIA DA FONSECA SALGADO M, BARCELO DE BRITO S, JOSé DE ALMEIDA A. Factor VIII and IX deficiencies related to acquired inhibitors in a patient with chronic hepatitis C virus infection receiving treatment with pegylated interferon plus ribavirin. Hematology [online] 2011 Mar, 16(2):80-5 [viewed 10 August 2014] Available from: doi:10.1179/102453311X12902908412156
  2. FIGLER TJ, KESHAVARZIAN A, NAND S, DEMOS TC. Retroperitoneal amyloidosis, factor IX and X deficiency,and gastrointestinal bleeding. Abdom Imaging [online] 1996 May-Jun, 21(3):266-8 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8661563
  3. PHILIP J, SARKAR RS, KUMAR S, PRATHIP BR, PATHAK A. Factor IX deficiency (Christmas disease) Med J Armed Forces India [online] 2012 Oct, 68(4):379-380 [viewed 10 August 2014] Available from: doi:10.1016/j.mjafi.2011.12.007
  4. STRBIAN D, MICHEL P, SEIFFGE DJ, SAVER JL, NUMMINEN H, MERETOJA A, MURAO K, WEDER B, FORSS N, PARKKILA AK, ESKANDARI A, CORDONNIER C, DAVIS SM, ENGELTER ST, TATLISUMAK T. Symptomatic intracranial hemorrhage after stroke thrombolysis: comparison of prediction scores. Stroke [online] 2014 Mar, 45(3):752-8 [viewed 10 August 2014] Available from: doi:10.1161/STROKEAHA.113.003806
  5. KIRTAVA A, SOUCIE M, EVATT B, MDIVINISHVILI M, ABASHIDZE M, IOSAVA G. National haemophilia programme development in the Republic of Georgia. Haemophilia [online] 2005 Sep, 11(5):529-34 [viewed 10 August 2014] Available from: doi:10.1111/j.1365-2516.2005.01127.x
  6. BERMEJO F, GARCíA-LóPEZ S. A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases World J Gastroenterol [online] 2009 Oct 7, 15(37):4638-4643 [viewed 11 August 2014] Available from: doi:10.3748/wjg.15.4638
  7. WILSON DA, NELSON MD JR, FENSTERMACHER MJ, BOHAN TP, HOPPER KD, TILTON A, MITCHELL WG, CONTANT CF JR, MAEDER MA, DONFIELD SM. Brain abnormalities in male children and adolescents with hemophilia: detection with MR imaging. The Hemophilia Growth and Development Study Group. Radiology [online] 1992 Nov, 185(2):553-8 [viewed 11 August 2014] Available from: doi:10.1148/radiology.185.2.1410372

Differential Diagnoses

Fact Explanation
Factor VIII deficiency[1] Clinical features are similar to factor IX deficiency. This is the most common hereditary clotting factor deficiency. Investigations such as assessment of the Factor VIII levels help in differentiation.
Von Willebrand disease[2] This is due to the qualitative/ quantitative reduction of the von Willebrand Factor(VWF). Bleeding time will be prolonged and the VWF level will be low.
Hereditary disorders of other rare coagulation factors[3] These are rare. Deficiency of fibrinogen, prothrombin, factor V, factor VI, combined factor V and VII, factor X, XI, XIII. Most are inherited as autosomal recessive. Risk of bleeding is comparatively less.
Vitamin K deficiency[4] Vitamin K is needed to activate factors II, VII, IX, X and protein C and S. Deficiency due to inadequate diet, malabsorption or due to Warfarin use, can lead to bleeding.
Liver disease[5] Liver disease can induce bleeding in several ways: biliary obstruction causing impaired absorption of fat soluble Vitamin K, reduction in factor production, abnormalities of produced fibrinogen, decreased thrombopoietin production leading to thrombocytopenia and hypersplenism causing thrombocytopenia.
References
  1. VERBRUGGEN B, MEIJER P, NOVáKOVA I, VAN HEERDE W. Diagnosis of factor VIII deficiency. Haemophilia [online] 2008 Jul:76-82 [viewed 11 August 2014] Available from: doi:10.1111/j.1365-2516.2008.01715.x
  2. BHARATI KP, PRASHANTH UR. Von Willebrand Disease: An Overview Indian J Pharm Sci [online] 2011, 73(1):7-16 [viewed 11 August 2014] Available from: doi:10.4103/0250-474X.89751
  3. SHARMA SK, KUMAR S, SETH T, MISHRA P, AGRAWAL N, SINGH G, SINGH AK, MAHAPATRA M, TYAGI S, PATI H, SAXENA R. Clinical Profile of Patients with Rare Inherited Coagulation Disorders: A Retrospective Analysis of 67 Patients from Northern India Mediterr J Hematol Infect Dis [online] , 4(1):e2012057 [viewed 11 August 2014] Available from: doi:10.4084/MJHID.2012.057
  4. MISRA D, BOOTH SL, TOLSTYKH I, FELSON DT, NEVITT MC, LEWIS CE, TORNER J, NEOGI T. Vitamin K deficiency is associated with incident knee osteoarthritis. Am J Med [online] 2013 Mar, 126(3):243-8 [viewed 11 August 2014] Available from: doi:10.1016/j.amjmed.2012.10.011
  5. AMITRANO L, GUARDASCIONE MA, BRANCACCIO V, BALZANO A. Coagulation disorders in liver disease. Semin Liver Dis [online] 2002 Feb, 22(1):83-96 [viewed 11 August 2014] Available from: doi:10.1055/s-2002-23205

Investigations - for Diagnosis

Fact Explanation
Activated partial thromboplastin time (aPTT)[3][5] Activated partial thromboplastin time (aPTT) will be prolonged. However in mild disease it may be within the normal range.
Prothrombin time (PT) and Bleeding time[3][5] Prothrombin time (PT) and Bleeding time will be normal.
Factor IX assay[3] Factor IX will be low and according to the Factor IX percentage activity level, severity can be assessed.
Full Blood Count(FBC)[5] Haemoglobin will be low in patient with repeated bleeding. However the level may be normal as in acute haemorrhage it takes time for haemodilution to occur. Platelet count will be normal.
Thromboelastography[6] This is a method useful in assessing clot formation characteristics and is being used to assist in determining bleeding tendency.
Imaging studies[5]: Ultrasonography, X rays, CT scan[2]/MRI, endoscopy/ cystoscopy Ultrasonography is useful in assessing the joint bleeding in haemarthrosis, haematoma formation, liver in suspected complication of liver involvement and in gastrointestinal bleeding X ray of the joints will give evidence of joint deformity and destruction, but is not helpful in acute haemarthrosis. CT scan/MRI[4] is helpful in assessing the bleeding/ haematoma formation in CNS when there is neurological signs. Endoscopy/ cystoscopy may be necessary in gastrointestinal bleeding/ Urinary bleeding to exclude other pathologies.
Genetic screening As this is an X linked recessive disorder of the gene locus is Xq27.1-q27.2. So identification of mutation[1] can be done using Karyotyping.
Stool and urine examination[5] In gastrointestinal bleeding occult blood/ fresh blood can be seen in stools while red coloured urine with macroscopic haematuria or RBC in urine with microscopic haematuria can be seen.
References
  1. LIN HF, MAEDA N, SMITHIES O, STRAIGHT DL, STAFFORD DW. A coagulation factor IX-deficient mouse model for human hemophilia B. Blood [online] 1997 Nov 15, 90(10):3962-6 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9354664
  2. FIGLER TJ, KESHAVARZIAN A, NAND S, DEMOS TC. Retroperitoneal amyloidosis, factor IX and X deficiency,and gastrointestinal bleeding. Abdom Imaging [online] 1996 May-Jun, 21(3):266-8 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8661563
  3. SMITH SB, GAILANI D. Update on the physiology and pathology of factor IX activation by factor XIa Expert Rev Hematol [online] 2008 Oct, 1(1):87-98 [viewed 10 August 2014] Available from: doi:10.1586/17474086.1.1.87
  4. BORKAR SA, PRASAD GL, SATYARTHEE GD, MAHAPATRA AK. Spontaneous spinal extradural hematoma in a child with hemophilia B, surgery or medical management - A dilemma? J Pediatr Neurosci [online] 2011, 6(2):131-133 [viewed 10 August 2014] Available from: doi:10.4103/1817-1745.92837
  5. PHILIP J, SARKAR RS, KUMAR S, PRATHIP BR, PATHAK A. Factor IX deficiency (Christmas disease) Med J Armed Forces India [online] 2012 Oct, 68(4):379-380 [viewed 10 August 2014] Available from: doi:10.1016/j.mjafi.2011.12.007
  6. DE PIETRI L, MASETTI M, MONTALTI R, BEGLIOMINI B, REGGIANI A, BARBIERI E, BIAGIONI E, MARIETTA M, ROMANO A, PASETTO A, GERUNDA GE. Use of recombinant factor IX and thromboelastography in a patient with hemophilia B undergoing liver transplantation: a case report. Transplant Proc [online] 2008 Jul-Aug, 40(6):2077-9 [viewed 11 August 2014] Available from: doi:10.1016/j.transproceed.2008.05.054

Investigations - Fitness for Management

Fact Explanation
Full Blood Count(FBC)[1] Useful in assessing the patient's general condition and need for blood transfusion and assessing the volume of blood that needs to be transfused.
Blood grouping and crossmatching[2] Needed for blood transfusion.
References
  1. PHILIP J, SARKAR RS, KUMAR S, PRATHIP BR, PATHAK A. Factor IX deficiency (Christmas disease) Med J Armed Forces India [online] 2012 Oct, 68(4):379-380 [viewed 10 August 2014] Available from: doi:10.1016/j.mjafi.2011.12.007
  2. HEAL JM, BLUMBERG N, MASEL D. An evaluation of crossmatching, HLA, and ABO matching for platelet transfusions to refractory patients. Blood [online] 1987 Jul, 70(1):23-30 [viewed 11 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3474041

Investigations - Followup

Fact Explanation
Factor IX assay[1] This is helpful for the follow up to decide the need for Factor IX replacement.
Inhibitor level assessment[2] Checking of the inhibitor levels should be considered at regular intervals according to the recommendations of the British Committee for Standards in Haematology (BCSH) in a patient who is provided regular factor replacement.
References
  1. MISHRA KL. Hereditary bleeding disorder, factor ix deficiency in females: a case series Cases J [online] :8940 [viewed 11 August 2014] Available from: doi:10.4076/1757-1626-2-8940
  2. KRAIEM I, HADHRI S, EL OMRI H, SASSI R, CHAABANI W, ENNABLI S, SKOURI H. Frequency of specific coagulation inhibitors and antiphospholipid antibodies in Tunisian haemophiliacs. Ann Biol Clin (Paris) [online] 2012 Nov-Dec, 70(6):659-65 [viewed 11 August 2014] Available from: doi:10.1684/abc.2012.0765

Investigations - Screening/Staging

Fact Explanation
Staging the severity using Factor IX percentage activity level[3] - Mild (6% to 25% functional factor IX): bleeding which occurs only after severe trauma or surgery, or following the use of drugs such as NSAIDs - Moderate (2% to 5% functional factor IX): bleeding which occurs following minor trauma or surgery, or the occasional spontaneous hemarthrosis. - Severe (≤ 1% of functional factor IX): spontaneous hemorrhages/hemarthrosis which date from infancy.
Prenatal screening by[4]: measuring factor IX activity level and genetic studies Hemophilia B can be detected prenatally by measuring Factor IX activity in fetal blood. The blood samples should be taken at 20 weeks of gestation by fetoscopy. Gene mutation[1] analysis can be performed using, chorionic villus sampling at 12 weeks or amniocentesis at 16-20 weeks.
Karyotyping for genetic screening and Factor IX level assay, APTT[2] Screening should be done in family members of a patient who has been diagnosed as having hereditary factor IX deficiency.
References
  1. LIN HF, MAEDA N, SMITHIES O, STRAIGHT DL, STAFFORD DW. A coagulation factor IX-deficient mouse model for human hemophilia B. Blood [online] 1997 Nov 15, 90(10):3962-6 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9354664
  2. PHILIP J, SARKAR RS, KUMAR S, PRATHIP BR, PATHAK A. Factor IX deficiency (Christmas disease) Med J Armed Forces India [online] 2012 Oct, 68(4):379-380 [viewed 10 August 2014] Available from: doi:10.1016/j.mjafi.2011.12.007
  3. CHUNG KS, MADAR DA, GOLDSMITH JC, KINGDON HS, ROBERTS HR. Purification and characterization of an abnormal factor IX (Christmas factor) molecule. Factor IX Chapel Hill. J Clin Invest [online] 1978 Nov, 62(5):1078-1085 [viewed 11 August 2014] Available from: doi:10.1172/JCI109213
  4. CHEN SH, YOSHITAKE S, CHANCE PF, BRAY GL, THOMPSON AR, SCOTT CR, KURACHI K. An intragenic deletion of the factor IX gene in a family with hemophilia B. J Clin Invest [online] 1985 Dec, 76(6):2161-2164 [viewed 11 August 2014] Available from: doi:10.1172/JCI112222

Management - General Measures

Fact Explanation
Life style modifications Lifestyle has to be adapted to minimise the bleeding risk. Contact sports[3] should be avoided as far as possible especially in severe deficiency as there is significant risk of trauma Home modifications can be done such as adequate lighting inside and out, minimize furniture.
Modifications in labour to protect the affected fetus[5] Manual labour should be avoided and ventouse delivery and fetal scalp monitors not be used during vaginal birth off known carriers of hemophilia.
Reach the full range of growth and development potentials[6] Early identification, early treatment, prevention of complications associated with continuous monitoring and evaluation of the child's growth and development, provide balanced diet supplying all nutrients,good social and mental support will help to reach the full range of growth and development potentials.
Physiotherapy in haemarthrosis[7] Haemarthrosis[2] limit the functional capacity and reduce the quality of joint movements. Physiotherapy is useful in this situation.
References
  1. LIN HF, MAEDA N, SMITHIES O, STRAIGHT DL, STAFFORD DW. A coagulation factor IX-deficient mouse model for human hemophilia B. Blood [online] 1997 Nov 15, 90(10):3962-6 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9354664
  2. SIMPSON ML, VALENTINO LA. Management of joint bleeding in hemophilia. Expert Rev Hematol [online] 2012 Aug, 5(4):459-68 [viewed 10 August 2014] Available from: doi:10.1586/ehm.12.27
  3. KöITER J, VAN GENDEREN FR, BRONS PP, NIJHUIS-VAN DER SANDEN MW. Participation and risk-taking behaviour in sports in children with haemophilia. Haemophilia [online] 2009 May, 15(3):686-94 [viewed 10 August 2014] Available from: doi:10.1111/j.1365-2516.2009.02006.x
  4. CHOWDARY P, DASANI H, JONES JA, LORAN CM, ELDRIDGE A, HUGHES S, COLLINS PW. Recombinant factor IX (BeneFix) by adjusted continuous infusion: a study of stability, sterility and clinical experience. Haemophilia [online] 2001 Mar, 7(2):140-5 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11260272
  5. WETZEL E, KINGMA P. Subgaleal hemorrhage in a neonate with factor X deficiency following a non-traumatic cesarean section J Perinatol [online] 2012 Apr, 32(4):10.1038/jp.2011.122 [viewed 11 August 2014] Available from: doi:10.1038/jp.2011.122
  6. WILSON DA, NELSON MD JR, FENSTERMACHER MJ, BOHAN TP, HOPPER KD, TILTON A, MITCHELL WG, CONTANT CF JR, MAEDER MA, DONFIELD SM. Brain abnormalities in male children and adolescents with hemophilia: detection with MR imaging. The Hemophilia Growth and Development Study Group. Radiology [online] 1992 Nov, 185(2):553-8 [viewed 11 August 2014] Available from:
  7. MORFINI M, COPPOLA A, FRANCHINI M, DI MINNO G. Clinical use of factor VIII and factor IX concentrates Blood Transfus [online] 2013 Sep, 11(Suppl 4):s55-s63 [viewed 11 August 2014] Available from: doi:10.2450/2013.010s

Management - Specific Treatments

Fact Explanation
In the acute bleeding state: Achieve haemostasis, Factor IX replacement[8], Pain management[10] and Reduce bleeding[11] Attention is needed for immediate cessation of bleeding, frequent monitoring for early identification of impending shock and fluid replacement to achieve haemostasis. While patient is being cannulated blood should be send for APTT, PT, FBC, grouping and crossmatching. [5] In the established patient, factor level assessment should be done. Replacement of the factor (Recombinant factor IX) will depend on the severity of the disease. According to the research evidence available 2 factor IX units per kilogram of body weight increase the factor level by 1%. If severe bleeding is present correct the level to 100%. If minor bleeding present correction to 50% will be adequate. Calculate the required dose required is based on the body weight, baseline factor IX level and the desired level to be achieved. Another dose should be given after 24 hours and should be half of the initial calculated dose. When recombinant factor IX is not available fresh frozen plasma[5] and cryoprecipitate can used. Minor haemorrhage will requires 1-3 doses of factor while major haemorrhage needs many doses and may need continued factor IX activity monitoring because the factor IX level should be maintained at least 50%. Haematoma and haemarthrosis can be very painful and require analgesic to reduce the pain as soon as possible. NSAIDs should not be given as it can induce gastrointestinal bleeding. Parenteral opiates will be needed as the pain is very severe.This must be intravenously (IV) or possibly subcutaneously (SC) but should not be given intramuscularly (IM) as it will leads to haematoma formation. Antifibrinolytic therapy (tranexamic acid) [5] is useful for oral mucosal haemorrhage to reduce bleeding and as prophylaxis.
In the chronic state: health education[9], vaccination[8], look for inhibitors, multidisciplinary management[6] Vaccination should be done against hepatitis A and hepatitis B subcutaneously. Assessment in developing inhibitors[2][3] by measuring the level of inhibitors. As inhibitors are developed(1-3% of severe cases after 11 days of exposure) for the factors further management will be complicated, so precautions should be taken with the hematologist's opinion[8] to replace the factor only in needful situations and duration. In case of development of antibodies, patient should be treated with immunosuppressants( eg; cyclophosphamide), IV immunoglobulin and high dose of factor VII. In some patients with inhibitor development is associated with anaphylaxis[2] on exposure to any factor IX product. So first exposure should take place in a specialist centre where resuscitation facilities available. Regular follow up should be done involving a multidisciplinary team.
Surgical considerations: prophylactic drugs[5], surgical treatments[12] In cardiac or orthopaedic surgery, tranexamic acid[5] should be given as it inhibits fibrinolysis without increasing thrombosis risk in healthy individuals undergoing cardiac or orthopaedic surgery. Avoid antiplatelet drugs before 1 week of urgery and in immediate postoperative period to minimize risk of bleeding. Use ice packs at surgical sites which will beneficial in reducing the size of the surgical site hematoma. Surgical treatments available: joint replacement in severely deformed joints following repeated haemarthrosis[7], evacuation of haematoma causing pressure symptoms( eg; CNS, in tissues), fasciotomy in compartment syndrome[13] caused by haematomas.
Prophylactic factor replacement[2] Routine prophylactic factor IX replacement is beneficial in patients with severe deficiency to prevent haematoma and haemarthrosis formation. Dose will be 50 IU/kg weekly or 100 IU/kg every 10 days. Prophylaxis Factor IX replacement should be 80-100 units/kg (80%-100%) in minor procedures like endoscopy or colonoscopy, stitches, biopsies, suturing, spinal tap, dental procedures, arterial blood gasses Prophylactic Factor IX replacement in major surgical procedures like oral surgery, orthopedic surgery, joint replacement, synovectomy, fasciotomy should be: 100 u/kg (100%) 30 minutes prior to procedure, 15-30 min after the procedure factor level should be checked, then repeated post operatively. Maintain a level of 50-60% and avoid trough level less than 75%.
References
  1. KISKER CT, EISBERG A, SCHWARTZ B, MONONINE STUDY GROUP. Prophylaxis in factor IX deficiency product and patient variation. Haemophilia [online] 2003 May, 9(3):279-84 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12694518
  2. ALEXANDER S, HOPEWELL S, HUNTER S, CHOUKSEY A. Rituximab and desensitization for a patient with severe factor IX deficiency, inhibitors, and history of anaphylaxis. J Pediatr Hematol Oncol [online] 2008 Jan, 30(1):93-5 [viewed 10 August 2014] Available from: doi:10.1097/MPH.0b013e31815cf742
  3. CAMPOS-DE-MAGALHãES M, EDUARDO BRANDãO-MELLO C, LúCIA ELIAS PIRES M, CECíLIA DA FONSECA SALGADO M, BARCELO DE BRITO S, JOSé DE ALMEIDA A. Factor VIII and IX deficiencies related to acquired inhibitors in a patient with chronic hepatitis C virus infection receiving treatment with pegylated interferon plus ribavirin. Hematology [online] 2011 Mar, 16(2):80-5 [viewed 10 August 2014] Available from: doi:10.1179/102453311X12902908412156
  4. OSTERUD B, RAPAPORT SI. Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc Natl Acad Sci U S A [online] 1977 Dec, 74(12):5260-5264 [viewed 10 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC431674
  5. SMITH SB, GAILANI D. Update on the physiology and pathology of factor IX activation by factor XIa Expert Rev Hematol [online] 2008 Oct, 1(1):87-98 [viewed 10 August 2014] Available from: doi:10.1586/17474086.1.1.87
  6. BORKAR SA, PRASAD GL, SATYARTHEE GD, MAHAPATRA AK. Spontaneous spinal extradural hematoma in a child with hemophilia B, surgery or medical management - A dilemma? J Pediatr Neurosci [online] 2011, 6(2):131-133 [viewed 10 August 2014] Available from: doi:10.4103/1817-1745.92837
  7. SIMPSON ML, VALENTINO LA. Management of joint bleeding in hemophilia. Expert Rev Hematol [online] 2012 Aug, 5(4):459-68 [viewed 10 August 2014] Available from: doi:10.1586/ehm.12.27
  8. PHILIP J, SARKAR RS, KUMAR S, PRATHIP BR, PATHAK A. Factor IX deficiency (Christmas disease) Med J Armed Forces India [online] 2012 Oct, 68(4):379-380 [viewed 10 August 2014] Available from: doi:10.1016/j.mjafi.2011.12.007
  9. LINDVALL K, COLSTRUP L, WOLLTER IM, KLEMENZ G, LOOGNA K, GRöNHAUG S, THYKJAER H. Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia. Haemophilia [online] 2006 Jan, 12(1):47-51 [viewed 10 August 2014] Available from: doi:10.1111/j.1365-2516.2006.01192.x
  10. HERMANS C, DE MOERLOOSE P, FISCHER K, HOLSTEIN K, KLAMROTH R, LAMBERT T, LAVIGNE-LISSALDE G, PEREZ R, RICHARDS M, DOLAN G, EUROPEAN HAEMOPHILIA THERAPY STANDARDISATION BOARD. Management of acute haemarthrosis in haemophilia A without inhibitors: literature review, European survey and recommendations. Haemophilia [online] 2011 May, 17(3):383-92 [viewed 11 August 2014] Available from: doi:10.1111/j.1365-2516.2010.02449.x
  11. SIMPSON ML, VALENTINO LA. Management of joint bleeding in hemophilia. Expert Rev Hematol [online] 2012 Aug, 5(4):459-68 [viewed 11 August 2014] Available from: doi:10.1586/ehm.12.27
  12. TAN YK, LAI HK, CHONG YY. Use of radiosynovectomy in recurrent warfarin-related haemarthrosis in degenerative arthritis. Singapore Med J [online] 2011 Sep, 52(9):e184-6 [viewed 11 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21947161
  13. SHERIDAN GW, MATSEN FA 3RD. Fasciotomy in the treatment of the acute compartment syndrome. J Bone Joint Surg Am [online] 1976 Jan, 58(1):112-5 [viewed 11 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/1249096