History

Fact Explanation
Introduction Hemophilia is a group of disorders that result from the deficiency of certain plasma clotting factors. Hemophilia A is caused by deficiency of factor VIII, whereas hemophilia B is caused by factor IX deficiency and hemophilia C by factor XI deficiency. Hemophilia A and B are of X-linked recessive inheritance, thus affecting mostly males and females are carriers, who would develop only mild symptoms. Hemophilia C has autosomal recessive inheritance and affects both men and women equally. Some people may develop acquired hemophilia which is due to development of auto antibodies against plasma clotting factors, in a previously normal individual. Most commonly these are against factor VIII.(acquired hemophilia A) [1][2][3][4][6][7][10]
History of and/or current unusual bleeding following trauma/surgery Hemophilia patients may develop significant bleeding out of proportion to trauma or following surgery(e.g. tooth extraction). Some patients may develop recurrent bleeding from wounds before complete healing.Presentation may depend on the severity of factor deficiency. Patients with severe factor deficiency presents early in life but those with mild deficiency may not be diagnosed till later in life.[1][2][3][4][6][7]
Joint pain and /or deformity Hemophilia patients may bleed in to joints spontaneously or following minor trauma. This is the commonest site of bleeding. Spontaneous bleeds occur in severe factor deficiency and usually develop within infancy or early childhood. Patient may present with joint pain, swelling or limping. If untreated chronic joint disease and deformity may result.[1][2][3]
Muscle pain/swelling These patients may develop muscle bleeds either spontaneously or following trauma. These muscle hematomas may cause severe pain. The increased pressure can lead to compartment syndrome and nerve palsies. Thus it is important to avoid intramuscular injections in these patients.[1][2][3]
Central nervous system symptoms Symptoms such as headache,(particularly early morning headache with vomiting) neck stiffness, lethargy, irritability, changed behaviour, sensory loss or paralysis etc. may indicate the presence of an intracranial hemorrhage.[1][2][3]
Gastrointestinal symptoms These include haematamesis and malena due to upper GI bleeding, per rectal bleeding due to lower GI Bleeding. Patient may also present with abdominal pain and distension. [1][2][3]
Genitourinary symptoms Presence of renal colics, hematuria may indicate bleeding to genitourinary system.[1][2][3]
Other bleeding manifestations Such as epistaxis, gum bleeding, hemoptysis, contusions, severe post-partum hemorrhage, increased menstrual blood loss etc. may be found in some patients. Hemophilia may present with hemothorax, in which case the patient may have difficulty in breathing and pleuritic chest pain. [1][2][3][7]
Family history of bleeding disorders As already stated hemophilia is an inherited disorder. Except in acquired hemophilia cases and sporadic mutations the patients will have a positive family history of bleeding disorders.[1][2][3]
History of chronic inflammatory disorders, autoimmune diseases etc Patients with acquired hemophilia may have history of autoimmune diseases or chronic inflammatory diseases or malignancies. Acquired hemophilia has shown to be associated with pregnancy, allergic drug reactions, diabetes and even infectious hepatitis. In many instances it can be idiopathic also.[4][5]
Non accidental injury(NAI) Recurrent bruising of a child should alert the physician regarding NAI or child abuse.[8][9]
References
  1. CAHILL MR, COLVIN BT. Haemophilia. Postgrad Med J [online] 1997 Apr, 73(858):201-6 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9156121
  2. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Hemophilia A [online] 1993 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301578
  3. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S. Hemophilia B. 2000 Oct 2 [Updated 2014 Jun 5]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. [viewed on 25 Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/books/NBK1495/
  4. DICKE C, HOLSTEIN K, SCHNEPPENHEIM S, DITTMER R, SCHNEPPENHEIM R, BOKEMEYER C, IKING-KONERT C, BUDDE U, LANGER F. Acquired hemophilia A and von Willebrand syndrome in a patient with late-onset systemic lupus erythematosus. Exp Hematol Oncol [online] 2014:21 [viewed 28 September 2014] Available from: doi:10.1186/2162-3619-3-21
  5. UğUR BILGIN A, OZCAN M, AYYıLDıZ E, ILHAN O. The treatment of acquired hemophilia with combination therapy of immunosuppressives and immunoadsorption. Turk J Haematol [online] 2014 Jun, 31(2):194-6 [viewed 28 September 2014] Available from: doi:10.4274/tjh.2013.0178
  6. SEETHALA S, GAUR S, ENDERTON E, CORRAL J. Postpartum acquired hemophilia: a rare cause of postpartum hemorrhage. Case Rep Hematol [online] 2013:735715 [viewed 28 September 2014] Available from: doi:10.1155/2013/735715
  7. PEYVANDI F, LAK M, MANNUCCI PM. Factor XI deficiency in Iranians: its clinical manifestations in comparison with those of classic hemophilia. Haematologica [online] 2002 May, 87(5):512-4 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12010665
  8. When To Suspect Child Maltreatment. National Collaborating Centre for Women's and Children's Health (UK).London: RCOG Press; 2009 Jul. (NICE Clinical Guidelines, No. 89.)[online][viewed on 30 Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/books/NBK57162/
  9. DAVID M. PRESSEL. Evaluation of Physical Abuse in Children. Am Fam Physician. [online]2000 May 15;61(10):3057-3064.[viewed on 30 Sep 2014] Available from; http://www.aafp.org/afp/2000/0515/p3057.html
  10. BOLTON-MAGGS P. H. B.. Factor XI deficiency--resolving the enigma?. Hematology [online] December, 2009(1):97-105 [viewed 30 September 2014] Available from: doi:10.1182/asheducation-2009.1.97

Examination

Fact Explanation
Signs of hypovolemia such as tachycardia, hypotension, tachypnea Presence of these sighs should alert to look for a hemorrage.[1][2][3]
General Examination Pallor, features of blood loss, restless (disoriented if heavy blood loss), petechiae, echimoses and purpura in the skin.[1][2][3]
Respiratory system Dyspnea, tachypnoea, reduce chest expansion, dullness on percussion and diminished breath sounds will be detected in the presence of hemothorax.[4][5]
Cardiovascular system Tachycardia with low volume pulse (rapid thready pulse), hypotension, flow murmurs will be present in significant hemorrhage. [1][2][3]
Central nervous system Neck stiffness ( in meningial irritation due to bleeding), photophobia, sensory or/motor abnormalities, altered mental status etc. may be seen in the presence of an intracranial hemorrhage.[1][2][3]
Abdominal examination Abdominal distension, tenderness, guarding/rigidity, dullness may be seen in an intraabdominal bleeding.[2][3][5]
Genital examination May reveal hematocele, meatal bleeding etc.
Musculoskeletal system Muscle tenderness, nerve palsy, compartment syndrome are seen if patient develops a muscle hematoma. Joint tenderness, swelling, increased warmth, pain with movement, limited joint mobility, limping will be seen in the presence of bleeding into a joint.[1][2][3]
References
  1. CAHILL MR, COLVIN BT. Haemophilia. Postgrad Med J [online] 1997 Apr, 73(858):201-6 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9156121
  2. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Hemophilia A [online] 1993 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301578
  3. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S. Hemophilia B. 2000 Oct 2 [Updated 2014 Jun 5]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. [viewed on 25 Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/books/NBK1495/
  4. HONIG E. An Overview of the Pulmonary System. In: WALKER HK, HALL WD, HURST JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 35. Available from: http://www.ncbi.nlm.nih.gov/books/NBK356/
  5. TUTEUR PG. Chest Examination. In: WALKER HK, HALL WD, HURST JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 46. Available from: http://www.ncbi.nlm.nih.gov/books/NBK368/
  6. FERGUSON CM. Inspection, Auscultation, Palpation, and Percussion of the Abdomen. In: WALKER HK, HALL WD, HURST JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 93. Available from: http://www.ncbi.nlm.nih.gov/books/NBK420/

Differential Diagnoses

Fact Explanation
Hemophilia A Hemophilia A is an X-linked recessively inherited disorder of clotting factor VIII deficiency. The commonest presentation is due to bleeding manifestations. This affects mostly males and females are carriers, and would develop only mild symptoms. [8][13][14]
Hemophilia B Also called Christmas disease is caused by clotting factor IX deficiency. This is also inherited in a X-linked recessive manner. Bleeding is usually less severe than hemophilia A.[9][13][14]
Hemophilia C Is caused by factor XI deficiency. Has autosomal recessive inheritance and affects both men and women equally.[11][12]
Acquired hemophilia Is seen in people with previously normal coagulation, due to novel development of auto antibodies against plasma clotting factors, commonly for factor VIII.[10]
Chronic liver disease This can lead to reduced clotting factor production, reduced vitamin K absorption and platelet dysfunction that produce a complicated bleeding disorder.[2][13][14]
Chronic malabsorption Can lead to vitamin K malabsorption. Vitamin K is essential for synthesis of clotting factors II.VII,IX,X by the liver.[4][13][14]
Idiopathic thrombocytopenic purpura Is a disease where there is thrombocytopenia with normal bone marrow and antibodies against some platelet glycoproteins. It is a diagnosis of exclusion. The patients present with bleeding manifestations such as epistaxis, gum bleeds, petechiae, purpura, menorrhagia etc.[3][13][14]
von Willebrand disease Is an inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor.[1][13][14]
Osler-Weber-Rendu syndrome This is a rare autosomal dominantly inherited congenital vascular disorder which can cause epistaxis, chronic gastrointestinal bleeds etc. with resultant iron deficiency anemia.[7][13][14]
Glanzmann Thrombasthenia Is an autosomal recessively inherited platelet disorder with defects of the fibrinogen receptor αIIbβ3.[5][13][14]
Ehlers- Danlos syndrome This is an inherited connective tissue disorder resulting in defective collagen synthesis. This can lead to arterial rupture and bleeding.[6][13][14]
References
  1. PARK JJ, KIM CH, LEE JG, CHO HJ. Von-Willebrand disease presenting as intractable epistaxis after nasal polypectomy. Case Rep Otolaryngol [online] 2014:902071 [viewed 28 September 2014] Available from: doi:10.1155/2014/902071
  2. TAKAMURA M, WATANABE J, SAKAMAKI A, HONDA Y, KAMIMURA K, TSUCHIYA A, YAMAGIWA S, SUDA T, MATSUDA Y, AOYAGI Y. Alcoholic liver disease complicated by deep bleeding into the muscles or retroperitoneum: report of three cases and a review of the literature. Intern Med [online] 2014, 53(16):1763-8 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25130107
  3. KAYAL L, JAYACHANDRAN S, SINGH K. Idiopathic thrombocytopenic purpura. Contemp Clin Dent [online] 2014 Jul, 5(3):410-4 [viewed 28 September 2014] Available from: doi:10.4103/0976-237X.137976
  4. NOWAK JK, GRZYBOWSKA-CHLEBOWCZYK U, LANDOWSKI P, SZAFLARSKA-POPLAWSKA A, KLINCEWICZ B, ADAMCZAK D, BANASIEWICZ T, PLAWSKI A, WALKOWIAK J. Prevalence and correlates of vitamin K deficiency in children with inflammatory bowel disease. Sci Rep [online] 2014 Apr 24:4768 [viewed 28 September 2014] Available from: doi:10.1038/srep04768
  5. VARKEY I, RAI K, HEGDE AM, VIJAYA MS, OOMMEN VI. Clinical Management of Glanzmann's Thrombasthenia: A Case Report. J Dent (Tehran) [online] 2014 Mar, 11(2):242-7 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24910701
  6. ABAYAZEED A, HAYMAN E, MOGHADAMFALAHI M, CAIN D. Vascular type Ehlers-Danlos Syndrome with fatal spontaneous rupture of a right common iliac artery dissection: case report and review of literature. J Radiol Case Rep [online] 2014 Feb, 8(2):63-9 [viewed 28 September 2014] Available from: doi:10.3941/jrcr.v8i2.1568
  7. MEIRELES SI, DE ANDRADE SM, GOMES MF, CASTRO FA, TEBCHERANI AJ. Syndrome in question. An Bras Dermatol [online] 2014 Jul-Aug, 89(4):679-80 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/25054766
  8. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Hemophilia A [online] 1993 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301578
  9. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S. Hemophilia B. 2000 Oct 2 [Updated 2014 Jun 5]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. [viewed on 25 Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/books/NBK1495/
  10. DICKE C, HOLSTEIN K, SCHNEPPENHEIM S, DITTMER R, SCHNEPPENHEIM R, BOKEMEYER C, IKING-KONERT C, BUDDE U, LANGER F. Acquired hemophilia A and von Willebrand syndrome in a patient with late-onset systemic lupus erythematosus. Exp Hematol Oncol [online] 2014:21 [viewed 28 September 2014] Available from: doi:10.1186/2162-3619-3-21
  11. PEYVANDI F, LAK M, MANNUCCI PM. Factor XI deficiency in Iranians: its clinical manifestations in comparison with those of classic hemophilia. Haematologica [online] 2002 May, 87(5):512-4 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12010665
  12. BOLTON-MAGGS P. H. B.. Factor XI deficiency--resolving the enigma?. Hematology [online] December, 2009(1):97-105 [viewed 30 September 2014] Available from: doi:10.1182/asheducation-2009.1.97
  13. MICHAEL BALLAS, ERIC H. KRAUT. Bleeding and Bruising: A Diagnostic Work-up. Am Fam Physician. [online]2008 Apr 15;77(8):1117-1124. [viewed on 30 Sep 2014] Available from;http://www.aafp.org/afp/2008/0415/p1117.html
  14. ALEXANDER K.C. LEUNG, KA WAH CHAN. Evaluating the Child with Purpura. Am Fam Physician. [online]2001 Aug 1;64(3):419-429.[viewed on 30 Sep 2014] Available from; http://www.aafp.org/afp/2001/0801/p419.html

Investigations - for Diagnosis

Fact Explanation
Complete blood count The hemoglobin level may be normal or low, due to bleeding. Platelet count and other cell counts will also be normal.[3][4][5][11]
Coagulation screen Bleeding time and prothrombin time will be normal. Activated partial thromboplastin time (aPTT) will be prolonged. But in mild or moderate hemophilia aPTT may be normal.[3][4][5][11]
Factor VIII assay In patients with hemophilia A, factor VIII clotting activity is usually lower than 30%-35%. In severe hemophilia A, factor VIII activity is <1%. In moderate hemophilia A, factor VIII activity is 1%-5%. In mild hemophilia A, factor VIII activity is >5%.[3][5][11]
Factor IX assay In patients with hemophilia B factor IX activity will be low. The classification of severity is similar to hemophilia A.[4][5][11]
Factor XI assay Assessing factor XI activity is needed when hemophilia C is suspected.[5][6][11]
Genetic testing Testing for known mutations is done. Mutations in the F8 gene are responsible for hemophilia A and mutations in the F9 gene cause hemophilia B. For hemophilia A patients molecular genetic testing such as targeted mutation analysis to identify the intron 22 or intron 1 inversion, sequence analysis of the 26 exons in F8, deletion/duplication analysis, linkage analysis can be done. For hemophilia B patients, sequence analysis of the eight exons and intron-exon boundaries in F9, deletion/duplication analysis and linkage analysis is done.[1][2][3][4]
Testing for inhibitors In patients with hemophilia, presence of clotting factor inhibitors should be suspected when bleeding is not controlled even though adequate amounts of factor concentrate is given. Patient's plasma is incubated with normal plasma at 37°C for 1-2 hours. Then aPTT is repeated. The inhibitor concentration can be titrated by the Bethesda method if the prolonged aPTT is not corrected,.[3][7][9]
Ultra sound scan of joints Is helpful to determine joint bleeds.[8]
Computed tomography scan of head Done when there is suspicion of an intracranial bleeding.[8]
Magnetic resonance imaging of joints Done to assess joint bleeds and deformity.[8]
Chest X ray Can be done if presence of hemothorax is suspected.[12]
Ultra sound scan of abdomen Done to detect acute intra abdominal bleeding and presence of hemoperitoneum.[10]
References
  1. Hemophilia. Genetics Home Reference. U.S. National Library of Medicine®[online]. Reviewed August 2012.[viewed on 25 Sep 2014]. Available from; http://ghr.nlm.nih.gov/condition/hemophilia
  2. SHETTY S. Haemophilia - diagnosis and management challenges. Mol Cytogenet [online] 2014, 7(Suppl 1 Proceedings of the International Conference on Human):I44 [viewed 28 September 2014] Available from: doi:10.1186/1755-8166-7-S1-I44
  3. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Hemophilia A [online] 1993 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301578
  4. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S. Hemophilia B. 2000 Oct 2 [Updated 2014 Jun 5]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. [viewed on 25 Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/books/NBK1495/
  5. VAN HERREWEGEN F, MEIJERS JC, PETERS M, VAN OMMEN CH. Clinical practice: the bleeding child. Part II: disorders of secondary hemostasis and fibrinolysis. Eur J Pediatr [online] 2012 Feb, 171(2):207-14 [viewed 28 September 2014] Available from: doi:10.1007/s00431-011-1571-x
  6. PEYVANDI F, LAK M, MANNUCCI PM. Factor XI deficiency in Iranians: its clinical manifestations in comparison with those of classic hemophilia. Haematologica [online] 2002 May, 87(5):512-4 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12010665
  7. SAKURAI Y, TAKEDA T. Acquired hemophilia A: a frequently overlooked autoimmune hemorrhagic disorder. J Immunol Res [online] 2014:320674 [viewed 28 September 2014] Available from: doi:10.1155/2014/320674
  8. CAHILL MR, COLVIN BT. Haemophilia. Postgrad Med J [online] 1997 Apr, 73(858):201-6 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9156121
  9. HUTH-KüHNE A, BAUDO F, COLLINS P, INGERSLEV J, KESSLER CM, LéVESQUE H, CASTELLANO ME, SHIMA M, ST-LOUIS J. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A Haematologica [online] 2009 Apr, 94(4):566-575 [viewed 30 September 2014] Available from: doi:10.3324/haematol.2008.001743
  10. BRENCHLEY J, WALKER A, SLOAN JP, HASSAN TB, VENABLES H. Evaluation of focussed assessment with sonography in trauma (FAST) by UK emergency physicians. Emerg Med J [online] 2006 Jun, 23(6):446-8 [viewed 30 September 2014] Available from: doi:10.1136/emj.2005.026864
  11. MICHAEL BALLAS, ERIC H. KRAUT. Bleeding and Bruising: A Diagnostic Work-up. Am Fam Physician. [online]2008 Apr 15;77(8):1117-1124. [viewed on 30 Sep 2014] Available from;http://www.aafp.org/afp/2008/0415/p1117.html
  12. CHARDOLI M, HASAN-GHALIAEE T, AKBARI H, RAHIMI-MOVAGHAR V. Accuracy of chest radiography versus chest computed tomography in hemodynamically stable patients with blunt chest trauma. Chin J Traumatol [online] 2013 Dec 1, 16(6):351-4 [viewed 30 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24295582

Investigations - Fitness for Management

Fact Explanation
Complete blood count Done to assess hemoglobin level, which may be normal or low, due to bleeding. Platelet count and white cell count will usually be normal.[1][2][3]
Serum creatinine If a patient present with hemorrhage and hypovolemia continues to have reduced urine out put despite of volume replacement, serum creatinine is done to detect acute kidney injury(AKI). An acute elevation of serum creatinine(i.e. within 48 hours) indicated AKI.[4]
References
  1. CAHILL MR, COLVIN BT. Haemophilia. Postgrad Med J [online] 1997 Apr, 73(858):201-6 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9156121
  2. VAN HERREWEGEN F, MEIJERS JC, PETERS M, VAN OMMEN CH. Clinical practice: the bleeding child. Part II: disorders of secondary hemostasis and fibrinolysis. Eur J Pediatr [online] 2012 Feb, 171(2):207-14 [viewed 28 September 2014] Available from: doi:10.1007/s00431-011-1571-x
  3. MICHAEL BALLAS, ERIC H. KRAUT. Bleeding and Bruising: A Diagnostic Work-up. Am Fam Physician. [online]2008 Apr 15;77(8):1117-1124. [viewed on 30 Sep 2014] Available from;http://www.aafp.org/afp/2008/0415/p1117.html
  4. MAHBOOB RAHMAN, FARIHA SHAD, MICHAEL C. SMITH. Acute Kidney Injury: A Guide to Diagnosis and Management. Am Fam Physician.[online] 2012 Oct 1;86(7):631-639. [viewed on 30 Sep 2014] Available from; http://www.aafp.org/afp/2012/1001/p631.html#sec-4

Investigations - Followup

Fact Explanation
Clotting factor assay Factor assay is done to define the severity of the disease, anticipate and manage complications.[1]
References
  1. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Hemophilia A [online] 1993 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301578

Management - General Measures

Fact Explanation
Emergency management The commonest emergency presentation will be an acute hemorrhage. Patient's airway and breathing should be assessed and secured. Assess the circulation.Volume replacement should be done as needed. Blood transfusion, fresh frozen plasma infusion, clotting factor replacement therapy should be carried out as needed. Surgical hemostasis, desmopressin, or antifibrinolytic therapy should be considered to control bleeding. Once the patient is adequately resuscitated, monitoring of vital signs should be done at regular intervals. Assessment neurological assessment and head to toe examination to detect injuries etc. should be done also. [6][7][8]
Pain management This is important because acute bleeding into joints and soft tissue can be very painful. Also the chronic arthropathy of hemophilia can be painful. analgesics should be selected according to the level of pain management required. It is better to avoid non steroidal anti inflammatory drugs as they can cause gastrointestinal bleeding. Aspirin has irreversible action on platelets and thus better avoided in these patients.[1][2][5]
Patient education and other care Patients should be advised to avoid contact sports. Intramuscular injections should be avoided in these patients as they can cause very painful muscle hematomas. They can be given deep subcutaneous injections instead. Hepatitis B vaccination should be done in all hemophilia patients.[2][4][5]
Genetic counselling Patient and the family should be educated regarding the nature and inheritance of hemophilia. Carrier testing should be offered to couples with family history of hemophilia. It may help to prevent births offspring with severe hemophilia. Prenatal diagnosis will help to plan delivery and neonatal management.[2][4][5]
Physiotherapy Is useful for patients with chronic hemophilia related arthropathy.[3]
References
  1. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S, PAGON RA, ADAM MP, ARDINGER HH, BIRD TD, DOLAN CR, FONG CT, SMITH RJH, STEPHENS K. Hemophilia A [online] 1993 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20301578
  2. JóźWIAK-BEBENISTA M, NOWAK JZ. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm [online] 2014 Jan-Feb, 71(1):11-23 [viewed 28 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24779190
  3. CUESTA-BARRIUSO R, GóMEZ-CONESA A, LóPEZ-PINA JA. Physiotherapy treatment in patients with hemophilia and chronic ankle arthropathy: a systematic review. Rehabil Res Pract [online] 2013:305249 [viewed 28 September 2014] Available from: doi:10.1155/2013/305249
  4. GIORDANO P, FRANCHINI M, LASSANDRO G, FAIENZA MF, VALENTE R, MOLINARI AC. Issues in pediatric haemophilia care. Ital J Pediatr [online] 2013 Apr 20:24 [viewed 28 September 2014] Available from: doi:10.1186/1824-7288-39-24
  5. KONKLE BA, JOSEPHSON NC, NAKAYA FLETCHER S. Hemophilia B. 2000 Oct 2 [Updated 2014 Jun 5]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. [viewed on 25 Sep 2014] Available from: http://www.ncbi.nlm.nih.gov/books/NBK1495/
  6. MICHAEL BALLAS, ERIC H. KRAUT. Bleeding and Bruising: A Diagnostic Work-up. Am Fam Physician. [online]2008 Apr 15;77(8):1117-1124. [viewed on 30 Sep 2014] Available from;http://www.aafp.org/afp/2008/0415/p1117.html
  7. ROLF ROSSAINT, BERTIL BOUILLON, VLADIMIR CERNY, TIMOTHY J COATS, JACQUES DURANTEAU,ENRIQUE FERNÁNDEZ-MONDÉJAR, BEVERLEY J HUNT, RADKO KOMADINA, GIUSEPPE NARDI,EDMUND NEUGEBAUER, YVES OZIER, LOUIS RIDDEZ, ARTHUR SCHULTZ, PHILIP F STAHEL,JEAN-LOUIS VINCENT AND DONAT R SPAHN. Management of bleeding following major trauma: an updated European guideline. Critical Care[online] 2010,[viewed on 30 Sep 2014] Available from: doi:10.1186/cc8943
  8. MOCK C, LORMAND JD, GOOSEN J, JOSHIPURA M, PEDEN M.Guidelines for essential trauma care. World Health Organization, 2004.[online][viewed on 30 Sep 2014] Available from; http://www.who.int/violence_injury_prevention/publications/services/en/guidelines_traumacare.pdf

Management - Specific Treatments

Fact Explanation
Treatment for hemophilia A Replacement of the deficient clotting factor is the mainstay of treatment. Intravenous infusion of recombinant (or plasma derived) factor VIII concentrate is the treatment for controlling bleeding episodes. Prophylactic clotting factor administration is recommended for children with severe hemophilia, three times a week or every other day to maintain factor activity above 1%. Prophylaxis should be considered before surgical procedures also. DDAVP (1-deamino-8-D-arginine vasopressin) is the treatment of choice for mild to moderate hemophilia A and most symptomatic carriers. Immediate but transient treatment for bleeding or prophylaxis can be achieved with desmopressin as it brings about a transient increase in plasma factor VIII levels. DDAVP intravenous solutions and intra-nasal sprays are available.[2][3][4][5][6]
Treatment for hemophilia B Factor IX replacement with infusion of either plasma derived or recombinant factor IX (FIX) concentrate is the treatment for hemophilia B. FIX replacement is done either on demand when a bleeding episode occurs or on scheduled intervals, given several times a week as prophylactic treatment. [5][6]
Treatment for hemophilia C Bleeding risk in hemophilia C is not related to factor XI plasma level. Therefore the need for factor replacement should be tailored to the individual circumstance. Replacement with factor XI or fresh frozen plasma helps to manage bleeding episodes. The risk of thrombotic events should be borne in mind when correcting FXI level. Some studies have shown that recombinant factor VIIa to be effective in the management of these patients. [7]
Treatment for acquired hemophilia In an acute hemorrhagic situation high amounts of factor VIII concentrate may help to control bleeding. Recombinant factor VII may help in cases of severe bleeding. Definitive treatment consists of irradicating the inhibitor. Intravenous steroids, cytotoxic agents such as cyclophosphamide, azathioprine, vincristine, mycophenolate mofetil etc. rituximab and cyclosporin are some of the agents used for irradication of the inhibitors by immunosuppression. For those who are unresponsive to drugs, intravenous immunoglobulin may be used. [1][8]
References
  1. UğUR BILGIN A, OZCAN M, AYYıLDıZ E, ILHAN O. The treatment of acquired hemophilia with combination therapy of immunosuppressives and immunoadsorption. Turk J Haematol [online] 2014 Jun, 31(2):194-6 [viewed 28 September 2014] Available from: doi:10.4274/tjh.2013.0178
  2. OZGöNENEL B, RAJPURKAR M, LUSHER JM. How do you treat bleeding disorders with desmopressin? Postgrad Med J [online] 2007 Mar, 83(977):159-63 [viewed 28 September 2014] Available from: doi:10.1136/pgmj.2006.052118
  3. MANNUCCI PM. Plasma-derived versus recombinant factor VIII concentrates for the treatment of haemophilia A: plasma-derived is better Blood Transfus [online] 2010 Oct, 8(4):288-291 [viewed 28 September 2014] Available from: doi:10.2450/2010.0072-10
  4. GRINGERI A. Factor VIII safety: plasma-derived versus recombinant products Blood Transfus [online] 2011 Oct, 9(4):366-370 [viewed 28 September 2014] Available from: doi:10.2450/2011.0092-10
  5. MORFINI M, COPPOLA A, FRANCHINI M, DI MINNO G. Clinical use of factor VIII and factor IX concentrates. Blood Transfus [online] 2013 Sep:s55-63 [viewed 28 September 2014] Available from: doi:10.2450/2013.010s
  6. FRANCHINI M, FRATTINI F, CRESTANI S, SISSA C, BONFANTI C. Treatment of hemophilia B: focus on recombinant factor IX. Biologics [online] 2013:33-8 [viewed 28 September 2014] Available from: doi:10.2147/BTT.S31582
  7. BOLTON-MAGGS P. H. B.. Factor XI deficiency--resolving the enigma?. Hematology [online] December, 2009(1):97-105 [viewed 30 September 2014] Available from: doi:10.1182/asheducation-2009.1.97
  8. HUTH-KüHNE A, BAUDO F, COLLINS P, INGERSLEV J, KESSLER CM, LéVESQUE H, CASTELLANO ME, SHIMA M, ST-LOUIS J. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A Haematologica [online] 2009 Apr, 94(4):566-575 [viewed 30 September 2014] Available from: doi:10.3324/haematol.2008.001743