History

Fact Explanation
Introduction Body’s normal mechanisms to stop the bleeding consists of main three responses: vascular, platelet and coagulatory response. Defect in any part of these responses can lead to abnormal bleeding manifestations. Coagulation cascade has main three pathways. Factors VII in extrinsic pathway, factors VIII, IX, XI and XII intrinsic pathway and V, X, fibrinogen and prothrombin in common pathway. [2] Factor XI (F XI) is a plasma protein that involves in the intrinsic blood coagulation pathway. FXI deficiency has an autosomal inheritance [10] with a severe deficiency is manifested in homozygotes and partial deficiency manifested in heterozygotes. [7,12] Three independent point mutations have been identified in the factor XI gene, such as occurring in the normal mRNA splicing (type I), premature polypeptide termination (type II), and result in a specific amino acid substitution (type III). [11] Though the bleeding manifestations are not severe, occasionally there can be lethal internal bleeding manifestations. [9] The are not correlating with the severity of the deficiency as in contrast to patients with hemophilia A and B. [14]
Easy bruising, excessive bleeding with routine dental procedures, venepuncture, circumcision, bleeding from the umbilical stump and following trauma Defective clotting mechanism leads to easy bleeding particularly after trauma, and even may be spontaneous in severe disease. [2] Easy bruising will become more evident once the child starts the ambulation. [1]
Joint and muscle problems: Tingling, cracking, pain, stiffness, and inability to move the joint Weight-bearing joints are commonly affected bleeding in patients with hemophilia. Knee, elbow and ankle are commonly affected. [5] Flexor muscles of the arms and gastrocnemius of the legs and iliopsoas muscles are frequently affected. Joint injury in hemophilia are associated with swelling of the joint, bleeding into soft tissue, increased cellular proliferation in the synovial membrane and intense inflammation. [7]
Nasal bleeds, gum bleeds Tissues like oral cavity, or nasopharyngeal area which have a high fibrinolytic activity are more prone to get bleeding following trauma or surgery. [14] Epistaxis is the bleeding from the nose that is due to the deficient clotting mechanism. [1]
Headache, stiff neck, vomiting, lethargy, irritability Spontaneous bleeding inside the central nervous system can cause intracranial haemorrhages and meningeal irritation. But this spontaneous bleeding is rare in haemophilia C patients. [14] Patients with factor level <1% of normal are more susceptible to spontaneous bleeding. Subarachnoid haemorrhage and intraventricular haemorrhage are also seen in these patients. [19]
Hematemesis, melena, frank red blood per rectum Spontaneous bleeding is rare even in patients with severe FXI deficiency. [13] If there is a spontaneous bleeding from the mucosal surface of the gastrointestinal tract [1] may cause passage of blood with vomitus, and black tary stools (malena) associated with upper GI bleeding. [8]
Hematuria, renal colics Same as above due to the bleeding tendency and clot colics may occur causing loin to groin pain. Haematuria may occur particularly after damaging to the urinary tract by any means. [4]
Muscle pain Bleeding into muscles may form haematoma [1] and may cause severe pain. [8]
Difficulty in breathing Massive haemothorax can be occured in haemophilic patients. [18] Spontaneous pneumotrhorax may be associated with bleeding into the pleural cavity. [18]
Excess menstrual bleeding Menorrhagia is a frequent finding in females. [3,8]
Excessive bleeding following child birth Excess bleeding following child birth can result in some patients with haemophilia. [16] Other causes of postpartum hemorrhage such as trauma, uterine atony, retained products of conception, uterine inversion and placenta previa need to be excluded. [17]
History of consanguity / family history As this is a autosomal recessive condition, consanguity [1] increases the risk of getting the disease to the offspring. There can be affected males in the family while females are the carriers. [10]
History of thromboebbolism/ immobolity Prolonged therapy with antifibrinolytic agents particularly in immobile patients or who are having history of thromboembolism have a high risk thrombus formation. [15]
References
  1. 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 01 October 2014] Available from: doi:10.4084/MJHID.2012.057
  2. RIZOLI SB, SCARPELINI S, CALLUM J, NASCIMENTO B, MANN KG, PINTO R, JANSEN J, TIEN H. Clotting Factor Deficiency in Early Trauma-Associated Coagulopathy J Trauma [online] 2011 Nov, 71(5 Suppl 1):S427-S434 [viewed 01 October 2014] Available from: doi:10.1097/TA.0b013e318232e5ab
  3. HOOD J. L., EBY C. S.. Evaluation of a Prolonged Prothrombin Time. Clinical Chemistry [online] 2008 April, 54(4):765-768 [viewed 01 October 2014] Available from: doi:10.1373/clinchem.2007.100818
  4. SILVERBERG DS, DOSSETOR JB, EID TC, MANT MJ, MILLER JD. Arteriovenous fistula and prolonged hematuria after renal biopsy: treatment with epsilon aminocaproic acid Can Med Assoc J [online] 1974 Mar 16, 110(6):671-677 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1947353
  5. STERNDALE H. Haemarthrosis and haemophilia. Proc R Soc Med [online] 1967 Jan, 60(1):37-38 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1901393
  6. INGLETON TC, KEANE M. Diagnostic and Therapeutic Challenges of Intracranial Hemorrhage in Neonates With Congenital Hemophilia: A Case Report and Review Ochsner J [online] 2012, 12(3):249-253 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448247
  7. GENTRY PA, ROSS ML. Coagulation factor XI deficiency in Holstein cattle: expression and distribution of factor XI activity. Can J Vet Res [online] 1994 Oct, 58(4):242-247 [viewed 09 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1263706
  8. SAHU S, LATA I, SINGH S, KUMAR M. Revisiting hemophilia management in acute medicine J Emerg Trauma Shock [online] 2011, 4(2):292-298 [viewed 01 October 2014] Available from: doi:10.4103/0974-2700.82225
  9. GENTRY PA, BRUSH PJ. Factor XI Deficiency in Canadian Holsteins Can Vet J [online] 1987 Mar, 28(3):110 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1680365
  10. MEYDAN H, YILDIZ MA, ÖZDIL F, GEDIK Y, ÖZBEYAZ C. Identification of factor XI deficiency in Holstein cattle in Turkey Acta Vet Scand [online] , 51(1):5 [viewed 09 October 2014] Available from: doi:10.1186/1751-0147-51-
  11. ASAKAI R, CHUNG DW, RATNOFF OD, DAVIE EW. Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations. Proc Natl Acad Sci U S A [online] 1989 Oct, 86(20):7667-7671 [viewed 09 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC298131
  12. LUO D, SZABA FM, KUMMER LW, JOHNSON LL, TUCKER EI, GRUBER A, GAILANI D, SMILEY ST. Factor XI-Deficient Mice Display Reduced Inflammation, Coagulopathy, and Bacterial Growth during Listeriosis Infect Immun [online] 2012 Jan, 80(1):91-99 [viewed 09 October 2014] Available from: doi:10.1128/IAI.05568-11
  13. CASTAMAN G., GIACOMELLI S. H., DRAGANI A., IULIANI O., DUGA S., RODEGHIERO F.. Severe factor XI deficiency in the Abruzzo region of Italy is associated to different FXI gene mutations. Haematologica [online] 2008 June, 93(6):957-958 [viewed 09 October 2014] Available from: doi:10.3324/haematol.12540
  14. 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):207-214 [viewed 09 October 2014] Available from: doi:10.1007/s00431-011-1571-x
  15. 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 09 October 2014] Available from: doi:10.1586/17474086.1.1.87
  16. MYTOPHER K, DUDEBOUT J, CARD R, GILLILAND B. Acquired hemophilia A presenting post partum CMAJ [online] 2007 Aug 14, 177(4):339-340 [viewed 10 October 2014] Available from: doi:10.1503/cmaj.070414
  17. EDHI MM, ASLAM HM, NAQVI Z, HASHMI H. "Post partum hemorrhage: causes and management" BMC Res Notes [online] :236 [viewed 10 October 2014] Available from: doi:10.1186/1756-0500-6-236
  18. BARRETT KE, ISRAëLS MC. Haemothorax in Haemophilia Thorax [online] 1965 Sep, 20(5):416-421 [viewed 10 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1018961
  19. ADELOYE A, SERIKI O, LUZZATTO L, ESSIEN EM. Intracranial ventricular haemorrhage as a first presentation of haemophilia. A case of successful surgical management. J Neurol Neurosurg Psychiatry [online] 1969 Oct, 32(5):470-473 [viewed 10 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC496561

Examination

Fact Explanation
Tachycardia, tachypnea, hypotension These signs are due to haemorrhage. [1]
Pallor Low hemoglobin due to anaemia may found as result of acute or chronic blood loss. [7]
Joint tenderness, warmth, decreased range of moments Joints are frequently affected with bleeding. [3] Joint may be complicated with effusion on certain situations. [4]
Bruising Due to the inufficient clotting mechanism. [2]
Neck stiffness These are due to the bleeding that causes meningeal irritation. [1]
Altered mental status, focal neurological signs, bulging fontanels Spontaneous bleeding inside the central nervous system can cause intracranial haemorrhages. [1] ICH may increase the intracranial pressure, causes cerebral edema, even neuronal death due to the direct mechanical effect. [1]
Hepatic/splenic tenderness, and peritoneal signs Hepatic/ splenic haematoma may rarely occur. [2]
Tenderness over the costovertebral angle Renal colics may occur due to bleeding inside the urinary tract that causes clot colics. [2]
Dyspnea Hematoma formation can lead to airway obstruction. [5]
Joint contractures [7] Mismanaged haemophilia with recurrent haemarthrosis will lead to joint damage and contracures. [3]
Features of compartment syndrome: severe tenderness, decreased sensation, pallor, parasthesia of the limb Compartment syndrome can occur due to the hematoma formation increasing the pressure inside the compartment. [7]
Signs of dehydration: Sunken eyes, dry skin, reduced skin turgor Dehydration may occur due to severe fluid loss. [7]
References
  1. SINGLETON TC, KEANE M. Diagnostic and Therapeutic Challenges of Intracranial Hemorrhage in Neonates With Congenital Hemophilia: A Case Report and Review Ochsner J [online] 2012, 12(3):249-253 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448247
  2. 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 01 October 2014] Available from: doi:10.4084/MJHID.2012.057
  3. STERNDALE H. Haemarthrosis and haemophilia. Proc R Soc Med [online] 1967 Jan, 60(1):37-38 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1901393
  4. LJUNG R, VAN DEN BERG M, VALENTINO LA, MANCO-JOHNSON M. The Fourth Annual Meeting of the International Network for Pediatric Hemophilia: Current Challenges and Recommendations in the Clinical Care of Children with Hemophilia Transfus Med Hemother [online] 2010 Aug, 37(4):209-212 [viewed 01 October 2014] Available from: doi:10.1159/000317114
  5. BIRKHOLZ T, KRöBER S, KNORR C, SCHIELE A, BUMM K, SCHMIDT J. A retropharyngeal-mediastinal hematoma with supraglottic and tracheal obstruction: The role of multidisciplinary airway management J Emerg Trauma Shock [online] 2010, 3(4):409-411 [viewed 01 October 2014] Available from: doi:10.4103/0974-2700.70776
  6. JOSEPHSON N.. The hemophilias and their clinical management. Hematology [online] December, 2013(1):261-267 [viewed 01 October 2014] Available from: doi:10.1182/asheducation-2013.1.261
  7. SAHU S, LATA I, SINGH S, KUMAR M. Revisiting hemophilia management in acute medicine J Emerg Trauma Shock [online] 2011, 4(2):292-298 [viewed 01 October 2014] Available from: doi:10.4103/0974-2700.82225

Differential Diagnoses

Fact Explanation
Hemophilia A Hemophilia A is due to the deficiency of functional plasma clotting factor VIII (FVIII), and is inherited as a X-linked, recessive manner and may be associated with spontaneous mutations. Acquired hemophilia is occurred due to the appearance of inhibitory antibodies to FVIII. [8] aPTT may be prolonged. Bleeding time and prothrombin time and International Normalized Ratio (INR) are normal as they assess the extrinsic coagulation pathway. [9] Factor VIII assay is reduced in haemophilia A due to the deficiency of factor 8. [9]
Haemophilia B Haemophilia B is due to the deficiency of factor IX , that hydrolyses one arginine-isoleucine bond in factor X to form the activated factor X (Xa). [7] Activated factor VIII (FVIIIa) is important to improve the efficiency of this factor. Clinical features are same as in haemophilia A and coagulation studies will be the same with normal level of factor VIII and reduced level of factor IX.
Von Willebrand disease This is an autosomal dominant condition and may be either inherited or acquired. [3] It is due to the defect in the Von Willebrand factor (vWF) which is important to maintain normal clotting functions. Von Willebrand factor is secreted by the endothelial cells and are circulate in the blood. When there is a endothelial injury, vWF is attached to the endothelium, then bind with platelets with the help of the glycoprotein complexes. [1] Absence of this factor causes increased tendency to bleeding giving the same clinical features as in haemophilia. Mucocutaneous bleeding is mild in type 1 disease. Severe joint bleeds are rare. [3] Diagnosis is by the decreased VWF activity assay. Platelet count is normal with the exception of decreased count in type 2 VWD patients. [3] Hemophilia A is different from von Willebrand disease as there is normal or elevated levels of vWF antigen and ristocetin cofactor activity in haemophilia.
Deficiency of other coagulation factors (factor V, VII, X, fibrinogen) These are rare inherited disorders due to the absence or reduced levels of clotting factors. Clinical manifestations may be depend on the type and magnitude of the deficient factor. These include deficiencies of factors II, V, VII, XIII and fibrinogen. Differentiation would be possible with coagulation factors assays. Factor XII assays are aPTT based and factors V, VII and X assays are PT based. Therefore deficiency of factor factors XII, IX, and VIII is associated with isolated prolongation of aPTT and deficiency of factor VII with isolated prolongation of PT. [4,5] Prolongation of both aPTT and PT occurs in deficiency of the common pathway coagulation factors, factor X, V, and II, or a qualitative or quantitative fibrinogen defect.[6]
Platelet disorders Platelets are an integral part in the haemostatic mechanism, once there is a vascular distruption the platelets get the contact with the vascular endothelium forming a platelet plug. [1] Platelet dysfunction may be due to a disorder of connective tissue, platelet adhesion, aggregation or platelet-release reaction. [1] Disorders of platelets may be either due to due inadequate count or disordered function. Platelet adhesion disorders, such as von Willebrand disease, Bernard-Soulier syndrome, disorders of aggregation such as Glanzmann thrombasthenia, and acquired disorders of platelet function due to the drugs such as aspirin, NSAIDs, alcohol are some of the functional disorders. [2] Cliinical manifestations may be either with skin or mucosal bleeding. Number of platelets may be normal with prolongation of bleeding . Factor VIII and von Willebrand factor complex and other tests of platelet function may required. [1]
References
  1. HUEBSCH LB, HARKER LA. Disorders of Platelet Function: Mechanisms, Diagnosis and Management West J Med [online] 1981 Feb, 134(2):109-127 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1272531
  2. SAHUD MA. Platelet disorders: a review of disturbances in adhesion, aggregation, and release reaction. Calif Med [online] 1972 Jan, 116(1):21-31 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518141
  3. SAHUD MA. Platelet disorders: a review of disturbances in adhesion, aggregation, and release reaction. Calif Med [online] 1972 Jan, 116(1):21-31 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518141
  4. BHARATI KP, PRASHANTH UR. Von Willebrand Disease: An Overview Indian J Pharm Sci [online] 2011, 73(1):7-16 [viewed 01 October 2014] Available from: doi:10.4103/0250-474X.89751
  5. 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 01 October 2014] Available from: doi:10.4084/MJHID.2012.057
  6. CASTAMAN G. Prophylaxis of bleeding episodes and surgical interventions in patients with rare inherited coagulation disorders Blood Transfus [online] 2008 Sep, 6(Suppl 2):s39-s44 [viewed 01 October 2014] Available from: doi:10.2450/2008.0036-08
  7. HOOD J. L., EBY C. S.. Evaluation of a Prolonged Prothrombin Time. Clinical Chemistry [online] 2008 April, 54(4):765-768 [viewed 01 October 2014] Available from: doi:10.1373/clinchem.2007.100818
  8. SAHU S, LATA I, SINGH S, KUMAR M. Revisiting hemophilia management in acute medicine J Emerg Trauma Shock [online] 2011, 4(2):292-298 [viewed 01 October 2014] Available from: doi:10.4103/0974-2700.82225
  9. 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 01 October 2014] Available from: doi:10.4084/MJHID.2012.057

Investigations - for Diagnosis

Fact Explanation
Activated partial thromboplastin time Activated partial thromboplastin time (aPTT) (reference interval 23–36 s) [4] measures the activity of the intrinsic pathway of the clotting mechanism, and is prolonged in factor XI deficiency. [1,2,3] Normal aPTT may be found in mild to moderate hemophilia.
Prothrombin time and International Normalized Ratio (INR) Bleeding time and prothrombin time (reference interval 11.0–15.0 s), and International Normalized Ratio (INR) (reference interval 0.9–1.2) [2] are normal as they assess the extrinsic coagulation pathway. [3]
Bleeding time Bleeding time assess the
Factor XI assay Is reduced in haemophilia A due to the deficiency of factor . [1]
Testing for inhibitors Patient's plasma is mixed with normal plasma at 37°C for 1-2 hours and aPTT is checked. If the prolonged aPTT is not corrected, that is due to the presence of inhibitors [2] and then the level of inhibitors need to be measured using the Bethesda method. [2]
Platelet count and morphology This is important to exclude the other bleeding disorders particularly thrombocytopenia and platelet dysfunction. [1] Platelet count has to be checked and it should be within the normal range as expected. [2]
Haemoglobin level Hemoglobin/hematocrit is important to assess theblood loss and severity of anemia. [2]
References
  1. GENTRY PA, ROSS ML. Coagulation factor XI deficiency in Holstein cattle: expression and distribution of factor XI activity. Can J Vet Res [online] 1994 Oct, 58(4):242-247 [viewed 09 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1263706
  2. SAHU S, LATA I, SINGH S, KUMAR M. Revisiting hemophilia management in acute medicine J Emerg Trauma Shock [online] 2011, 4(2):292-298 [viewed 10 October 2014] Available from: doi:10.4103/0974-2700.82225
  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 01 October 2014] Available from: doi:10.4084/MJHID.2012.057

Investigations - Fitness for Management

Fact Explanation
Hemoglobin and hematocrit levels Hemoglobin and hematocrit levels may vary from normal as in a rapid blood loss, both blood (fluid) and cells are loss maintaining the relative ratio hence the concentration and the time is taken for the fluid balances to occur following an acute bleeding. It may be decreased depending on the type and severity of the bleeding problem in bleeding disorders. [3]
Factor XI level [1] Should be done prior to any surgery as correction of the deficient state is needed before the surgery. (as mentioned in the management section) [2]
References
  1. GENTRY PA, ROSS ML. Coagulation factor XI deficiency in Holstein cattle: expression and distribution of factor XI activity. Can J Vet Res [online] 1994 Oct, 58(4):242-247 [viewed 09 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1263706
  2. SAHU S, LATA I, SINGH S, KUMAR M. Revisiting hemophilia management in acute medicine J Emerg Trauma Shock [online] 2011, 4(2):292-298 [viewed 01 October 2014] Available from: doi:10.4103/0974-
  3. BHARATI KP, PRASHANTH UR. Von Willebrand Disease: An Overview Indian J Pharm Sci [online] 2011, 73(1):7-16 [viewed 01 October 2014] Available from: doi:10.4103/0250-474X.89751

Investigations - Followup

Fact Explanation
Factor XI level This will give a guide to the current state of disease. [1] Particularly after a surgery, the factor level needs to be maintained at least 5-7 days following minor surgery and and 10-14 days after major surgery. [1]
Factor innhibitor testing It is important to check the level of inhibitors as patients with high-titer inhibitors (> 5-10 BU)may need bypass clotting factors such as activated prothrombin complex concentrate, or rVIIa. [2]
References
  1. CASTAMAN G. Prophylaxis of bleeding episodes and surgical interventions in patients with rare inherited coagulation disorders Blood Transfus [online] 2008 Sep, 6(Suppl 2):s39-s44 [viewed 01 October 2014] Available from: doi:10.2450/2008.0036-08
  2. JOSEPHSON N.. The hemophilias and their clinical management. Hematology [online] December, 2013(1):261-267 [viewed 01 October 2014] Available from: doi:10.1182/asheducation-2013.1.261

Investigations - Screening/Staging

Fact Explanation
Serum bilirubin Serum bilirubin may be elevated due to excessive catabolism of red blood cells. [3]
CT / MRI scan of the brain Spontaneous or traumatic intracranial hemorrhage may be evaluated using CT/MRI scan. Joint cartilage, synovium, and joint space evaluation may also be possible with MRI. [4]
Ultrasonography USS is useful to evaluate the joints with effusions. [3]
References
  1. BHARATI KP, PRASHANTH UR. Von Willebrand Disease: An Overview Indian J Pharm Sci [online] 2011, 73(1):7-16 [viewed 01 October 2014] Available from: doi:10.4103/0250-474X.89751
  2. 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 01 October 2014] Available from: doi:10.4084/MJHID.2012.057
  3. SAHU S, LATA I, SINGH S, KUMAR M. Revisiting hemophilia management in acute medicine J Emerg Trauma Shock [online] 2011, 4(2):292-298 [viewed 01 October 2014] Available from: doi:10.4103/0974- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448247
  4. SINGLETON TC, KEANE M. Diagnostic and Therapeutic Challenges of Intracranial Hemorrhage in Neonates With Congenital Hemophilia: A Case Report and Review Ochsner J [online] 2012, 12(3):249-253 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448247

Management - General Measures

Fact Explanation
Immediate management Assessment of airway and breathing, is particularly important as they can present with upper airway obstruction following retropharyngeal. [3] The immediate surgical airway may be needed. Circulatory collapse may occur in a massive haemorrhage. Disability and exposure will follow later.
Multidesciplinary approach Haematologist, physician, orthopedic surgeon, physiotherapist etc should be involved in the management of haemophilic patients. [1]
Patient education Parents of the affected child need a full explanation of the nature of the disease, its complications and importance of complying with the treatment. Precautions to minimize bleeding tendency such as avoiding contact sports, injuries when handling the equipments are needed. It is better to inform the teachers at school with permission of the parents and educate them on what to do as immediate measures. [5]
Management of other complications Upper GI bleeding, haematuria, intracranial haemorrhage may need specific supportive management after correcting the factor level. [4] Associated psychological disturbances , learning problems due to recurrent school abstinence may need special attention.
Follow up Apart from the routine assessment for features of bleeding manifestations, patients with complications such as intracranial haemorrhages need specific attention as they are more likely to have neurocognitive, academic, behavioral, adaptive, and motor functioning deficienciesrequiring long-term follow-up. [2]
References
  1. STERNDALE H. Haemarthrosis and haemophilia. Proc R Soc Med [online] 1967 Jan, 60(1):37-38 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1901393
  2. SINGLETON TC, KEANE M. Diagnostic and Therapeutic Challenges of Intracranial Hemorrhage in Neonates With Congenital Hemophilia: A Case Report and Review Ochsner J [online] 2012, 12(3):249-253 [viewed 01 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448247
  3. BIRKHOLZ T, KRöBER S, KNORR C, SCHIELE A, BUMM K, SCHMIDT J. A retropharyngeal-mediastinal hematoma with supraglottic and tracheal obstruction: The role of multidisciplinary airway management J Emerg Trauma Shock [online] 2010, 3(4):409-411 [viewed 01 October 2014] Available from: doi:10.4103/0974-2700.70776
  4. SAHU S, LATA I, SINGH S, KUMAR M. Revisiting hemophilia management in acute medicine J Emerg Trauma Shock [online] 2011, 4(2):292-298 [viewed 01 October 2014] Available from: doi:10.4103/0974-2700.82225
  5. MEYDAN H, YILDIZ MA, ÖZDIL F, GEDIK Y, ÖZBEYAZ C. Identification of factor XI deficiency in Holstein cattle in Turkey Acta Vet Scand [online] , 51(1):5 [viewed 09 October 2014] Available from: doi:10.1186/1751-0147-51-5

Management - Specific Treatments

Fact Explanation
Management of high risk bleeding situations Central nervous system hemorrhage including intracranial hemorrhage and spinal hematoma, soft-tissue hemorrhage predisposing to airway compromise retropharyngeal hemorrhage, hemorrhage along facial planes, neck hematoma associated with dissection, large tongue hematoma, gastrointestinal bleeding including hematemesis, hematochezia or melena from bleeding telangiectasia, splenic rupture, kidney capsular rupture, liver laceration, hematoma of bowel wall and haemorrhage around the eye are some of these high risk bleeding manifestations. [1] Hemostasis has to be restored and blood should be sent for investigations. Immediate infusion of factor 8, 50 IU/kg body weight. [1] Continuous clotting factor infusions needs to be given with measured factor level til the acute bleeding is settled. [1]
Factor replacement Factor XI replacement ia done with antifibrinolytics, fresh-frozen plasma (FFP), and factor XI concentrates. [2] The plasma factor XI level does not respond to L-desamino-8-D-arginine vasopressin, and cryoprecipitate as it does not contain factor XI. [3] The plasma half-life of factor XI is usually 45 h, and once-daily administration of a factor XI-containing product is recomended. [3]
Preparing for a surgery Major surgeries involving the central nervous system, cardiothoracic, vascular, head and neck and abdomen or procedures involving tissues with high fibrinolytic activity (oropharynx or urinary tract) are at high risk of bleeding in patients with haemophilia C. They should be given prophylactic therapy with factor replacement upto 40–45% for 10–14 days in severe deficiency. [3]
Prophylaxis Bleeding risk is more with surgical prcedures than spontaneous bleeding as in haemophilia A and B. Factor replacement should be used for epidural anesthesia. Dental procedures such as tooth extraction and minor surgical procedures are given antifibrinolytic therapy (ε-amino caproic acid 5–6 g four-times daily or tranexamic acid 1 g four-times daily), starting 12 h prior to the procedure and continuing for 7 days, as prophylaxis. These drugs inhibit urokinase and fibrinolytic activity. [3]
Management of inhibitor formation Patients with very low (<1%) plasma factor XI levels are more likely to develop inhibitory antibodies when exposed to plasma products. [3] High-titer inhibitors (> 5-10 BU) or patients who are having an anamnestic response to FVIII will be treated with bypass clotting factors such as an activated prothrombin complex concentrate, or rVIIa. [2]
References
  1. SAHU S, LATA I, SINGH S, KUMAR M. Revisiting hemophilia management in acute medicine J Emerg Trauma Shock [online] 2011, 4(2):292-298 [viewed 01 October 2014] Available from: doi:10.4103/0974-2700.82225
  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):207-214 [viewed 09 October 2014] Available from: doi:10.1007/s00431-011-1571-x