History

Fact Explanation
Neonates with symptoms of hemorrhages (as described below) The transmission of maternal vitamin K to the fetus is limited during the pregnancy, so the newborns have a low liver stores of it.Hemorrhagic disease of the newborn manifests early following birth and can cause fatal hemorrhages. [1] [2] [3] [4] [6] It's customary to give paraentral vitamin K megadose to the infants soon after birth to prevent the complications [5]. Special attention should be given to mothers who took antiepileptic medications during pregnancy. [7] Even though the typical scenario is to present with bleeding early, there have been reported cases of late hemorrhagic disease of the newborn [8] [9] [10] , some of them have been given prophylactic vitamin K too. [11] [12]
A history of ingesting oral anticoagulant drugs. Vitamin K is an important factor in post-translational modifications of coagulation factors II, VII, IX and X. oral anticoagulants, widely known warfarin, is an Vit K antagonist, so blocks this action, causing low levels of above mentioned coagulation factors. Symptoms start manifesting a week or so later, following starting of therapy since already manufactured coagulation factors are still circulating. [13] [14] Bleeding can be manifested in various sites. [15] [16] [17]
Chronic diarrhea. Vitamin K absorption is linked with fat absorption. As a result the conditions leading to fat malabsorption, leads to vitamin K deficiency and following that, coagulation factor deficiency. [18] [19] [20]
A history of liver disorder. Usually chronic liver diseases more than acute ones. Vitamin K is a fat-soluble essential vitamin and needs bile for it's absorption. Bile is synthesized by the liver and when hepatocytes are damaged, and once the half-time of already existing Vitamin K is spent, acquired Vitamin K deficiency and resulting acquired coagulation factor deficiency occurs. [21] [22] The clotting factors themselves are also synthesized by the liver, so there is a gross deficiency of them in liver diseases. [23] [24] Even the synthesized ones are also functionally subnormal. [24] [25] Some liver pathologies like hepatic portal hypertension are associated with spelenomegaly and hypersplenism, so the resulting thrombocytopenias [24] [26] [27] are also causative factors of coagulation deficits.
A history of massive transfusion of blood. massive blood transfusion is defined as transfusion of at least 5 units of blood in 4 hours. [28] There is a hemodilution and secondary clotting factor deficiency and thrombocytopenia. [29] [30] [31] [32]
No family history of coagulation factor deficiency. i. e. Hemophilias Which is the differentiating factor from congenital coagulation factor deficiencies. [33] This is usually due to presence of inhibiting factors for coagulation components. [34]
A history of ingesting an offending drug. i.e. antibiotic, psychotrophic or immunomodulatory drug. The reaction to the drug causes formation of inhibitors to coagulation factors. Over 30 drugs have been documented causing this reaction. [35] [36]
A probable triggering factor. i.e. pregnancy, autoimmune disease flare up, malignancy or infection In most cases a probable triggering factor can be identified. [37]
Sudden episodes of bleeding tendencies The patients usually present with no previous family or personal history of bleeding manifestations [33] and sudden bleeding episodes in varying sites of the body. [38] [39] [40]
References
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  3. EHLING L. REX. Hemorrhagic Disease of the Newborn. Arch Pediatr Adolesc Med [online] 1961 February [viewed 13 May 2014] Available from: doi:10.1001/archpedi.1961.04020030105016
  4. SUTHERLAND JAMES M.. Hemorrhagic Disease of the Newborn. Am J Dis Child [online] 1967 May [viewed 13 May 2014] Available from: doi:10.1001/archpedi.1967.02090200056003
  5. HANDEL J, TRIPP JH. Vitamin K prophylaxis against haemorrhagic disease of the newborn in the United Kingdom. BMJ [online] 1991 Nov 2, 303(6810):1109 [viewed 13 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1671284
  6. ROSS M. B., DE ALARCON P.. Hemolytic Disease of the Fetus and Newborn. NeoReviews [online] December, 14(2):e83-e88 [viewed 13 May 2014] Available from: doi:10.1542/neo.14-2-e83
  7. KAZMIN A et al. Antiepileptic drugs in pregnancy and hemorrhagic disease of the newborn- An update. Canadian Family Physician December [online] 2010 vol. 56 no. 12 1291-1292. [viewed 13 May 2014] Available from http://www.cfp.ca/content/56/12/1291.full
  8. ALPAN G, AVITAL A, PELEG O, DGANI Y. Late presentation of haemorrhagic disease of the newborn. Arch Dis Child [online] 1984 May, 59(5):482-483 [viewed 13 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1628491
  9. ZENGIN EMINE, SARPER NAZAN, TüRKER GüLCAN, ÇORAPçIOğLU FUNDA, ETUş VOLKAN. Late haemorrhagic disease of the newborn. Annals of Tropical Paediatrics [online] 2006 September, 26(3):225-231 [viewed 13 May 2014] Available from: doi:10.1179/146532806X120327
  10. BOR OZCAN, AKGUN NEJAT, YAKUT AYTEN, SARHUS FATIH, KOSE SUNA. Late hemorrhagic disease of the newborn. Pediatr Int [online] 2000 January, 42(1):64-66 [viewed 13 May 2014] Available from: doi:10.1046/j.1442-200x.2000.01173.x
  11. FLOOD VERONICA H., GALDERISI FAITH C., LOWAS STEFANIE R., KENDRICK ANGELA, BOSHKOV LYNN K.. Hemorrhagic disease of the newborn despite vitamin K prophylaxis at birth. Pediatr. Blood Cancer [online] December, 50(5):1075-1077 [viewed 13 May 2014] Available from: doi:10.1002/pbc.21383
  12. MORRICE LM, JAGDIS FA, THOMMASEN H. Case report: fatal hemorrhagic disease in a newborn despite vitamin K prophylaxis. Can Fam Physician [online] 1998 Sep:1893-1896 [viewed 13 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277887
  13. LURIE YAEL, LOEBSTEIN RONEN, KURNIK DANIEL, ALMOG SHLOMO, HALKIN HILLEL. Warfarin and vitamin K intake in the era of pharmacogenetics. [online] December, 70(2):164-170 [viewed 13 May 2014] Available from: doi:10.1111/j.1365-2125.2010.03672.x
  14. LOWENTHAL J., BIRNBAUM H.. Vitamin K and Coumarin Anticoagulants: Dependence of Anticoagulant Effect on Inhibition of Vitamin K Transport. Science [online] 1969 April, 164(3876):181-183 [viewed 13 May 2014] Available from: doi:10.1126/science.164.3876.181
  15. SHAH M., AVGIL TSADOK M., JACKEVICIUS C. A., ESSEBAG V., EISENBERG M. J., RAHME E., HUMPHRIES K. H., TU J. V., BEHLOULI H., GUO H., PILOTE L.. Warfarin Use and the Risk for Stroke and Bleeding in Patients With Atrial Fibrillation Undergoing Dialysis. Circulation [online] December, 129(11):1196-1203 [viewed 13 May 2014] Available from: doi:10.1161/CIRCULATIONAHA.113.004777
  16. DAHRI KAREN, LOEWEN PETER. The risk of bleeding with warfarin: A systematic review and performance analysis of clinical prediction rules. Thromb Haemost [online] 2007 October [viewed 13 May 2014] Available from: doi:10.1160/TH07-04-0297
  17. WIEDERMANN CHRISTIAN J., STOCKNER INGRID. Warfarin-induced bleeding complications — clinical presentation and therapeutic options. Thrombosis Research [online] 2008 January, 122:S13-S18 [viewed 13 May 2014] Available from: doi:10.1016/S0049-3848(08)70004-5
  18. YıLMAZ SEBAHAT, TAVIL BETüL, SARı SINAN, CINAZ PEYAMI. Vitamin K Deficiency Because of Ceftriaxone Usage and Prolonged Diarrhoea. [online] December, 47(5):314-315 [viewed 13 May 2014] Available from: doi:10.1111/j.1440-1754.2011.02090.x
  19. MOUZAKI MARIALENA, VRESK LAURA, GONSKA TANJA. An Infant With Vomiting, Diarrhea, and Failure to Thrive. Gastroenterology [online] 2014 April, 146(4):912-1138 [viewed 13 May 2014] Available from: doi:10.1053/j.gastro.2013.11.035
  20. SAVVIDOU SAVVOULA. Pneumobilia, chronic diarrhea, vitamin K malabsorption: A pathognomonic triad for cholecystocolonic fistulas. WJG [online] 2009 December [viewed 13 May 2014] Available from: doi:10.3748/wjg.15.4077
  21. PHILLIPS JASON R., ANGULO PAUL, PETTERSON TANYA, LINDOR KEITH D.. Fat-soluble vitamin levels in patients with primary biliary cirrhosis. Am J Gastroenterology [online] 2001 September, 96(9):2745-2750 [viewed 14 May 2014] Available from: doi:10.1111/j.1572-0241.2001.04134.x
  22. SAJA MAHA F., ABDO AYMAN A., SANAI FAISAL M., SHAIKH SHAFFI A., GADER ABDEL GALIL M. ABDEL. The coagulopathy of liver disease. Blood Coagulation & Fibrinolysis [online] 2013 January, 24(1):10-17 [viewed 14 May 2014] Available from: doi:10.1097/MBC.0b013e32835975ed
  23. AMITRANO LUCIO, GUARDASCIONE MARIA A., BRANCACCIO VINCENZO, BALZANO ANTONIO. Coagulation Disorders in Liver Disease. Semin Liver Dis [online] 2002 December, 22(1):083-096 [viewed 14 May 2014] Available from: doi:10.1055/s-2002-23205
  24. TRIPODI A., ANSTEE Q. M., SOGAARD K. K., PRIMIGNANI M., VALLA D. C.. Hypercoagulability in cirrhosis: causes and consequences1. [online] December, 9(9):1713-1723 [viewed 14 May 2014] Available from: doi:10.1111/j.1538-7836.2011.04429.x
  25. MONROE DOUGALD M., HOFFMAN MAUREANE. The Coagulation Cascade in Cirrhosis. Clinics in Liver Disease [online] 2009 February, 13(1):1-9 [viewed 14 May 2014] Available from: doi:10.1016/j.cld.2008.09.014
  26. AFDHAL NEZAM, MCHUTCHISON JOHN, BROWN ROBERT, JACOBSON IRA, MANNS MICHAEL, POORDAD FRED, WEKSLER BABETTE, ESTEBAN RAFAEL. Thrombocytopenia associated with chronic liver disease. Journal of Hepatology [online] 2008 June, 48(6):1000-1007 [viewed 14 May 2014] Available from: doi:10.1016/j.jhep.2008.03.009
  27. HAYASHI HIROMITSU. Management of thrombocytopenia due to liver cirrhosis: A review. WJG [online] 2014 December [viewed 14 May 2014] Available from: doi:10.3748/wjg.v20.i10.2595
  28. MITRA BISWADEV, CAMERON PETER A., GRUEN RUSSELL L., MORI ALFREDO, FITZGERALD MARK, STREET ALISON. The definition of massive transfusion in trauma. European Journal of Emergency Medicine [online] 2011 June, 18(3):137-142 [viewed 14 May 2014] Available from: doi:10.1097/MEJ.0b013e328342310e
  29. SIHLER KRISTEN C.. Complications of Massive Transfusion. CHEST [online] 2010 January [viewed 14 May 2014] Available from: doi:10.1378/chest.09-0252
  30. HARDY JF, DE MOERLOOSE P and SAMAMA M. Massive transfusion and coagulopathy: pathophysiology and implications for clinical management. Can J Anaesth. [online] 2004 Apr;51(4):293-310. [viewed 14 May 2014] Available from DOI 10.1007/BF03018233
  31. LEVY JERROLD H.. Massive Transfusion Coagulopathy. Seminars in Hematology [online] 2006 January, 43:S59-S63 [viewed 14 May 2014] Available from: doi:10.1053/j.seminhematol.2005.11.019
  32. HARDY J.-F., DE MOERLOOSE P., SAMAMA C. M.. The coagulopathy of massive transfusion. Vox Sang [online] 2005 October, 89(3):123-127 [viewed 14 May 2014] Available from: doi:10.1111/j.1423-0410.2005.00678.x
  33. FRANCHINI MASSIMO, GANDINI GIORGIO, DI PAOLANTONIO TIZIANA, MARIANI GUGLIELMO. Acquired hemophilia A: A concise review. Am. J. Hematol. [online] December, 80(1):55-63 [viewed 14 May 2014] Available from: doi:10.1002/ajh.20390
  34. FRANCHINI MASSIMO, LIPPI GIUSEPPE, FAVALORO EMMANUEL. Acquired Inhibitors of Coagulation Factors: Part II. Semin Thromb Hemost [online] December, 38(05):447-453 [viewed 14 May 2014] Available from: doi:10.1055/s-0032-1305779
  35. FRANCHINI M, CAPRA F, NICOLINI N, VENERI D, MANZATO F, BAUDO F, LIPPI G. Drug-induced anti-factor VIII antibodies: a systematic review. Med Sci Monit [online] 2007 Apr, 13(4):RA55-61 [viewed 14 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/17392659
  36. HWANG HYE WON, KONG JEE HYUN, YU DONG WOOK, KIM WOO TAEK, KIM HYUN SOO, LEE CHONG IN. A patient with acquired hemophilia A induced by clopidogrel. Korean J Hematol [online] 2012 December [viewed 14 May 2014] Available from: doi:10.5045/kjh.2012.47.1.80
  37. SHETTY SHRIMATI, BHAVE MANALI, GHOSH KANJAKSHA. Acquired hemophilia A: Diagnosis, aetiology, clinical spectrum and treatment options. Autoimmunity Reviews [online] 2011 April, 10(6):311-316 [viewed 14 May 2014] Available from: doi:10.1016/j.autrev.2010.11.005
  38. CHENG QIANSONG, YU GUOHUI, YE YONGQING. Acquired hemophilia A in a patient associated with community-acquired pneumonia. Blood Coagulation & Fibrinolysis [online] 2013 October, 24(7):774-776 [viewed 14 May 2014] Available from: doi:10.1097/MBC.0b013e3283626213
  39. KIM MIN SUN, KILGORE PAUL E., KANG JU SUNG, KIM SUN YOUNG, LEE DAE YEOL, KIM JUNG SOO, HWANG PYOUNG HAN. Transient Acquired Hemophilia Associated with Mycoplasma Pneumoniae Pneumonia. J Korean Med Sci [online] 2008 December [viewed 14 May 2014] Available from: doi:10.3346/jkms.2008.23.1.138
  40. MATSUOKA MASATAKE, MAJIMA TOKIFUMI, ONODERA TOMOHIRO, IEKO MASAHIRO, SOURI MASAYOSHI, ICHINOSE AKITADA, KURITA TAKASHI, KASAHARA YASUHIKO, INOUE MASAHIRO, TAKAHASHI DAISUKE. Hemorrhagic-acquired factor XIII deficiency associated with tocilizumab for treatment of rheumatoid arthritis. Int J Hematol [online] December, 96(6):781-785 [viewed 14 May 2014] Available from: doi:10.1007/s12185-012-1191-x

Examination

Fact Explanation
Evidence of bleeding into skin, mucus membranes, soft tissues and muscles. Congenital hemophilia is characterized by bleeding into joint spaces leading to hemarthrosis, but in acquired types, it's rarely seen. Instead, bleeding into skin (purpura, ecchymosis) mucus membranes (purpura) soft tissues (subcutaneous bruising) and muscles (tender swelling of muscles) is present. It's usually more severe than congenital type bleeding. In most of the cases bleeding is spontaneous. [1] [2] [3] [4] [5] [6] [7]
References
  1. FRANCHINI MASSIMO, GANDINI GIORGIO, DI PAOLANTONIO TIZIANA, MARIANI GUGLIELMO. Acquired hemophilia A: A concise review. Am. J. Hematol. [online] December, 80(1):55-63 [viewed 14 May 2014] Available from: doi:10.1002/ajh.20390
  2. FRANCHINI M., MANNUCCI P. M.. Acquired haemophilia A: A 2013 update. Thromb Haemost [online] 2013 September, 110(6):1114-1120 [viewed 14 May 2014] Available from: doi:10.1160/TH13-05-0363
  3. BOGGIO LISA N., GREEN DAVID. ACQUIRED HEMOPHILIA. Rev Clin Exp Hematol [online] 2001 December, 5(4):389-404 [viewed 14 May 2014] Available from: doi:10.1046/j.1468-0734.2001.00049.x
  4. COLLINS P. W., HIRSCH S., BAGLIN T. P., DOLAN G., HANLEY J., MAKRIS M., KEELING D. M., LIESNER R., BROWN S. A., HAY C. R. M.. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood [online] 2007 March, 109(5):1870-1877 [viewed 14 May 2014] Available from: doi:10.1182/blood-2006-06-029850
  5. FRANCHINI M, GIRELLI D, OLIVIERI O, BOZZINI C, GUIOTTO M, ZARDINI G, LIPPI G, MANZATO F, GANDIN G. Clinical heterogeneity of acquired hemophilia A: a description of 4 cases. Haematologica [online] 2005 Mar, 90(3):ECR16 [viewed 14 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15753057
  6. YEE T. T., TAHER A., PASI K. J., LEE C. A.. A survey of patients with acquired haemophilia in a haemophilia centre over a 28-year period. Clin Lab Haematol [online] 2000 October, 22(5):275-278 [viewed 14 May 2014] Available from: doi:10.1046/j.1365-2257.2000.00316.x
  7. BAUDO F., COLLINS P., HUTH-KUHNE A., LEVESQUE H., MARCO P., NEMES L., PELLEGRINI F., TENGBORN L., KNOEBL P.. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood [online] December, 120(1):39-46 [viewed 14 May 2014] Available from: doi:10.1182/blood-2012-02-408930

Differential Diagnoses

Fact Explanation
Congenital hemophilias There are three congenital hemophilia types. Hemophilia A the most common is an X-linked recessive disorder which caused by deficiency of clotting factor VIII, which may be due to inheritance from parents or a spontaneous mutation. Hemophilia B is also an X-linked recessive disorder that results in deficiency of coagulation factor IX. [1] [2] [3] [4] The hallmark feature of congenital hemophilias is the bleeding into joints, or hemearthrosis, [5] which is rare in acquired form. Hemophilia C is a rarer, newer entity which is characterized by an unpredictable form of bleeding . [6] [7] The patients with congenital hemophilia usually manifests early in life, and a clear family history can be identified, whereas in acquired types, there is no family history and the bleeding happens later in life usually following a triggering event. The severity of bleeding in hemophilias A and B is related to the severity of factor defect, which is not so in acquired type.
Administration of anticoagulant Subcutaneous heparin use can also mimic acquired coagulopathy because of hematomas in the injection site and probable purpura in the skin, and gastrointestinal/ urinary tract bleeding. There is usually a clear indication like acute coronary syndrome for starting the treatment. [8] [9]
Von Willebrand disease It is an inherited, clinically heterogeneous hemorrhagic disorder caused by the deficiency of the protein von Willebrand factor. Primary hemostasis is impaired by defective vWF interaction between platelets and the vessel wall. Clinical differentiating by symptom analysis might be different since the presentation is vastly heterogeneous, but doing vWF assays in plasma is a reliable test in diagnosing. [10] [11] [12] [13]
Disseminated Intravascular Coagulation DIC or consumption coagulopathy is characterized by systemic widespread activation of blood coagulating cascade which results in deposition of fibrin, leading to multiple-organ dysfunction syndrome caused by microvascular thrombi in various organs. It usually follows a stressful factor,i.e. hemorrhage, sepsis, trauma, where there is a marked vascular endothelial damage. It rapidly progresses to multiple organ failure and death, if untreated. Blood concentrations of Fibrin-Degradation Products should be tested in all patients with acute hemorrhagic manifestations. [14] [15] [16]
References
  1. COLLINS PETER W., CHALMERS ELIZABETH, HART DANIEL P., LIESNER RI, RANGARAJAN SAVITA, TALKS KATE, WILLIAMS MIKE, HAY CHARLES R.. Diagnosis and treatment of factor VIII and IX inhibitors in congenital haemophilia: (4th edition). Br J Haematol [online] December, 160(2):153-170 [viewed 14 May 2014] Available from: doi:10.1111/bjh.12091
  2. SRIVASTAVA A., BREWER A. K., MAUSER-BUNSCHOTEN E. P., KEY N. S., KITCHEN S., LLINAS A., LUDLAM C. A., MAHLANGU J. N., MULDER K., POON M. C., STREET A.. Guidelines for the management of hemophilia. Haemophilia [online] December, 19(1):e1-e47 [viewed 14 May 2014] Available from: doi:10.1111/j.1365-2516.2012.02909.x
  3. MAKRIS M., KASPER C.. The World Federation of Hemophilia guideline on management of haemophilia. Haemophilia [online] December, 19(1):1-1 [viewed 14 May 2014] Available from: doi:10.1111/hae.12074
  4. ZIMMERMAN B., VALENTINO L. A.. Hemophilia: In Review. Pediatrics in Review [online] December, 34(7):289-295 [viewed 14 May 2014] Available from: doi:10.1542/pir.34-7-289
  5. CARCAO MANUEL. The Diagnosis and Management of Congenital Hemophilia. Semin Thromb Hemost [online] 2012 September, 38(07):727-734 [viewed 14 May 2014] Available from: doi:10.1055/s-0032-1326786
  6. CAWTHERN KM, VAN 'T VEER C, LOCK JB, DILORENZO ME, BRANDA RF, MANN KG. Blood coagulation in hemophilia A and hemophilia C. Blood [online] 1998 Jun 15, 91(12):4581-92 [viewed 14 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/9616154
  7. BOLTON-MAGGS . Factor XI deficiency and its management. Haemophilia [online] 2000 July, 6(s1):100-109 [viewed 14 May 2014] Available from: doi:10.1046/j.1365-2516.2000.00053.x
  8. SCHULMAN SAM. Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment . Chest [online] 2008 June [viewed 14 May 2014] Available from: doi:10.1378/chest.08-0674
  9. LEVINE MARK N.. Hemorrhagic Complications of Anticoagulant Treatment. Chest [online] 2004 September [viewed 14 May 2014] Available from: doi:10.1378/chest.126.3_suppl.287S
  10. Hemophilia and von Willebrand's disease: 1. Diagnosis, comprehensive care and assessment. Association of Hemophilia Clinic Directors of Canada. CMAJ [online] 1995 Jul 1, 153(1):19-25 [viewed 14 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/7796372
  11. JAMES PAULA, LILLICRAP DAVID. The Diagnosis and Management of on Willebrand Disease in Canada . Semin Thromb Hemost [online] December, 37(05):522-527 [viewed 14 May 2014] Available from: doi:10.1055/s-0031-1281038
  12. RUGGERI ZM, ZIMMERMAN TS. von Willebrand factor and von Willebrand disease. Blood [online] 1987 Oct, 70(4):895-904 [viewed 14 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3307951
  13. VISCHER U. M.. von Willebrand factor, endothelial dysfunction, and cardiovascular disease. J Thromb Haemost [online] 2006 June, 4(6):1186-1193 [viewed 14 May 2014] Available from: doi:10.1111/j.1538-7836.2006.01949.x
  14. LEVI M, TOH C. H., THACHIL J, WATSON H. G.. Guidelines for the diagnosis and management of disseminated intravascular coagulation. [online] 2009 April, 145(1):24-33 [viewed 14 May 2014] Available from: doi:10.1111/j.1365-2141.2009.07600.x
  15. WADA HIDEO. Disseminated intravascular coagulation. Clinica Chimica Acta [online] 2004 June, 344(1-2):13-21 [viewed 14 May 2014] Available from: doi:10.1016/j.cccn.2004.02.015
  16. LEVI MARCEL. Disseminated intravascular coagulation. Critical Care Medicine [online] 2007 September, 35(9):2191-2195 [viewed 14 May 2014] Available from: doi:10.1097/01.CCM.0000281468.94108.4B

Investigations - for Diagnosis

Fact Explanation
Platelet count As a part of complete blood cell count. Platelets are a component in primary hemostasis. [1] In bleeding disorders that are due to coagulation factors, platelet count is essentially normal. [1]
Liver function profile Since the liver disorders are one of the commonest reasons for coagulopathy [2] , liver function screening should be done in all patients presenting with bleeding disorders. [3] [4] [5] [6]
Bleeding time BT is a tool to assess platelet function [7], and by that, primary hemostasis. Where thrombocytopenia is not a prominent feature, bleeding time is usually normal. [8] [9] [10]
Prothrombin time/ Inernational Normalized Ratio PT evaluates the extrinsic pathway of coagulation cascade (which assesses the factors VII, X, V, II, and fibrinogen) and INR standardizes it. It's prolonged in patients on anticoagulant therapy, liver disease, vitamin K deficiency and DIC. [1] [10] [11] [12] [13]
Activated Partial Thromboplastin Time (APTT) aPTT is a screening tool in coagulation disorders. It assesses intrinsic pathway of the coagulation cascade and elevated in vitamin K deficiency, hemophilias, vWF deficiency, liver diseases and other isolated coagulation factor deficiencies. In acquired type of coagulopathies the change in aPTT is noticed suddenly. [1] [10] [14] [15] [16] [17] [18] [19] [20] It's only useful if tested in patients who complain of a bleeding tendency. [21]
Von Willebrand Factor assays Abnormal vWF assay reports exclude vWF disease. [1] [10] [22] [23] [24]
Coagulation factor assays Quantitative and qualitative assessment of factors (mainly VII, IX, XI) is the confirmation of diagnosis. [1] [10] [25] [26]
Assays for inhibiting factors There are various biochemical methods assessing inhibitors of coagulating factors. Quantitative assessment of them is important in management. Measured in Bethesda Units. [27] [28] [29] [30]
Lupus anticoagulant As an indicator of autoimmune disease. High titers are associated with bleeding and thrombosis. [31] [32] [33]
References
  1. TRIPLETT DA. Coagulation and bleeding disorders: review and update. Clin Chem [online] 2000 Aug, 46(8 Pt 2):1260-9 [viewed 14 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10926920
  2. STAUDINGER THOMAS, LOCKER GOTTFRIED, FRASS MICHAEL. Management of Acquired Coagulation Disorders in Emergency and Intensive-Care Medicine. Semin Thromb Hemost [online] December, 22(01):93-104 [viewed 14 May 2014] Available from: doi:10.1055/s-2007-998995
  3. FRANCIS JL, ARMSTRONG DJ. Acquired dysfibrinogenaemia in liver disease. J Clin Pathol [online] 1982 Jun, 35(6):667-672 [viewed 14 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC497747
  4. PAPADOPOULOS V, FILIPPOU D, MANOLIS E, MIMIDIS K. Haemostasis impairment in patients with obstructive jaundice. J Gastrointestin Liver Dis [online] 2007 Jun, 16(2):177-86 [viewed 14 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/17592568
  5. CALDWELL STEPHEN H., HOFFMAN MAUREANE, LISMAN TON, MACIK B. GAIL, NORTHUP PATRICK G., REDDY K. RAJENDER, TRIPODI ARMANDO, SANYAL ARUN J.. Coagulation disorders and hemostasis in liver disease: Pathophysiology and critical assessment of current management. Hepatology [online] December, 44(4):1039-1046 [viewed 14 May 2014] Available from: doi:10.1002/hep.21303
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  7. NIEUWENHUIS HK, AKKERMAN JW, SIXMA JJ. Patients with a prolonged bleeding time and normal aggregation tests may have storage pool deficiency: studies on one hundred six patients. Blood [online] 1987 Sep, 70(3):620-3 [viewed 14 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3620697
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Management - General Measures

Fact Explanation
Control of bleeding. The first priority is to stop acute bleeding. Some cases might need surgical procedures, i.e. draining of hematomas, resection of the organ or a part of it, to arrest life threatening internal bleeding. [1] [2] [3] [4] [5] [6] [7] [8]
Observe vitals. The patients with acquired hemophilia bleed without relation to the serum level of inhibitors. So, continuous close monitoring of vitals is essential, like in any other major bleeds. [9]
Manage concomitant diseases Most of the patients with acquired coagulopathy are older and secondary to some other disease. It's important to manage the patient as whole, giving them a holistic care.
Physical resting The patients might bleed spontaneously and unpredictably, so it's important to keep the patients physically resting as much as possible.
References
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  6. PATTED S et al. Unsuspected Acquired Hemophilia in a Patient with Severe Postpartum Hemorrhage. International Journal of Infertility and Fetal Medicine, [web] 2011 Jan. Vol. 2(1). [viewed 15 May 2014] Available from http://www.jaypeejournals.com/eJournals/ShowText.aspx
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  9. JOHANSSON PäR I.. Goal-directed hemostatic resuscitation for massively bleeding patients: The Copenhagen concept. Transfusion and Apheresis Science [online] 2010 December, 43(3):401-405 [viewed 15 May 2014] Available from: doi:10.1016/j.transci.2010.09.002

Management - Specific Treatments

Fact Explanation
Intravenous fresh frozen plasma Even though there are fatal adverse effects reported, in emergency setting fresh frozen plasma (FFP) is indicated in factor IX deficiency. [1] [2] [3] [4]
Intravenous cryoprecipitate FFP has no or low factor VIII. In emergency setting when recombinant factor is pending, cryoprecipitate which is a rich medium in FVIII and other coagulation factors can be used. [1] [2] [3] [4] [5] [6]
Recombinant coagulation factors Recombinant factors as to the deficient factor in assays. the most commonly used factor is the first ever developed rFVIII. [7] There are lesser reported adverse effects than giving plasma components. [8] [9] [10] [11] [12]
Activated prothrombin complex concentrate It's a FVIII bypassing agent used to ensure that coagulation cascade completes when there are inhibitors present. There are reported good response to APCC alone or combinations with rFVIII. [13] [14] [15] [16] [17] [18]
Immunosuppression Since the presence of auto-antibodies to the coagulation factors is the pathology, immunosuppression has proved to be effective in eradicating inhibitors. The drugs that been used are steroids and cyclophosphamide, alone or combined. The recovery rate has been proved to be significant is studies. The prescribed time is 5 weeks. [19] [20] [21] [22] [23] Steroid pulses, calcineurin inhibitors and ciclosporin has also proved to be beneficial. [24]
Rituximab Rituximab is a monoclonal chimeric antibody to the CD20 antigen [25] and has proved to be ebenficial in eradicating inhibitors, especially in those who do not respond to or tolerate first line treatment. [26] [27] [28] [29] [30]
Intravenous immunoglobulin therapy Used as the second line treatment modality in the patients who are critical and do not respond to conventional treatment. [31] [32] [33] [34] [35] There have been fatal adverse effects reported. [35]
Plasmapheresis Plasma exchange and immunoadsorption has removed inhibitors successfully but there have been reports of inhibitors in blood a couple of weeks later in some patients, so it's suggested to be combined with immunosuppression. [36] [37] [38]
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