Health Dictionary
Reliable, easy-to-read patient information on common medical conditions β written in plain language, free of jargon, and grounded in current evidence. Browse the most frequent diagnoses, understand what they mean for everyday life, and learn which steps and questions help you have a focused conversation with your doctor.
Hemophilia differential diagnosis
Introduction
Overview
Overview
Hemophilia must be differentiated from other diseases leading to spontaneous bleeding and bleeding following injuries or surgery such as von Willebrand disease, hepatic failure, thrombocytopenia, vitamin K deficiency, disseminated intravascular coagulation, uremia, congenital afibrinogenemia, factor V deficiency, factor X deficiency as seen in amyloid purpura, glanzmann’s thrombasthenia, Bernard-Soulier syndrome, factor XII deficiency and C1-inhibitor (C1INH) deficiency.
Differentiating Hemophilia from other Diseases
Differentiating Hemophilia from other Diseases
Hemophilia must be differentiated from other diseases leading to spontaneous bleeding and bleeding following injuries or surgery such as:
- Von Willebrand Disease[1][2]
- Vitamin K deficiency or Warfarin use[3][4]
- Lupus Anticoagulant[5]
- Heparin administration
- Disseminated intravascular coagulation[6]
- Dysfibrinogenemia[7]
- Thrombocytopenia
- Hepatic failure[8][9][10]
- Uremia[11]
- Congenital afibrinogenemia[12][13]
- Factor V deficiency[14][15]
- Amyloid purpura[16]
- Glanzmann’s thrombasthenia[17]
- Bernard-Soulier syndrome[18][19]
- Factor XII deficiency[20][21]
- C1-inhibitor (C1INH) deficiency[22][23]
The most important differential diagnoses are enlisted in the table below:[24][25][26][27][28][29][30]
| Diseases | Clinical Manifestations | Para-clinical Findings | Additional Findings | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Symptoms | Physical Examination | |||||||||||||||
| Lab Findings | ||||||||||||||||
| Joint Bleeding | Gastrointestinal Bleeding | Genitourinary Bleeding | Skin Bruises | Skeletal Deformity | Muscle Hematoma | CBC | PT | PTT | BT | Factor VIII | Factor IX | Fibrinogen | U/A:RBC | S/E:RBC | ||
| Hemophilia A | + | + | + | + | + | + | N | N | β | N | β | N | N | + | + | -/+Family history |
| Hemophilia B | + | + | + | + | + | + | N | N | β | N | N | β | N | + | + | -/+Family history |
| von Willebrand disease | -/+ | -/+ | -/+ | -/+ | -/+ | -/+ | N | N | β/N | β | β/N | N | N | -/+ | -/+ | -/+Family history |
| Vitamin K deficiency | -/+ | + | -/+ | + | – | -/+ | N | β | β/N | N | N | β | N | + | + | Mostly in infants/GI disorders |
| Warfarin Toxicity | -/+ | + | -/+ | + | – | -/+ | N | β | β/N | N | N | β | N | + | + | +Drug history |
| Platelets disorders | – | -/+ | -/+ | + | – | – | βPlt | N | N | β | N | N | N | -/+ | -/+ | Cause-based specific findings |
| Liver Failure | – | + | + | -/+ | – | -/+ | βPlt/N | β | β | β/N | β/N | β | β/N | -/+ | + | Neurological findings/Ascites |
References
References
- β Goodeve A (December 2016). “Diagnosing von Willebrand disease: genetic analysis”. Hematology Am Soc Hematol Educ Program. 2016 (1): 678β682. doi:10.1182/asheducation-2016.1.678. PMCΒ 6065508. PMIDΒ 27913546.
- β “Diagnosis of von Willebrand’s disease. A comparative study of diagnostic tests on nine families with von Willebrand’s disease and its differential diagnosis from hemophilia and thrombocytopathy”. The American Journal of Medicine. 60 (3): A70. 1976. doi:10.1016/0002-9343(76)90768-3. ISSNΒ 0002-9343.
- β Napolitano M, Mariani G, Lapecorella M (July 2010). “Hereditary combined deficiency of the vitamin K-dependent clotting factors”. Orphanet J Rare Dis. 5: 21. doi:10.1186/1750-1172-5-21. PMCΒ 2913942. PMIDΒ 20630065.
- β Hart C, Schmid S (June 2016). “[Coagulation disorders in the intensive care unit – what is new?]”. Dtsch. Med. Wochenschr. (in German). 141 (11): 777β80. doi:10.1055/s-0042-103058. PMIDΒ 27254626.
- β Kumano O, Ieko M, Naito S, Yoshida M, Takahashi N, Suzuki T, Komiyama Y (July 2016). “New formulas for mixing test to discriminate between lupus anticoagulant and acquired hemophilia A”. Thromb. Res. 143: 53β7. doi:10.1016/j.thromres.2016.05.004. PMIDΒ 27182981.
- β Matsumoto T, Wada H, Fujimoto N, Toyoda J, Abe Y, Ohishi K, Yamashita Y, Ikejiri M, Hasegawa K, Suzuki K, Imai H, Nakatani K, Katayama N (July 2018). “An Evaluation of the Activated Partial Thromboplastin Time Waveform”. Clin. Appl. Thromb. Hemost. 24 (5): 764β770. doi:10.1177/1076029617724230. PMIDΒ 28884611.
- β Hua B, Li K, Lee A, Poon MC, Zhao Y (November 2015). “Coexisting congenital dysfibrinogenemia with a novel mutation in fibrinogen Ξ³ chain (Ξ³322 PheβIle, Fibrinogen Beijing) and haemophilia B in a family”. Haemophilia. 21 (6): 846β51. doi:10.1111/hae.12712. PMIDΒ 25982359.
- β Hartmann M, Szalai C, Saner FH (January 2016). “Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment”. World J. Gastroenterol. 22 (4): 1541β50. doi:10.3748/wjg.v22.i4.1541. PMIDΒ 26819521.
- β Stravitz RT, Ellerbe C, Durkalski V, Schilsky M, Fontana RJ, Peterseim C, Lee WM (May 2018). “Bleeding complications in acute liver failure”. Hepatology. 67 (5): 1931β1942. doi:10.1002/hep.29694. PMIDΒ 29194678.
- β Tischendorf M, Miesbach W, Chattah U, Chattah Z, Maier S, Welsch C, Zeuzem S, Lange CM (2016). “Differential Kinetics of Coagulation Factors and Natural Anticoagulants in Patients with Liver Cirrhosis: Potential Clinical Implications”. PLoS ONE. 11 (5): e0155337. doi:10.1371/journal.pone.0155337. PMCΒ 4865185. PMIDΒ 27171213.
- β Andrassy K, Ritz E (1985). “Uremia as a cause of bleeding”. Am. J. Nephrol. 5 (5): 313β9. doi:10.1159/000166955. PMIDΒ 3904449.
- β Santoro C, Massaro F, Venosi S, Capria S, Baldacci E, FoΓ R, Mazzucconi MG (July 2016). “Severe Thrombotic Complications in Congenital Afibrinogenemia: A Pathophysiological and Management Dilemma”. Semin. Thromb. Hemost. 42 (5): 577β82. doi:10.1055/s-0036-1581103. PMIDΒ 27253088.
- β Stanciakova L, Kubisz P, Dobrotova M, Stasko J (July 2016). “Congenital afibrinogenemia: from etiopathogenesis to challenging clinical management”. Expert Rev Hematol. 9 (7): 639β48. doi:10.1080/17474086.2016.1200967. PMIDΒ 27291795.
- β Boujrad S, El Hasbaoui B, Echahdi H, Malih M, Agadr A (2017). “[Factor V congenital deficiency: about a case]”. Pan Afr Med J (in French). 27: 182. doi:10.11604/pamj.2017.27.182.12285. PMCΒ 5579429. PMIDΒ 28904709.
- β Thalji N, Camire RM (September 2013). “Parahemophilia: new insights into factor v deficiency”. Semin. Thromb. Hemost. 39 (6): 607β12. doi:10.1055/s-0033-1349224. PMIDΒ 23893775.
- β Colucci G, Alberio L, Demarmels Biasiutti F, LΓ€mmle B (2014). “Bilateral periorbital ecchymoses. An often missed sign of amyloid purpura”. Hamostaseologie. 34 (3): 249β52. doi:10.5482/HAMO-14-03-0018. PMIDΒ 24975676.
- β Iqbal I, Farhan S, Ahmed N (August 2016). “Glanzmann Thrombasthenia: A Clinicopathological Profile”. J Coll Physicians Surg Pak. 26 (8): 647β50. doi:2396 Check
|doi=value (help). PMIDΒ 27539755. - β Boeckelmann D, Hengartner H, Greinacher A, Nowak-GΓΆttl U, Sachs UJ, Peter K, Sandrock-Lang K, Zieger B (September 2017). “Patients with Bernard-Soulier syndrome and different severity of the bleeding phenotype”. Blood Cells Mol. Dis. 67: 69β74. doi:10.1016/j.bcmd.2017.01.010. PMIDΒ 28131619.
- β Andrews RK, Berndt MC (September 2013). “Bernard-Soulier syndrome: an update”. Semin. Thromb. Hemost. 39 (6): 656β62. doi:10.1055/s-0033-1353390. PMIDΒ 23929303.
- β Fernandes HD, Newton S, Rodrigues JM (June 2018). “Factor XII Deficiency Mimicking Bleeding Diathesis: A Unique Presentation and Diagnostic Pitfall”. Cureus. 10 (6): e2817. doi:10.7759/cureus.2817. PMCΒ 6093754. PMIDΒ 30128221.
- β SimΓ£o F, Feener EP (2017). “The Effects of the Contact Activation System on Hemorrhage”. Front Med (Lausanne). 4: 121. doi:10.3389/fmed.2017.00121. PMCΒ 5534673. PMIDΒ 28824910.
- β Otani IM, Banerji A (August 2017). “Acquired C1 Inhibitor Deficiency”. Immunol Allergy Clin North Am. 37 (3): 497β511. doi:10.1016/j.iac.2017.03.002. PMIDΒ 28687105.
- β Castelli R, Cicardi M, Gardinali M, Zingale LC, Savi C, Munari M, Agostoni A (March 1997). “Cardiopulmonary by-pass in a patient with acquired C1 inhibitor deficiency”. Int J Artif Organs. 20 (3): 175β7. PMIDΒ 9151154.
- β Hathaway WE (1993)Vitamin K deficiency. Southeast Asian J Trop Med Public Health 24 Suppl 1 ():5-9. PMID: 7886607
- β Santagostino E, Fasulo MR (2013) Hemophilia a and hemophilia B: different types of diseases? Semin Thromb Hemost 39 (7):697-701. DOI:10.1055/s-0033-1353996 PMID: 24014073
- β Israels SJ (2015). “Laboratory testing for platelet function disorders”. Int J Lab Hematol. 37 Suppl 1: 18β24. doi:10.1111/ijlh.12346. PMIDΒ 25976956.
- β Lechner K, Niessner H, Thaler E (1977) Coagulation abnormalities in liver disease. Semin Thromb Hemost 4 (1):40-56. PMID: 199944
- β Buga-Corbu I, Arion C (2014) Up to date concepts about Von Willebrand disease and the diagnose of this hemostatic disorder. J Med Life 7 (3):327-34. PMID: 25408749
- β Giangrande P (2005) Haemophilia B: Christmas disease. Expert Opin Pharmacother 6 (9):1517-24. DOI:10.1517/14656566.6.9.1517 PMID: 16086639
- β Deaton JG, Bhimji SS. Toxicity, Warfarin. [Updated 2017 May 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-.Available from: https://www.ncbi.nlm.nih.gov/books/NBK431112/
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