Hemophilia differential diagnosis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]Simrat Sarai, M.D. [3]Vahid Eidkhani, M.D.Fahd Yunus, M.D. [4]
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
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 | ↑ | N | ↓ | N | N | + | + | -/+Family history |
| Hemophilia B | + | + | + | + | + | + | N | N | ↑ | N | N | ↓ | N | + | + | -/+Family history |
| von Willebrand disease | -/+ | -/+ | -/+ | -/+ | -/+ | -/+ | N | N | ↑/N | ↑ | ↓/N | N | N | -/+ | -/+ | -/+Family history |
| Vitamin K deficiency | -/+ | + | -/+ | + | - | -/+ | N | ↑ | ↑/N | N | N | ↓ | N | + | + | Mostly in Infants/GI disorders |
| Warfarin Toxicity | -/+ | + | -/+ | + | - | -/+ | N | ↑ | ↑/N | N | N | ↓ | N | + | + | +Drug history |
| Platelets disorders | - | -/+ | -/+ | + | - | - | ↓Plt | N | N | ↑ | N | N | N | -/+ | -/+ | Cause-based Specific findings |
| Liver Failure | - | + | + | -/+ | - | -/+ | ↓Plt/N | ↑ | ↑ | ↑/N | ↑/N | ↓ | ↑/N | -/+ | + | Neurological findings/Ascitis |
References
- ↑ Goodeve A (December 2016). "Diagnosing von Willebrand disease: genetic analysis". Hematology Am Soc Hematol Educ Program. 2016 (1): 678–682. doi:10.1182/asheducation-2016.1.678. PMC 6065508. PMID 27913546.
- ↑ "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. ISSN 0002-9343.
- ↑ 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. PMC 2913942. PMID 20630065.
- ↑ Hart C, Schmid S (June 2016). "[Coagulation disorders in the intensive care unit - what is new?]". Dtsch. Med. Wochenschr. (in German). 141 (11): 777–80. doi:10.1055/s-0042-103058. PMID 27254626.
- ↑ 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: 53–7. doi:10.1016/j.thromres.2016.05.004. PMID 27182981.
- ↑ 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): 764–770. doi:10.1177/1076029617724230. PMID 28884611.
- ↑ Hua B, Li K, Lee A, Poon MC, Zhao Y (November 2015). "Coexisting congenital dysfibrinogenemia with a novel mutation in fibrinogen γ chain (γ322 Phe→Ile, Fibrinogen Beijing) and haemophilia B in a family". Haemophilia. 21 (6): 846–51. doi:10.1111/hae.12712. PMID 25982359.
- ↑ Hartmann M, Szalai C, Saner FH (January 2016). "Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment". World J. Gastroenterol. 22 (4): 1541–50. doi:10.3748/wjg.v22.i4.1541. PMID 26819521.
- ↑ 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): 1931–1942. doi:10.1002/hep.29694. PMID 29194678.
- ↑ 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. PMC 4865185. PMID 27171213.
- ↑ Andrassy K, Ritz E (1985). "Uremia as a cause of bleeding". Am. J. Nephrol. 5 (5): 313–9. doi:10.1159/000166955. PMID 3904449.
- ↑ Santoro C, Massaro F, Venosi S, Capria S, Baldacci E, Foà R, Mazzucconi MG (July 2016). "Severe Thrombotic Complications in Congenital Afibrinogenemia: A Pathophysiological and Management Dilemma". Semin. Thromb. Hemost. 42 (5): 577–82. doi:10.1055/s-0036-1581103. PMID 27253088.
- ↑ Stanciakova L, Kubisz P, Dobrotova M, Stasko J (July 2016). "Congenital afibrinogenemia: from etiopathogenesis to challenging clinical management". Expert Rev Hematol. 9 (7): 639–48. doi:10.1080/17474086.2016.1200967. PMID 27291795.
- ↑ 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. PMC 5579429. PMID 28904709.
- ↑ Thalji N, Camire RM (September 2013). "Parahemophilia: new insights into factor v deficiency". Semin. Thromb. Hemost. 39 (6): 607–12. doi:10.1055/s-0033-1349224. PMID 23893775.
- ↑ Colucci G, Alberio L, Demarmels Biasiutti F, Lämmle B (2014). "Bilateral periorbital ecchymoses. An often missed sign of amyloid purpura". Hamostaseologie. 34 (3): 249–52. doi:10.5482/HAMO-14-03-0018. PMID 24975676.
- ↑ Iqbal I, Farhan S, Ahmed N (August 2016). "Glanzmann Thrombasthenia: A Clinicopathological Profile". J Coll Physicians Surg Pak. 26 (8): 647–50. doi:2396 Check
|doi=value (help). PMID 27539755. - ↑ Boeckelmann D, Hengartner H, Greinacher A, Nowak-Göttl 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: 69–74. doi:10.1016/j.bcmd.2017.01.010. PMID 28131619.
- ↑ Andrews RK, Berndt MC (September 2013). "Bernard-Soulier syndrome: an update". Semin. Thromb. Hemost. 39 (6): 656–62. doi:10.1055/s-0033-1353390. PMID 23929303.
- ↑ 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. PMC 6093754. PMID 30128221.
- ↑ Simão F, Feener EP (2017). "The Effects of the Contact Activation System on Hemorrhage". Front Med (Lausanne). 4: 121. doi:10.3389/fmed.2017.00121. PMC 5534673. PMID 28824910.
- ↑ Otani IM, Banerji A (August 2017). "Acquired C1 Inhibitor Deficiency". Immunol Allergy Clin North Am. 37 (3): 497–511. doi:10.1016/j.iac.2017.03.002. PMID 28687105.
- ↑ 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): 175–7. PMID 9151154.
- ↑ Hathaway WE (1993)Vitamin K deficiency. Southeast Asian J Trop Med Public Health 24 Suppl 1 ():5-9. PMID: 7886607
- ↑ 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
- ↑ Israels SJ (2015). "Laboratory testing for platelet function disorders". Int J Lab Hematol. 37 Suppl 1: 18–24. doi:10.1111/ijlh.12346. PMID 25976956.
- ↑ Lechner K, Niessner H, Thaler E (1977) Coagulation abnormalities in liver disease. Semin Thromb Hemost 4 (1):40-56. PMID: 199944
- ↑ 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
- ↑ Giangrande P (2005) Haemophilia B: Christmas disease. Expert Opin Pharmacother 6 (9):1517-24. DOI:10.1517/14656566.6.9.1517 PMID: 16086639
- ↑ 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/