Bleeding disorder resident survival guide

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Bleeding disorder
Resident Survival Guide
Overview
Causes
Diagnosis
Management
Dos
Don'ts


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Javaria Anwer M.D.[2]
Synonyms and Keywords: Approach to bleeding diathesis, Bleeding diathesis workup, Bleeding diathesis management

Overview

A bleeding disorder can be due to coagulopathy, platelet dysfunction, or vessel pathology. They can be genetic or acquired. History of the site, duration, associated symptoms, and a thorough physical exam to evaluate the type of bleeding (subcutaneous vs deep tissue) are essential to diagnosis. Screening tests include CBC with peripheral blood smear, platelet count, PT, aPTT, PFA-100. Management depends upon the type of disorder, severity, and active bleeding. Plasma exchange, fresh frozen plasma, and factor replacement are the main treatment options available. The initial clinical impression based on the baseline screening tests should direct specialized laboratory tests to save time, effort, and money.

Causes

Common causes of bleeding (bleeding disorders) are enlisted below.[1][2][3][4]

 
 
 
 
 
 
 
Causes of bleeding disorders
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Platelet disorders
 
 
Coagulopathy
 
 
 
Vessel/ Supporting tissue defect
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Acquired
 
Genetic
 
 
 
 
 
 
 
❑Aging
Corticosteroid use
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Myeloproliferative disorders

Uremia
❑ Drugs (NSAIDs, asprin, clopidogrel, etc.)
Neoplasia
❑ Monoclonal gammopathies
DIC
Ehrlichiosis
❑ Retroviral infection
❑ Snake venom

Cirrhosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Genetic
 
 
Acquired
 
Prothrombotic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Prohemorrhagic liver diseases

Vitamin K deficiency
❑ Drug-induced such as warfarin and heparin
❑ Hemodilution and massive transfusion
Disseminated Intravascular Coagulation (DIC)
Immunoglobulin mediated Factor Deficiency (VIII, V, XIII, X)
Hyperfibrinolysis

Venom induced
 
 
 
 
 
 
 
 
 
Hemorrhagic disorders
 
 
 
Hypercoaguable disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Factor VIII deficiency (Hemophilia A)

Factor IX Deficiency (Hemophilia B)
Von Willebrand factor deficiency
Factor XI deficiency (Hemophilia C)
❑ Factor II, V, VII, X deficiency (Common Pathway Proteins)

Factor XIII deficiency and fibrinogen deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Diagnosis

The algorithm illustrates the approach to the diagnosis of bleeding disorder.[1][5][6][7][8]
Abbreviations: HEENT: Head, Eyes, Ears. Nose, and Throat exam; CBC: Complete blood count; APTT Partial thromboplastin time; CMP: Comprehensive metabolic panel; LFTs:Liver function tests
Boxes in red signify that an urgent management is needed.

 
 
 
 
 
 
 
 
 
History

Demographics: Patient age, gender,and race to screen for inherited disorders.
Bleeding history:

❑ Onset of bleed: Differentiate between spontaneous vs post-trauma or post-surgery bleed. Post-trauma may suggest an inherited bleeding disorder.
❑ Duration of bleed: Lifelong vs recent. coagulation factor defect.
❑ Type and site of bleed (skin or muscle): Petechiae, purpura, epistaxis, gingival bleeding, and bruises may suggest a vascular or platelet abnormality. Joint or muscle bleed may suggest coagulation factor abnormality.

Past medical history: For the underlying disease. History of blood or blood components transfusion. Childhood history of epistaxis, bleeding post-circumcision, and umbilical stump bleeding may suggest an inherited bleeding disorder.
Past surgical history: May reveal post-surgical bleed such as after a tooth extraction. History of poor wound healing. ❑ Drug history: For the drugs causing bleeding. Distinguish between drug induced thrombocytopenia and idiopathic thrombocytopenic purpura, or other forms of thrombocytopenia.
Family history: Certain bleeding disorders. Consanguineous marriage history.

Gynaecological history: Menorrhagia or hematuria may suggest vascular or platelet abnormality.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical exam

Appearance of the patient
Petechie, bruises, or hemorrhages

Vital signs: Temperature; heart rate (tachycardia with regular pulse may demonstrate hypovolemia); respiratory rate, blood pressure (hypotension); and oxygen saturation may be low due to anemia.
❑ Assess the sites and severity of the bleeding.
❑ Assess if the bleeding is due to systemic disorder, local defect, or hemostatic disorder; inherited or acquired; platelet abnormality, coagulation disorder, or vascular defect. ❑ HEENT
Cardiovascular examination
Respiratory examination
Gastrointestinal system exam includes oral examination, abdominal examination, and digital rectal exam.
Extremities exam

❑ Skin exam: Evaluate for petechie, bruises, hemorrhages. Location, symmetry, and pattern are important.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening Labs

CBC with differential
Platelet count
Prothrombin time (PT)
APTT
Peripheral smear
Thrombin time

Bleeding time/ PFA-100
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Soft tissue hematoma, deep internal hemorrhage, hemarthrosis
 
 
 
 
 
 
 
 
 
 
Superficial cutaneous or mucous membrane bleeding
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PT normal, aPTT prolonged
 
PT prolonged, aPTT normal
 
 
PT prolonged, aPTT prolonged
 
 
Low platelet count
 
 
 
 
Normal platelet count
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Check thrombin time
 
 
Idiopathic Thrombocytopenic Purpura (ITP)
❑ Hereditary platelet disorder
Bone marrow failure
 
 
 
 
Check PFA-100
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prolonged
 
Normal
 
 
 
 
 
Prolonged closure time
 
 
Normal
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fibrinogen deficiency
Liver disease
Heparin
 
Factor II, factor V, factor X deficiency
Vitamin K deficiency
Liver disease
 
 
 
Full blood count

vWF screen

Platelet function testing
 
 
High clinical suspician
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
vWF screen
Platelet function testing (required to exclude abnormal platelet function)
 
 

Management

The following tables illustrate the treatment to common bleeding disorders.[9][10][11][12][13][14][15][16][17][18]

Disorder Labs Treatment
Factor VII deficiency
  • Measure factor VII coagulant activity for isolated prolonged PT
  • Diagnosis is confirmed with a repeat factor VII assay
  • Consider the type (such as type I: quantitative defects, type II: qualitative defects, for the management.
  • Replacement therapy: Recombinant FVIIa (rFVIIa) is most used. Median dosage of 60 μg/kg is safe for bleeding such as hematomas, hemarthrosis, and epistaxis.
Hemophilia A and Hemophilia B
Factor X deficiency
Hemophilia C
Von Willebrand disease
Microangiopathic hemolytic anemia
Glanzmann's thrombasthenia
Bernard-Soulier syndrome
Thrombocytopenia of pregnancy
SLE
Liver disease
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency

Dos

  • A study by Wahlberg et al. demonstrated that the patient's perception of his/her own bleeding may be understated or exaggerated, so labs are vital in the assessment of bleeding disorders.[20]
  • The initial clinical impression based on the baseline screening tests should direct specialized laboratory tests to save time, effort and money.[21]

Don'ts

References

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  2. George JN (April 2000). "Platelets". Lancet. 355 (9214): 1531–9. doi:10.1016/S0140-6736(00)02175-9. PMID 10801186.
  3. Al-Fawaz IM, Gader AM, Bahakim HM, Al-Mohareb F, Al-Momen AK, Harakati MS (May 1996). "Hereditary bleeding disorders in Riyadh, Saudi Arabia". Ann Saudi Med. 16 (3): 257–61. doi:10.5144/0256-4947.1996.257. PMID 17372424.
  4. Bick, Rodger (2002). Disorders of thrombosis and hemostasis : clinical and laboratory practice. Philadelphia: Lippincott Williams & Wilkins. ISBN 978-0397516902.
  5. Hayward CP (2005). "Diagnosis and management of mild bleeding disorders". Hematology Am Soc Hematol Educ Program: 423–8. doi:10.1182/asheducation-2005.1.423. PMID 16304414.
  6. Blanchette VS, Sparling C, Turner C (April 1991). "Inherited bleeding disorders". Baillieres Clin Haematol. 4 (2): 291–332. doi:10.1016/s0950-3536(05)80162-3. PMID 1912663.
  7. Favaloro, Emmanuel J. (2002). "Clinical application of the PFA-100®". Current Opinion in Hematology. 9 (5): 407–415. doi:10.1097/00062752-200209000-00004. ISSN 1065-6251.
  8. Harrison, Paul (2005). "The role of PFA-100R testing in the investigation and management of haemostatic defects in children and adults". British Journal of Haematology. 130 (1): 3–10. doi:10.1111/j.1365-2141.2005.05511.x. ISSN 0007-1048.
  9. Powell JS (April 2009). "Recombinant factor VIII in the management of hemophilia A: current use and future promise". Ther Clin Risk Manag. 5 (2): 391–402. doi:10.2147/tcrm.s4412. PMC 2697540. PMID 19536318.
  10. Kozek-Langenecker SA, Afshari A, Albaladejo P, Santullano CA, De Robertis E, Filipescu DC, Fries D, Görlinger K, Haas T, Imberger G, Jacob M, Lancé M, Llau J, Mallett S, Meier J, Rahe-Meyer N, Samama CM, Smith A, Solomon C, Van der Linden P, Wikkelsø AJ, Wouters P, Wyffels P (June 2013). "Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology". Eur J Anaesthesiol. 30 (6): 270–382. doi:10.1097/EJA.0b013e32835f4d5b. PMID 23656742.
  11. Gopinath R, Sreekanth Y, Yadav M (September 2014). "Approach to bleeding patient". Indian J Anaesth. 58 (5): 596–602. doi:10.4103/0019-5049.144664. PMC 4260306. PMID 25535422.
  12. Meeks SL, Batsuli G (December 2016). "Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches". Hematology Am Soc Hematol Educ Program. 2016 (1): 657–662. doi:10.1182/asheducation-2016.1.657. PMC 6142469. PMID 27913543.
  13. Napolitano M, Siragusa S, Mariani G (March 2017). "Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy". J Clin Med. 6 (4). doi:10.3390/jcm6040038. PMC 5406770. PMID 28350321.
  14. Hayward CP, Pai M, Liu Y, Moffat KA, Seecharan J, Webert KE, Cook RJ, Heddle NM (April 2009). "Diagnostic utility of light transmission platelet aggregometry: results from a prospective study of individuals referred for bleeding disorder assessments". J Thromb Haemost. 7 (4): 676–84. doi:10.1111/j.1538-7836.2009.03273.x. PMID 19143930.
  15. Uprichard, James; Perry, David J. (2002). "Factor X deficiency". Blood Reviews. 16 (2): 97–110. doi:10.1054/blre.2002.0191. ISSN 0268-960X.
  16. Bertina RM, Broekmans AW, Krommenhoek-van Es C, van Wijngaarden A (February 1984). "The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency". Thromb. Haemost. 51 (1): 1–5. PMID 6547008.
  17. Faioni EM, Franchi F, Asti D, Sacchi E, Bernardi F, Mannucci PM (1993). "Resistance to activated protein C in nine thrombophilic families: interference in a protein S functional assay". Thromb Haemost. 70 (6): 1067–71. PMID 8165605.
  18. Brown, D. L.; Kouides, P. A. (2008). "Diagnosis and treatment of inherited factor X deficiency". Haemophilia. 14 (6): 1176–1182. doi:10.1111/j.1365-2516.2008.01856.x. ISSN 1351-8216.
  19. Zauber NP, Stark MW (May 1986). "Successful warfarin anticoagulation despite protein C deficiency and a history of warfarin necrosis". Ann. Intern. Med. 104 (5): 659–60. PMID 3754407.
  20. Wahlberg T, Blombäck M, Hall P, Axelsson G (October 1980). "Application of indicators, predictors and diagnostic indices in coagulation disorders. I. Evaluation of a self-administered questionnaire with binary questions". Methods Inf Med. 19 (4): 194–200. PMID 7432180.
  21. Bick, Rodger (2002). Disorders of thrombosis and hemostasis : clinical and laboratory practice. Philadelphia: Lippincott Williams & Wilkins. ISBN 978-0397516902.