Bleeding diathesis

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Bleeding diathesis main page

Overview

Classification

Differential Diagnosis

Platelet disorders
Immune Thrombocytopenic Purpura
Thrombotic Thrombocytopenic Purpura
Hemolytic Uremic Syndrome
Thrombocytosis
Von Willebrand Disease
Coagulation disorders
Fibrinogen deficiency
Prothrombin deficiency
Factor V deficiency
Factor VII deficiency
Factor VIII deficiency
Factor IX deficiency
Factor X deficiency
Factor XI deficiency
Factor XII deficiency
High-molecular-weight kininogen deficiency
Prekallikrein deficiency
Factor XIII deficiency
Hemophilia
Rare diseases
Disseminated Intravascular Coagulation
Vitamin K Deficiency

Different types of Von-Willebrand diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2], Nazia Fuad M.D., Sogand Goudarzi, MD

Synonyms and Keywords: Hypocoagulopathy; blood coagulation disorders; hemorrhagic diathesis; hemostasis abnormality; bleeding tendency


Overview

Bleeding diathesis is susceptibility to bleed due to coagulopathy disorders or platelets disorders. These diseases can occur due to a disorder of homeostasis, localized process (tissue injury), or medications. Bleeding diathesis can be resulted from vessel wall injury, platelet disorders, and coagulation factor disorders. Clinical manifestation of bleeding disorders can have a wide range of symptoms from asymptomatic to symptomatic massive and life threatening bleeding. Platelet disorders mostly have skin manifestations such as petechiae, and ecchymoses. In order to find the cause of hypo-coagulopathy; there are established laboratory tests, such as peripheral blood smear, platelet count and platelet function analysis, coagulation factor deficiencies and inhibitors, fibrinolysis tests (eg. D-dimer level), bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and reptilase time. In the case of any abnormal bleeding, first line of screening tests are CBC, PT, PTT, BT, and TT.

Classification

Disorders of hemostasis can be classified into two main categories: platelet disorders, and disorders of coagulation. Each category can be further classified as bellow:

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abnormal hemostasis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

• Patient history-sign & symptom: deep soft tissue & mucocutaneus bleeding
• Screen test CBC-Plt-PT&PTT-BT-TT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hx of deep soft tissue bleeding
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hx of mucocotaneus bleeding
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coagulopathy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plt disorder
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Family history
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal plt count
 
 
Low plt count
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(+)
• Inherited coagulpathy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(-)
• Aquired coagulopathy
 
 
 
 
 
 
Functional Plt disorder
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
↑Plt
• Hemophillia
• VWD
• Factor VIII or IX deficiency
 
↑PT
• Factor VII deficiensy
 
↑PT&↑PTT
• Fibrinogen deficiency
• Factor II deficiency
• Factor V deficiency
• Factor X deficiency
 
 
↑PTT
• Factor inhibitor
• Anti phospholipid A6syndrome
 
↑PT
• Factor inhibitor
• Vit K deficiency
• Liver disease
 
↑PT&↑PTT
• Factor inhibit
• DIC
• Liver failure
• Late stage of Vit K deficincy
 
↑ Afibrinogenia
• Heparin inhibitor
• Direct thrombin inhibitor
 
 
 
 
Abnormal solobity
• Factor XIII deficincy
• Cross-linkin inhibitor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Not corrected with mixing with NL plasma
 
 
 
 
 
 
 
 
HX(+)
 
HX(-)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

• Factor inhibitors
• Lupus anti coagulant
• DIC
• Heparin or direct thrombin inhibitors
 
 
 
 
 
 
 
 
Congenital
 
Acquired
 
 
 
 
 

Differentiating Bleeding Disorders from Other Diseases

Different causes of bleeding disorders can be differentiated based on their clinical manifestation and laboratory findings.

These features have discussed in the below table:

Category Subcategory Disease History Clinical manifestation Laboratory testing Comments
Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT
Platelet disorders Thrombocytopenia Infection-Induced thrombocytopenia[1]
  • History of prior infection
+ + + + + + Nl Nl Nl
Medication-Induced Thrombocytopenia[2] + + + + + + Nl Nl Nl Most important part of treatment is discontinuing of the medication.
Heparin-Induced thrombocytopenia[3] + + + + + + Nl Nl For more information click here: Heparin-induced thrombocytopenia.
Immune Thrombocytopenic Purpura[4] + + + + + + Nl Nl Nl
Inherited Thrombocytopenia[5]
  • Positive family history
+ + + + + + Nl Nl Nl
Thrombotic Thrombocytopenic Purpura[6] History of: + + + + + + Nl Nl Nl
Hemolytic Uremic Syndrome[7] History of: + + + + + + Nl Nl Nl
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
Thromobcytosis Iron deficiency anemia

Inflammatory diseases

Splenectomy

Essential thrombocytosis

± ± Nl or ↑ Nl Nl Nl
Qualitative Disorders of Platelet Function Inherited Disorders of Platelet Function Glanzmann’s thrombasthenia
  • Positive family history
+ + + + Rare Nl or ↓ Nl Nl Nl
  • AR inheritance
  • Absence of the platelet Gp IIb/IIIa receptor
  • Diminished for GP 2B-3A on flow cytometry
Bernard-Soulier syndrome
  • Positive family history
+ + + + Nl or ↓ Nl Nl Nl
  • AR inheritance
  • Absence of the platelet Gp Ib-IX-V receptor
  • On PBS: giant platelets
  • Ristocetin - no aggregation
Wiskott-Aldrich syndrome
  • Positive family history
+ + + + Nl or ↓ Nl Nl Nl
  • Anti-WASP antibody can be used to detect presence or absence of WAS protein
  • In Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts.
Platelet storage pool disorder: + + + + Nl or ↓ Nl Nl Nl
  • AD inheritance
  • AbNlities of platelet granule formation
Acquired Disorders of Platelet Function + + + + ± ± Nl or ↓ Nl Nl Nl
Von Willebrand Disease + + + + ± ± Nl Nl See the table below for the details about different types.
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
Vessel wall disorders Metabolic and Inflammatory Disorders
  • History of the underlying disease
+ + ± Nl Nl or ↑ Nl Nl Nl
Inherited Disorders of the Vessel Wall
  • Positive family history
+ + ± Nl Nl or ↑ Nl Nl Nl
Coagulation factor disorders

[8]

Fibrinogen deficiency

Different types of the fibrinogen disorders:

+ + ± + Nl
  • Impaired fibrin cross-linking or clot dissolution
  • Mild or severe bleeding idepend on levels of functional fibrinogen
  • Variable age of onset
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
Prothrombin deficiency + + + + + Nl Nl
Factor V deficiency + + + + Nl Nl
  • The severity of bleeding related to the degree of factor V deficiency
Factor VII deficiency + + + Nl Nl Nl
  • Thrombosis in inherited factor VII deficiency
  • Treatment with the administration of factor VII replacement therapy
Factor X deficiency
  • Prolonged bleeding following circumcision
  • Easy bruising
  • Hematuria
  • Menorrhagia
  • Abortion
  • Postpartum hemorrhage
  • Epistaxis
  • Pseudotumors
  • Intracranial bleeding
  • Hemarthroses
+ + + + + Nl Nl Nl
Factor XII deficiency
  • Asymptomatic
  • Recurrent miscarriages
  • Painful leg ulcers
Nl Nl Nl Nl
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
High molecular weight kininogen (HMWK) deficiency
  • Positive family history of bleeding
Nl Nl Nl Nl
Prekallikrein deficiency
  • Positive family history of bleeding
Nl Nl Nl Nl
Factor XIII deficiency[9]
  • Sub unit A mutation disease (more common)
  • Sub unit B mutation disease
  • Positive family history of bleeding
± ± ± ± ± ± Nl Nl Nl or ↑ Nl Nl
  • Impaired fibrin cross-linking or clot dissolution
  • The severity of factor XIII deficiency bleeds can be different in different patients
Hemophilia[10] Type A deficiency + + + Nl Nl Nl Nl
Type B deficiency + + + Nl Nl Nl Nl
Type C deficiency
  • Positive family history
  • Bleeding after surgery or injury
+ Rare Rare Nl Nl Nl Nl
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
Rare diseases Disseminated Intravascular Coagulation[11][12][13][14][15] + + + + + + Nl
Vitamin K Deficiency[16] + + + + + Nl Nl or mildly prolonged Nl

Different types of Von-Willebrand diseases

Type of VWD Type of factor deficiency Prevalence Inheritance pattern Clinical manifestations VWF activity RIPA Factor VIII
Type 1 Quantitative/ partial 60-70% AD
  • Bleeding severity mild to severe
Type 2 2A Qualitative 10% AD/AR N or ↓
2B Qualitative 5% AD N or ↓
2M Qualitative <1% AD/AR N or ↓
2N Qualitative <1% AR N N
Type 3 Complete deficiency 1-2% AR Absent Low, 1-10%

For more information on Von Willebrand disease, click here.

References

  1. Herbinger, K.-H.; Schunk, M.; Nothdurft, H. D.; von Sonnenburg, F.; Löscher, T.; Bretzel, G. (2012). "Comparative study on infection-induced thrombocytopenia among returned travellers". Infection. 40 (4): 373–379. ISSN 0300-8126. doi:10.1007/s15010-012-0242-9. 
  2. Elting, Linda S.; Cantor, Scott B.; Martin, Charles G.; Hamblin, Lois; Kurtin, Danna; Rivera, Edgardo; Vadhan-Raj, Saroj; Benjamin, Robert S. (2003). "Cost of chemotherapy-induced thrombocytopenia among patients with lymphoma or solid tumors". Cancer. 97 (6): 1541–1550. ISSN 0008-543X. doi:10.1002/cncr.11195. 
  3. Miller, Penny L. (2003). "Heparin-induced Thrombocytopenia Recognition and Treatment". AORN Journal. 78 (1): 79–89. ISSN 0001-2092. doi:10.1016/S0001-2092(06)61348-3. 
  4. Curtis, Brian R.; Kaliszewski, James; Marques, Marisa B.; Saif, M. Wasif; Nabelle, Lisle; Blank, Jules; McFarland, Janice G.; Aster, Richard H. (2006). "Immune-mediated thrombocytopenia resulting from sensitivity to oxaliplatin". American Journal of Hematology. 81 (3): 199–201. ISSN 0361-8609. doi:10.1002/ajh.20516. 
  5. Drachman, J. G. (2004). "Inherited thrombocytopenia: when a low platelet count does not mean ITP". Blood. 103 (2): 390–398. ISSN 0006-4971. doi:10.1182/blood-2003-05-1742. 
  6. George, James N. (2006). "Thrombotic Thrombocytopenic Purpura". New England Journal of Medicine. 354 (18): 1927–1935. ISSN 0028-4793. doi:10.1056/NEJMcp053024. 
  7. Noris, M. (2005). "Hemolytic Uremic Syndrome". Journal of the American Society of Nephrology. 16 (4): 1035–1050. ISSN 1046-6673. doi:10.1681/ASN.2004100861. 
  8. Dorgalaleh A, Naderi M, Hosseini MS, Alizadeh S, Hosseini S, Tabibian S, et al. (2015). "Factor XIII Deficiency in Iran: A Comprehensive Review of the Literature. Seminars in thrombosis and hemostasis;". 41 (3 (41)): 323–329. 
  9. Peyvandi F, Garagiola I, Young G (July 2016). "The past and future of haemophilia: diagnosis, treatments, and its complications". Lancet. 388 (10040): 187–97. PMID 26897598. doi:10.1016/S0140-6736(15)01123-X. 
  10. Siegal T, Seligsohn U, Aghai E, Modan M (February 1978). "Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases". Thromb. Haemost. 39 (1): 122–34. PMID 580488. 
  11. Levi M, Toh CH, Thachil J, Watson HG (April 2009). "Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology". Br. J. Haematol. 145 (1): 24–33. PMID 19222477. doi:10.1111/j.1365-2141.2009.07600.x. 
  12. Ghosh K, Shetty S (March 2008). "Blood coagulation in falciparum malaria--a review". Parasitol. Res. 102 (4): 571–6. PMID 18066597. doi:10.1007/s00436-007-0832-0. 
  13. Siegal T, Seligsohn U, Aghai E, Modan M (February 1978). "Clinical and laboratory aspects of disseminated intravascular coagulation (DIC): a study of 118 cases". Thromb. Haemost. 39 (1): 122–34. PMID 580488. 
  14. Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Marey A, Lestavel P (March 1992). "Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies". Chest. 101 (3): 816–23. PMID 1531791. 
  15. Dezee KJ, Shimeall WT, Douglas KM, Shumway NM, O'malley PG (2006). "Treatment of excessive anticoagulation with phytonadione (vitamin K): a meta-analysis.". Arch Intern Med. 166 (4): 391–7. PMID 16505257. doi:10.1001/.391. 

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