Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Try free for 5 days
Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer.

Hemostasis and bleeding disorders

Last updated: January 8, 2021

Summarytoggle arrow icon

Bleeding disorders are characterized by defects in hemostasis that lead to an increased susceptibility to bleeding (also known as hemorrhagic diathesis). Bleeding disorders can be caused by platelet disorders (primary hemostasis defects), coagulation defects (secondary hemostasis defects), or increased clot degradation (hyperfibrinolysis). Coagulation defects may be general or further divided into either intrinsic or extrinsic defects according to the specific pathway of the coagulation cascade that is affected. Bleeding disorders may be inherited or acquired. Although clinical features may overlap, mucocutaneous bleeding (e.g., epistaxis, petechiae, gastrointestinal bleeding) is associated more with platelet disorders, while bleeding into potential spaces (e.g., hemarthrosis, muscular bleeding) is more characteristic of coagulation defects. A basic understanding of physiological processes during hemostasis and fibrinolysis is necessary for properly interpreting laboratory studies and accurately diagnosing bleeding disorders. Treatment depends on the underlying cause and may involve blood transfusion and replacement of coagulation factors.

Overview [1][2]

Hemostasis is the physiological process by which a bleeding stops. Its final result is a thrombus (blood clot), which consists of blood cells and fibrin strands. Hemostasis involves the following mechanisms:

Primary hemostasis

Secondary hemostasis

Overview of coagulation factors
Factor number Descriptive name Activated by Involvement in pathways Function
Common Intrinsic Extrinsic
I
II
III

IV

V*
  • Proaccelerin
VII*
  • Proconvertin
VIII*
IX*
  • Factor XIa
X*
  • Complexes TF-VIIa and VIIIa-IXa
XI*
XII*
XIII*
  • Stabilizes the fibrin network by introducing crosslinks

* = preferred term [3]
= rarely used term

The coagulation cascade requires the presence of calcium ions (factor IV).

A helpful way of remembering the coagulation factors of the extrinsic pathway is 3 + 7 = 10: Tissue factor (factor III) and factor VII form a complex that activates factor X of the common pathway.
A helpful way of remembering the coagulation factors of the common pathway is 10/5 = 2 × 1: Factors Xa and Va form a complex that cleaves prothrombin (factor II) to thrombin (IIa). Factor IIa then cleaves fibrinogen (I) into insoluble fibrin monomers (Ia).

Inhibition of hemostasis

In order to prevent hypercoagulability as well as excessive bleeding, activation of the coagulation cascade and the processes that inhibit it occur simultaneously in the circulatory system (procoagulant-anticoagulant balance).

Diseases that affect the inhibitors of the coagulation cascade may lead to hypercoagulability.

Overview [2]

Fibrinolytic therapy [4]

Alteplase is a synthetic tissue plasminogen activator that converts plasminogen to plasmin. It is used in the treatment of STEMI, massive pulmonary embolism, and ischemic stroke.

Hemorrhagic diathesis is the abnormally increased susceptibility to bleeding.

Disorders of primary hemostasis

Disorders of secondary hemostasis (disorders of the coagulation cascade)

In disorders of primary hemostasis, platelet aggregation is impaired, whereas in disorders of secondary hemostasis it is the coagulation cascade that is impaired.

Hyperfibrinolysis [10]

Clinical features of bleeding disorders [11][12]
Disorder Onset of bleeding Manifestations

Primary hemostasis disorders [7]

  • Immediately after trauma
Secondary hemostasis disorders
  • Delayed (minutes to hours after trauma)
Disseminated intravascular coagulation
  • Variable (depends on underlying cause)
  • Bleeding symptoms may include:
  • Symptoms of hypercoagulation (see “Clinical features” in “DIC”)
  • A thorough physical examination is essential for diagnosing bleeding disorders and should include the inspection of the entire skin, mucosa (esp. oral cavity), and joints.
  • Watch out for signs of physical abuse, which may produce patterns of bruising that resemble those of bleeding disorders. Signs of physical abuse include:

Superficial, petechial bleeding indicates defects of primary hemostasis, whereas large, palpable ecchymoses and deep tissue bleeding suggest defects of secondary hemostasis!

History [13]

Laboratory studies

Laboratory findings of bleeding disorders [14]

Defective pathway Disorders

Platelets

Bleeding time

INR PT aPTT
Disorders of primary hemostasis
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
Disorders of secondary hemostasis
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
  • Normal
Disorders that affect primary and secondary hemostasis
  • Normal
  • Normal
  • Normal
  • Normal/↑

See also the articles on the conditions listed in “Etiology” above for more specific treatment details.

  1. Girolami A, Luzzatto G, Varvarikis C, Pellati D, Sartori R, Girolami B. Main clinical manifestations of a bleeding diathesis: an often disregarded aspect of medical and surgical history taking. Haemophilia. 2005; 11 (3): p.193-202. doi: 10.1111/j.1365-2516.2005.01100.x . | Open in Read by QxMD
  2. Drews RE. Approach to the adult patient with a bleeding diathesis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/approach-to-the-adult-patient-with-a-bleeding-diathesis?source=machineLearning&search=hemostasis%20disorders&selectedTitle=1~150§ionRank=2&anchor=H10#H6.Last updated: January 11, 2017. Accessed: February 8, 2017.
  3. Overview of Platelet Disorders. http://www.merckmanuals.com/professional/hematology-and-oncology/thrombocytopenia-and-platelet-dysfunction/overview-of-platelet-disorders. Updated: September 1, 2014. Accessed: February 8, 2017.
  4. Neutze D, Roque J. Clinical Evaluation of Bleeding and Bruising in Primary Care. Am Fam Physician. 2016; 93 (4): p.279-86.
  5. Clinical Use of Coagulation Tests.
  6. Leung LLK, Mannucci PM, Tirnauer JS. Overview of Hemostasis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/overview-of-hemostasis.Last updated: December 15, 2016. Accessed: August 29, 2017.
  7. Hall JE. Guyton and Hall Textbook of Medical Physiology. Elsevier ; 2016
  8. Giangrande PLF. Six Characters in Search of An Author: The History of the Nomenclature of Coagulation Factors. Br J Haematol. 2003; 121 (5): p.703-712. doi: 10.1046/j.1365-2141.2003.04333.x . | Open in Read by QxMD
  9. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education ; 2014
  10. Marder VJ, Novokhatny V.. Direct fibrinolytic agents: biochemical attributes, preclinical foundation and clinical potential.. Journal of Thrombosis and Haemostasis. 2010 .
  11. Nazari J, Davison R, Kaplan K, Fintel D. Adverse Reactions to Thrombolytic Agents. Med Toxicol. 1987; 2 (4): p.274-286. doi: 10.1007/bf03259869 . | Open in Read by QxMD
  12. Weerasinghe A, Taylor KM. The platelet in cardiopulmonary bypass. Ann Thorac Surg. 1998; 66 (6): p.2145-2152. doi: 10.1016/s0003-4975(98)00749-8 . | Open in Read by QxMD
  13. Franchini M, Castaman G, Coppola A, et al. Acquired inhibitors of clotting factors: AICE recommendations for diagnosis and management. Blood Transfus. 2015; 13 (3): p.498-513. doi: 10.2450/2015.0141-15 . | Open in Read by QxMD
  14. Fay WP, Leung LLK, Tirnauer JS. Thrombotic and Hemorrhagic Disorders due to Abnormal Fibrinolysis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/thrombotic-and-hemorrhagic-disorders-due-to-abnormal-fibrinolysis.Last updated: May 26, 2017. Accessed: August 28, 2017.