Definition

Hemostatic defects characterized by a lack of one or more procoagulant proteins (coagulation factors).

Pathophysiology

• Coagulation involves a complex series of enzymatic reactions that generate a burst of thrombin (factor IIa) at sites of blood vessel injury. Thrombin then cleaves plasma fibrinogen into fibrin monomers that are subsequently polymerized and cross-linked to form an insoluble fibrin clot.
• Functional and/or quantitative coagulation factor deficiencies cause a failure of fibrin clot formation.
• The liver is the sole or primary site of synthesis of most coagulation factors. After synthesis, factors II, VII, IX, and X require a vitamin K–dependent modification to become fully active.

Systems Affected

• Coagulation factor deficiency can cause spontaneous hemorrhage, prolonged post-traumatic hemorrhage, and ultimately blood loss anemia.
• Spontaneous hemorrhage-often develops in body cavities or potential spaces (i.e., hemothorax, hemoperitoneum, hemarthrosis, subcutaneous or intramuscular hematoma).

Signalment

• Acquired factor deficiencies-depends on underlying disease process.
• Hereditary factor deficiencies-severe defects manifest by 3–6 months of age, milder hemostatic defects manifest after surgery or trauma.
• Hemophilia A and B (factor VIII and IX deficiencies)-X-linked recessive traits (males express the bleeding tendency, female carriers are clinically normal).
• Hemophilia A is a common hereditary factor deficiency and is seen in all breeds and mixed-breed dogs and cats.
• All other factor deficiencies-autosomal traits; males and females express signs with equal frequency. Specific defects are more likely to be propagated within a single breed, but all breeds are at risk for developing new mutations.
• Factor XII deficiency is common in cats but does not cause a clinical bleeding tendency.

Signs

• Hematoma formation
• Intracavitary hemorrhage
• Prolonged hemorrhage post-surgery, trauma
• Blood loss anemia

Causes

• Acquired-synthetic failure (liver disease); vitamin K deficiency (cholestasis, anticoagulant rodenticide toxicity, malabsorption, long-term antibiotics, coumadin); factor inhibition (heparin overdose, envenomation); factor consumption and depletion (DIC); factor dilution (high-volume transfusion, plasma expanders); hyperfibrinolysis (secondary fibrinogen depletion).
• Hereditary-distinct mutations in coagulation factor genes.

Risk Factors

See acquired causes above.

Differential Diagnosis

• Thrombocytopenia should be the first rule-out for any patient with abnormal hemorrhage.
• Acquired coagulopathies often develop because of liver disease, anticoagulant rodenticide ingestion, and DIC.
• Liver disease is accompanied by changes in CBC and chemistry profiles (see Coagulopathy of Liver Disease).
• Anticoagulant rodenticide toxicity prolongs the APTT and PT screening tests but does not affect TCT or fibrinogen.
• DIC always develops secondary to systemic disease (especially sepsis or neoplasia) and is often accompanied by low or falling platelet count.
• Massive transfusion (>1 blood volume) with stored blood products may dilute functional factors, fibrinogen, and platelets below hemostatic levels.
• Hyperfibrinolysis may develop after hypovolemic shock and traumatic blood loss but generally does not cause prolongation of APTT and PT screening tests.
• Hereditary coagulation factor deficiencies cause prolongation of coagulation screening tests, whereas vWD does not.

Laboratory Findings

CBC/Biochemistry/Urinalysis

• Regenerative anemia develops after blood loss.
• Platelet count is normal unless the patient has DIC or massive bleeding.
• Resorption of blood from large hematoma may cause high bilirubin.

Other Laboratory Tests

• Coagulation screening tests (ACT, APTT, PT, TCT) are functional tests that measure the time for in vitro clot formation. Coagulation factor and fibrinogen deficiencies prolong clotting time (see algorithm, Figure 1).
• ACT is a point-of-care screening test that detects severe deficiencies of all factors (except factor VII). The ACT may be influenced by anemia, thrombocytopenia, and changes in blood viscosity.
• APTT is a screening test of the contact pathway (prekallikrein, high molecular weight kininogen, factor XII) intrinsic system (factors XI, IX, VIII), common system (factors X, V, II), and severe fibrinogen deficiency.
• PT is a screening test of factor VII, common system, and severe fibrinogen deficiency.
• The TCT is a screening test of functional fibrinogen and is sensitive to the presence of fibrinogen inhibitors.
• Acquired coagulation factor deficiencies generally cause prolongation of more than one screening test. The most common hereditary factor deficiencies (hemophilia and factor XII deficiency) specifically prolong APTT.
• Individual factor assays can be performed for definitive diagnosis of hereditary or complex coagulopathies.

Imaging

N/A

Diagnostic Procedures

The buccal mucosa bleeding time is prolonged in patients with severe thrombocytopenia, platelet dysfunction, von Willebrand disease, and fibrinogen deficiency, but BMBT is insensitive to coagulation factor deficiencies.

Drug(s) Of Choice

Vitamin K₁ is an effective treatment for patients with anticoagulant rodenticide poisoning and other causes of vitamin K deficiency.

Contraindications

NSAIDs, anticoagulants, and plasma expanders should be avoided to prevent further compromise of hemostasis.

Precautions

• Intramuscular injections and jugular catheter placement should be avoided because of the risk of inducing additional bleeding.
• Intravenous administration of vitamin K is not recommended because of the risk of anaphylaxis.

Possible Interactions

None

Alternative Drug(s)

Alternatives such as antifibrinolytic drugs (EACA and tranexamic acid) may prove useful to reduce or eliminate transfusion requirements, but have not yet been evaluated in veterinary clinical trials.

Patient Monitoring

• PT or factor VII assays can be used to monitor effectiveness of vitamin K administration in animals with anticoagulant toxicity. Test results should normalize after 24–48 hours of initiating therapy.
• ACT is a less specific but reasonable substitute for monitoring response to vitamin K.
• Hereditary defects can be monitored by clinical arrest of bleeding, stabilization of Hct, resolution of hematoma, and, if needed, specific factor analyses.

Possible Complications

Transfusion poses a risk of immune reactions (e.g., RBC sensitization, urticaria) and non-immune reactions (disease transmission, volume overload).

Associated Conditions

None

Age-Related Factors

None

Zoonotic Potential

None

Pregnancy/Fertility/Breeding

Patients with hereditary factor deficiencies should not be bred.

Synonyms

• Coagulation defects
• Coagulopathies

See Also

• Coagulopathy of Liver Disease
• Disseminated Intravascular Coagulation
• Von Willebrand Disease

Abbreviations

• ACT = activated clotting time
• APTT = activated partial thromboplastin time
• BMBT = buccal mucosal bleeding time
• DIC = disseminated intravascular coagulation
• NSAID = nonsteroidal anti-inflammatory drug
• PT = prothrombin time
• RBC = red blood cell
• TCT = thrombin clotting time
• vWD = von Willebrand disease

Internet Resources

http://www.labtestsonline.org/understanding/analytes/coagulation_factors/test.html.