Laboratory considerations for patients with a suspected bleeding disorder of secondary hemostasis, clot stabilization, or fibrinolysis and normal or nondiagnostic initial tests (routine clotting times, fibrinogen)
| Problem . | Laboratory considerations . |
|---|---|
| Factor deficiencies | |
| Mild factor deficiencies may not prolong clotting times | - Perform factor activity assays with a stepwise approach focusing on more common deficiencies first (factors VIII, IX, and XI), followed by less common deficiencies (factors II, V, VII, and X). - Consider chromogenic factor VIII and IX assays due to potential for clinically significant discrepant results in nonsevere hemophilia; chromogenic factor IX assays are less widely available. - In discrepant nonsevere HA, a VWD panel may provide a clue in the form of a decreased FVIII activity/VWF:Ag ratio, even if the absolute FVIII result is normal; this is also seen in type 2N VWD. - Factor activities may be borderline, confirm mild cases and female carriers of HA and HB with genetic testing. |
| Prolongation of clotting times by a lupus anticoagulant may mask a factor deficiency or inhibitor | - Perform factor assays if there is a history of bleeding or a clinical condition strongly associated with factor deficiencies. Lupus anticoagulants often interfere with quantification of factor activity in clot-based factor assays; exercise caution in interpretation. |
| FXIII deficiency does not prolong clotting times | - Clot solubility tests are most widely available worldwide but lack sensitivity (pick up only the most severe deficiencies) and specificity (abnormal with fibrinogen and other abnormalities). - Activity assays are the preferred first-line tests but may not accurately quantify the most severe deficiencies or may overestimate FXIII activity. - Consider FXIII antigen testing (sensitive to severe deficiency at the cost of missing qualitative abnormalities) and use of testing combinations for diagnosis. - FXIII deficiency subtyping should be performed by antigen testing or genetic testing due to important treatment implications. |
| Fibrinolytic disorders are poorly defined and do not prolong clotting times | - Conditions are rare, and testing has limited availability. - Results are significantly affected by blood draw timing and quality. - Results are difficult to interpret due to acute phase responses, complex interactions between fibrinolytic system components, and technical limitations of assays (deficiencies are difficult to identify). - Test PAI-1 (activity and/or antigen) and tissue plasminogen activator antigen concurrently to look for expected patterns. - Platelet aggregation is mostly normal in Quebec platelet syndrome; perform genetic testing for PLAU duplication. - Viscoelastic studies are sensitive to severe defects but may lack sensitivity for mild or moderate abnormalities. - Fibrinolytic disorders remain difficult to diagnose; genetic testing has some clinical utility but is not in widespread clinical use. Consider treating undiagnosed disorders with tranexamic acid and desmopressin |
| Problem . | Laboratory considerations . |
|---|---|
| Factor deficiencies | |
| Mild factor deficiencies may not prolong clotting times | - Perform factor activity assays with a stepwise approach focusing on more common deficiencies first (factors VIII, IX, and XI), followed by less common deficiencies (factors II, V, VII, and X). - Consider chromogenic factor VIII and IX assays due to potential for clinically significant discrepant results in nonsevere hemophilia; chromogenic factor IX assays are less widely available. - In discrepant nonsevere HA, a VWD panel may provide a clue in the form of a decreased FVIII activity/VWF:Ag ratio, even if the absolute FVIII result is normal; this is also seen in type 2N VWD. - Factor activities may be borderline, confirm mild cases and female carriers of HA and HB with genetic testing. |
| Prolongation of clotting times by a lupus anticoagulant may mask a factor deficiency or inhibitor | - Perform factor assays if there is a history of bleeding or a clinical condition strongly associated with factor deficiencies. Lupus anticoagulants often interfere with quantification of factor activity in clot-based factor assays; exercise caution in interpretation. |
| FXIII deficiency does not prolong clotting times | - Clot solubility tests are most widely available worldwide but lack sensitivity (pick up only the most severe deficiencies) and specificity (abnormal with fibrinogen and other abnormalities). - Activity assays are the preferred first-line tests but may not accurately quantify the most severe deficiencies or may overestimate FXIII activity. - Consider FXIII antigen testing (sensitive to severe deficiency at the cost of missing qualitative abnormalities) and use of testing combinations for diagnosis. - FXIII deficiency subtyping should be performed by antigen testing or genetic testing due to important treatment implications. |
| Fibrinolytic disorders are poorly defined and do not prolong clotting times | - Conditions are rare, and testing has limited availability. - Results are significantly affected by blood draw timing and quality. - Results are difficult to interpret due to acute phase responses, complex interactions between fibrinolytic system components, and technical limitations of assays (deficiencies are difficult to identify). - Test PAI-1 (activity and/or antigen) and tissue plasminogen activator antigen concurrently to look for expected patterns. - Platelet aggregation is mostly normal in Quebec platelet syndrome; perform genetic testing for PLAU duplication. - Viscoelastic studies are sensitive to severe defects but may lack sensitivity for mild or moderate abnormalities. - Fibrinolytic disorders remain difficult to diagnose; genetic testing has some clinical utility but is not in widespread clinical use. Consider treating undiagnosed disorders with tranexamic acid and desmopressin |