Laboratory considerations for patients with a suspected bleeding disorder of primary hemostasis and normal or nondiagnostic initial tests (normal platelet count/morphology, routine clotting times, VWD panel, and platelet function testing)
| Problem . | Laboratory considerations . |
|---|---|
| VWD | |
| Normal vs low VWF vs VWD masked by acute phase response | PFA-100 lacks sensitivity and specificity for VWD; initial panel should include VWF antigen, activity, and FVIII activity. Avoid testing during acute bleeding episodes, illness, and stress. Use care to avoid traumatic phlebotomy. Repeated measurements may be necessary due to normal biologic variability of VWF, particularly with VWF antigen and activity values between 30 IU/dL and 50 IU/dL. Consider values of other acute phase reactants drawn concurrently (FVIII, fibrinogen). |
| Less common VWD subtypes/phenotypes | Consider type 2M due to a collagen binding defect. First-line activity tests assess platelet binding function rather than collagen binding function. Order VWF:CB to assess for decreased VWF:CB/antigen ratio. Consider type 2B due to a mutation that results in a nonclassic laboratory phenotype (relatively normal activity and antigen without decreased activity/antigen ratio, normal multimers and platelet count). Perform LD-RIPA to assess for abnormally high affinity for platelets. LD-RIPA mixing studies (if available) can be used to differentiate type 2B from platelet-type VWD. VWD genetic testing can be performed and is most useful for type 2 cases with challenging laboratory phenotypes or when phenotypic testing is not available (LD-RIPA not possible if local laboratories do not perform aggregation testing and LD-RIPA mixing studies are not widely performed). Also useful to differentiate type 2B from platelet-type VWD and type 2N from HA. |
| Acquired VWS | Consideration of and appropriate testing for associated disorders such as autoimmune, lymphoproliferative or myeloproliferative neoplasms, plasma cell dyscrasia, and so on. Absolute VWF activity and antigen values often in the normal range; look for decreased activity/antigen ratio. VWF multimer analysis recommended as a first-line test since subtle defects of large multimers may be the only abnormality observed. |
| Platelet function | |
| Platelet function tests are nonstandardized and variably sensitive to the most common disorders | PFA-100 lacks sensitivity and specificity for the most common platelet function disorders. Platelet aggregometry is considered the gold-standard test but has more limited availability. Some laboratories offer aggregometry with an extended agonist panel. Aggregometry is often normal in common disorders such as dense granule deficiency and secretion defects. Consider platelet EM and lumiaggregometry. Mild PFDs 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 . |
|---|---|
| VWD | |
| Normal vs low VWF vs VWD masked by acute phase response | PFA-100 lacks sensitivity and specificity for VWD; initial panel should include VWF antigen, activity, and FVIII activity. Avoid testing during acute bleeding episodes, illness, and stress. Use care to avoid traumatic phlebotomy. Repeated measurements may be necessary due to normal biologic variability of VWF, particularly with VWF antigen and activity values between 30 IU/dL and 50 IU/dL. Consider values of other acute phase reactants drawn concurrently (FVIII, fibrinogen). |
| Less common VWD subtypes/phenotypes | Consider type 2M due to a collagen binding defect. First-line activity tests assess platelet binding function rather than collagen binding function. Order VWF:CB to assess for decreased VWF:CB/antigen ratio. Consider type 2B due to a mutation that results in a nonclassic laboratory phenotype (relatively normal activity and antigen without decreased activity/antigen ratio, normal multimers and platelet count). Perform LD-RIPA to assess for abnormally high affinity for platelets. LD-RIPA mixing studies (if available) can be used to differentiate type 2B from platelet-type VWD. VWD genetic testing can be performed and is most useful for type 2 cases with challenging laboratory phenotypes or when phenotypic testing is not available (LD-RIPA not possible if local laboratories do not perform aggregation testing and LD-RIPA mixing studies are not widely performed). Also useful to differentiate type 2B from platelet-type VWD and type 2N from HA. |
| Acquired VWS | Consideration of and appropriate testing for associated disorders such as autoimmune, lymphoproliferative or myeloproliferative neoplasms, plasma cell dyscrasia, and so on. Absolute VWF activity and antigen values often in the normal range; look for decreased activity/antigen ratio. VWF multimer analysis recommended as a first-line test since subtle defects of large multimers may be the only abnormality observed. |
| Platelet function | |
| Platelet function tests are nonstandardized and variably sensitive to the most common disorders | PFA-100 lacks sensitivity and specificity for the most common platelet function disorders. Platelet aggregometry is considered the gold-standard test but has more limited availability. Some laboratories offer aggregometry with an extended agonist panel. Aggregometry is often normal in common disorders such as dense granule deficiency and secretion defects. Consider platelet EM and lumiaggregometry. Mild PFDs 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. |
Abbreviations: EM, electron microscopy; LD-RIPA, low-dose ristocetin-induced platelet activation; PFD, platelet function disorder.