How can delayed or unavailable lab results affect treatment, particularly for medications requiring close monitoring of blood levels, such as anticoagulants (e.g. warfarin) or certain antibiotics?

Impact of Delayed or Unavailable Lab Results on Anticoagulation Treatment

Failure to obtain timely lab results for anticoagulation monitoring can lead to life-threatening complications including over-anticoagulation with major bleeding, under-anticoagulation with thrombotic events, and treatment delays that increase mortality risk—particularly critical for conditions like heparin-induced thrombocytopenia (HIT) where the rate of thrombosis is approximately 5% per day without treatment. 1

Critical Time-Sensitive Scenarios

Heparin-Induced Thrombocytopenia (HIT)

• When clinical probability of HIT is intermediate or high (4T score ≥4), heparin must be stopped immediately and replaced with non-heparin anticoagulant therapy at curative doses without waiting for laboratory results. 1
• The decision to discontinue heparin and replace it with another immediate antithrombotic should not be delayed by waiting for laboratory results, as untreated patients face a 5% per day risk of thrombosis. 1
• If anti-PF4 antibody testing is delayed or unavailable, treatment decisions must be based solely on clinical probability scoring (4T score), with immediate anticoagulant substitution for scores ≥6. 1

Warfarin Monitoring

• Delays in PT/INR turnaround time can result in over- or under-anticoagulation for prolonged periods and should be avoided. 1
• Measurements should be made 6 hours after any warfarin dosage change and used to adjust infusion until PT/INR exhibits therapeutic levels. 1
• The PT should be determined daily after initial warfarin dosing until PT/INR results stabilize in the therapeutic range. 2
• Acceptable intervals for PT/INR determinations are normally within the range of one to four weeks after stable dosage is determined. 2

Emergency Situations (Stroke, Acute MI)

• Laboratory testing should not delay anticoagulation in emergency situations unless there is clinical suspicion of bleeding abnormality, thrombocytopenia, or unknown anticoagulant use. 1, 3
• Thrombolytic therapy should not be delayed while waiting for coagulation test results (PT, aPTT, platelet count) unless: (1) there is clinical suspicion of bleeding abnormality or thrombocytopenia, (2) the patient has received heparin or warfarin, or (3) use of anticoagulants is not known. 1

Consequences of Hemolyzed Samples

Prevalence and Impact

• Hemolyzed specimens account for up to 40%-70% of all unsuitable specimens identified in clinical laboratories, with prevalence as high as 3.3% of all routine samples. 4
• Missed results leading to clinically important treatment delays are an important and likely underappreciated source of diagnostic error. 5

Management of Hemolyzed Samples for Anticoagulation

• When the hemolysis index (H-index) is associated with analyte variation exceeding clinically significant bias (variation exceeds the reference change value), results of hemolysis-sensitive tests should be suppressed and replaced with a comment advising recollection of another sample. 6
• If H-index values reach a critical cut-off corresponding to cell-free hemoglobin concentration ≥10 g/L, all laboratory data may be unreliable and should be suppressed with a comment that the sample is grossly hemolyzed. 6
• Suppressing data in unsuitable (hemolyzed) samples and promptly notifying clinicians about the need to recollect samples remains the most clinically and analytically safe practice. 7

Specific Anticoagulant Monitoring Requirements

Baseline Testing Before Initiation

• Complete blood count with platelet count, renal function tests, and coagulation studies including PT/INR and aPTT must be obtained before initiating anticoagulation therapy to establish baseline coagulation status and identify potential bleeding risks. 3
• For direct oral anticoagulants (DOACs), renal function is critical as these agents require dose adjustment for renal impairment. 3

Ongoing Monitoring

• For unfractionated heparin, aPTT measurements should be made 6 hours after any dosage change to avoid prolonged periods of inappropriate anticoagulation. 1
• In usual care monitoring without structured anticoagulation management, patients are in therapeutic range only 33%-64% of the time, compared to 56%-93% in anticoagulation clinics. 2

Clinical Outcomes of Inadequate Monitoring

Mortality and Morbidity

• Approximately 5%-10% of patients with HIT die, usually as a result of thrombotic complications that occur when diagnosis and treatment are delayed. 1
• Untreated HIT patients have a 17%-55% risk of developing deep vein thrombosis and/or pulmonary embolism. 1
• Arterial thrombotic events including limb artery thrombosis, thrombotic stroke, and myocardial infarction occur in 3%-10% of HIT patients. 1

Treatment Delays from Missed Results

• In a survey of 106 primary care providers, 64 patients with missed results were encountered during a two-week period, with 52 patients experiencing treatment delays. 5
• The most common diagnostic delays from missed results were cancer (34%), endocrine problems (26%), and cardiac problems (16%). 5

Practical Recommendations for Lab Companies

Communication Protocols

• Immediate clinician notification is required when hemolysis is detected in samples for anticoagulation monitoring, with clear documentation that results cannot be released and urgent recollection is needed. 4, 6
• Systematic detection and quantification of hemolysis should occur in every sample, with automatic measurement of H-index highly advisable. 6
• Registration of non-conformity should be completed, with tests unaffected by hemolysis completed and a second specimen requested for those potentially affected. 4

Quality Improvement

• Pre-analytical errors account for 46%-68.2% of total laboratory errors, making prevention of hemolysis a critical quality target. 8
• Continuous education of healthcare personnel on proper blood collection techniques is essential to reduce hemolysis rates. 4

Common Pitfalls to Avoid

• Do not report results with comments in hemolyzed samples for critical anticoagulation parameters—the risk that comments may be overlooked in short-stay and frequently overcrowded units (e.g., emergency department) makes suppression and recollection the safer approach. 7
• Do not use corrective formulas for adjusting data of hemolysis-sensitive tests, as inaccuracy and imprecision make this approach unreliable. 6
• Do not delay treatment decisions for suspected HIT while awaiting confirmatory laboratory testing—clinical probability scoring should drive immediate therapeutic changes. 1
• Do not assume that visual inspection alone is adequate for hemolysis assessment—automatic H-index measurement provides more reliable quantification. 6