What is the workup for lactic acidosis and thrombocytopenia (low platelet count)?

From the Guidelines

The workup for lactic acidosis and thrombocytopenia should begin with a comprehensive assessment including complete blood count, comprehensive metabolic panel, arterial blood gas, lactate level, coagulation studies, and peripheral blood smear, and consider computed tomography angiography (CTA) as soon as possible if acute mesenteric ischemia (AMI) is suspected, as recommended by the World Society of Emergency Surgery 1. First, stabilize the patient with intravenous fluids, oxygen, and address any hemodynamic instability. Identify and treat the underlying cause, which may include sepsis, tissue hypoperfusion, liver disease, hematologic malignancies, disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or drug toxicity. For sepsis, administer broad-spectrum antibiotics like piperacillin-tazobactam 4.5g IV every 6 hours or meropenem 1g IV every 8 hours. If TTP is suspected, urgent plasma exchange and hematology consultation are needed. For DIC, treat the underlying condition and provide supportive care with platelets (for counts <10,000/μL or active bleeding) and fresh frozen plasma for coagulopathy. Discontinue any potentially causative medications. Serial monitoring of lactate levels, platelet counts, and acid-base status is essential to assess response to treatment. This combined presentation often indicates serious illness with high mortality, so prompt ICU admission may be necessary for close monitoring and aggressive management. Some key points to consider in the workup include:

• Elevated l-lactate, leukocytosis, and D-dimer may assist in the diagnosis of AMI, although no laboratory parameters are sufficiently accurate to conclusively identify the presence or absence of ischemic or necrotic bowel 1.
• The presence of lactic acidosis in combination with abdominal pain should lead to consideration of early CTA, even if the patient does not otherwise appear clinically ill 1.
• CTA should be performed as soon as possible for any patient with suspicion for AMI, despite the presence of renal failure, as the consequences of delayed diagnosis are far more detrimental to the kidneys and the patient than exposure to the iodinated contrast agent 1.
• A comprehensive biphasic CTA includes pre-contrast scans, arterial and venous phases, and multi-planar reconstructions to assess the origin of the mesenteric arteries and detect vascular calcification, hyper-attenuating intravascular thrombus, and intra-mural hemorrhage 1.
• Other biomarkers reported to be of use in the diagnosis of AMI include intestinal fatty acid-binding protein (I-FABP), serum alpha-glutathione S-transferase (alpha-GST), and cobalt–albumin binding assay (CABA), although further research is required to specify their accuracy and values 1.
• Prophylactic platelet transfusion should be administered to patients with thrombocytopenia resulting from impaired bone marrow function to reduce the risk of hemorrhage when the platelet count falls below a predefined threshold level, which varies according to the patient’s diagnosis, clinical condition, and treatment modality 1.
• The platelet transfusion must be closely coordinated with the timing of the planned surgical intervention, and post-transfusion counts obtained 10 minutes after transfusion can be helpful in determining the achievement of a hemostatic platelet count level 1.

From the FDA Drug Label

ZYVOX has been associated with thrombocytopenia when used in doses up to and including 600 mg every 12 hours for up to 28 days. In Phase 3 comparator-controlled trials, the percentage of adult patients who developed a substantially low platelet count (defined as less than 75% of lower limit of normal and/or baseline) was 2.4% (range among studies: 0.3 to 10. 0%) with ZYVOX and 1.5% (range among studies: 0.4 to 7.0%) with a comparator. Thrombocytopenia associated with the use of ZYVOX appears to be dependent on duration of therapy, (generally greater than 2 weeks of treatment). The platelet counts for most patients returned to the normal range/baseline during the follow-up period. No related clinical adverse events were identified in Phase 3 clinical trials in patients developing thrombocytopenia Bleeding events were identified in thrombocytopenic patients in a compassionate use program for ZYVOX; the role of linezolid in these events cannot be determined

Workup for lactic acidosis and thrombocytopenia should include:

• Monitoring of platelet count, especially in patients receiving linezolid for more than 2 weeks
• Monitoring for signs and symptoms of thrombocytopenia, such as bleeding or bruising
• Consideration of alternative treatments if thrombocytopenia occurs
• Monitoring of laboratory parameters, including hemoglobin, white blood cell count, and serum chemistry values
• Consideration of the potential for lactic acidosis, although the label does not provide direct information on the workup for this condition in the context of linezolid use 2

From the Research

Workup for Lactic Acidosis and Thrombocytopenia

• Lactic acidosis is a metabolic complication that can be caused by various factors, including medication-induced hyperlactatemia 3
• Thrombocytopenia, or low platelet count, can be associated with lactic acidosis, as seen in a case report of a patient treated with linezolid therapy 4
• The workup for lactic acidosis and thrombocytopenia should include:
  • Laboratory tests to measure lactate levels and assess for other metabolic abnormalities
  • Review of medication list to identify potential causes of hyperlactatemia 3
  • Assessment for underlying conditions that may be contributing to lactic acidosis, such as sepsis or low-flow states 5
• Classification of lactic acidosis can be based on whether the pathophysiology is due to increased production or decreased removal of L-lactic acid 6

Diagnostic Approach

• Measurement of lactate levels is crucial in diagnosing lactic acidosis 7
• Methods used to measure lactate in blood or plasma should be carefully selected to avoid interferences, especially in cases of ethylene glycol poisoning 7
• A systematic review of the literature can provide valuable information on medication-induced lactate level elevations and help clinicians in diagnosing and managing this rare adverse drug effect 3

Management Strategies

• Eliminating the triggering conditions remains the most effective therapy for lactic acidosis 5
• Administration of sodium bicarbonate may not be recommended, as it can have untoward effects such as reduction in serum calcium concentration and generation of excess carbon dioxide 5
• Other buffers, such as THAM or Carbicarb, or dialysis might provide base with fewer untoward effects 5
• Selective NHE1 inhibitors may improve cardiovascular function, ameliorate lactic acidosis, and reduce mortality in animal studies, supporting future research into their possible use in humans 5