Utility of the Ratio between Lactate Dehydrogenase (LDH) Activity and Total Nucleated Cell Counts in Effusions (LDH/TNCC Ratio) for the Diagnosis of Feline Infectious Peritonitis (FIP)

Abstract

Background: We tested the hypothesis that the ratio between lactate dehydrogenase activity (LDH) and total nucleated cell counts (TNCC) in effusions may be useful to diagnose feline infectious peritonitis (FIP). Methods: LDH/TNCC ratio was retrospectively evaluated in 648 effusions grouped based on cytology and physicochemical analysis (step 1), on the probability of FIP estimated by additional tests on fluids (step 2) or on other biological samples (step 3, n = 471). Results of different steps were statistically compared. Receiver Operating Characteristic (ROC) curves were designed to assess whether the ratio identify the samples with FIP “probable/almost confirmed”. The cut-offs with the highest positive likelihood ratio (LR+) or Youden Index (YI) or with equal sensitivity and specificity were determined. Results: A high median LDH/TNCC ratio was found in FIP effusions (step1: 2.01) and with probable or almost confirmed FIP (step 2: 1.99; 2.20 respectively; step 3: 1.26; 2.30 respectively). The optimal cut-offs were 7.54 (LR+6.58), 0.62 (IY 0.67, sensitivity: 89.1%; specificity 77.7%), 0.72 (sensitivity and specificity: 79.2%) in step 2 and 2.27 (LR+ 10.39), 0.62 (IY 0.65, sensitivity: 82.1%; specificity 83.0%), 0.54 (sensitivity: 82.1%; specificity 81.9%) in step 3. Conclusions: a high LDH/TNCC ratio support a FIP diagnosis.

Measurement of Feline Alpha-1 Acid Glycoprotein in Serum and Effusion Using an ELISA Method: Analytical Validation and Diagnostic Role for Feline Infectious Peritonitis

“…According to the Bayesian approach [ 49 ], if the pre-test the probability of FIP is low, as in the example of septic effusions described above, the diagnosis of FIP remains unlikely, even in the presence of high AGP values. Conversely, AGP may be used as a confirmatory test when other findings consistent with FIP are present (e.g., yellowish and sticky, gross appearance of the fluid; high protein content; high LDH:TNCC ratio; and non-specific inflammatory cytology) [ 3 , 12 , 13 ] or may act as a discriminating marker for FIP when some but not all of the findings listed above are present and, therefore, the pre-test probability is intermediate. Conversely, independent of the clinical scenario, low AGP values in sera or effusions may allow FIP to be ruled out.…”

“…Using the data generated with the diagnostic approach, samples were grouped as follows: FIP: 20 cases on which all the following changes were present: hyperproteinemia, hypoalbuminemia, inverted A/G ratio, serum protein electrophoresis characterized by increased α 2 and γ-globulin (polyclonal peak), effusions macroscopically consistent with FIP (yellowish and thick, possibly with fibrin clots) and characterized by high SG (>1.015), high protein content (>20 g/L), albumin:globulin ratio <1.0, low cellularity (<5 × 10 9 /L), high LDH/TNCC ratio (>0.62), cytology consistent with FIP (non-degenerated neutrophils, absence of bacteria, low numbers of macrophages and lymphocytes, and presence of a proteinaceous granular background), and positive RT-PCR for FCoV [ 11 , 13 , 14 , 15 , 16 ]. Not FIP: 15 cases on which macroscopical, physicochemical, and cytological analyses of the fluid were not consistent with FIP; RT-PCR for FCoV was negative; and cytology revealed the presence of a disease other than FIP (e.g., neoplastic, septic, or lymphocyte-rich effusions/chylous effusions), possibly associated with chemical findings suggestive of another condition (e.g., low protein content or high triglyceride content).…”

“…FIP: 20 cases on which all the following changes were present: hyperproteinemia, hypoalbuminemia, inverted A/G ratio, serum protein electrophoresis characterized by increased α 2 and γ-globulin (polyclonal peak), effusions macroscopically consistent with FIP (yellowish and thick, possibly with fibrin clots) and characterized by high SG (>1.015), high protein content (>20 g/L), albumin:globulin ratio <1.0, low cellularity (<5 × 10 9 /L), high LDH/TNCC ratio (>0.62), cytology consistent with FIP (non-degenerated neutrophils, absence of bacteria, low numbers of macrophages and lymphocytes, and presence of a proteinaceous granular background), and positive RT-PCR for FCoV [ 11 , 13 , 14 , 15 , 16 ].…”

“…The diagnosis of dry FIP may be challenging because only the demonstration of typical lesions by histology, possibly followed by the detection of intralesional FCoV antigens by immunohistochemistry or viral RNA by PCR, can confirm the disease. On the contrary, the diagnosis of FIP in the wet forms may be supported by several findings, such as the typical macroscopic appearance of the fluid; high specific gravity; high protein content; a positive Rivalta test; the presence of a non-specific inflammatory cell population with a proteinaceous background; and, more accurately, by a high ratio between the activity of the lactate dehydrogenase enzyme and the total nucleated cell count (LDH/TNCC ratio) or by a high delta-Total Nucleated Cells (TNC) measured with a Sysmex XT-2000iV laser-based automated cell counter [ 9 , 10 , 11 , 12 , 13 ]. Additionally, in both dry and wet forms, the disease may be highly suspected if routine bloodwork evidences anemia; microcytosis; lymphopenia; and, in particular, hyperproteinemia, hypoalbuminemia, hyperglobulinemia, and increased α 2 and γ-globulin with polyclonal appearance in serum protein electrophoresis [ 12 , 14 , 15 ].…”