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Adenosine Deaminase (ADA)(Ascitic fluid)

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Primarily used in evaluating tuberculous peritonitis

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Adenosine Deaminase (ADA) in Ascitic Fluid - Complete Medical Guide

  • Why is it done?
    • Test Purpose: Adenosine deaminase (ADA) is an enzyme that catalyzes the deamination of adenosine and deoxyadenosine. This test measures ADA levels in ascitic fluid (fluid accumulated in the abdominal cavity) to aid in the differential diagnosis of ascites, particularly to identify tuberculous peritonitis and distinguish it from other causes of peritoneal inflammation.
    • Primary Indications: Suspected tuberculous peritonitis in patients presenting with ascites; Fever with ascites of unknown etiology; Lymphocytic ascites when tuberculosis needs to be ruled in or out; Differentiation of tuberculous from non-tuberculous causes of peritoneal effusion; Immunocompromised patients with ascites requiring tuberculosis evaluation.
    • Typical Timing: Performed when ascitic fluid is obtained through paracentesis; Should be done at the time of initial fluid collection before fluid degradation; Useful as part of initial diagnostic workup in patients with new-onset or unexplained ascites; Particularly important in endemic areas or high-risk populations for tuberculosis.
  • Normal Range
    • Normal/Reference Values: ADA levels in ascitic fluid <4 U/L (Units per Liter) are generally considered negative or normal; Values of 4-10 U/L are considered borderline or intermediate; Values >10 U/L are considered significantly elevated and suggestive of tuberculous peritonitis; Some laboratories use a cutoff of ≥10 U/L or >11 U/L as the threshold for abnormality; Units of Measurement: U/L (International Units per Liter) or sometimes expressed as IU/mL.
    • Result Interpretation - Negative Result: <4 U/L indicates ADA levels are within normal limits; Suggests tuberculous peritonitis is unlikely; Other causes of ascites should be investigated (cirrhosis, malignancy, heart failure, spontaneous bacterial peritonitis, etc.); High negative predictive value for tuberculosis (>95%).
    • Result Interpretation - Borderline Result: 4-10 U/L represents an intermediate or equivocal range; Requires careful clinical correlation with patient symptoms, signs, and other diagnostic findings; May warrant repeat testing or additional investigations; Clinical judgment and supplementary testing are essential for decision-making.
    • Result Interpretation - Positive Result: ≥10 U/L is highly suggestive of tuberculous peritonitis; Sensitivity ranges from 65-100% depending on the test methodology and patient population; Specificity ranges from 84-99% depending on the population studied; Likelihood ratio for tuberculosis increases significantly with elevated ADA levels.
    • What Normal vs. Abnormal Means: Normal values effectively exclude tuberculous peritonitis and support alternative diagnoses; Elevated values strongly suggest active tuberculosis infection of the peritoneum; The test is most reliable when combined with other clinical and laboratory findings; Ascitic fluid cell count pattern (lymphocytic predominance) is typically present with elevated ADA.
  • Interpretation
    • Elevated ADA (≥10 U/L) Interpretation: Highly suggestive of tuberculous peritonitis; Particularly significant when ascitic fluid shows lymphocytic predominance (>50% lymphocytes); When combined with clinical symptoms (fever, night sweats, weight loss) and imaging findings, strongly supports TB diagnosis; Warrants initiation of anti-tuberculous therapy pending culture confirmation; May precede positive acid-fast bacilli (AFB) smear or culture results.
    • Low/Normal ADA (<4 U/L) Interpretation: Effectively excludes tuberculous peritonitis (high negative predictive value); Guides investigation toward other etiologies including cirrhosis, malignancy, spontaneous bacterial peritonitis, cardiac ascites, or other inflammatory conditions; Reduces need for prolonged anti-tuberculous therapy if TB was being considered; Particularly reassuring in immunocompromised patients with low ADA.
    • Factors Affecting Results - Clinical Factors: Presence of lymphocytic ascites (increases pre-test probability of TB); Duration of symptoms (longer duration may correlate with higher ADA); Immunocompetence status (HIV-positive patients may have variable ADA response); Previous TB infection or treatment history; Co-infections that may affect immune response.
    • Factors Affecting Results - Laboratory/Technical Factors: Timing of fluid collection relative to symptom onset; Fluid handling and storage conditions (ADA degrades with time); Presence of blood contamination in the specimen; Different laboratory methodologies may produce slightly different cutoff values; Testing methodology variations (some labs use enzymatic assays, others use different detection methods).
    • Factors Affecting Results - False Positive Considerations: Elevated ADA may occur in non-tuberculous infections causing peritonitis (fungal, certain bacterial infections); Malignancy-related ascites with reactive inflammation; Rheumatologic conditions affecting the peritoneum; These false positives are less common but should be considered in clinical context.
    • Clinical Significance of Result Patterns: Very high ADA levels (>20 U/L) are almost always indicative of TB; Moderate elevation (10-20 U/L) with lymphocytic ascites strongly suggests TB; Serial ADA measurements during treatment may show declining values with successful anti-TB therapy; ADA level is most valuable when combined with ascitic fluid cell count differential, protein content, and culture results.
  • Associated Organs
    • Primary Organ System: Peritoneum and abdominal cavity; The peritoneum is a membrane that lines the abdominal cavity and covers abdominal organs; Ascitic fluid is the fluid that accumulates within the peritoneal space; This test evaluates fluid obtained from the peritoneal space to assess for peritoneal inflammation from tuberculosis.
    • Conditions Associated with Elevated ADA - Tuberculous Peritonitis: Active mycobacterial infection of the peritoneum; Can occur in immunocompetent and immunocompromised individuals; Often associated with pulmonary TB but can be isolated peritoneal TB; Mortality is significant if untreated (ranging from 5-50% depending on treatment status and patient factors).
    • Other Organ Systems Potentially Involved: Liver - affected in cirrhotic ascites (usually has low ADA); Lungs - may have concurrent pulmonary TB; Lymph nodes - mesenteric lymphadenitis common in TB; Heart - peritoneal effusions can occur with cardiac diseases; Kidneys - renal TB can cause ascites; Gastrointestinal tract - TB can involve bowel causing ascites.
    • Diseases This Test Helps Diagnose - Primary: Tuberculous peritonitis (TB peritonitis); Distinguishes TB from other causes of lymphocytic ascites; Helps identify patients who need anti-tuberculous therapy; Particularly valuable in high-prevalence TB areas.
    • Diseases This Test Helps Rule Out or Differentiate From: Cirrhotic ascites (usually low ADA with low albumin ascites-to-serum ratio); Malignant ascites (usually low ADA unless with TB co-infection); Spontaneous bacterial peritonitis (usually low ADA, different cell count pattern); Pancreatitis-related ascites; Cardiac ascites; Systemic lupus erythematosus and other autoimmune conditions.
    • Complications of Abnormal Results - Tuberculous Peritonitis Complications: Peritoneal fibrosis and adhesions leading to bowel obstruction; Malnutrition and cachexia; Septic shock if untreated; Multi-organ involvement; Dissemination of infection; Death if treatment is delayed; Peritoneal dialysis complications in patients on dialysis with TB peritonitis.
    • Risks of Missing TB Diagnosis (Low/False Negative ADA): Delayed diagnosis and treatment of tuberculosis; Disease progression with severe organ damage; Increased mortality; Continued transmission risk in immunocompromised patients; Development of drug-resistant TB if prolonged untreated period occurs; These risks emphasize the importance of clinical correlation and not relying solely on ADA when TB suspicion is high.
  • Follow-up Tests
    • When ADA is Elevated (≥10 U/L) - Recommended Follow-up Tests: Ascitic fluid AFB smear microscopy (Ziehl-Neelsen or auramine-rhodamine staining); Ascitic fluid mycobacterial culture on appropriate media (Lowenstein-Jensen or MGIT); Ascitic fluid TB-PCR or GeneXpert MTB/RIF for rapid detection; Ascitic fluid cell count with differential to confirm lymphocytic predominance; Ascitic fluid total protein, LDH, and glucose levels.
    • When ADA is Elevated (≥10 U/L) - Additional Investigations: Chest X-ray to assess for pulmonary TB involvement; Abdominal ultrasound or CT scan to evaluate peritoneal thickening, loculated ascites, and lymphadenopathy; TB skin test (tuberculin skin test/Mantoux test) or interferon-gamma release assay; Serum TB markers if available; Blood culture (though yield is low in TB); HIV testing if not already known.
    • When ADA is Normal/Low (<4 U/L) - Recommended Follow-up Tests: Ascitic fluid cell count differential (to assess for other patterns); Ascitic fluid albumin and total protein; Ascitic-to-serum albumin ratio (to determine if ascites is portal hypertensive); Ascitic fluid culture for bacteria and fungi; Ascitic fluid bilirubin if concerned about biliary peritonitis.
    • When ADA is Normal/Low (<4 U/L) - Additional Investigations: Liver function tests (AST, ALT, bilirubin, albumin) if cirrhosis suspected; Renal function tests (creatinine, BUN); Prothrombin time/INR if hepatic synthetic function assessment needed; Abdominal imaging (ultrasound or CT) to evaluate for cirrhosis, masses, or other pathology; Serum-ascites albumin gradient (SAAG) calculation; Consider malignancy workup if indicated.
    • Monitoring Frequency for TB Peritonitis: If TB diagnosed, repeat paracentesis with ADA measurement at 1-2 weeks after starting anti-TB therapy to assess response (ADA levels typically decline with successful treatment); Regular clinical assessment during treatment (monthly or as clinically indicated); Repeat imaging at 1-3 months to assess radiologic response; Repeat paracentesis if clinical deterioration or lack of expected improvement occurs.
    • Monitoring Frequency for Other Diagnoses: For cirrhotic ascites - paracentesis as clinically indicated (usually not repeated unless symptoms change); For malignant ascites - imaging follow-up based on underlying cancer treatment plan; For SBP - paracentesis to confirm cure after treatment completion; For cardiac ascites - follow-up based on heart failure management.
    • Related Complementary Tests: Pleural fluid ADA (if pleural effusion present with suspicion of TB); Cerebrospinal fluid ADA (if TB meningitis suspected); Serum ADA level (though less specific for TB than ascitic fluid ADA); TB-IGRA (interferon-gamma release assay) - complements ADA for TB diagnosis; Lactate dehydrogenase (LDH) - elevated in TB peritonitis; Ascitic fluid adenosine deaminase isoenzymes (ADA1 and ADA2) - ADA1 elevation is more specific for TB.
  • Fasting Required?
    • Fasting Status: NO - Fasting is NOT required for this test.
    • Rationale: This test requires a paracentesis procedure to obtain ascitic fluid from the peritoneal cavity; The test measures ADA enzyme levels in the collected ascitic fluid itself, not in blood; Therefore, fasting status of the patient does not affect ADA measurement in ascitic fluid; The test can be performed at any time of day regardless of food intake.
    • Pre-Procedure Preparation: Patient should wear loose, comfortable clothing for easy access to the abdomen; Typically performed in a procedure room or clinical setting; Patient should empty bladder before the procedure (reduces risk of bladder perforation); Informed consent required explaining the paracentesis procedure and risks; Patient should be in a comfortable recumbent or semi-recumbent position.
    • Medications - No Restrictions Required: No medications need to be avoided specifically for the ADA test itself; However, patient's coagulation status should be assessed if on anticoagulants (may increase bleeding risk during paracentesis); Anticoagulants may need to be held 24 hours before procedure after physician consultation; NSAIDs should ideally be avoided 24 hours before procedure if possible; Aspirin continuation may be acceptable depending on clinical scenario.
    • Special Instructions for Paracentesis: Baseline vital signs and platelet count/coagulation profile should be obtained before procedure; NPO status may be recommended (check with institution) - typically 2-4 hours before procedure is sufficient; Local anesthesia will be used at the puncture site; Procedure typically takes 15-30 minutes; Patient should remain still during the procedure; Sterile technique is essential to prevent contamination.
    • Specimen Collection Handling: Ascitic fluid should be collected in sterile tubes, typically 5-10 mL for various studies; Separate tubes needed for different tests (cell count, culture, ADA, chemistry); ADA testing does not require special additives (plain sterile container); Specimen should be labeled immediately with patient identifiers; Fluid should be transported to the laboratory promptly (ideally within 1-2 hours) to prevent ADA degradation; Delayed processing can result in falsely low ADA values.
    • Post-Procedure Instructions: Rest for at least 1-2 hours after procedure; Avoid heavy lifting or strenuous activity for 24 hours; Monitor puncture site for signs of infection or excessive bleeding; Report to physician if experiencing severe pain, persistent bleeding, fever, or shortness of breath; Most patients can resume normal activity within 24 hours; Pain at puncture site is common and usually resolves within days.

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