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Plasma vs. Serum

Core Difference

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Composition

• Plasma = water (~92%) + proteins (albumin, globulins, fibrinogen, clotting factors) + electrolytes + hormones + waste products
• Serum = plasma minus fibrinogen and other coagulation factors

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Key Practical Differences

• Serum has slightly higher potassium (released from platelets during clotting) — plasma is preferred for K⁺ measurement
• Glucose is best measured in plasma (fluoride-oxalate tube) — clotting delays allow glycolysis to lower glucose in serum
• Coagulation tests (PT, aPTT) require plasma (citrate tube), not serum

• Plasma can be separated immediately after centrifugation (no need to wait for clot formation, ~30 min)
• Serum requires 30–60 minutes for clot retraction before centrifugation

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Why It Matters Clinically

• Pseudohyperkalemia: Using serum in thrombocytosis (very high platelets) can falsely elevate K⁺ because platelets release K⁺ during clotting — plasma K⁺ is more accurate in such cases.
• Diabetes diagnosis: WHO and ADA guidelines specify venous plasma glucose thresholds (e.g., fasting ≥ 7.0 mmol/L). Serum glucose is not recommended for diagnosis.
• Protein electrophoresis: Both can be used, but serum is conventional; plasma shows an extra fibrinogen band that can be mistaken for a paraprotein.

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Quick Memory Aid

Serum = Plasma − Clotting factors Blood clots → clotting factors are consumed/removed → what's left is serum.

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Feline Immunodeficiency Virus (FIV)

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1. Etiology & Virology

• Genome: Single-stranded RNA; encodes gag, pol, env, and accessory genes (vif, orf-A/vpr, rev)
• Subtypes: Five major clades (A–E); subtype A and B predominate in North America and Europe, respectively
• Target cells: CD4⁺ T lymphocytes (primary), CD8⁺ T cells, B cells, macrophages, microglia, and astrocytes

Greene's Infectious Diseases of the Dog and Cat (5th ed.) describes FIV as the premier model for HIV immunopathogenesis, noting that CD4⁺:CD8⁺ ratio inversion is a hallmark of advanced disease.

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2. Epidemiology & Transmission

Ettinger & Feldman — Textbook of Veterinary Internal Medicine (8th ed.) emphasizes that FIV is not efficiently transmitted by casual contact, so FIV-positive cats can safely cohabitate with FIV-negative cats in stable, non-fighting households.

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3. Pathogenesis

Phase 1 — Acute (weeks 2–4 post-infection)

• Viremia, fever, lymphadenopathy, neutropenia
• Often subclinical or mild; frequently missed

Phase 2 — Asymptomatic / Latent (months to years)

• Persistent viral replication at low levels
• Progressive, slow decline in CD4⁺ T cells
• Cat appears clinically normal; can last years

Phase 3 — Terminal / AIDS-like

• Profound CD4⁺ lymphopenia, CD4⁺:CD8⁺ ratio inversion (normal ~2:1 → <0.5:1)
• Severe immunosuppression → opportunistic infections, neoplasia, neurological disease

Sykes — Canine and Feline Infectious Diseases (2014, p. 194–202) details that neurological signs arise partly from direct FIV neurotropism (viral replication in microglia/astrocytes) and not only from opportunistic infection.

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4. Clinical Signs

Acute Phase

• Fever, generalized lymphadenopathy
• Mild neutropenia, anemia
• Lethargy, anorexia (self-limiting)

Chronic / Terminal Phase

Norsworthy — The Feline Patient (4th ed.) notes that chronic stomatitis/gingivitis is the single most common presenting sign in FIV-positive cats and often prompts initial testing.

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5. Diagnosis

Serology (First-line)

• ELISA (in-clinic snap tests): Detect anti-FIV antibodies (not antigen); highly sensitive. Result positive ~60 days post-infection.
  • False positives: Recently vaccinated cats (FIV vaccine, no longer available in many countries)
  • False negatives: Acute phase (pre-seroconversion), end-stage (antibody exhaustion — rare)

Confirmatory Tests

Key Diagnostic Pitfalls

• Kittens born to FIV+ mothers: Maternal antibodies persist until ~6 months; ELISA may be positive in uninfected kittens. Retest at 6 months or use PCR.
• Vaccinated cats (with the old Fel-O-Vax FIV vaccine): Will test ELISA-positive for life; PCR or Western blot required.

Ettinger & Feldman (8th ed.) and Greene's Infectious Diseases (5th ed.) both recommend retesting all ELISA-positive cats with a second method before a definitive diagnosis of FIV infection is made.

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6. Treatment

1. Antiretroviral therapy (to suppress viral replication)
2. Immunomodulation
3. Management of secondary/opportunistic infections
4. Supportive care

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6A. Antiretroviral Agents

Zidovudine (AZT / Azidothymidine)

• Mechanism: Nucleoside reverse transcriptase inhibitor (NRTI); inhibits FIV reverse transcriptase
• Dose: 5–10 mg/kg PO or SC q12h (controversial — lower end preferred due to toxicity)
• Efficacy: Reduces viral load, improves CD4⁺ counts, and improves neurological signs and stomatitis
• Toxicity: Non-regenerative anemia (Heinz body hemolytic anemia) is the major dose-limiting side effect; requires CBC monitoring every 2–4 weeks
• Verdict: The most evidence-supported antiretroviral for FIV

Greene's Infectious Diseases of the Dog and Cat (5th ed., p. 21): "Zidovudine at 5 mg/kg BID has been shown to reduce FIV viral load and improve clinical signs, but hematologic monitoring is mandatory given the risk of severe anemia."

Sykes — Canine and Feline Infectious Diseases (p. 200) notes that AZT is the only antiretroviral with robust feline clinical trial data, but emphasizes the narrow therapeutic window.

Lamivudine (3TC)

• Also an NRTI; used in combination with AZT in human HIV therapy
• Limited feline data; some in vitro activity against FIV
• Combination AZT + 3TC studied but evidence base is weak compared to human medicine
• Not routinely recommended as monotherapy

Stavudine (d4T)

• NRTI; in vitro activity against FIV but significant neurotoxicity potential
• Not commonly used clinically

Tenofovir

• Nucleotide reverse transcriptase inhibitor; active against FIV in vitro
• Nephrotoxicity concerns in cats; not established for routine clinical use

Protease Inhibitors (e.g., TL-3, experimental)

• Feline-specific lentiviral protease inhibitors have been studied experimentally
• Not commercially available; research stage only

Ettinger & Feldman (8th ed.) states: "Antiretroviral combinations analogous to human HAART have not been validated for routine clinical use in FIV-infected cats; AZT remains the only agent with documented clinical benefit."

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6B. Immunomodulatory Therapy

Interferon-ω (Omega Interferon — Virbagen Omega)

• Species: Recombinant feline interferon-omega (rFeIFN-ω), available in Europe and some countries; not FDA-approved in the US
• Dose: 1 MU/kg SC q24h for 5 days, repeated at intervals (protocols vary)
• Mechanism: Antiviral + immunomodulatory; upregulates innate immune responses
• Efficacy: Randomized controlled trial (de Mari et al.) showed improved survival and clinical scores in FIV/FeLV co-infected cats; effect in FIV alone is less certain
• Tolerability: Generally well-tolerated; mild transient fever possible

Sykes (p. 201): "Recombinant feline interferon-omega has shown promise in improving quality of life in FIV-positive cats, particularly those with concurrent FeLV infection."

Human Interferon-α (hIFN-α)

• Used at very low oral doses (30 IU/cat/day PO) as an immunomodulator
• Mechanism at low oral doses: likely mucosal immune stimulation rather than direct antiviral effect
• Evidence: Weak and largely anecdotal; inexpensive and safe
• Used in practice as a palliative/supportive measure

LTCI (Lymphocyte T-Cell Immunomodulator)

• T-cyte Therapeutics' LTCI: USDA-licensed biologic for treatment of FIV in the US
• Derived from bovine thymic extracts (thymosin-like factors)
• Dose: 1 unit SC once weekly for 3 weeks, then monthly
• Efficacy: Increases CD4⁺ cell counts and reduces viral load in some studies; improves clinical signs
• Considered a first-line option by some practitioners in the US given its regulatory approval

Norsworthy — The Feline Patient (4th ed.) identifies LTCI as the only USDA-licensed immunomodulator specifically for FIV and recommends it as an adjunct in cats with declining CD4⁺ counts.

Staphylococcal Protein A (SPA)

• Older immunostimulant; largely fallen out of favor; inconsistent results

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6C. Management of Secondary Infections & Complications

Greene's Infectious Diseases (5th ed.) stresses that treating secondary infections aggressively is the cornerstone of FIV management, as most morbidity and mortality is attributable to opportunistic pathogens, not FIV directly.

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6D. Supportive & Nutritional Care

• High-quality, cooked or commercial diet (avoid raw food — immunosuppressed cats at risk for Salmonella, Toxoplasma)
• Regular veterinary monitoring (CBC, chemistry, urinalysis every 6 months in stable cats)
• Environmental enrichment and stress reduction (stress accelerates progression)
• Keep cats indoors (reduces exposure to pathogens and prevents transmission to other cats)

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7. Vaccination

• A killed, adjuvanted FIV vaccine (Fel-O-Vax FIV, Fort Dodge) was previously available in the US but was withdrawn from the market (~2015–2017)
• Main issue: Vaccine-induced seropositivity was indistinguishable from natural infection on standard ELISA tests
• Currently no commercially available FIV vaccine exists in the US or Europe
• Prevention relies on reducing bite wound exposure (neutering, indoor housing)

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8. Prognosis

• FIV-positive cats can live many years with appropriate management
• A large retrospective study (Levy et al.) found FIV-positive cats had a median survival of 4.9 years post-diagnosis vs. 6.0 years in FIV-negative cats — a modest difference
• Cats in the asymptomatic phase have an excellent short-to-medium term prognosis
• Progression to AIDS-like terminal phase carries a guarded to poor prognosis
• Co-infection with FeLV significantly worsens prognosis

Ettinger & Feldman (8th ed.): "FIV infection alone should not be a reason for euthanasia. With appropriate monitoring and management of secondary conditions, quality of life can be maintained for extended periods."

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Summary Table: Treatment Options by Source