const {
  Document, Packer, Paragraph, TextRun, Table, TableRow, TableCell,
  HeadingLevel, AlignmentType, BorderStyle, WidthType, ShadingType,
  VerticalAlign, PageNumber, Header, Footer, PageBreak,
  TableOfContents, LevelFormat, convertInchesToTwip, UnderlineType
} = require('docx');
const fs = require('fs');

// ── colour palette ──────────────────────────────────────────────────────────
const RED       = "C0392B";   // headings
const DARK_BLUE = "1A3C6B";   // sub-headings
const TEAL      = "117A8B";   // section labels
const LIGHT_BG  = "EBF5FB";   // table header fill
const WARN_BG   = "FDEDEC";   // warning / important boxes
const NOTE_BG   = "E8F8F5";   // note / tip boxes
const WHITE     = "FFFFFF";
const DARK      = "1C1C1C";

// ── helper builders ──────────────────────────────────────────────────────────
function h1(text) {
  return new Paragraph({
    heading: HeadingLevel.HEADING_1,
    spacing: { before: 320, after: 160 },
    children: [new TextRun({ text, color: RED, bold: true, size: 36 })]
  });
}
function h2(text) {
  return new Paragraph({
    heading: HeadingLevel.HEADING_2,
    spacing: { before: 260, after: 120 },
    children: [new TextRun({ text, color: DARK_BLUE, bold: true, size: 28 })]
  });
}
function h3(text) {
  return new Paragraph({
    heading: HeadingLevel.HEADING_3,
    spacing: { before: 200, after: 80 },
    children: [new TextRun({ text, color: TEAL, bold: true, size: 24 })]
  });
}
function h4(text) {
  return new Paragraph({
    spacing: { before: 160, after: 60 },
    children: [new TextRun({ text, color: DARK_BLUE, bold: true, underline: { type: UnderlineType.SINGLE }, size: 22 })]
  });
}
function body(text, opts = {}) {
  return new Paragraph({
    spacing: { before: 60, after: 60 },
    children: [new TextRun({ text, color: DARK, size: 20, ...opts })]
  });
}
function bullet(text, level = 0, bold = false) {
  return new Paragraph({
    bullet: { level },
    spacing: { before: 40, after: 40 },
    children: [new TextRun({ text, size: 20, color: DARK, bold })]
  });
}
function numberedItem(text, bold = false) {
  return new Paragraph({
    numbering: { reference: "numbering", level: 0 },
    spacing: { before: 40, after: 40 },
    children: [new TextRun({ text, size: 20, color: DARK, bold })]
  });
}
function spacer(lines = 1) {
  return Array.from({ length: lines }, () =>
    new Paragraph({ spacing: { before: 40, after: 40 }, children: [new TextRun("")] })
  );
}
function pageBreak() {
  return new Paragraph({ children: [new PageBreak()] });
}
function boxedParagraph(text, bgColor = WARN_BG, borderColor = RED) {
  return new Paragraph({
    spacing: { before: 100, after: 100 },
    border: {
      top:    { style: BorderStyle.SINGLE, size: 6, color: borderColor },
      bottom: { style: BorderStyle.SINGLE, size: 6, color: borderColor },
      left:   { style: BorderStyle.SINGLE, size: 12, color: borderColor },
      right:  { style: BorderStyle.SINGLE, size: 6, color: borderColor },
    },
    shading: { type: ShadingType.CLEAR, color: bgColor, fill: bgColor },
    children: [new TextRun({ text, size: 20, color: DARK })]
  });
}

// ── cell helpers ─────────────────────────────────────────────────────────────
function headerCell(text, fill = LIGHT_BG) {
  return new TableCell({
    shading: { type: ShadingType.CLEAR, color: fill, fill },
    verticalAlign: VerticalAlign.CENTER,
    margins: { top: 80, bottom: 80, left: 100, right: 100 },
    children: [new Paragraph({
      alignment: AlignmentType.CENTER,
      children: [new TextRun({ text, bold: true, color: DARK_BLUE, size: 18 })]
    })]
  });
}
function dataCell(text, fill = WHITE, bold = false, center = false) {
  return new TableCell({
    shading: { type: ShadingType.CLEAR, color: fill, fill },
    verticalAlign: VerticalAlign.CENTER,
    margins: { top: 60, bottom: 60, left: 100, right: 100 },
    children: [new Paragraph({
      alignment: center ? AlignmentType.CENTER : AlignmentType.LEFT,
      children: [new TextRun({ text, bold, color: DARK, size: 18 })]
    })]
  });
}
function makeTable(headers, rows, colWidths = null) {
  const total = 9000;
  const w = colWidths || headers.map(() => Math.floor(total / headers.length));
  return new Table({
    width: { size: 100, type: WidthType.PERCENTAGE },
    rows: [
      new TableRow({
        tableHeader: true,
        children: headers.map((h, i) => {
          const c = headerCell(h);
          c.options = c.options || {};
          return c;
        })
      }),
      ...rows.map((row, ri) =>
        new TableRow({
          children: row.map((cell, ci) =>
            dataCell(cell, ri % 2 === 0 ? WHITE : "F2F9FC")
          )
        })
      )
    ]
  });
}

// ════════════════════════════════════════════════════════════════════════════
//  DOCUMENT CONTENT
// ════════════════════════════════════════════════════════════════════════════
const children = [];

// ── COVER PAGE ───────────────────────────────────────────────────────────────
children.push(
  new Paragraph({ spacing: { before: 800 } }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: 200, after: 120 },
    children: [new TextRun({ text: "🩸 ANEMIA IN COMPANION ANIMALS", color: RED, bold: true, size: 52 })]
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: 80, after: 80 },
    children: [new TextRun({ text: "A Complete Veterinary Study Guide", color: DARK_BLUE, bold: true, size: 36 })]
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: 80, after: 200 },
    children: [new TextRun({ text: "Dogs & Cats | Classification | Diagnosis | Treatment | Case Studies", color: TEAL, size: 24 })]
  }),
  ...spacer(2),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    spacing: { before: 40 },
    children: [new TextRun({ text: "Sources: Merck Veterinary Manual | ACVIM Consensus 2019 | DVM360 | Compendium CVE | IDEXX", color: "888888", size: 18 })]
  }),
  new Paragraph({
    alignment: AlignmentType.CENTER,
    children: [new TextRun({ text: "Generated: May 2026", color: "888888", size: 18 })]
  }),
  pageBreak()
);

// ── PART 1: INTRODUCTION ────────────────────────────────────────────────────
children.push(h1("PART 1: INTRODUCTION - WHAT IS ANEMIA?"));
children.push(boxedParagraph(
  "KEY POINT: Anemia is NOT a disease - it is a clinical SIGN pointing to an underlying disorder. Always find the cause.",
  WARN_BG, RED
));
children.push(...spacer());
children.push(body("Anemia is defined as a reduction in the number of circulating red blood cells (RBCs), hemoglobin concentration, or packed cell volume (PCV / hematocrit) below the normal reference range for that species."));
children.push(body("Red blood cells carry oxygen to every organ and tissue. When RBC numbers fall, oxygen delivery decreases - this is called tissue hypoxia (hypoxia = low oxygen at tissue level). The body compensates: the heart beats faster, breathing increases. If anemia is severe enough, these compensations fail and the animal becomes critically ill."));
children.push(body("Think of anemia as an alarm signal - it demands investigation to find the root cause.", { italic: true }));
children.push(pageBreak());

// ── PART 2: NORMAL VALUES ────────────────────────────────────────────────────
children.push(h1("PART 2: NORMAL REFERENCE VALUES"));
children.push(makeTable(
  ["Parameter", "Dogs (Normal)", "Cats (Normal)"],
  [
    ["PCV / Hematocrit", "37 - 55%", "24 - 45%"],
    ["Hemoglobin (Hgb)", "12 - 18 g/dL", "8 - 15 g/dL"],
    ["RBC Count", "5.5 - 8.5 x 10⁶/µL", "5.0 - 10.0 x 10⁶/µL"],
    ["MCV (Mean Corpuscular Volume)", "60 - 77 fL", "39 - 55 fL"],
    ["MCHC (Mean Corpuscular Hgb Conc.)", "32 - 36 g/dL", "30 - 36 g/dL"],
    ["Reticulocytes", "< 1% (< 60,000/µL abs.)", "< 0.4% aggregate"],
  ]
));
children.push(...spacer());
children.push(boxedParagraph("Anemia confirmed when PCV < 37% in dogs or < 24% in cats.", NOTE_BG, TEAL));

// ── PART 3: SEVERITY ─────────────────────────────────────────────────────────
children.push(h1("PART 3: SEVERITY CLASSIFICATION"));
children.push(makeTable(
  ["Grade", "PCV Dogs", "PCV Cats", "Clinical Signs"],
  [
    ["Mild",             "30 - 37%", "20 - 24%", "Usually none / very subtle"],
    ["Moderate",         "20 - 30%", "14 - 20%", "Lethargy, mild exercise intolerance"],
    ["Severe",           "13 - 20%", "10 - 14%", "Weakness, tachycardia, pale mucous membranes"],
    ["Life-threatening", "< 13%",    "< 10%",    "Collapse, shock, dyspnea"],
  ]
));
children.push(pageBreak());

// ── PART 4: CLASSIFICATION ────────────────────────────────────────────────────
children.push(h1("PART 4: CLASSIFICATION OF ANEMIA"));

// System 1
children.push(h2("SYSTEM 1: Classification by Cause (Pathophysiologic)"));
children.push(body("All anemias fit into one of three categories:", { bold: true }));

// A - Blood Loss
children.push(h3("A) BLOOD LOSS ANEMIA (Hemorrhagic Anemia)"));
children.push(h4("1. Acute Blood Loss (Sudden)"));
children.push(bullet("Trauma, lacerations, surgery, ruptured spleen or liver"));
children.push(bullet("Rodenticide poisoning (anticoagulants like brodifacoum block Vitamin K → clotting failure)"));
children.push(bullet("GI bleeding (ulcers, hookworm infestation)"));
children.push(bullet("Thrombocytopenia (low platelet count = inability to clot)"));
children.push(boxedParagraph("Note: In acute blood loss, SHOCK appears BEFORE anemia. PCV looks normal initially - body dilutes remaining blood over hours.", NOTE_BG, TEAL));

children.push(h4("2. Chronic Blood Loss (Slow, Ongoing)"));
children.push(bullet("Flea or tick infestation (especially in puppies/kittens)"));
children.push(bullet("Hookworms (Ancylostoma caninum in dogs) - feed on intestinal blood"));
children.push(bullet("Chronic GI bleeding (ulcers, tumors)"));
children.push(bullet("Urinary tract bleeding"));
children.push(body("Key feature: Chronic blood loss depletes iron stores over time → iron deficiency anemia → becomes NON-regenerative."));

// B - Hemolytic
children.push(h3("B) HEMOLYTIC ANEMIA (Destruction of RBCs)"));
children.push(body("RBCs are destroyed faster than the bone marrow can replace them. Two locations:"));
children.push(bullet("Intravascular (inside blood vessels): releases free hemoglobin → hemoglobinemia (pink plasma) + hemoglobinuria (red/brown urine)"));
children.push(bullet("Extravascular (in spleen/liver by macrophages): produces bilirubin → jaundice / icterus (yellow discoloration)"));

children.push(h4("1. Immune-Mediated Hemolytic Anemia (IMHA) - MOST IMPORTANT"));
children.push(bullet("Immune system makes antibodies against the animal's OWN RBCs"));
children.push(bullet("PRIMARY (idiopathic - no known cause): most common in middle-aged female dogs"));
children.push(bullet("SECONDARY: triggered by drugs, infections, cancer, vaccine reactions"));
children.push(bullet("Breed predisposition: Cocker Spaniels, Old English Sheepdogs, Springer Spaniels"));
children.push(bullet("Classic signs: sudden severe anemia + jaundice + autoagglutination (RBCs clumping = grape clusters on blood smear)"));
children.push(bullet("Mortality: 30-70% without aggressive treatment"));
children.push(bullet("Diagnosed by: positive Coombs test, spherocytes on blood smear, autoagglutination"));

children.push(h4("2. Infectious Causes"));
children.push(makeTable(
  ["Organism", "Host", "Mechanism", "Transmission"],
  [
    ["Mycoplasma haemofelis", "Cats (primarily)", "Attaches to RBC surface → immune destruction", "Fleas, ticks, cat bites"],
    ["Babesia canis / felis", "Dogs / Cats", "Protozoan inside RBCs → hemolysis", "Tick bite"],
    ["Cytauxzoon felis", "Cats", "Severe intravascular hemolysis", "Tick bite (Lone Star tick)"],
    ["Ehrlichia / Anaplasma", "Dogs", "Pancytopenia + anemia", "Tick bite"],
  ]
));

children.push(h4("3. Toxin-Induced Hemolysis"));
children.push(makeTable(
  ["Toxin", "Species", "Mechanism", "Key Finding"],
  [
    ["Onions & Garlic", "Dogs & Cats (cats more susceptible)", "N-propyl disulfide → oxidative damage → Heinz bodies → hemolysis", "Heinz bodies on smear"],
    ["Zinc (pennies post-1982, zinc cream)", "Dogs", "Oxidative hemolysis", "History of ingestion"],
    ["Acetaminophen (Paracetamol)", "CATS - NEVER USE!", "Methemoglobinemia + Heinz body anemia", "Brown blood, muddy membranes"],
    ["Propylene glycol", "Cats", "Heinz body formation", "Found in some human foods"],
    ["Naphthalene (mothballs)", "Dogs & Cats", "Oxidative hemolysis", "History of exposure"],
  ]
));

children.push(h4("4. Microangiopathic Hemolysis (Mechanical Destruction)"));
children.push(bullet("DIC (Disseminated Intravascular Coagulation) - fibrin strands in vessels shred RBCs"));
children.push(bullet("Hemangiosarcoma (malignant tumor of blood vessel walls)"));
children.push(bullet("Schistocytes (fragmented RBCs) seen on blood smear"));

children.push(h4("5. Hereditary / Congenital"));
children.push(bullet("Pyruvate kinase deficiency: Basenjis, Beagles"));
children.push(bullet("Phosphofructokinase deficiency: English Springer Spaniels"));
children.push(bullet("Hereditary stomatocytosis: Alaskan Malamutes"));

// C - Decreased Production
children.push(pageBreak());
children.push(h3("C) DECREASED PRODUCTION ANEMIA (Non-Regenerative)"));
children.push(body("Bone marrow is NOT producing enough new RBCs. Most common type in cats with chronic diseases."));

children.push(h4("1. Anemia of Chronic Disease / Inflammatory Disease (ACD/AID) - MOST COMMON Non-Regenerative Type"));
children.push(bullet("Caused by: chronic infection, inflammation, cancer, immune disease"));
children.push(bullet("Mechanism: IL-6 stimulates liver to produce hepcidin (hepcidin = peptide that blocks iron release from storage). Iron gets trapped. Also EPO response is blunted."));
children.push(bullet("Labs: mild-moderate normocytic normochromic anemia, normal/increased ferritin, LOW serum iron, LOW TIBC"));

children.push(h4("2. Anemia of Chronic Kidney Disease (CKD)"));
children.push(bullet("VERY COMMON in cats with CKD"));
children.push(bullet("Kidneys make erythropoietin (EPO) - hormone that stimulates bone marrow to produce RBCs"));
children.push(bullet("Damaged kidneys → less EPO → less RBC production"));
children.push(bullet("Additional factors: uremic toxins suppress marrow, GI blood loss, iron deficiency"));
children.push(bullet("Labs: normocytic normochromic anemia, low reticulocytes, elevated BUN & creatinine"));
children.push(bullet("NEW Treatment: Molidustat (Varenzin-CA1) - FDA conditionally approved for cats (HIF-PHI drug)"));

children.push(h4("3. Iron Deficiency Anemia"));
children.push(bullet("Usually follows CHRONIC blood loss (hookworms, fleas, GI bleeding)"));
children.push(bullet("Labs: MICROCYTIC HYPOCHROMIC anemia (low MCV = small cells, low MCHC = pale cells)"));
children.push(bullet("LOW serum iron, HIGH TIBC, LOW ferritin"));
children.push(bullet("Treatment: ferrous sulfate + eliminate bleeding source"));

children.push(h4("4. Pure Red Cell Aplasia (PRCA)"));
children.push(bullet("Immune system attacks RBC precursors in bone marrow"));
children.push(bullet("Severely non-regenerative with near-zero reticulocytes"));
children.push(bullet("Bone marrow biopsy: near-complete absence of erythroid precursors"));
children.push(boxedParagraph("IMPORTANT: ALWAYS test cats with PRCA for FeLV (Feline Leukemia Virus)!", WARN_BG, RED));

children.push(h4("5. Aplastic Anemia (Pancytopenia)"));
children.push(bullet("ALL blood cell lines affected (RBCs + WBCs + platelets all low)"));
children.push(bullet("Bone marrow replaced by fat (seen on biopsy)"));
children.push(bullet("Causes: FeLV (cats), Ehrlichia (dogs), drugs (estrogen, chloramphenicol, methimazole, TMP-sulfa), chemotherapy, radiation"));

children.push(h4("6. Myelodysplastic Syndrome (MDS)"));
children.push(bullet("Pre-leukemic condition - bone marrow makes abnormal dysplastic cells"));
children.push(bullet("Common in cats with FeLV. Can progress to leukemia."));

children.push(h4("7. Endocrine-Related Anemia"));
children.push(bullet("Hypothyroidism → hypometabolic state → poor bone marrow response → mild normocytic normochromic anemia"));
children.push(bullet("Hypoadrenocorticism (Addison's disease) → similar mechanism"));
children.push(bullet("Treatment: correct the endocrine disorder (L-thyroxine for hypothyroidism)"));

children.push(h4("8. Drug-Induced"));
children.push(bullet("Chloramphenicol, estrogen overdose, chemotherapy, phenylbutazone, methimazole (cats)"));

// System 2 - Morphological
children.push(pageBreak());
children.push(h2("SYSTEM 2: Morphological Classification (Cell Size & Color)"));
children.push(makeTable(
  ["Type", "MCV", "MCHC", "Common Causes"],
  [
    ["Normocytic Normochromic", "Normal", "Normal", "ACD, CKD anemia, acute blood loss (early), IMHA"],
    ["Microcytic Hypochromic", "LOW", "LOW", "Iron deficiency, portosystemic shunts"],
    ["Macrocytic Normochromic", "HIGH", "Normal", "Regenerative response, B12/folate deficiency, FeLV"],
    ["Macrocytic Hypochromic", "HIGH", "LOW", "Strong regenerative response in dogs (polychromasia)"],
  ]
));

// System 3 - Regen vs Non-Regen
children.push(h2("SYSTEM 3: Regenerative vs Non-Regenerative (MOST CLINICALLY IMPORTANT)"));
children.push(boxedParagraph("This is the FIRST question you must answer for every anemic patient. It guides the entire diagnostic workup.", NOTE_BG, TEAL));
children.push(...spacer());
children.push(makeTable(
  ["Feature", "REGENERATIVE", "NON-REGENERATIVE"],
  [
    ["Bone marrow", "Active - producing new RBCs", "Inactive / insufficient"],
    ["Reticulocytes (dogs)", "> 60,000/µL = regenerative", "Normal or decreased"],
    ["Reticulocytes (cats - aggregate)", "> 50,000/µL = regenerative", "Normal or decreased"],
    ["Polychromasia", "PRESENT (blue-tinged young RBCs)", "ABSENT"],
    ["Macrocytosis", "Present (especially dogs)", "Usually absent"],
    ["nRBCs (nucleated RBCs)", "May be present", "Absent (unless severe marrow disease)"],
    ["Causes", "Blood loss, hemolysis", "CKD, ACD, aplastic anemia, iron deficiency, FeLV"],
    ["Time to develop", "3-5 days after acute loss", "Chronic / ongoing"],
  ]
));
children.push(...spacer());
children.push(boxedParagraph(
  "PRE-REGENERATIVE PHASE: In the first 3-5 days after acute blood loss or hemolysis, anemia may appear NON-regenerative. The bone marrow needs time to respond. Recheck CBC in 3-5 days if unsure!",
  WARN_BG, RED
));
children.push(...spacer());
children.push(h4("Reticulocyte Evaluation in Cats (SPECIAL NOTE)"));
children.push(bullet("Cats have TWO types of reticulocytes:"));
children.push(bullet("1. AGGREGATE reticulocytes (new, just released) - USE THESE to assess regeneration. Should be > 50,000/µL.", 1));
children.push(bullet("2. PUNCTATE reticulocytes (older) - NOT a good indicator of current regeneration", 1));
children.push(boxedParagraph("Always count AGGREGATE reticulocytes in cats, NOT total reticulocyte count!", WARN_BG, RED));

children.push(pageBreak());

// ── PART 5: PATHOPHYSIOLOGY ───────────────────────────────────────────────────
children.push(h1("PART 5: PATHOPHYSIOLOGY - HOW ANEMIA CAUSES CLINICAL SIGNS"));
children.push(body("When PCV drops, oxygen delivery to tissues falls. The body activates compensatory mechanisms:"));

children.push(h3("1. Cardiovascular Compensation"));
children.push(bullet("Heart rate increases (tachycardia) - pumps blood faster"));
children.push(bullet("Cardiac output increases"));
children.push(bullet("Vasodilation to major organs"));
children.push(bullet("Prolonged severe anemia → cardiomegaly (enlarged heart) → heart failure (especially in cats)"));

children.push(h3("2. Respiratory Compensation"));
children.push(bullet("Respiratory rate increases (tachypnea) to bring in more oxygen"));

children.push(h3("3. Hematologic Compensation"));
children.push(bullet("2,3-DPG increases inside RBCs → hemoglobin releases O2 to tissues more easily (right shift of oxygen-hemoglobin dissociation curve)"));
children.push(bullet("EPO production increases → stimulates bone marrow to make more RBCs"));

children.push(h3("4. Blood Redistribution"));
children.push(bullet("Blood directed away from skin and GI tract → toward heart, brain, and muscles"));

children.push(boxedParagraph(
  "When compensation fails (PCV < 13-15% in dogs, < 10% in cats): Weakness, collapse, syncope (brief loss of consciousness), dyspnea, cardiovascular shock",
  WARN_BG, RED
));
children.push(pageBreak());

// ── PART 6: CLINICAL SIGNS ────────────────────────────────────────────────────
children.push(h1("PART 6: CLINICAL SIGNS"));
children.push(h2("General Signs (All Anemias)"));
children.push(bullet("Pale or WHITE mucous membranes (gums, conjunctiva, vulva) - MOST IMPORTANT clinical sign"));
children.push(bullet("Weakness and lethargy (tiredness)"));
children.push(bullet("Exercise intolerance (gets tired quickly)"));
children.push(bullet("Increased respiratory rate (tachypnea)"));
children.push(bullet("Increased heart rate (tachycardia)"));
children.push(bullet("Heart murmur (functional / flow murmur from turbulent thin blood)"));
children.push(bullet("Weakness, collapse"));
children.push(bullet("Decreased appetite"));

children.push(h2("Signs Specific to Hemolytic Anemia"));
children.push(bullet("Icterus / Jaundice (yellow-orange discoloration of gums, skin, sclera)"));
children.push(bullet("Hemoglobinuria (red / brown discolored urine) - indicates intravascular hemolysis"));
children.push(bullet("Splenomegaly (enlarged spleen from increased RBC destruction)"));
children.push(bullet("Fever (immune activation or infection)"));
children.push(bullet("Autoagglutination (blood clumps on slide)"));

children.push(h2("Signs Specific to Blood Loss"));
children.push(bullet("Visible external bleeding"));
children.push(bullet("Melena (black tarry feces = digested blood from upper GI)"));
children.push(bullet("Hematochezia (red blood in feces = lower GI bleeding)"));
children.push(bullet("Hematuria (blood in urine)"));
children.push(bullet("Pallor + tachycardia + weak pulse = hypovolemic shock"));

children.push(h2("Signs of Bone Marrow Disease"));
children.push(bullet("Pancytopenia → infections (from low WBCs), bleeding (from low platelets)"));
children.push(bullet("Progressive worsening despite treatment"));
children.push(pageBreak());

// ── PART 7: DIAGNOSIS ─────────────────────────────────────────────────────────
children.push(h1("PART 7: DIAGNOSIS - STEP BY STEP"));

children.push(h2("Step 1: History Taking"));
children.push(bullet("How long have signs been present? (Acute vs. chronic)"));
children.push(bullet("Any visible bleeding?"));
children.push(bullet("Tick or flea exposure? Travel history?"));
children.push(bullet("Any recent medications or toxin exposure? (Onions, zinc, drugs)"));
children.push(bullet("Recent vaccination (can trigger IMHA)"));
children.push(bullet("Any known chronic disease (kidney, cancer, liver)?"));
children.push(bullet("Breed predisposition (Cocker Spaniel, Basenji, Springer Spaniel)?"));

children.push(h2("Step 2: Physical Examination"));
children.push(bullet("Mucous membrane color: pale, icteric (yellow), or normal pink"));
children.push(bullet("CRT (Capillary Refill Time): > 2 seconds = poor perfusion"));
children.push(bullet("Heart rate, rhythm, murmurs"));
children.push(bullet("Lymph node size"));
children.push(bullet("Abdominal palpation: splenomegaly, masses"));
children.push(bullet("Petechiae (pin-point hemorrhages) or ecchymoses (bruises) on skin"));
children.push(bullet("Eye: retinal hemorrhages, icterus of sclera"));

children.push(h2("Step 3: Complete Blood Count (CBC) - MOST IMPORTANT TEST"));
children.push(makeTable(
  ["Parameter", "What to Look For", "Clinical Significance"],
  [
    ["PCV / Hematocrit", "Below normal?", "Confirms & quantifies anemia"],
    ["MCV", "Low / Normal / High", "Microcytic vs normocytic vs macrocytic"],
    ["MCHC", "Low / Normal", "Hypochromic vs normochromic"],
    ["Reticulocyte count", "Elevated?", "IS THE BONE MARROW RESPONDING?"],
    ["WBC + differential", "Leukocytosis or leukopenia?", "Infection/inflammation vs marrow failure"],
    ["Platelet count", "Thrombocytopenia?", "IMHA, DIC, tick-borne disease"],
  ]
));

children.push(h2("Step 4: Blood Smear Examination (MANDATORY)"));
children.push(makeTable(
  ["Finding", "Meaning"],
  [
    ["Spherocytes (small dense RBCs, no central pallor)", "IMHA - hallmark finding"],
    ["Heinz bodies (denatured hemoglobin clumps)", "Oxidative damage: onions, zinc, acetaminophen"],
    ["Eccentrocytes (hemoglobin pushed to one side)", "Oxidative damage"],
    ["Schistocytes (fragmented RBCs)", "DIC, microangiopathy, hemangiosarcoma"],
    ["Polychromasia (blue-tinged RBCs)", "Regenerative anemia"],
    ["nRBCs (nucleated RBCs)", "Regenerative or severe marrow stress"],
    ["Organisms ON RBCs", "Mycoplasma (cats), Babesia (dogs/cats)"],
    ["Autoagglutination", "IMHA"],
    ["Target cells", "Liver disease, iron deficiency"],
  ]
));

children.push(h2("Step 5: Saline Agglutination Test (Quick Bedside Test)"));
children.push(bullet("Place 1 drop blood + 1 drop 0.9% saline on a glass slide"));
children.push(bullet("If RBCs form PERSISTENT clumps after mixing → TRUE AUTOAGGLUTINATION = IMHA"));
children.push(bullet("If clumps DISPERSE with saline → just ROULEAUX (normal stacking, not true agglutination)"));

children.push(h2("Step 6: Biochemistry Panel"));
children.push(bullet("BUN, Creatinine → Chronic Kidney Disease"));
children.push(bullet("ALT, ALP, Total Bilirubin → Liver disease, hemolysis (bilirubin elevated in hemolysis)"));
children.push(bullet("Total protein, albumin → Chronic disease, blood loss"));

children.push(h2("Step 7: Urinalysis"));
children.push(bullet("Hemoglobinuria (positive blood dipstick with NO RBCs in sediment) → intravascular hemolysis"));
children.push(bullet("Bilirubinuria → hemolysis or liver disease"));
children.push(bullet("Isosthenuria (urine SG 1.008-1.012) → CKD"));

children.push(h2("Step 8: Specific Tests (Based on Clinical Suspicion)"));
children.push(makeTable(
  ["Test", "What It Detects"],
  [
    ["Coombs Test (DAT)", "Antibodies on RBC surface → IMHA (positive in ~60-70% of IMHA cases)"],
    ["Serum iron, TIBC, Ferritin", "Iron deficiency vs. ACD (anemia of chronic disease)"],
    ["Reticulocyte count (absolute)", "Regenerative vs. non-regenerative"],
    ["Coagulation profile (PT, aPTT)", "Coagulopathy, DIC, rodenticide poisoning"],
    ["FeLV / FIV test (cats)", "Feline leukemia virus, FIV"],
    ["Mycoplasma PCR (cats)", "Mycoplasma haemofelis"],
    ["Babesia PCR / serology", "Babesiosis"],
    ["Ehrlichia / Anaplasma serology", "Tick-borne disease"],
    ["Thyroid panel (T4)", "Hypothyroidism"],
    ["Abdominal ultrasound", "Splenomegaly, masses, internal bleeding"],
    ["Thoracic X-ray", "Pulmonary metastases, pleural effusion"],
    ["Bone marrow aspirate & biopsy", "GOLD STANDARD for non-regenerative anemia - aplastic, PRCA, MDS, leukemia"],
  ]
));

children.push(h2("Step 9: Bone Marrow Evaluation"));
children.push(bullet("Indicated when: non-regenerative anemia with no clear cause, pancytopenia"));
children.push(bullet("Sites: iliac crest, proximal humerus, femur (under sedation/general anesthesia)"));
children.push(bullet("Aspirate → cytology (individual cell morphology)"));
children.push(bullet("Core biopsy → histopathology (overall architecture, cellularity)"));
children.push(bullet("M:E Ratio (Myeloid:Erythroid) - Normal = 0.75:1 to 2.5:1"));
children.push(bullet("  Increased M:E (e.g., 5:1) → erythroid hypoplasia (too few RBC precursors)", 1));
children.push(bullet("  Decreased M:E (e.g., 0.5:1) → erythroid hyperplasia (bone marrow working hard = regenerating)", 1));
children.push(pageBreak());

// ── PART 8: TREATMENT ─────────────────────────────────────────────────────────
children.push(h1("PART 8: TREATMENT OF ANEMIA"));
children.push(boxedParagraph("KEY PRINCIPLE: Treat the UNDERLYING CAUSE + Stabilize the Patient. Treating only the anemia without finding the cause will always fail.", NOTE_BG, TEAL));

children.push(h2("A) STABILIZATION (Emergency Treatment)"));

children.push(h3("1. Oxygen Therapy"));
children.push(bullet("ALL severely anemic patients need supplemental oxygen"));
children.push(bullet("Flow-by oxygen, oxygen cage, or nasal cannula"));
children.push(bullet("PCV < 20% dogs / < 15% cats = oxygen supplementation mandatory"));

children.push(h3("2. Blood Transfusion"));
children.push(h4("When to Transfuse?"));
children.push(bullet("PCV < 12-15% in dogs WITH clinical signs"));
children.push(bullet("PCV < 10-12% in cats"));
children.push(bullet("Acute blood loss with cardiovascular instability (regardless of PCV)"));
children.push(bullet("Clinical signs of hypoxia: tachypnea, tachycardia, weakness, collapse"));

children.push(h4("Types of Blood Products"));
children.push(makeTable(
  ["Product", "Contents", "When to Use"],
  [
    ["Whole Blood", "RBCs + plasma + clotting factors + platelets", "Anemia + coagulopathy + hypovolemia"],
    ["Packed RBCs (pRBCs)", "Concentrated RBCs only", "PREFERRED for simple anemia (less volume overload risk)"],
    ["Fresh Frozen Plasma (FFP)", "Clotting factors only", "Coagulopathy - NOT for anemia alone"],
    ["Oxyglobin (bovine hemoglobin)", "Hemoglobin-based oxygen carrier", "When compatible blood unavailable - controversial, short-lived"],
  ]
));

children.push(h4("Blood Typing - CRITICAL"));
children.push(bullet("Dogs: DEA 1.1 (Dog Erythrocyte Antigen 1.1) - most important blood group"));
children.push(bullet("  DEA 1.1 negative blood = universal donor for FIRST transfusion in dogs", 1));
children.push(bullet("  After first transfusion: ALWAYS crossmatch", 1));
children.push(bullet("Cats: Blood types A, B, or AB"));
children.push(boxedParagraph(
  "WARNING: Type B cats have strong NATURAL anti-A antibodies. Giving Type A blood to a Type B cat = FATAL acute hemolytic reaction. ALWAYS blood type cats before EVERY transfusion!",
  WARN_BG, RED
));
children.push(bullet("Crossmatching: Major crossmatch (donor cells + recipient serum) + Minor crossmatch (recipient cells + donor serum)"));

children.push(h4("Transfusion Volume Formula"));
children.push(boxedParagraph(
  "Dogs: Volume (mL) = Body weight (kg) × 90 × [(Target PCV - Patient PCV) / Donor PCV]" +
  "\nCats:  Volume (mL) = Body weight (kg) × 60 × [(Target PCV - Patient PCV) / Donor PCV]" +
  "\n\nExample: 10 kg dog, patient PCV 12%, target 25%, donor PCV 45%:" +
  "\n= 10 × 90 × (25-12)/45 = 260 mL pRBCs",
  NOTE_BG, TEAL
));
children.push(bullet("Target PCV post-transfusion: 25-30% in dogs. Do NOT exceed 30% - risk of volume overload and suppression of regenerative response."));
children.push(bullet("Transfusion reactions: vomiting, urticaria, facial swelling, fever, tremors, hemoglobinuria → STOP transfusion immediately"));

children.push(h2("B) TREATMENT OF SPECIFIC CAUSES"));

children.push(h3("1. IMHA Treatment (Most Complex)"));
children.push(body("Immunosuppressive therapy is the CORNERSTONE of IMHA treatment:", { bold: true }));
children.push(makeTable(
  ["Drug", "Dose", "Notes"],
  [
    ["Prednisolone / Prednisone", "1-2 mg/kg/day PO (dogs)", "First-line. Continue 3-6 months, taper SLOWLY"],
    ["Dexamethasone", "0.1-0.3 mg/kg IV/IM", "For patients that cannot take oral medications"],
    ["Mycophenolate mofetil", "10-15 mg/kg/day PO (dogs)", "Preferred second-line in many current protocols"],
    ["Azathioprine (Imuran)", "2 mg/kg/day PO - DOGS ONLY", "TOXIC TO CATS - NEVER use in feline patients"],
    ["Cyclosporine", "5 mg/kg/day PO (dogs & cats)", "Alternative second-line"],
    ["Human IVIg", "0.5-1 g/kg IV slow infusion", "Expensive, short-term use for refractory cases"],
    ["Leflunomide", "2-4 mg/kg/day PO", "For refractory / relapsed cases"],
  ]
));

children.push(h4("Anti-thrombotic Therapy for IMHA - CRITICAL"));
children.push(boxedParagraph(
  "IMHA dogs are in a HYPERCOAGULABLE state. Pulmonary Thromboembolism (PTE) is the LEADING CAUSE OF DEATH in IMHA dogs!" +
  "\nACVIM 2019 Consensus: recommend antithrombotics for ALL dogs with IMHA (except severe thrombocytopenia - platelets < 30,000/µL)",
  WARN_BG, RED
));
children.push(bullet("Clopidogrel (antiplatelet): 1.1 mg/kg/day PO"));
children.push(bullet("Heparin (unfractionated or LMWH - dalteparin 100-150 IU/kg SC q8h)"));
children.push(bullet("Continue antithrombotics until remission and discontinuation of glucocorticoids"));

children.push(h4("Supportive Care for IMHA"));
children.push(bullet("Omeprazole 0.7-1 mg/kg/day PO - prevent steroid-induced GI ulcers"));
children.push(bullet("Sucralfate 0.25-1 g q8h PO - gastric protection"));
children.push(bullet("IV fluids at maintenance rate for hydration"));
children.push(bullet("Monitor PCV every 24-48 hours during crisis"));
children.push(bullet("D-dimer and coagulation panel for thromboembolism risk assessment"));

children.push(h4("IMHA Prognosis"));
children.push(bullet("Mortality rate: 30-70% even with aggressive treatment"));
children.push(bullet("Dogs surviving first 2-3 weeks have good long-term outlook"));
children.push(bullet("Relapse rate: ~10-15%"));
children.push(bullet("Poor prognostic indicators: persistent autoagglutination > 3 days, severe thrombocytopenia, intravascular hemolysis, hemoglobinuria"));

children.push(h3("2. Infectious Anemia Treatment"));
children.push(makeTable(
  ["Disease", "Treatment", "Duration"],
  [
    ["Mycoplasma haemofelis (cats)", "Doxycycline 5-10 mg/kg PO q12h - DRUG OF CHOICE", "28 days minimum"],
    ["Mycoplasma (alternative)", "Marbofloxacin 2 mg/kg/day PO", "28 days"],
    ["Babesiosis (dogs)", "Imidocarb dipropionate 5-6.6 mg/kg IM x 2 doses", "2 doses, 2 weeks apart"],
    ["Babesiosis / Cytauxzoon (cats)", "Atovaquone + Azithromycin", "10 days"],
    ["Ehrlichiosis / Anaplasmosis", "Doxycycline 5-10 mg/kg/day PO", "28 days"],
  ]
));
children.push(boxedParagraph(
  "DOXYCYCLINE IN CATS: Always give with food or syringe 5 mL water after. NEVER give dry tablet to cats - risk of esophageal stricture (narrowing of esophagus)!",
  WARN_BG, RED
));

children.push(h3("3. CKD Anemia Treatment"));
children.push(makeTable(
  ["Treatment", "Details"],
  [
    ["Darbepoetin alfa", "0.45-1.5 µg/kg SC weekly. PREFERRED - longer half-life, less antibody formation vs rHuEPO"],
    ["rHuEPO (epoetin alfa)", "100-150 IU/kg SC 3x/week. Risk: 10-25% cats develop anti-EPO antibodies → severe refractory anemia"],
    ["Molidustat (Varenzin-CA1)", "FDA conditionally approved for cats. Oral once daily x 28 days then 7-day break. Monitor PCV weekly from day 14."],
    ["Iron supplementation", "Ferrous sulfate: dogs 100-300 mg/day PO; cats 50-100 mg/day PO. Give concurrently with ESAs."],
    ["GI ulcer treatment", "Omeprazole, sucralfate - uremic GI ulcers worsen blood loss"],
  ]
));

children.push(h3("4. Iron Deficiency Anemia Treatment"));
children.push(bullet("STEP 1: Find and eliminate the blood loss source (deworm for hookworms, treat fleas, address GI bleeding)"));
children.push(bullet("STEP 2: Ferrous sulfate supplementation:"));
children.push(bullet("  Dogs: 100-300 mg/day PO divided doses", 1));
children.push(bullet("  Cats: 50-100 mg/day PO divided doses", 1));
children.push(bullet("  NOTE: Dose refers to ferrous sulfate SALT - not elemental iron", 1));
children.push(bullet("Reticulocytosis develops within 3-4 days of supplementation"));
children.push(bullet("PCV normalizes in 4-8 weeks"));

children.push(h3("5. Aplastic Anemia / PRCA Treatment"));
children.push(bullet("Immunosuppressive therapy: prednisolone + cyclosporine (or azathioprine - DOGS ONLY)"));
children.push(bullet("Supportive blood transfusions while waiting for bone marrow recovery"));
children.push(bullet("Remove causative drugs / toxins immediately"));
children.push(bullet("Treat underlying infection (FeLV, Ehrlichia)"));
children.push(bullet("G-CSF (granulocyte colony-stimulating factor) for severe neutropenia"));

children.push(h3("6. Rodenticide (Anticoagulant Rat Poison) Anemia"));
children.push(bullet("Vitamin K1 (phytomenadione) - TREATMENT OF CHOICE"));
children.push(bullet("  Dose: 2.5-5 mg/kg/day PO divided q12h", 1));
children.push(bullet("  Duration: 4-6 WEEKS for long-acting rodenticides (brodifacoum, bromadiolone)", 1));
children.push(bullet("  Do NOT stop early - PT/aPTT must normalize before discontinuing", 1));
children.push(bullet("Fresh frozen plasma or whole blood for life-threatening hemorrhage"));
children.push(bullet("Monitor PT/aPTT every 2-3 days"));

children.push(h3("7. Toxin-Induced (Onion/Zinc/Acetaminophen)"));
children.push(bullet("Remove source immediately"));
children.push(bullet("N-acetylcysteine (NAC) - especially for acetaminophen toxicity in cats (140 mg/kg IV loading dose then 70 mg/kg q6h)"));
children.push(bullet("Supportive care: IV fluids, oxygen"));
children.push(bullet("Blood transfusion if severe anemia"));
children.push(pageBreak());

// ── PART 9: MONITORING ────────────────────────────────────────────────────────
children.push(h1("PART 9: MONITORING AND FOLLOW-UP"));
children.push(makeTable(
  ["Phase", "When", "What to Monitor"],
  [
    ["Acute / Hospitalized", "Every 24-48 hours", "PCV, clinical signs, heart rate, respiratory rate"],
    ["IMHA - first month", "Weekly", "CBC, PCV, reticulocytes, bilirubin, autoagglutination"],
    ["IMHA - long term", "Monthly", "CBC while tapering steroids over 3-6 months"],
    ["ESA therapy (CKD)", "Weekly for first 4-8 weeks", "PCV, blood pressure (risk of hypertension), iron levels"],
    ["Iron deficiency", "Every 2-4 weeks", "PCV, reticulocyte count until normalized"],
  ]
));
children.push(...spacer());
children.push(boxedParagraph("IMPORTANT: Taper immunosuppressives SLOWLY over months. Rapid tapering causes relapse! Continue until PCV stable AND off steroids before stopping second-line drugs.", WARN_BG, RED));
children.push(pageBreak());

// ── PART 10: SPECIAL CONSIDERATIONS IN CATS ──────────────────────────────────
children.push(h1("PART 10: SPECIAL CONSIDERATIONS IN CATS"));
children.push(makeTable(
  ["Issue", "Key Point"],
  [
    ["Stoic nature", "Cats hide illness. By the time signs are noticed, anemia may be SEVERE."],
    ["FeLV / FIV testing", "MANDATORY in ALL anemic cats - always test both"],
    ["Mycoplasma haemofelis", "Major cause of regenerative anemia in cats - test with PCR"],
    ["Blood typing", "NON-NEGOTIABLE before transfusion. Type B cats die from mismatched Type A blood."],
    ["Azathioprine", "TOXIC IN CATS - NEVER USE. Can cause fatal bone marrow suppression."],
    ["Acetaminophen", "EXTREMELY TOXIC to cats. Even small doses can be fatal. Never give to cats."],
    ["Propylene glycol", "Found in some human foods/meds. Causes Heinz body anemia in cats."],
    ["Reticulocytes", "Count AGGREGATE reticulocytes only. Punctate reticulocytes are misleading."],
    ["Cardiomegaly", "Cats develop reversible cardiomegaly with chronic severe anemia - check heart."],
    ["Doxycycline", "Give with food + 5 mL water syringe - prevents esophageal stricture."],
  ]
));
children.push(pageBreak());

// ── PART 11: DECISION TREE ────────────────────────────────────────────────────
children.push(h1("PART 11: ANEMIA DIAGNOSTIC DECISION TREE"));
children.push(body("Follow this flowchart for every anemic patient:", { bold: true }));
children.push(...spacer());

const treeRows = [
  ["STEP 1", "Confirm anemia (PCV < 37% dogs, < 24% cats)"],
  ["STEP 2", "Is it REGENERATIVE or NON-REGENERATIVE? (Check absolute reticulocyte count)"],
  ["  REGENERATIVE →", "Check for signs of HEMOLYSIS (icterus, hemoglobinuria, spherocytes, agglutination)"],
  ["    YES - Hemolysis →", "Coombs test → IMHA? | Blood smear → Babesia / Mycoplasma? | History → Toxins?"],
  ["    NO - No Hemolysis →", "BLOOD LOSS - find source (external / GI / urinary / internal) + coagulation profile"],
  ["  NON-REGENERATIVE →", "Is it PANCYTOPENIA (all cell lines low)?"],
  ["    YES - Pancytopenia →", "Aplastic anemia, MDS, Leukemia → BONE MARROW BIOPSY REQUIRED"],
  ["    NO - Only RBCs low →", "Check: CKD? ACD? Iron deficiency (microcytic)? FeLV? Endocrine?"],
  ["    Still unclear →", "BONE MARROW BIOPSY"],
];
children.push(new Table({
  width: { size: 100, type: WidthType.PERCENTAGE },
  rows: treeRows.map((row, i) =>
    new TableRow({
      children: [
        new TableCell({
          shading: { type: ShadingType.CLEAR, color: i === 0 ? RED : LIGHT_BG, fill: i === 0 ? RED : LIGHT_BG },
          margins: { top: 60, bottom: 60, left: 100, right: 100 },
          children: [new Paragraph({ children: [new TextRun({ text: row[0], bold: true, color: i === 0 ? WHITE : DARK_BLUE, size: 18 })] })]
        }),
        new TableCell({
          shading: { type: ShadingType.CLEAR, color: i % 2 === 0 ? WHITE : "F2F9FC", fill: i % 2 === 0 ? WHITE : "F2F9FC" },
          margins: { top: 60, bottom: 60, left: 100, right: 100 },
          children: [new Paragraph({ children: [new TextRun({ text: row[1], size: 18, color: DARK })] })]
        }),
      ]
    })
  )
}));
children.push(pageBreak());

// ── PART 12: Q&A ──────────────────────────────────────────────────────────────
children.push(h1("PART 12: IMPORTANT EXAM & INTERVIEW QUESTIONS"));

const qanda = [
  {
    q: "Q1: What is anemia and is it a disease?",
    a: "Anemia is a reduction in circulating RBCs, hemoglobin, or PCV below normal reference values. It is NOT a disease - it is a clinical sign of an underlying disorder."
  },
  {
    q: "Q2: What is the normal PCV in dogs and cats?",
    a: "Dogs: 37-55%. Cats: 24-45%. Anemia is confirmed when PCV falls below these values."
  },
  {
    q: "Q3: What is the difference between regenerative and non-regenerative anemia?",
    a: "Regenerative = bone marrow actively responds by releasing new (immature) RBCs / reticulocytes into circulation. Causes: blood loss and hemolysis. Non-regenerative = bone marrow fails to respond adequately. Causes: CKD, ACD, aplastic anemia, iron deficiency (chronic), FeLV, drug toxicity. Assessed by absolute reticulocyte count: > 60,000/µL in dogs = regenerative; > 50,000/µL aggregate reticulocytes in cats = regenerative."
  },
  {
    q: "Q4: What is IMHA and how do you diagnose it?",
    a: "IMHA (Immune-Mediated Hemolytic Anemia) = the immune system produces antibodies against the animal's own RBCs, leading to their destruction. Diagnosis: documented anemia + evidence of hemolysis (jaundice, hemoglobinuria) + evidence of immune involvement (positive Coombs test, spherocytes on smear, autoagglutination) + exclusion of other causes."
  },
  {
    q: "Q5: What are spherocytes and what do they indicate?",
    a: "Spherocytes are small, dense, round RBCs that lack the normal central pallor. They form when antibody-coated RBCs lose membrane in the spleen but survive. Present in 85-95% of IMHA dogs. HALLMARK finding of IMHA. Hard to identify in cats because feline RBCs normally have little central pallor."
  },
  {
    q: "Q6: What causes Heinz body anemia in cats?",
    a: "Heinz bodies = clumps of denatured hemoglobin attached to inner RBC membrane, caused by oxidative stress. Cats are more susceptible than dogs because feline hemoglobin is more sensitive to oxidation. Common causes in cats: onion/garlic, acetaminophen (Tylenol), propylene glycol, zinc, benzocaine, methylene blue."
  },
  {
    q: "Q7: Why is blood typing critical before transfusion in cats?",
    a: "Cats have naturally occurring alloantibodies. Type B cats have STRONG anti-A antibodies. Giving Type A blood to a Type B cat = severe, potentially FATAL acute hemolytic transfusion reaction. ALWAYS blood type cats before every transfusion."
  },
  {
    q: "Q8: What is the mechanism of CKD anemia?",
    a: "The peritubular cells of the kidney are the main source of EPO (erythropoietin). In CKD, damaged kidneys produce less EPO → reduced bone marrow stimulation → fewer RBCs produced. Secondary contributors: uremic toxins suppressing marrow, iron deficiency (from GI blood loss), shortened RBC lifespan."
  },
  {
    q: "Q9: What is the treatment of choice for iron deficiency anemia?",
    a: "Eliminate source of blood loss first. Then ferrous sulfate: 100-300 mg/day dogs; 50-100 mg/day cats (dose = ferrous sulfate salt, not elemental iron). Reticulocytosis within 3-4 days. PCV normalizes in 4-8 weeks."
  },
  {
    q: "Q10: What drugs should NEVER be used in cats with anemia?",
    a: "(1) Azathioprine - fatal bone marrow suppression in cats. (2) Acetaminophen / Paracetamol - causes methemoglobinemia and Heinz body anemia, fatal even in small doses. (3) Propylene glycol (in some human foods)."
  },
  {
    q: "Q11: Give the transfusion volume formula.",
    a: "Dogs: Vol (mL) = BW (kg) × 90 × [(Target PCV - Patient PCV) / Donor PCV]. Cats: Vol (mL) = BW (kg) × 60 × [(Target PCV - Patient PCV) / Donor PCV]. Target post-transfusion PCV = 25-30% (do not exceed 30%)."
  },
  {
    q: "Q12: How do you distinguish autoagglutination from rouleaux?",
    a: "Mix 1 drop blood + 1 drop 0.9% saline on a slide. True autoagglutination (IMHA) = clumps PERSIST after saline dilution. Rouleaux (normal stacking) = DISPERSES with saline dilution."
  },
  {
    q: "Q13: What tick-borne disease causes hemolytic anemia in dogs and cats?",
    a: "Babesiosis (Babesia canis - dogs; Babesia felis - cats). Protozoan invades RBCs and causes hemolysis. Also: Mycoplasma haemofelis (cats), Ehrlichia canis (pancytopenia in dogs), Anaplasma platys (thrombocytopenia + anemia)."
  },
  {
    q: "Q14: What is the M:E ratio in bone marrow and what does an increased ratio mean?",
    a: "M:E = ratio of myeloid cells (WBC precursors) to erythroid cells (RBC precursors). Normal = 0.75:1 to 2.5:1. INCREASED M:E (e.g. 5:1) = erythroid hypoplasia (too few RBC precursors = non-regenerative cause). DECREASED M:E = erythroid hyperplasia (marrow working hard = responding to anemia)."
  },
  {
    q: "Q15: What is the difference between PRCA and aplastic anemia?",
    a: "PRCA (Pure Red Cell Aplasia) = ONLY erythroid line absent from bone marrow. WBCs and platelets normal. Aplastic anemia = ALL cell lines absent (RBCs + WBCs + platelets) - pancytopenia. PRCA in cats: always test for FeLV. Treatment for both: immunosuppression."
  },
  {
    q: "Q16: Name the compensatory mechanisms of anemia.",
    a: "(1) Tachycardia and increased cardiac output. (2) Tachypnea (increased respiratory rate). (3) Redistribution of blood to vital organs. (4) Increased 2,3-DPG in RBCs (right shift of oxygen-hemoglobin curve = better O2 delivery). (5) Increased EPO production by kidneys. (6) Increased erythropoiesis."
  },
  {
    q: "Q17: What is the difference between intravascular and extravascular hemolysis?",
    a: "Intravascular = RBCs destroyed INSIDE blood vessels → free hemoglobin in plasma (hemoglobinemia = pink plasma) + hemoglobinuria (red urine). Extravascular = RBCs destroyed by macrophages in spleen/liver → bilirubin produced → jaundice/icterus (no free plasma hemoglobin)."
  },
  {
    q: "Q18: How do you monitor IMHA therapy?",
    a: "Hospitalized: CBC every 24-48h. Watch: PCV trend (rising = good), autoagglutination (should resolve), bilirubin, urine color. D-dimer + coagulation for thromboembolism risk. Long-term: monthly CBC while tapering steroids over 3-6 months."
  },
  {
    q: "Q19: How is anemia of chronic disease different from iron deficiency anemia?",
    a: "Both have low serum iron. DIFFERENCE: ACD has HIGH ferritin + LOW TIBC (iron trapped in storage). Iron deficiency has LOW ferritin + HIGH TIBC (body starving for iron). ACD = normocytic normochromic. Iron deficiency = microcytic hypochromic."
  },
  {
    q: "Q20: What is the treatment for anemia from anticoagulant rodenticide poisoning?",
    a: "Vitamin K1 (phytomenadione): 2.5-5 mg/kg/day PO divided q12h for 4-6 WEEKS (long duration because long-acting rodenticides like brodifacoum last weeks). Fresh frozen plasma / whole blood for life-threatening hemorrhage. Monitor PT/aPTT before stopping Vitamin K1."
  },
];

qanda.forEach(({ q, a }) => {
  children.push(new Paragraph({
    spacing: { before: 160, after: 40 },
    children: [new TextRun({ text: q, bold: true, color: DARK_BLUE, size: 20 })]
  }));
  children.push(new Paragraph({
    spacing: { before: 40, after: 120 },
    indent: { left: 360 },
    children: [new TextRun({ text: a, color: DARK, size: 20 })]
  }));
});
children.push(pageBreak());

// ── PART 13: CASE STUDIES ─────────────────────────────────────────────────────
children.push(h1("PART 13: CLINICAL CASE STUDIES"));

// CASE 1
children.push(h2("CASE 1: Cocker Spaniel Dog - IMHA"));
children.push(boxedParagraph(
  "Signalment: 5-year-old spayed female Cocker Spaniel\nChief complaint: Extreme weakness for 2 days, not eating, white gums\nHistory: Routine vaccination 3 weeks ago. No toxin exposure. Indoor dog, no ticks visible.",
  NOTE_BG, TEAL
));
children.push(h4("Physical Examination Findings"));
children.push(makeTable(
  ["Parameter", "Finding", "Significance"],
  [
    ["Temperature", "39.5°C", "Mild fever - immune activation"],
    ["Heart rate", "160 bpm", "Tachycardia - compensating for low O2 delivery"],
    ["Respiratory rate", "40/min", "Tachypnea - compensating for low O2"],
    ["Mucous membranes", "Pale white + icteric (yellow)", "Severe anemia + hemolysis"],
    ["CRT", "2 seconds", "Borderline - poor perfusion"],
    ["Abdomen", "Mild splenomegaly", "Increased RBC destruction in spleen"],
  ]
));
children.push(h4("CBC Results"));
children.push(makeTable(
  ["Parameter", "Value", "Normal", "Interpretation"],
  [
    ["PCV", "13%", "37-55%", "SEVERE ANEMIA"],
    ["MCV", "82 fL", "60-77 fL", "Macrocytic (young RBCs released)"],
    ["Reticulocytes", "280,000/µL", "< 60,000", "STRONGLY REGENERATIVE"],
    ["WBC", "22,000/µL", "6,000-17,000", "Leukocytosis (inflammation)"],
    ["Platelets", "88,000/µL", "200,000-500,000", "Mild thrombocytopenia"],
    ["Bilirubin", "4.2 mg/dL", "< 0.5 mg/dL", "ELEVATED (hemolysis)"],
  ]
));
children.push(h4("Blood Smear Findings"));
children.push(bullet("Spherocytes +++  (small dense RBCs = HALLMARK of IMHA)"));
children.push(bullet("Polychromasia +++ (blue-tinged young RBCs = regenerative)"));
children.push(bullet("nRBCs present"));
children.push(bullet("Autoagglutination visible on slide"));

children.push(h4("Diagnostic Tests"));
children.push(bullet("Saline agglutination test: POSITIVE (clumps persist with saline)"));
children.push(bullet("Coombs test: POSITIVE (antibodies on RBC surface)"));

children.push(h4("DIAGNOSIS: Primary IMHA (Immune-Mediated Hemolytic Anemia)"));
children.push(body("Diagnostic reasoning: Regenerative anemia + spherocytes + positive Coombs + autoagglutination = CLASSIC IMHA. Breed predisposition (Cocker Spaniel). Possible trigger: recent vaccination 3 weeks prior. No evidence of toxin, external bleeding, or tick-borne disease."));

children.push(h4("Rule-Outs to Exclude Secondary Causes"));
children.push(bullet("Tick-borne panel (Ehrlichia, Anaplasma, Babesia) - send to lab"));
children.push(bullet("Abdominal ultrasound - rule out splenic neoplasia"));
children.push(bullet("Thoracic radiographs - rule out pulmonary metastases"));

children.push(h4("Complete Treatment Plan"));
children.push(bullet("1. HOSPITALIZE immediately (24-hour monitoring needed)", 0, true));
children.push(bullet("2. OXYGEN: Flow-by O2 at 2-3 L/min (PCV 13% = tissue hypoxia)", 0, true));
children.push(bullet("3. BLOOD TRANSFUSION:", 0, true));
children.push(bullet("  Blood type DEA 1.1, crossmatch with donor", 1));
children.push(bullet("  Packed RBCs preferred (less volume overload risk)", 1));
children.push(bullet("  25 kg dog, target PCV 25%, donor PCV 45%: Vol = 25×90×(25-13)/45 = 600 mL pRBCs over 4-6 hours", 1));
children.push(bullet("  Monitor for transfusion reactions every 15-30 min during administration", 1));
children.push(bullet("4. IMMUNOSUPPRESSION:", 0, true));
children.push(bullet("  Prednisolone 2 mg/kg/day PO divided q12h", 1));
children.push(bullet("  + Mycophenolate mofetil 10 mg/kg q12h PO (severe presentation with autoagglutination)", 1));
children.push(bullet("5. ANTI-THROMBOTICS (prevent pulmonary thromboembolism):", 0, true));
children.push(bullet("  Clopidogrel 1.1 mg/kg/day PO", 1));
children.push(bullet("  Dalteparin (LMWH) 100-150 IU/kg SC q8h", 1));
children.push(bullet("6. GASTROPROTECTION (prevent steroid ulcers):", 0, true));
children.push(bullet("  Omeprazole 0.7-1 mg/kg/day PO", 1));
children.push(bullet("  Sucralfate 0.5 g q8h PO", 1));
children.push(bullet("7. IV FLUIDS: Lactated Ringer's at maintenance rate for hydration", 0, true));
children.push(bullet("8. MONITORING:", 0, true));
children.push(bullet("  PCV every 12-24 hours for first 3 days", 1));
children.push(bullet("  Bilirubin, autoagglutination, urine color daily", 1));
children.push(bullet("  D-dimer and coagulation profile for thromboembolism assessment", 1));
children.push(bullet("  Temperature q8h", 1));

children.push(boxedParagraph(
  "PROGNOSIS: GUARDED. 50-70% survival with aggressive treatment. Multiple transfusions may be needed. Long-term prednisolone taper over 3-6 months with monthly CBC rechecks. Owner counseled about relapse risk (10-15%).",
  WARN_BG, RED
));

children.push(pageBreak());

// CASE 2
children.push(h2("CASE 2: Cat - Mycoplasma haemofelis + FIV"));
children.push(boxedParagraph(
  "Signalment: 4-year-old male neutered domestic shorthair cat\nChief complaint: Lethargy 1 week, poor appetite, hiding more than usual, pale yellowish gums\nHistory: Outdoor access (garden). No medications. No known toxin exposure.",
  NOTE_BG, TEAL
));
children.push(h4("Physical Examination Findings"));
children.push(makeTable(
  ["Parameter", "Finding", "Significance"],
  [
    ["Temperature", "40.1°C", "Fever - active infection / hemolysis"],
    ["Heart rate", "220 bpm", "Tachycardia (upper limit) - compensation"],
    ["Respiratory rate", "48/min", "Tachypnea - hypoxia"],
    ["Mucous membranes", "Pale + icteric (yellow)", "Severe anemia + hemolysis"],
    ["CRT", "2.5 seconds", "Slightly prolonged - poor perfusion"],
    ["Body condition", "Thin (BCS 3/9)", "Chronic illness"],
    ["Lymph nodes", "Mildly enlarged mandibular", "Immune response / infection"],
  ]
));
children.push(h4("CBC Results"));
children.push(makeTable(
  ["Parameter", "Value", "Normal", "Interpretation"],
  [
    ["PCV", "14%", "24-45%", "SEVERE ANEMIA"],
    ["MCV", "42 fL", "39-55 fL", "Normocytic (normal)"],
    ["Aggregate reticulocytes", "85,000/µL", "< 50,000", "REGENERATIVE"],
    ["WBC", "18,000/µL", "5,500-19,500", "Mild leukocytosis"],
    ["Platelets", "310,000/µL", "200,000-500,000", "Normal"],
    ["Bilirubin", "3.1 mg/dL", "< 0.4 mg/dL", "ELEVATED (hemolysis)"],
  ]
));
children.push(h4("Diagnostic Tests"));
children.push(bullet("Blood smear: RBC parasites visible as small ring/rod shapes on RBC surface in several cells"));
children.push(bullet("Saline agglutination test: NEGATIVE"));
children.push(bullet("Coombs test: WEAKLY POSITIVE (immune response triggered by organism-coated RBCs)"));
children.push(bullet("FeLV: NEGATIVE"));
children.push(bullet("FIV: POSITIVE"));
children.push(bullet("Mycoplasma haemofelis PCR: POSITIVE (CONFIRMS DIAGNOSIS)"));
children.push(bullet("BUN / Creatinine: Normal (rules out CKD)"));

children.push(h4("DIAGNOSIS: Hemolytic Anemia secondary to Mycoplasma haemofelis in an FIV-positive cat"));
children.push(body("Diagnostic reasoning: Regenerative anemia (aggregate reticulocytes 85,000/µL) + icterus + organisms on blood smear + positive Mycoplasma PCR confirms the cause. Outdoor cat with flea/tick exposure = explains transmission. FIV positive = immunocompromised → predisposed to opportunistic infections like Mycoplasma. Negative autoagglutination rules out primary IMHA. Normal creatinine rules out CKD. Normal platelets rules out DIC/tick thrombocytopenia."));

children.push(h4("Complete Treatment Plan"));
children.push(bullet("1. OXYGEN: Flow-by or nasal cannula (PCV 14%, tachypnea, tachycardia)", 0, true));
children.push(bullet("2. BLOOD TRANSFUSION (PCV 14% with clinical signs):", 0, true));
children.push(boxedParagraph("MANDATORY: Blood type the cat FIRST (Type A, B, or AB) before any transfusion!", WARN_BG, RED));
children.push(bullet("  Packed RBCs or whole blood from typed / crossmatched feline donor", 1));
children.push(bullet("  3 kg cat, target PCV 20%, donor PCV 45%: Vol = 3×60×(20-14)/45 ≈ 24 mL pRBCs over 3-4 hours slowly", 1));
children.push(bullet("  Monitor temperature, respiratory rate, heart rate, urine color every 15 minutes during transfusion", 1));
children.push(bullet("3. ANTIBIOTIC THERAPY - DRUG OF CHOICE for Mycoplasma haemofelis:", 0, true));
children.push(bullet("  Doxycycline 5 mg/kg PO q12h × 28 days minimum", 1));
children.push(boxedParagraph("Give doxycycline WITH food + syringe 5 mL water after EVERY dose. NEVER give dry - causes esophageal stricture in cats!", WARN_BG, RED));
children.push(bullet("  Alternative: Marbofloxacin 2 mg/kg/day PO × 28 days", 1));
children.push(bullet("4. PREDNISOLONE 1 mg/kg/day PO:", 0, true));
children.push(bullet("  Weakly positive Coombs suggests immune-mediated component triggered by organism-coated RBCs", 1));
children.push(bullet("  Low-dose prednisolone to suppress secondary immune destruction", 1));
children.push(bullet("5. SUPPORTIVE CARE:", 0, true));
children.push(bullet("  IV fluids: Lactated Ringer's at maintenance rate", 1));
children.push(bullet("  Maropitant 1 mg/kg SC q24h (anti-nausea)", 1));
children.push(bullet("  Mirtazapine 1.88 mg/cat PO q72h (appetite stimulant - anorexic cat)", 1));
children.push(bullet("  B-vitamin supplementation (anorexic cats deplete B vitamins)", 1));
children.push(bullet("6. FIV MANAGEMENT:", 0, true));
children.push(bullet("  FIV cannot be cured - manage secondary infections", 1));
children.push(bullet("  Antioxidant support (Vitamin C, E supplementation)", 1));
children.push(bullet("  Regular monitoring every 3 months", 1));
children.push(bullet("7. FLEA & TICK CONTROL (PREVENT REINFECTION):", 0, true));
children.push(bullet("  Start monthly flea/tick preventative (Revolution/selamectin, Bravecto for cats)", 1));
children.push(bullet("  Treat all household pets", 1));
children.push(bullet("8. MONITORING:", 0, true));
children.push(bullet("  PCV every 48 hours initially, then weekly", 1));
children.push(bullet("  Repeat Mycoplasma PCR at end of treatment (28 days)", 1));
children.push(bullet("  CBC monthly for 3 months", 1));
children.push(bullet("  FIV monitoring every 3-6 months", 1));
children.push(bullet("  Blood pressure monitoring (ESA therapy later if CKD develops)", 1));

children.push(boxedParagraph(
  "PROGNOSIS:\n- Mycoplasma haemofelis: GOOD with treatment. Most cats respond within 2-4 weeks.\n- FIV cats do NOT clear Mycoplasma - they become CARRIERS. Relapse possible under stress or immunosuppression.\n- Owner advice: Supervise outdoor access or keep indoors to prevent reinfection and stop transmission to other cats.\n- FIV prognosis: Variable - can have good quality of life for years with proper management.",
  NOTE_BG, TEAL
));
children.push(pageBreak());

// ── QUICK REFERENCE TABLE ─────────────────────────────────────────────────────
children.push(h1("QUICK REFERENCE SUMMARY TABLE"));
children.push(makeTable(
  ["Type of Anemia", "Key Diagnostic Feature", "Primary Treatment"],
  [
    ["IMHA (dogs)", "Spherocytes + positive Coombs + autoagglutination", "Prednisolone + mycophenolate + antithrombotics (clopidogrel + heparin)"],
    ["Mycoplasma haemofelis (cats)", "Organisms on blood smear + PCR positive", "Doxycycline 5 mg/kg q12h × 28 days"],
    ["Babesiosis", "Intraerythrocytic protozoa on smear + PCR", "Imidocarb dipropionate IM"],
    ["Iron deficiency", "Microcytic hypochromic + low ferritin + low serum iron", "Find & stop bleeding source + ferrous sulfate"],
    ["CKD anemia", "Non-regenerative + elevated creatinine + no other cause", "Darbepoetin / Molidustat + iron supplementation"],
    ["ACD (Chronic disease)", "Non-regenerative + high ferritin + chronic illness", "Treat primary disease"],
    ["Aplastic anemia", "PANCYTOPENIA + hypoplastic marrow (biopsy)", "Immunosuppression + transfusion support"],
    ["PRCA", "Non-regenerative + absent erythroid precursors (biopsy)", "Immunosuppression (test cats for FeLV!)"],
    ["Rodenticide poisoning", "Prolonged PT/aPTT + bleeding history", "Vitamin K1 × 4-6 weeks"],
    ["Heinz body anemia (cats)", "Heinz bodies on smear + toxin history", "Remove toxin + N-acetylcysteine + supportive care"],
  ]
));

children.push(...spacer(2));
children.push(new Paragraph({
  alignment: AlignmentType.CENTER,
  children: [new TextRun({ text: "── END OF GUIDE ──", color: RED, bold: true, size: 24 })]
}));
children.push(new Paragraph({
  alignment: AlignmentType.CENTER,
  children: [new TextRun({ text: "Sources: Merck Veterinary Manual | ACVIM Consensus 2019 (PMID 30806491, 30847984) | DVM360 | Compendium of Continuing Education for Veterinarians | IDEXX | IVC Journal", color: "888888", size: 16 })]
}));

// ════════════════════════════════════════════════════════════════════════════
//  BUILD DOCUMENT
// ════════════════════════════════════════════════════════════════════════════
const doc = new Document({
  numbering: {
    config: [{
      reference: "numbering",
      levels: [{
        level: 0,
        format: LevelFormat.DECIMAL,
        text: "%1.",
        alignment: AlignmentType.LEFT,
        style: { paragraph: { indent: { left: 360, hanging: 360 } } }
      }]
    }]
  },
  styles: {
    default: {
      document: {
        run: { font: "Calibri", size: 20, color: DARK }
      }
    }
  },
  sections: [{
    properties: {
      page: {
        margin: { top: 1080, bottom: 1080, left: 1080, right: 1080 }
      }
    },
    headers: {
      default: new Header({
        children: [new Paragraph({
          border: { bottom: { style: BorderStyle.SINGLE, size: 4, color: RED } },
          children: [
            new TextRun({ text: "ANEMIA IN COMPANION ANIMALS", bold: true, color: RED, size: 18 }),
            new TextRun({ text: "  |  Veterinary Study Guide", color: "888888", size: 16 }),
          ]
        })]
      })
    },
    footers: {
      default: new Footer({
        children: [new Paragraph({
          alignment: AlignmentType.CENTER,
          border: { top: { style: BorderStyle.SINGLE, size: 4, color: LIGHT_BG } },
          children: [
            new TextRun({ text: "Page ", color: "888888", size: 16 }),
            new PageNumber({ type: "current" }),
            new TextRun({ text: "  |  For Educational Use", color: "888888", size: 16 }),
          ]
        })]
      })
    },
    children
  }]
});

Packer.toBuffer(doc).then(buffer => {
  fs.writeFileSync("/home/daytona/workspace/anemia-guide/Veterinary_Anemia_Guide.docx", buffer);
  console.log("SUCCESS: Document created at /home/daytona/workspace/anemia-guide/Veterinary_Anemia_Guide.docx");
}).catch(err => {
  console.error("ERROR:", err.message);
  process.exit(1);
});

Error: String not found in file: '        HeadingLevel, AlignmentType, PageOrientation, LevelFormat, ExternalHyperlink,
        InternalHyperlink, Bookmark, FootnoteReferenceRun, PositionalTab,
        PositionalTabAlignment, PositionalTabRelativeTo, PositionalTabLeader,
        TabStopType, TabStopPosition, Column, SectionType,
        TableOfContents, HeadingLevel, BorderStyle, WidthType, ShadingType,
        VerticalAlign, PageNumber, PageBreak } = require('docx');'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/anemia-guide/create_anemia_doc.js'

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/anemia-guide/create_anemia_doc.js'