GS2 – Day Three: Tutorials

April 25, 2025 Daily

Tutorial note on blood transfusion and chemotherapy

Day Three

1. Complications of Blood Transfusion

A. Classification

  • Air embolism
  • Infection (viral, bacterial)
  • Phlebitis / extravasation
  • Allergic reactions: urticaria → anaphylaxis (IgE-mediated against donor plasma proteins)
  • Acute hemolytic transfusion reaction (AHTR): ABO incompatibility → fever, flank pain, hypotension, DIC, acute renal failure
  • Febrile non-hemolytic transfusion reaction (FNHTR): cytokines or recipient anti-leukocyte antibodies → fever, chills
  • Transfusion-related acute lung injury (TRALI): donor anti-leukocyte Abs → neutrophil-mediated pulmonary capillary leak → non-cardiogenic pulmonary edema
  • Transfusion-associated circulatory overload (TACO): volume overload → hypertension, crackles, pulmonary edema
  • Delayed hemolytic reaction: secondary recipient Abs → jaundice, anemia (days–weeks later)
  • Graft-versus-host disease (GVHD): viable donor lymphocytes engraft → rash, marrow aplasia, transaminitis

B. Massive Transfusion-specific Complications

Defined as:

  • 10 units in 24 hours

  • 50% blood volume in 1 hour

  • Total blood volume in <48 hours
  • Citrate toxicity → hypocalcemia → hypotension, prolonged QT, tetany
  • Dilutional coagulopathy
  • Hypothermia (cold stored units)
  • Hyperkalemia
  • Metabolic acidosis (lactic acid production + excess citrate from ACD)

2. Storage Anticoagulants & Shelf Life

Anticoagulant Composition Storage duration
ACD Citrate, dextrose 21 days
CPD Citrate, phosphate, dextrose 21 days
CPDA-1 CPD + adenine 35 days
SAGM Saline, adenine, glucose, mannitol 42 days

3. Citrate Toxicity & Calcium

  • Mechanism: Citrate chelates ionized Ca²⁺ → ↓ myocardial contractility, arrhythmia risk
  • Systole: ↓ inotropy due to hypocalcemia
  • Diastole: Rebound hypercalcemia (as citrate metabolizes)
  • Correction: 1g IV calcium gluconate per 1L blood transfused

4. Transfusion Protocol

Pre-transfusion

  • Confirm indication (Hb threshold, bleeding, instability)
  • Group & cross-match; verify unit ID, expiry, identities
  • Establish IV access, record baseline vitals

During transfusion

  • Warm blood to prevent hypothermia
  • Infuse slowly for first 15 min; monitor closely

If reaction occurs:

  1. Stop transfusion
  2. Start new IV line with 1L NS
  3. High-flow O₂
  4. IV hydrocortisone ± antihistamine
  5. Send patient & donor blood for:
    • Coombs test
    • Cultures

Post-transfusion

  • Monitor vitals: every 30 min initially, then hourly × 4 h
  • Consider furosemide (elderly, whole-blood), though not routinely done in our center

5. Clinical Case Vignettes

  • Case 1 (TACO): 68 y/o CHF patient → 4 PRBCs → dyspnea, crackles, HTN → treated with diuretics
  • Case 2 (FNHTR): 25 y/o multiparous woman → fever + chills 30 min post-transfusion → blood culture (-)
  • Case 3 (Citrate toxicity): 55 y/o trauma patient on massive transfusion → tetany, prolonged QT → IV calcium gluconate
  • Case 4 (TRALI): 40 y/o leukemia patient → acute hypoxemia 2 h post-transfusion, BNP normal → bilateral infiltrates
  • Case 5 (Delayed hemolytic): 30 y/o SCD patient → 3 weeks post-transfusion → jaundice, low Hb, ↑ LDH → positive DAT

6. Blood Donation Criteria

General

  • Age: 18–65 years
  • Weight: ≥ 50 kg
  • No donation in past 3 months
  • No transfusion in past 6 months
  • Not pregnant or <6 weeks postpartum

Risk Exclusion

  • High-risk behavior: tattoos, sex work, long-distance drivers
  • No chronic infections or uncontrolled diseases (e.g., HIV, hepatitis, uncontrolled DM/HTN)

7. Cancer & Chemotherapy Fundamentals

A. Overview

  • Cancer: clonal proliferation of malignant cells with local invasion and metastasis
  • Multimodal therapy: surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy
  • Managed by: multidisciplinary team (MDT)

Chemotherapy = 1 of 3 main pillars (with surgery and radiotherapy)

B. Cell-Cycle Phases & Chemo Targets

Phase Description Chemo Targets & Examples
G0 (Quiescent) Resting phase Evades chemotherapy
G1 (Presynthetic) Cell growth CDK inhibitors (Palbociclib), hormonal agents
S (Synthesis) DNA replication Antimetabolites (Methotrexate, 5-FU, Cytarabine)
G2 (Premitotic) DNA repair Bleomycin, Etoposide
M (Mitosis) Cell division Mitotic inhibitors (Vincristine, Paclitaxel)

C. Classification by Timing

  • Neoadjuvant: Before surgery; shrinks tumor, stages disease, checks chemo response

    • Disadvantage: Cancer may progress if unresponsive

  • Adjuvant: After surgery; eradicates micrometastases

D. Classification by Mechanism

  • Cell-cycle specific:

    • Antimetabolites
    • Vinca alkaloids
    • Taxanes

  • Cell-cycle nonspecific:

    • Alkylating agents (Cyclophosphamide, Chlorambucil)
    • Cytotoxic antibiotics (Doxorubicin)
    • Mnemonic: CAN
      • C = Chlorambucil
      • A = Cytotoxic Antibiotics
      • N = [Unspecified]

  • Targeted/Hormonal agents:

    • Tamoxifen
    • Aromatase inhibitors
    • Imatinib
    • Finasteride

  • Immunomodulators:

    • Checkpoint inhibitors
    • Levamisole (colon cancer adjuvant)

E. Chemotherapy Logistics

  • Cycles: Usually every 21 days; 6–8 cycles typical
  • Pre-infusion:
    • H₂-blocker (Ranitidine)
    • Antiemetic (Ondansetron)
  • Delivery: Central line preferred; 2 h infusion
  • Post-infusion: Monitor 2–3 h, then follow up for delayed toxicity

F. Clinical Case Vignettes (Oncology)

  1. Case 6:
    52-year-old woman with stage II breast cancer → neoadjuvant AC-T (doxorubicin + cyclophosphamide × 4 cycles, then paclitaxel) → 40% tumor reduction → lumpectomy performed.

  2. Case 7:
    65-year-old man with prostate cancer on LHRH agonist → develops hot flushes and osteoporosis risk → add bisphosphonate prophylaxis.

  3. Case 8:
    45-year-old woman, colon cancer adjuvant FOLFOX → on day 4 develops Grade 3 diarrhea → managed with loperamide + 20% dose reduction.

  4. Case 9:
    28-year-old Hodgkin lymphoma on ABVD → 6 months later CT shows pulmonary fibrosis → discontinue bleomycin + start pulmonary rehab.

  5. Case 10:
    38-year-old patient on high-dose cyclophosphamide → develops hemorrhagic cystitis → instituted MESNA + vigorous hydration prophylaxis.

Classification of Chemotherapy Based on Mechanism of Action

1. Cell-Cycle Specific Agents

Class Phase Targeted Mechanism Examples
Antimetabolites S Inhibit DNA synthesis Methotrexate, 5-FU, Cytarabine, 6-Mercaptopurine
Vinca Alkaloids M Inhibit microtubule polymerization Vincristine, Vinblastine
Taxanes M Stabilize microtubules, prevent disassembly Paclitaxel, Docetaxel
Topoisomerase Inhibitors S & G2 Inhibit topoisomerase I/II Irinotecan (Topo I), Etoposide (Topo II)

2. Non-Cell-Cycle Specific Agents

Class Mechanism Examples
Alkylating Agents Cross-link DNA Cyclophosphamide, Chlorambucil, Ifosfamide
Cytotoxic Antibiotics Intercalate DNA, free radicals, inhibit topo Doxorubicin, Daunorubicin, Bleomycin
Platinum Compounds DNA cross-links Cisplatin, Carboplatin

3. Hormonal Agents

Class Mechanism Examples
Anti-estrogens Estrogen receptor antagonists Tamoxifen, Fulvestrant
Aromatase Inhibitors Block peripheral estrogen synthesis Anastrozole, Letrozole
Anti-androgens Androgen receptor blockers Flutamide, Bicalutamide
5-α Reductase Inhibitors Inhibit T → DHT conversion Finasteride, Dutasteride

4. Immunomodulators

Agent Use
Levamisole Adjuvant with 5-FU in colon cancer
Thalidomide/Lenalidomide Multiple myeloma

Triple Assessment in Cancer Diagnosis

  1. History & Physical Exam
  2. Imaging (e.g., mammogram, CT, MRI, PET)
  3. Tissue Diagnosis (FNAC, core biopsy, excisional biopsy)

Aim: confirm diagnosis → assess spread → stage with TNM.

Chemotherapy Protocol

  • Cycles: typically every 21 days (6–8 cycles)
  • Pre-infusion: H₂-blocker (ranitidine), antiemetic (ondansetron)
  • Delivery: central line preferred; infuse over ~2 hours
  • Monitoring: observe 2–3 hours post-infusion, then routine follow-up for delayed toxicity

Side Effects of Chemotherapy

  • GIT: diarrhea, mucositis → give H₂ blockers
  • Alopecia: hair loss
  • Skin/Nail: hyperpigmentation, melanonychia
  • Pulmonary: fibrosis (e.g., bleomycin)
  • Bladder: hemorrhagic cystitis (cyclophosphamide; prevent with MESNA)
  • Cardiac: cardiomyopathy (doxorubicin)
  • Neurologic: central neurotoxicity, cerebral edema
  • Emesis: nausea/vomiting → antiemetics (ondansetron)

Patient Counseling

  • Explain diagnosis, stage, and treatment plan
  • Discuss prognosis and expected side effects
  • Address fertility, psychosocial support, and long-term follow-up
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