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Case DT:
“I’m turning yellow…”
October 8, 2015
Neha Mehta-Shah
Fellow, Department of Medicine
Memorial Sloan Kettering Can...
Case DT
CC: Anemia
• 59 yo with recently diagnosed uterine serous cancer s/p robotically assisted
TAH/BSO, sentinel LN map...
Case DT
PMH:
- Breast Cancer (stage II,T1cN1Mx ER+,
PR+, Her2 Neg; 2007;CMF completed
tamoxifenletrozole 2013),
- uterine...
Laboratory Evaluation
9.7
6.5 292
28.5
140 101 15
3.9 28 1.16
11.9 at discharge (POD2)
7.9
5.3 272
23.2
POD 13
POD 14 Hapt...
Laboratory Evaluation
9.7
6.5 292
28.5
140 101 15
3.9 28 1.16
11.9 at discharge (POD2)
7.9
5.3 272
23.2
POD 13
POD 14 Hapt...
Diagnosis?
What was the culprit?
Drug Induced Hemolytic Anemia
• First described in 1950s
• Incidence: 1/1,000,000
– Drug induced neutropenia: 2-15/1,000,0...
Drug Induce Hemolytic Anemia
Garraty G, Drug Induced Hemolytic Anemia. Hematology 2009
Evaluation
• Must show:
– Antibodies that reaction ONLY in presence of drug
• CoombsTest
CoombsTest
"Coombs test schematic” https://commons.wikimedia.org/wiki/
Evaluation
• Must show:
– Antibodies that reaction ONLY in presence of drug
CoombsTest Positive
Eluate
• RBCs washed of un...
Evaluation
Pierce and Nester Am J Clin Pathol 2011
Mechanism
https://www.med-ed.virginia.edu/courses/path/innes/rcd/antibody.cfm/
Hapten Mechanism
• Drug binds covalently to proteins on RBC
membrane
• Antibody binds to drug-RBC membrane
complex
• Examp...
Immune Complexes Mechanism
• Drug and carrier protein epitope form complex
• Complex then attaches to RBC membrane and
lea...
Autoantibody Mechanism
• Drug induces warm autoimmune hemolytic
anemia
• Antibodies persist 2/2 uninhibited B-cell
antibod...
Nonimmune Mechanism
• Drug modifies RBC membrane
• Drug binds nonimmunologically to RBC
membrane
• Examples:
– Cefotetan
–...
Cefotetan Induced Hemolytic Anemia
• 1985-1997: 85 cases of cefotetan induced hemolytic anemia
– 15/85 (18%) fatalities
– ...
Management
• Withhold drug
• Tends to be self limited
• Steroids have limited utility
• Support with transfusions
What Drugs Should I Avoid?
Our patient, DT
• DAT with polyspecific 3+, IgG 2+, C3 2+
• Initial eluate was negative
• Sent to NY Blood bank and perfor...
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Drug induced hemolytic anemia cc 10 8-15 - dr mehta-shah

Drug induced hemolytic anemia cc 10 8-15 - dr mehta-shah

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Drug induced hemolytic anemia cc 10 8-15 - dr mehta-shah

  1. 1. Case DT: “I’m turning yellow…” October 8, 2015 Neha Mehta-Shah Fellow, Department of Medicine Memorial Sloan Kettering Cancer Center
  2. 2. Case DT CC: Anemia • 59 yo with recently diagnosed uterine serous cancer s/p robotically assisted TAH/BSO, sentinel LN mapping and omental biopsy (POD 14) • POD #2: discharged • POD #10: notes dark urine and yellowing of her eyes
  3. 3. Case DT PMH: - Breast Cancer (stage II,T1cN1Mx ER+, PR+, Her2 Neg; 2007;CMF completed tamoxifenletrozole 2013), - uterine CA PSH: Bilateral Mastectomy with Reconstruction (9/2007), bunionectomy, ORIF Medications: Lexapro 10mg, oxycodone acetaminophen 5/325mg prn All: NKDA Social History: never smoker, social EtOH, denies ilicits, lives inWestchester FH: father (MI), paternal GM (kidney Ca in 90s), Mat Gm (LungCa 80s) PHYSICAL EXAM - General: well developed, well nourished, KPS 90% - HEENT: +scleral and sublingual icterus - CV: RRR normal S1S2 no m/r/g - Chest:CTAB no r/r/w - Abd: well healing abdominal laparoscopic incision sites, soft NT, ND +BS, no HSM - Extremities: no c/c/e
  4. 4. Laboratory Evaluation 9.7 6.5 292 28.5 140 101 15 3.9 28 1.16 11.9 at discharge (POD2) 7.9 5.3 272 23.2 POD 13 POD 14 Haptoglobin <1 LDH 388 Retic count 6.0% (Abs 145.4) AST 58 ALT 133 ALK Phos 166 T Bili 10.4 Conj Bili 0.6 (6%) LDH 388
  5. 5. Laboratory Evaluation 9.7 6.5 292 28.5 140 101 15 3.9 28 1.16 11.9 at discharge (POD2) 7.9 5.3 272 23.2 POD 13 POD 14 Haptoglobin <1 LDH 508 Retic count 6.0% (Abs 145.4) Peripheral smear with spherocytes AST 58 ALT 133 ALK Phos 166 T Bili 10.4 Conj Bili 0.6 (6%) LDH 388
  6. 6. Diagnosis?
  7. 7. What was the culprit?
  8. 8. Drug Induced Hemolytic Anemia • First described in 1950s • Incidence: 1/1,000,000 – Drug induced neutropenia: 2-15/1,000,000 – Drug induced thrombocytopenia: 10-18/1,000,000
  9. 9. Drug Induce Hemolytic Anemia Garraty G, Drug Induced Hemolytic Anemia. Hematology 2009
  10. 10. Evaluation • Must show: – Antibodies that reaction ONLY in presence of drug • CoombsTest
  11. 11. CoombsTest "Coombs test schematic” https://commons.wikimedia.org/wiki/
  12. 12. Evaluation • Must show: – Antibodies that reaction ONLY in presence of drug CoombsTest Positive Eluate • RBCs washed of unbound antibody • Bound antibodies stripped from RBCs (via acid) • Resultant fluid = Eluate (contains antibodies from the RBCs) • Eluate then tested against reagent RBCs In drug induced hemolysis, eluant analysis is negative or weakly positive.
  13. 13. Evaluation Pierce and Nester Am J Clin Pathol 2011
  14. 14. Mechanism https://www.med-ed.virginia.edu/courses/path/innes/rcd/antibody.cfm/
  15. 15. Hapten Mechanism • Drug binds covalently to proteins on RBC membrane • Antibody binds to drug-RBC membrane complex • Examples: – Penicillin – Cefotetan • If high drug concentrations, RBCs can be coated with drug and lead to Fc-mediated destruction
  16. 16. Immune Complexes Mechanism • Drug and carrier protein epitope form complex • Complex then attaches to RBC membrane and leads to complement mediated destruction • Examples: – Quinidine
  17. 17. Autoantibody Mechanism • Drug induces warm autoimmune hemolytic anemia • Antibodies persist 2/2 uninhibited B-cell antibody production • Examples: – Methyldopa
  18. 18. Nonimmune Mechanism • Drug modifies RBC membrane • Drug binds nonimmunologically to RBC membrane • Examples: – Cefotetan – Cephaolthin – Cisplatin/oxaliplatin/carboplatin – Diglycoaldehyde – Suramin – Sulbactam – Clavulonate – Tazobactam
  19. 19. Cefotetan Induced Hemolytic Anemia • 1985-1997: 85 cases of cefotetan induced hemolytic anemia – 15/85 (18%) fatalities – Mean fall in Hgb 6.7 g/dL • As high as 1.4%of cefotetan exposures • Acute reaction can occur 7-21 days asfter exposure • Cefotetan bound antibodies can be seen up to 98 days post drug exposure • Can be mistaken for transfusion reactions in perioperative setting Viraghavan et al. Adv Drug ReactToxicol Re 2002 Davenport et alTransfusion 2004 Martin and Laber Am J Hematology 2006
  20. 20. Management • Withhold drug • Tends to be self limited • Steroids have limited utility • Support with transfusions
  21. 21. What Drugs Should I Avoid?
  22. 22. Our patient, DT • DAT with polyspecific 3+, IgG 2+, C3 2+ • Initial eluate was negative • Sent to NY Blood bank and performed testing with cefotetan and was positive • Required 1-2 transfusions per day for 48 hours • Discharged 4 days after admission • Repeat labs 2 weeks after discharge – Hgb 13.0, LDH 271, Haptoglobin 32 – Direct cooombs: positive weak

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