Putting the Pieces Together. Anne Longtine MD Internal Medicine Residency, Maine Medical Center Maine ACP Annual Meeting Clinical Vignette 9/16/2017
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1 Putting the Pieces Together Anne Longtine MD Internal Medicine Residency, Maine Medical Center Maine ACP Annual Meeting Clinical Vignette 9/16/2017
2 One Week Ago: Outpatient Clinic 64 y/o female presenting for routine follow up CAD HTN COPD Chronic fatigue URI sx Lower extremity edema and cramping Labs are ordered
3 Outpatient Labs Urinalysis Neg. Protein 500 LE 1-3 erythrocytes 100 Leukocytes 4+ bacteria Rare renal epithelial cells Bilirubin 2.9 Alk Phos 155 AST 38 ALT MCV Previous creatinine 0.8
4 To the Emergency Department Possible UTI PCP prescribes Trimethoprim- Sulfamethoxazole Blood transfusion x 1 Discharged home Outpatient work up
5 One Week Later: Outpatient Follow microcytes 2 + macrocytes 1+ ovalocytes 2+ polychromsia 1+ hypochromasia 1+ schistocytes 1+ acanthocytes 1+ echinocytes 1+ spherocytes Up Bilirubin 1.8 Alk Phos 159 AST 53 ALT
6 Direct Admission: HPI Fatigue Chronic but now progressive Dyspnea on exertion Worse over weeks No lightheadedness or syncope No chest pain No orthopnea 1 mo diarrhea No black/bloody stools No bloody emesis, other bleeding 10 lb wt loss over 6 months Recent URI, no fevers
7 Past Medical History Medical Hx: CAD: RCA, LAD stents 5 yrs ago COPD HTN Family Hx: Mother: CAD, CKD, Ovarian Cancer Father: Dementia Social Hx: Former smoker 40 pack years No EtOH, other drugs Single mother of disabled grown son Medications Amlodipine Losartan Metoprolol Asa Sertraline Albuterol Sulfamethoxazole- Trimethoprim: completed
8 Direct Admission: Exam 107/ % Room Air General: A&Ox3, ill but no acute distress HEENT: Scleral icterus, dry mucous membranes Neck: full rom, no LAD, thyromegaly or masses CV: RRR, No m/r/g, 2+ pulses, no JVD Chest: clear Abdomen: mild distention, non-tender,?splenomegaly Neuro: nl Skin: no rashes, petechiae, or jaundice
9 Admission Labs LDH 713 (high) Coombs negative Reticulocytes 486 Index 5.15 GGT 107 (high) Clear chest xray Haptoglobin, B12, and folate pending
10 Summary 64 year old female presenting with progressive anemia Coombs negative Elevated reticulocytes Smear as discussed
11
12 Microangiopathic Hemolytic Anemia: Differential Diagnosis TMA Thrombotic Thrombocytopenic Purpura Hemolytic Uremic Syndrome Complement Mediated HUS DIC HELLP +/- Other Malignant Hypertension Foreign Bodies Vasculitis Drug Induced Scleroderma Cancer Related
13 Most Urgent Diagnosis Thrombotic Thrombocytopenic Purpura Urgent hematology consult Consider plasma exchange
14 Hematology Consult TTP less likely Normal platelets Hold plasma exchange ADAMTS13? Splenomegaly Ultrasound Normal spleen and kidneys Concern for liver metastases
15 Morning Following Admission Multiple liver mets CT Chest Abdomen Pelvis Pancreatic head mass Multiple lung nodules 1 2.2x1.5 cm AKI is resolved
16 Liver Biopsy
17 Liver Biopsy The histologic sections show an atypical glandular proliferation eliciting a strong desmoplastic stromal reaction The immunomorphologic features are consistent with adenocarcinoma showing intestinal differentiation; however, they do not pinpoint to a definitive, specific point of origin. The differential diagnosis includes the gastrointestinal tract (including pancreaticobiliary tract) ; however other primary sources, as lung cannot be entirely ruled out
18 Final Diagnosis Microangiopathic hemolytic anemia as the presenting symptom of metastatic pancreatic adenocarcinoma
19 Comments?
20 Case Discussion
21 Learning Objectives Discuss the prevalence of CR-MAHA Distinguish CR-MAHA from other etiologies Consider the pathogenesis of CR-MAHA Understand the treatment and prognosis
22 Epidemiology Gastric>breast>prostate>abdominal Metastatic cancer with bone marrow infiltration In patients with TTP/HUS-like presentation 3-7% 2046 metastatic breast cancer patients 0%
23 CR-MAHA vs. Other Cancer symptoms Weight loss, elevated alk phos Bone pain Not responding to plasma exchange Vs. TTP or HUS May not have low platelets ADAMTS13 nl Less renal, neurologic symptoms Possibly more pulmonary symptoms
24 Pathogenesis Not autoimmune Lack of response to plasmapheresis Tumor microemboli Endothelial injury and associated microthrombi Platelet consumption Chronic DIC Unclear why it only happens in some widely metastatic cancers
25 But why weren t the platelets low? Best explanation Previous platelets: 270 Platelets on admission: 188 On discharge: 27 MAHA TMA Tumor Microemboli Platelets Platelets
26 Treatment Plasmapheresis rarely effective 14 vs. 86% Chemotherapy helps Cancer-Related Microangiopathic Hemolytic Anemia: Clinical and Laboratory Features in 168 Reported Cases. Lechner, Klaus; Obermeier, Hanna Medicine. 91(4): , July DOI: /MD.0b013e
27 Prognosis 30 day mortality vs. TTP: 71% vs. 14% Chemo vs. Other Cancer-Related Microangiopathic Hemolytic Anemia: Clinical and Laboratory Features in 168 Reported Cases. Lechner, Klaus; Obermeier, Hanna Medicine. 91(4): , July DOI: /MD.0b013e
28 Clinical Course Options discussed with patient Hospice vs. palliative chemotherapy Patient becomes DNR Chooses to attempt palliative chemotherapy Gemcitabine selected Abraxane considered but held due to transaminases
29 Clinical Course Gemcitabine initiated hospital day 10 No response to chemotherapy Increasing transfusion requirements One week later Patient elects home hospice Dies at home soon after
30 Summary Consider malignancy in the differential for MAHA Prognosis is poor in the setting of metastatic cancer Plasmapheresis is ineffective but chemotherapy may be beneficial
31 Thanks Dr. Stephen Hayes Dr. Christian Thomas Warene Eldridge
32 References Humphreys, B. D., Sharman, J. P., Henderson, J. M., Clark, J. W., Marks, P. W., Rennke, H. G., Zhu, A. X. and Magee, C. C. (2004), Gemcitabineassociated thrombotic microangiopathy. Cancer, 100: doi: /cncr JN, G. (2011). Systemic Malignancies as a cause of unexpected microangiopathic hemolytic anemia and thrombocytopenia. Oncology, Lechner, K. M., & Obermeier, H. L. (2012). Cancer-Related Microangiopathic Hemolytic Anemia: Clinical and Laboratory Features in 168 Reported Cases. Medicine, MA, E., L, L., DA, G., JL, W., RK, P., & JA, H. (2010). Cancer-associated microangiopathic hemolytic anemia with thrombocytopenia: an important diagnostic consideration. Eur J Haematology, Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, Lichinitser M, Fujiwara Y, Yardley DA, Viniegra M, Fan M, Jiang Q, Dansey R, Jun S, Braun A. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010; 28:
33 Discussion
34 Gemcitabine Induced MAHA 0.31% incidence 8 months to development of TMA 3-18 months Hypertension frequently associated
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