Cancer-associated microangiopathic hemolytic anemia (MAHA)-experience in CCH 鍾智淵 張正雄 郭集慶* 葉坤土**
彰化基督教醫院 內科部血液腫瘤科 *腫 瘤科 **病理部
Introduction
• Cancer-associated MAHA is a rare complication of neoplasms. • We present 14 cases of cancer-associated MAHA in CCH between 1990-1996. • The clinical course, labarotory datas and treatments pertaining to these patients will be presented.
Dignosis of Cancer-associated MAHA
• Disseminated carcinoma • Sudden onset of decrease of Hb without overt bleeding site. • PB smear disclose many schizocytes, thrombocytopenia and leukoerythoblastic change. • CBC c DC: anemia, thrombocytopenia. • Biochemitry: decrease of heptoglobin indirect Bil↑. • Bone marrow: cancer cell (+ ). • Fatal outcome of clinical course.
Characterics of 14 patients with cancer-association MAHA (一)
• These were 8 femals and 6 male patients. • gastric cancer 3 Adenocaricinoma of unknown primary 3 Breast cancer 2 Nasopharyngeal cancer 3 Cervical cancer 2 Bladder cancer 1 Total 14
Characterics of 14 patients with cancer -associated MAHA (二)
Age (years) Hb plat APTT LDH total Bilinubin indirect Bilinubin Surrvival period from 8-230 day diagnosis MAHA to death Range 38-69 4.7-10.9 7-180x10 mean 54 6.9 4.3x10
90 day
Patients G1 G2 G3 A1
A2
Sex Age(year) F 38 M 38 M 61 M
M
66
61
A3 B1 B2 N1 N2 N3
C1 C2 T1
F F F F F M
F F M
40 55 36 69 45 45
45 50 56
Pathologic findings Adenocarcinoma " " Mucin stain (+) " Mucin stain (+) " Mucin stain (+) "
surrival time 23 days alive 10 days 8 days
19 days
anaplastic epidermoid undifferentiated squamous cell carcinoma non-keratinizing carcinoma epidermoid adenosequanour carcinoma epidermoid Transition cell carcinoma
230 days 160 days 100 days 19 days 210 days 120 days
150 days 60 days 80 days
Henatologic data on MAHA
Patients G1 G2 G3 A1 A2 A3 B1 B2 N1 N2 N3 C1 C2 T1 Mean Range Hb 6.7 6.5 3.0 9.1 9.3 6.0 4.3 9.7 10.9 5.6 8.7 4.7 5.2 7.5 6.9 3.0 - 10.9 plat x 1000 48 23 25 22 12.9 23.5 7 70 95 14 26 21 2.8 180 4.3 7 - 180 leukoerythroblastosis + + + + + + + + + + + -
Coagulation studies of cancer-associated MAHA
Patient G1 G2 G3 A1 A2 A3 B1 B2 N1 N2 N3 C1 C2 T1 Mean Range PT 17.5 13.3 14.1 14.8 13.9 13.0 12.5 12.2 11.5 13.7 13.1 17 13.6 APTT 30.5 27.4 35.5 29.3 30.7 26.9 34.2 38 30.7 36.3 30.4 29.7 48.2 Fibrinogen 49 186 195 183 281 351 288 239 184 27.9 361 515 FDP >80 >2000 80 1000 1000 10 >2000 >2000 80 10 1000
Biochemistry Studies of MAHA
Patient G1 G2 G3 A1 A2 A3 B1 B2 N1 N2 N3 C1 C2 T1 Mean Range LDH 2560 1981 3213 5562 4666 1690 1668 1510 1325 738 2788 707 922 2256 707-5562 Bil/T 4.48 2.10 3.68 2.1 0.98 2.32 1.50 0.69 0.53 0.81 3.63 0.7 2.81 0.69 1.93 0.7-4.48 Bil/I 3.57 1.52 3.06 1.7 2.0 1.22 0.48 0.57 2.52 0.3 1.76 0.39 1.55 0.3-3.57 heptoglobin 7.48 <5.82 <5.82 52 <5.82 <5.0 <5.83 <5.82 <5.0 Coombs' test Negative Negative Negative Negative Negative Negative Negative Negative
MAHA as initial presentation of Metastatic cancer
Patient
G1
clinical features
dizziness UG2bleeding Gu (A2) lymph nodes Meta hemoptysis old TB bone and bone marrow Meta multiple hard mass liver, spleen, lymph nodes Meta melena, lower back pain bone and bone marrow Meta
Treatment
chemotherapy plasma exchange
supportive
Survival
23 days
A1
8 days
A2
A3
supportive
chemotherapy Radiotherapy
8 days
230 days
Discussion
Pathogenesis of cancer-associated MAHA
• Both tumor emboli and fibrin thrombi play an important role • Intima prolifuration particularly in the small pulmonary arteries.
Chest x-ray in MAHA
G1 G2 G3 A1 A2 A3 B1 B2 N1 N2 N3 C1 C2 T1 Interstial infiltration + + + + + + + + + + Alveolar lesior lung nodule + + + Pleuel effusion + + + + + + Osteolytic lysion + + + +
Incidence of cancer-associated MAHA(一)
• By Lohman prospective study, though MAHA in overall cancer is quite low only 0.25%, the incidence of MAHA in metastatic carcinoma occurs as high as 5.7%.
- 1. Annals of Int Med 79: 368-375, 1973-
• Tumors with MAHA are almost mucin-producing adenocarcinoma, particular with cases of gastric adenocarnoma were over 50% of reviewed cases. There are a great many differences between our study and previous reparts.
• Reported tumors associated with MAHA No. of patients Gastric 30
Breast Unknown primary Lung Porstate Pancreatic Seminal vesicle Colon Ovary Hepatoma Cholangiocarcinoma Total 7 5 4 2 2 1 1 1 1 1 55
Incidence of cancer-associated MAHA (二)
- 2. Medicine 1979, vol 58-
Incidence of cancer-associated MAHA(三)
• There were only 3 case (21%) of gastric carcinoma with MAHA in this study. • The reasons of low incidence of gastric carcinoma with MAHA may be due to underestimation or de novo low incidence in Taiwainese; but need further investigation.
• There are 4 cases represented cancer with MAHA as initial presentation. • MAHA should first rule out disserinated carcinoma. • DDx of MAHA
Disseminated carcinoma TTP HUS DIC Chemotherapy induce Preeclampsia Malignant hypertension Immune mechanism Hemagiomas
Cancer with MAHA as initial presentation
Non-adenocarcinoma with MAHA (一)
• Patient Metastatic site
N1 N2 N3 C2 T1
Leukoerythroblastic change
+ + + + -
lung skin, bone lymph nodes lung, bone marrow bone lung, liver bone marrow lymph nodes lung, meta lung T-spine lymph nodes bone
Non-adenocarcinoma with MAHA (二)
• Five cases with MAHA in Non-adenocarcinoma were composed of 3 cases of NPC, 1 case of cervical cancer and 1 case of bladder cancer. These three different carcinomas have not been reported in our Medline research. • We consider that ocurrence of MAHA wasn't frequent in mucin-production adenocarcinoma but often in other disseminated neoplasms, particularly carcinoma tend to marrow metastasis of lung or bone marrow.
Nasopharyngeal carcinoma with MAHA
• Patient pathologic finding N1 anaplastic epidermoid N2 undifferentiated squamous N3 non-keratinizing epidermoid • Though NPC with MAHA has not been reported in our Medline research, relatively common in our cases. • The reasons may be due to higher incidence of NPC in Chinese than in the West, and more advanced disease when diagnosed.
Treatment and Porgnosis
• Still fatal outcome. • The mean duration from the time of diagnosis was 90 days. • Though plasmapheresis had been reported as effective treatment of MAHA while waiting for management of tumor. Only one case of ours performed plasnapheresis, but it seemed no benefits.
1. Annales de Medicine Interne. 145(5):365-8, 1994-
• Six cases had survived more than 3 months since MAHA was diagnosed. They all responsed to initial chemotherapy. • The prognosis for these patients seems directly related to the underlying cancer and the response to therapy rather than management of MAHA.
2. Lin. et al southern Med. Journal June 1995-
Conclusion
• High incidence of now-adenocarcinoma and NPC associated MAHA in our study was greatly different from previous views. • MAHA may be as initial presentation of disseminated carcinoma. • Prolongingthe survival time depends on the treatment of underlying carcinoma.