Microangiopathic hemolytic anemia (MAHA), is one of the causes of extra vascular hemolysis. It is seen in settings with pathologically altered small blood vessels. Disseminated carcinomas may rarely present as MAHA. A case of a 28 year old female with carcinoma stomach, who presented with MAHA as a first manifestation is reported. Acute onset of MAHA, may be the first manifestation of malignancy. In the absence of relatively common causes like disseminated intravascular coagulation,/Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura, MAHA warrants extensive rapid investigations including bone marrow aspiration for possible metastatic deposits

B Nordstrom

F Ozkalemkas

J Foerster

Karuna Rameshkumar

MC Brain

Vanamala Alwar

YC Lin

English

PubMed

Springer - Publisher Connector

BioMed CentralCases Journal
ssOpen AcceCase Report
The MAHA clue - A case report
Vanamala Alwar and Karuna Rameshkumar*
Address: Department of Clinical Pathology, St. John's Medical College Hospital, Bangalore -34, India
Email: Vanamala Alwar - vanalwar@yahoo.com; Karuna Rameshkumar* - karunark@yahoo.com
* Corresponding author    
Abstract
Microangiopathic hemolytic anemia (MAHA), is one of the causes of extra vascular hemolysis. It is
seen in settings with pathologically altered small blood vessels. Disseminated carcinomas may rarely
present as MAHA. A case of a 28 year old female with carcinoma stomach, who presented with
MAHA as a first manifestation is reported. Acute onset of MAHA, may be the first manifestation
of malignancy. In the absence of relatively common causes like disseminated intravascular
coagulation,/Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura, MAHA warrants
extensive rapid investigations including bone marrow aspiration for possible metastatic deposits.
Introduction
Brain, Dacie and Hourihane popularized the term Micro-
angiopathic hemolytic anemia to designate anemias refer-
ring to red cell fragmentation occurring in association
with small vessel disease [1]. MAHA is commonly
encountered in clinical settings like- Hemolytic uremic
syndrome (HUS), Thrombotic thrombocytopenic pur-
pura (TTP) and Disseminated intravascular Coagulation
(DIC). Rarely MAHA presents as a lethal manifestation of
malignant tumours especially in mucin producing adeno-
carcinomas, but the pathogenesis of tumour associated
mechanical hemolysis remains unclear. Many probable
explanations have been put forth to explain the pathogen-
esis of this rare phenomenon:
(1) Some authors have proposed that mucin itself is
directly responsible for the intravascular coagulation,
and that the deposition of fibrin within microvascula-
ture is in turn responsible for the red cell fragmenta-
tion.
(2) Another explanation is that the presence of
tumour microemboli in pulmonary vasculature may
lead to secondary intimal proliferation which in turn
may be responsible for red cell fragmentation.
Unfortunately no effective or standard therapy is known
for cancer associated MAHA. A small number of patients
show a transient response to heparin. Hormonal or chem-
otherapy can also result in temporary remission [2].
Case Report
A 28 year old female came with history of backache (Lum-
bar Region) for three weeks, fever and abdominal pain for
15 days and spontaneous ecchymotic patches over the
lower limbs. She also gave history of loss of weight of
approximately 10 kilograms over a period of one month.
There was no history joint bleeds, bleeding per vagina or
similar family or past history.
On Examination
She had marked pallor and was febrile. Abdominal exam-
ination revealed, hepatomegaly (8 cm)and splenomegaly
(8 cm). Sternal and spinal tenderness was noted over D7
and D10-11. The clinical diagnosis was a hematological
Published: 22 December 2009
Cases Journal 2009, 2:9385 doi:10.1186/1757-1626-2-9385
Received: 15 October 2009
Accepted: 22 December 2009
This article is available from: http://www.casesjournal.com/content/2/1/9385
© 2009 Alwar and Rameshkumar; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 3
(page number not for citation purposes)
Cases Journal 2009, 2:9385 http://www.casesjournal.com/content/2/1/9385malignancy in view of hepatosplenomegaly and rapid loss
of weight.
Laboratory Investigations
Hemoglobin 4.9 gm/dl:Total count: 17,000 cells/cmm
Differential count:Neutrophils:49%, Lymphocytes: 40%,
Eosinophils: 3%, Monocyte:1%
Metamyelocytes:5%, Myelocytes:2% nRBCS: 19/100
WBCs
Platelet Count: 31,000/cmm
The peripheral smear showed burr cells, schistocytes,
spherocytes and nucleated RBCs which were consistent
with features of MAHA (Figure 1).
Bone Marrow done yielded a Dry Tap, however the
imprint smears showed presence of few large cells with
foamy cytoplasm.(Figure 2)
Trephine biopsy done showed cells arranged in an
attempted glandular pattern, suggestive of metastatic ade-
nocarcinoma. PAS stain showed positivity of the cyto-
plasm indicating the presence of mucin (Figure 3)
Radiology
Lumbar X Ray, showed collapse of D12. Ultrasound
examination of the abdomen showed para-aortic lym-
phadenopathy.
Course in the hospital
During her hospital stay, she developed hematemesis
(300 ml). Initial endoscopy was inconclusive due to
improper visualization. Antral erosion was suggested as a
probable cause. A repeat endoscopy done showed a
stomal ulcer (1 × 1.5 cm) along the greater curvature.
Biopsy was taken from the ulcer to rule out malignancy.
The histopathological evaluation of the biopsy from ulcer
was reported as adenocarcinoma. The patient was given
packed red cell transfusion for the anemia. Before a com-
prehensive treatment was established the patient opted
Peripheral smear with presence of schistocytes, polychro-matophilic cells and nucleat d RBCFigur  1
Peripheral smear with presence of schistocytes, poly-
chromatophilic cells and nucleated RBCs. Leishman's 
stain × 1000.
The imprint smears showed presence of few large cells with foamy cytoplasm (Leishman's stainX1000) which stained PAS positive (PAS ×1000)Figure 2
The imprint smears showed presence of few large 
cells with foamy cytoplasm (Leishman's stainX1000) 
which stained PAS positive (PAS ×1000).
Cytoplasm: PAS 
Positive
Trephine biopsy done showed cells arranged in an attempted glandular pattern, suggestive of met st tic adenocarcinoma (H motoxylin a  Eosin stain × 400)Figure 3
Trephine biopsy done showed cells arranged in an 
attempted glandular pattern, suggestive of meta-
static adenocarcinoma (Hemotoxylin and Eosin stain 
× 400). PAS stain showed positivity of the cytoplasm indicat-
ing the presence of mucin (Periodic acid Schiff × 400).
H&E stained section: 
malignant cells (arrows) in 
attempted glandular pattern
PAS positivity of the 
cytoplasmPage 2 of 3
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Discussion
MAHA is a rare complication of carcinomas and it can
present as a paraneoplastic syndrome. Such patients may
present with Coombs negative acute hemolytic anemia.
MAHA may exist in two forms when associated with carci-
noma:
1. May be associated with disseminated disease or
2. May be as a complication of chemotherapy, esp.
with Mitomycin.
Both forms give rise to a severe hemolytic anemia and the
latter is also associated with renal insufficiency [3]. Aden-
ocarcinomas of the stomach, prostate, lungs in the order
of occurrence are more commonly associated with MAHA
compared to others. In a majority of cases the primary is
not found [4]. Though a rare manifestation, the onset of
MAHA heralds a lethal course within a few weeks [2]. It
therefore warrants an immediate intervention. All efforts
must be taken to find the primary tumour. Quick intro-
duction of antineoplastic therapy, not only reduces the
tumour bulk, but also causes remission of the MAHA. In
cases where the primary was not found as reported by Lin
et al, the anemia and thrombocytopenia responded dra-
matically to chemotherapy (5-furouracil, Mitomycin, Cis-
platin) [5]. Plasmapheresis may also be useful.
Conclusion
• Acute onset MAHA, may be the first manifestation of
malignancy. In the absence of common causes (like
DIC/HUS/TTP), it warrants extensive rapid investiga-
tions including bone marrow aspiration for possible
metastatic deposits.
• Cancer associated MAHA is a life threatening condi-
tion with poor prognosis, warranting urgency in diag-
nosis and subsequent therapy.
Consent
Written informed consent could not be obtained. The
patient is anonymised and we believe the patient or their
family would not object to publication of this case report.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
During the process of routine reporting, authors reported
this case. VA wrote the article, KR edited the article and
added the photographs to illustrate the contents.
References
1. Brain MC, et al.: Microangiopathic hemolytic anemia: The pos-
sible role of vascular lesions in pathogenesis.  Br J Hematol 1962,
8:358.
2. Foerster J: Red cell fragmentation syndrome.  Wintrobe's Clinical
Hematology, Pennsylvania 9th edition. 1993, Chapter 43:1211-1231.
3. Nordstrom B, Strang P: Microangiopathic hemolytic anemia
(MAHA) in cancer. A case report and review.  Anticancer Res
1993, 13(5):1845-49.
4. Ozkalemkas F, Ali R, Ozkocaman V, Ozcelik T, Kurt E, Evrensel T,
Yerci O, Tunali A: The bone marrow aspirate and biopsy in the
diagnosis of unsuspected nonhematologic malignancy: a clin-
ical study of 19 cases.  Cancer 2005, 1(5):144.
5. Lin YC, Chang HK, Sun CF, Shih LY: Microangiopathic hemolytic
anemia as an initial presentation of metastatic cancer of
unknown primary origin.  South Med J 1995, 88(6):683-87.Page 3 of 3
(page number not for citation purposes)


The MAHA clue - A case report

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