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CASE REPORT
Year : 2018  |  Volume : 45  |  Issue : 1  |  Page : 36-39

Fatal microangiopathic hemolytic anemia: Two case reports


1 Department of Laboratory Medicine, Yashoda Hospital, Malakpet, Hyderabad, Telangana, India
2 Department of Department of Critical Care, Yashoda Hospital, Malakpet, Hyderabad, Telangana, India

Date of Web Publication27-Jul-2018

Correspondence Address:
Majed Abdul Basit Momin
Department of Laboratory Medicine, Yashoda Hospital, Malakpet Nalgonda X-Roads, Hyderabad... - 500. 036, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jss.JSS_9_18

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  Abstract 


The microangiopathic hemolytic anemia (MAHA) characterizing hemolytic anemia with fragmented red blood cells (RBCs) in the peripheral blood smears. Hemolytic Uremic Syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are classified under MAHA. We report two cases who presented to emergency room (ER), a 7-year-old female child who was diagnosed with atypical HUS with malignant hypertension on the basis of classic triad of hemolytic anemia, thrombocytopenia, and acute kidney injury. Second case was a 45-year-old female presented with altered sensorium, fever, and multiorgan failure. And finally diagnosed as TTP. Both the cases partially treated at private nursing home initially for few days and then referred to our hospital. This case report emphasizes the importance of correlation of emergency and laboratory physicians’ findings to approach a case of MAHA. As delay in early recognition of these conditions resulting in fatal outcome.

Keywords: Blood films schistocytes, Hemolytic Uremic Syndrome, microangiopathic hemolytic anemias, thrombotic thrombocytopenic purpura


How to cite this article:
Basit Momin MA, Prusty SK, Aluri A, Soumya V. Fatal microangiopathic hemolytic anemia: Two case reports. J Sci Soc 2018;45:36-9

How to cite this URL:
Basit Momin MA, Prusty SK, Aluri A, Soumya V. Fatal microangiopathic hemolytic anemia: Two case reports. J Sci Soc [serial online] 2018 [cited 2018 Aug 16];45:36-9. Available from: http://www.jscisociety.com/text.asp?2018/45/1/36/237766




  Introduction Top


Microangiopathic hemolytic anemias (MAHAs) are mechanical hemolytic anemias in which red cell fragmentation is due to contact between red cells and abnormal intima of partially thrombosed, narrowed, or necrotic small vessels.[1]

Hemolytic Uremic Syndrome (HUS) can be classified as typical or atypical. The peak incidence in children is younger than 5 years (6.1/100,000). It is characterized by a triad of thrombocytopenia, hemolytic anemia, and acute kidney injury.[2]

Thrombotic thrombocytopenic purpura (TTP) presents with thrombocytopenia and hemolytic anemia but usually presents with predominant central nervous system involvement, while HUS predominantly presents with renal involvement. It is more common in females and occurs around the age of 40 years. It is a rare disease and is fatal in 50%–80% of cases.[3]

The finding of schistocytes in the blood film together with anemia and thrombocytopenia should lead to a prompt action to exclude the presence of underlying thrombotic microangiopathy (TMA).[4]


  Case Reports Top


Case 1

A 6-year-old female child, first issue of nonconsanguineous parents, got admitted with complaints of fever, yellowish discoloration of skin, vomiting, pallor, and puffiness of face for 7 days. Initially, she was taken to a local hospital and was investigated and found to have anemia and thrombocytopenia with hyperbilirubinemia. Ultrasonography abdomen showed hepatosplenomegaly and received blood transfusions. Child did not respond with increasing serum creatinine and progressive fall in counts and was referred us for further management.

On admission, she was irritable, puffiness of face, and pallor. Clinical examination revealed Fever (101.6F), tachycardia(128 beats/min), increased blood pressure 130/90 mmHg, and respiratory rate was 28/min. Hepatomegaly and splenomegaly on palpation. Immediate investigation revealed severe anemia (4.8 gm%) and thrombocytopenia (50,000/ul). Peripheral smear shows microcytic hypochromic pictures, moderate anisopoikilocytosis, many schistocytes (helmet shape and triangular RBCs), polychromasia, and 1–2 nucleated RBCs/100 WBCs seen [Figure 1]. WBCs count was normal (6300/cumm), normal in differential and morphology. Reticulocyte count was 15%. Erythrocyte sedimentation rate (ESR) was high (60mm/h) and Coombs (direct/indirect) test was negative.
Figure 1: Peripheral smear show schistocyte - Helmet-shaped red blood cells (red arrow) and triangular form red blood cells (blue arrow) (Leishman stained, ×40)

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Serum creatinine was 3.1 mg/dl and serum urea was 120 mg/dl. Coagulation test prothrombin time (PT) and activated partial thromboplastin time (PTT) were normal; electrolytes, serum Vitamin B12, and folic acid were normal. There was elevated levels of lactate dehydrogenase enzyme(LDH) 3150 U/L and serum ferritin 1470 ng/ml.

Antinuclear antibodies with IF study were negative. Complete urine examination showed proteinuria with no pus cells.

Chest X-ray shows normal study. Based on anemia, peripheral blood schistocytes, thrombocytopenia, and renal dysfunction, she was diagnosed as atypical hemolytic uremic syndrome.

Patient was treated conservatively with fluid, salt restricted diet, and pulse dose methylprednisolone was started along with plasmapheresis. Five cycles of plasmapheresis were done with supportive packed RBC and fresh frozen plasma transfusion. Hemodialysis was done but showed poor response and urine output progressed from oliguria to anuria. Patient condition rapidly deteriorated and died.

Case 2

A previously healthy 45-year-old female presented to ER with fever moderate-to-high grade, associated with generalized weakness for 8 days, and altered sensorium for 2 days. Four days before the ER visit, she was admitted for similar complaints at a district local hospital, was treated and transfused with single donor platelet, and referred here for further management. On general examination, patient was irritable, pallor and icterus were seen. Clinical examination includes Fever (101.2°F), tachycardia (108 beats/min), and hepatosplenomegaly noted on palpation.

Laboratory workup showed a hemoglobin (Hgb) level of 5.9 g/dL and a platelet count of 8000/μl (severe thrombocytopenia), with normal PT, PTT, fibrinogen, and fibrinogen degradation products. Peripheral smear examination shows many schistocytes.

(Helmet shape and triangular RBCs) with dimorphic RBCs. 1–2 nucleated RBCs were seen [Figure 2]. WBCs count was high (21,200/cumm) with neutrophilic leukocytosis. ESR was high 110/mm at the end of 1 h. Coombs (direct/indirect) test was negative. Other laboratory examination for hemolysis was positive with elevated reticulocyte count 18%, marked elevations in lactate dehydrogenase (LDH) (3525 U/L), and elevated unconjugated bilirubin 2.7 mg/dL and direct bilirubin at 0.5 mg/dL.
Figure 2: Peripheral smear dimorphic red blood cells with Helmet (red arrow) and triangular red blood cells (blue arrow) (schistiocytes) (Leishman stained, ×40)

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Based on clinical findings and laboratory parameters, diagnosis of TTP made and treatment started with steroids and plasmapheresis. During plasmapheresis, patient developed cardiac arrest and died after 8 h of admission. The patient's ADAMTS 13 not send in view of financial constraint of patient.


  Discussion Top


MAHA is now used to designate any hemolytic anemia related to RBC fragmentation, occurring in association with small vessel disease. The term “TMA” is also used to describe syndromes. The most prominent diagnoses associated with TMA are TTP and HUS. MAHAs are characteristically accompanied by thrombocytopenia in the absence of defects in coagulation. MAHA can occur in diseases of various origins, including infectious, autoimmune (systemic lupus erythematosus), malignant, and iatrogenic.[5]

The pathogenesis of MAHA starts with the formation of microthrombi and platelet and fibrin mesh in the vessels of smaller diameter such as arterioles and capillaries. During the passage of erythrocytes through these partially obstructed blood vessels, severe damage to the erythrocyte wall occurs and results in cell lysis and fragmentation. The hallmark of MAHA is the development of schistocytes (fragmented RBCs) and hemoglobinemia because Hgb is released during RBC lysis.[2] About 50% of TTP cases are considered idiopathic. Idiopathic TTP is related to decreased levels of ADAMTS-13 (specific von Willebrand factor-cleaving protease).[6]

Fatigue, malaise, and fever are present in virtually all patients, while dehydration, rash, altered mental state, diarrhea, vomiting, abdominal pain, dark urine, and many other symptoms may also be present. The diagnosis is made after performing a thorough diagnostic panel, including complete blood count, which will reveal anemia and low platelet count (since they are all used up in the process of clot formation). In addition, kidney function tests may be abnormal, bilirubin levels are high, and enzymes that show accelerated cellular degradation may be elevated such as LDH.[7]

The International Council for Standardization in Hematology (ICSH) Schistocyte Working Group agreed that a schistocyte percentage above 1% in a peripheral blood smear in adults is a robust cytomorphological indication in favor of a diagnosis of TMA, when additional features suggesting an alternative diagnosis are absent. According to the ICSH Schistocyte Working Group, spherocytes, irregularly contracted cells, dacryocytes, acanthocytes, and echinocytes, as well as bite cells that are a feature of oxidant damage, should not be included within the schistocyte count. If schistocytes are absent and there is a high suspicion of TMA, blood smear screening for schistocytes should be repeated daily, as the appearance of schistocytes can occasionally be delayed for several days.[8]

Classic triad of fever, thrombocytopenia, and renal failure was seen in HUS. Hypertension is frequent in atypical HUS and difficult to manage due to volume overload in case of oliguria/anuria and to hyperammonemia secondary to renal TMA. Since assay of complement factors, assay of serum proteins, expression of membrane complex protein on mononuclear cells and genetic study of mutation not easily available and due financial constraint, diagnosis is made on history, clinical examinations, and related investigation.

A classic pentad of thrombocytopenia, MAHA, fever, neurological abnormalities, and renal dysfunction has been described in TTP but rarely seen in its entirety nowadays. Two major diagnostic criteria, thrombocytopenia and microangiopathic hemolytic anemia are enough to suspect the diagnosis of the TTP and initiate treatment.[9] As in our second case, since patient peripheral smear for schistocytes not reviewed and treated as sepsis.

The initial management of HUS includes supportive care, initiation of dialysis in cases for worsening renal failure that is refractory to medical therapy. Definitive management is with plasmapheresis and eculizumab, a monoclonal antibody to C5. Plasmapheresis has been thought to be effective due to its ability to remove mutated proteins and antibodies to complement factor H and restore the patient's blood with normal complement proteins and is most effective when initiated within the first 24 h.[10]

There are several widely accepted prognostic indicators in TTP/HUS. Some poor prognostic indicators carrying high mortality include duration of illness before onset of HUS >14 days, anuria >3 days, age <18 months and >5 years, nondiarrhea associated HUS, HUS associated with convulsion and hypertension, WBC >30, 000/mm3, platelets <30, 000/mm3, creatinine level >700 μmol/L, and serum potassium level 5.6–7.5 mmol/L.[11]


  Conclusion Top


To conclude, this case report reminds the clinician to keep MAHA in mind in cases of anemia and thrombocytopenia. Clinicians should also remember that the absence of fever, neurological deficits, or renal abnormalities should not be used to rule out TTP. Since peripheral smear examination plays crucial role in the diagnosis of MAHA and as such no easy availability of definitive diagnostic test, effective discussion is required between the clinician and hematopathologist for prompt recognition, treatment, and good prognosis of these diseases, which have high mortality. In present case report cases, early admission perhaps treats them at the onset of diagnosis and may prevent fatal outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Antman KH, Skarin AT, Mayer RJ, Hargreaves HK, Canellos GP. Microangiopathic hemolytic anemia and cancer: A review. Medicine (Baltimore) 1979;58:377-84.  Back to cited text no. 1
    
2.
Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005;16:1035-50.  Back to cited text no. 2
    
3.
Marcur AJ. Haemorrhagic disorders: Abnormalities of platelet and vascular function. In: Wyngaarden JB, Smith LH, editors. Cecil Textbook of Medicine. 17th ed. Philadelphia, London and Toronto: W. B. Saunders Co.; 1985. p. 1028-40.  Back to cited text no. 3
    
4.
Frank firkin, colinchesterman, david penington & bryan rush-De Gruchys clinical Haematology in medical practice- 5th edn.  Back to cited text no. 4
    
5.
Moake JL. Thrombotic microangiopathies. N Engl J Med 2002;347:589-600.  Back to cited text no. 5
    
6.
Tsai HM. Thrombotic thrombocytopenic purpura: A thrombotic disorder caused by ADAMTS13 deficiency. Hematol Oncol Clin North Am 2007;21:609-32, v.  Back to cited text no. 6
    
7.
Tsai HM. Thrombotic thrombocytopenic purpura and the atypical hemolytic uremic syndrome: An update. Hematol Oncol Clin North Am 2013;27:565-84.  Back to cited text no. 7
    
8.
Zini G, d'Onofrio G, Briggs C, Erber W, Jou JM, Lee SH, et al. ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes. Int J Lab Hematol 2012;34:107-16.  Back to cited text no. 8
    
9.
Kessler CS, Khan BA, Lai-Miller K. Thrombotic thrombocytopenic purpura: A hematological emergency. J Emerg Med 2012;43:538-44.  Back to cited text no. 9
    
10.
George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010;116:4060-9.  Back to cited text no. 10
    
11.
Malla K, Malla T, Hanif M. Prognostic indicators in haemolytic uraemic syndrome. Kathmandu Univ Med J (KUMJ) 2004;2:291-6.  Back to cited text no. 11
    


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