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Indian J Pediatr 1989; 56 : 243-247
Bleeding Manifestations In Megaloblastic Anemia
R.K. Marwaha, Surjit Singh, G. Garewal*, N. Marwaha*, B.N.S Walia and Lata Kumar
Departments of Pediatrics and *Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh
Ten children with megaloblastic anemia and a hemorrhagic diathesis are reported. Four of them had life-threatening bleeds necessitating an emergency blood transfusion. Seven had platelet counts of less than 30,O00/cu mm, and nine had hemoglobin values of _~ 5.2 g/dl at initial presentation. Deficiency of vitamin B12 was more frequently encountored. Response to therapy was excellent and hemostasis was possible within 12 to 24 hours of initiating treatment.
Key Words : Thrombocytopenia; Hemorrhage; Anemia; Megalo- blastic anemia.
Megaloblastic anemia is not uncommon in children. 1 Its presentation, however, with hemorrhagic manifestations and/or throm- bocytopenia is distinctly unusual, z 3 The bleeds may sometimes be severe enough to warrant emergency blood transfusions. 2 We report ten cases of megaloblastic anemia seen over a period of 4 years. We wish to highlight this rare clinical presenta- tion of a common childhood problem.
MATERIALS AND METHODS
Children presenting with bleeding mani- festations and anemia registered in the Pe- diatric Hematology Clinic of PGIMER, Chandigarh were prospectively studied. A
Reprint requests : Dr. R.K. Marwaha, Assistant Professor, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012.
detailed history was recorded and a thor- ough clinical examination carried out. In patients where a peripheral blood f'dm ex-
' amination suggested a diagnosis of mega- loblastic anemia, further investigations were performed. In addition to a routine hemogram, platelet counts were done by phase-contrast microscopy and bone-mar- row aspirates obtained. Assays of serum vi- tamin B12, serum folate and red cell folate were determined: The serum iron and total binding capacity was also estimated: All children documented to be having megaloblastic anemia by examination of bone-marrow aspirates and/or vitamin as- says were given injection vitamin B~2 (1,000 gg weekly for 3-4 doses) and/or folic acid (5 mg OD). The response to therapy was monitored clinically and by hematological investigations.
Cas
e A
ge/
Sex
P
EM
S
ES
H
emat
- N
o.
O r
) em
esis
1 ll
M
2 8
M
3 10
F
4 6
F
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7
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280
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247
220
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246 THE INDIAN JOURNAL OF PEDIATRICS Vol. 56, No. 2
RESULTS
Ten patients of megaloblastic anemia with hemorrhagic manifestations.were seen over a period of 4 years. These constituted 5.8% of all patients presenting with anemia and bleeds. The clinical data are summa- rized in Table I. Their ages ranged from 2 to 12 years (mean age 8 years). Three chil- dren were severely malnourished and six came from poor socio-economic strata. The patients had been symptomatic for pe- riods ranging from 8 days to 3 months prior to hospitalization. Apart from significant pallor, these children had bleeds from the gastro-intestinal tract, epistaxis and/or skin and mucosal bleeds. Physical examination showed significant hepatomegaly in five and.splenomegaly in six cases.
The details of investigations carried out are shown in Table 2. Nine out of ten pa- tients had severe anemia with hemoglobin values of less than 5.2 g/dl. Seven patients had severe thrombocytopenia (platelet count < 30,000/cu. mm). Case No. 4, how- ever, had a normal platelet count even though he presented with hematemesis and skin bleeds. Bone marrow aspiration was done in all cases and showed classical fea- tures of megaloblastic anemia. Vitamin as- says confirmed a ~leficiency of vitamin B12 alone in thre~-cases (Nos. 1, 5, 7) of folate alone in 1 case (No. 9) and of both B12 and folate in three (Nos. 3, 4, 6). Case No. 8 had normal levels of B12 and folate proba- bly because of hematinics received outside. Assays could not be done in 2 patients (No. 2, 10). Additionally, cases No. 8 and 9 had biochemical evidence of iron deficiency anemia even though the morphological fea- tures in "the marrow were those of mega- loblastic anemia. Response to therapy was quick and very gratifying in all cases.
Bleeding stopped within 12 to 24 hours of initiating therapy and platelet counts re- turned to normal within 5-14 days.
DISCUSSION
The diagnosis of megaloblastic anemia was based on bone-marrow findings and the results of vitamin assays. Deficiency of vitamin B n. was found to be commoner than that of folate (Table 2). Though de- tailed studies were not carried out, the un- derlying etiology of the anemia was thought to be nutritional. Dalai et all in their study of megaloblastic anemia, em- phasized the fact that the only rich sources of vitamin B~z are animal protein and liver; the average Indian diet is lacking in both. Moreover, even though vegetables are fairly rich in folio acid, this can be easily lost or destroyed by improper methods of cooking.
Though thrombocytopenia is a well- known finding in megaloblastic anemia, most Indian studies do not comment on the platelet number and/or overt bleeding. 1, s. Khair et al 6, in 1975, reported 30 cases of megaloblastic anemia diagnosed on periph- eral smear examination and the bone mar- row picture. Vitamin assays, however, were not done. Eight of their patients had thrombocytopenia (platelet count < 100,000/cu.mm) and five had overt bleed- ing. None of these patients, however, had life-threatening bleeds and only one of them had severe thrombocytopenia (platelets < 30,000/cu. mm). Our findings are somewhat different in that atleast four of our cases had serious and life-threaten- ing bleeds requiring emergency blood transfusion. Moreover, seven patients had platelet counts of < 30,000/cu mm. Replacement with B~2 and folate resulted
MARWAHA ET AL : THROMBOCYTOPENIA IN MEGALOBLASTIC ANEMIA 247
in almost immediate hemostasis. There were no fatalities. Smith et al 2 have also reported similar episodes of life-threaten- hag bleeds due to megaloblastic anemia i0. adults. These findings thereby suggest that the possible presentation of megaloblastic anemia as a hemorrhagic diathesis must be clearly appreciated. Apart from throm- bocytopenia, platelet dysfunction is also a recognized feature of megaloblastie ane- mia 7. This possibly explains the bleeding in case No. 4 in whom the platelet count was normal ~Table 2). Platelet function tests were, however, not carried out.
We wish to emphasize that the clinical picture ha most of our patients simulated an acute leukemia. It was only on receiving the peripheral smear report that a diagno- sis of megaloblastic anemia was consid- ered, and later confirmed by a marrow as- pirate and vitamin assays. Megaloblastic anemia should therefore, be a possible dif- ferential diagnosis in children presenting with bleeds and disproportionate anemia.
REFERENCES
1. Dalal N J, Udani PM, Parekh SG. Mega- loblastic anemia in infancy artd childhood. Indian Pediatr 1969; 6 : 255-261.
2. Smith MD, Smith DA, Fletcher M. Hem- orrhage associated with thrombocytopenia in megaloblastic anemia. Br Med J 1962; 1 : 982-985.
3. Cocnett JE, Macleod In. Retinal hemor- rhage in severe anemia. Br Med 1 1959; 2 : 1002-1004.
4. Dacie JV, Lewis SM, Hoffbrand AV. In- vestigations of megaloblastic and iron deft- ciency anemia. In : Practical Hematology. 6th Edition, Churchill Livingstone, Ed- inburgh, 1984; 313-336.
5. Mathur GP, Dayal RS, Prasad R, et al. Tremors, mental and physicalretardation light coloured hairs and anemia in mal- nourished children. Indian Pediatr 1969; ~i : 483-487.
6. Khair SR, Kaddu JA, Vislakshi S. Bleeding manifestations in megaloblastic anemia. Indian Pediatr 1975; 12 : 171-173.
7. Ingeberg S, Stoffersen E. Platelet dysfunc- tion in patients with Vitamin B~2 deft- ciency.Acta Hernatol 1979; 61 : 75-79.
