immune hemolysis is a shortening of red blood cell survival due , directly or indirectly to antibodies . it is necessary to identify these atypical antibodies in the patient s serum in order to select appropriate blood for transfusion . even in the most vexing situation encountered by a transfusion specialist where no compatible units are available for a patient with severe anemia transfusion requirement should be considered as a medical emergency even if serologic testing is incomplete . a 20-year - old female was referred to our hospital with complaints of icterus and breathlessness . she had similar complaints one year back and was treated for jaundice by a local physician . prior to her referral , she had been transfused three units of ab positive blood over one week . on general physical examination , there was mild leucocytosis and blood film showed autoagglutination with the presence of nucleated red cells ( 19/100 wbcs ) . plasma and urine hemoglobin were raised . direct antiglobulin test with poly - specific coomb 's reagent ( igg + c3d ) ( tulip diagnostics ) was positive . patient also had a positive antibody screen with all three reagent cells in the anti - human globulin test ( ortho cell panel , ortho diagnostics ) . since the patient had life - threatening anemia with urgent requirement for transfusion , detailed phenotyping was not done and crossmatching was performed with several random a rh - positive packed red cells but no compatible unit was detected . she received three  least incompatible a rh - positive non - leuco reduced packed red cell units over three days as a life - saving measure after informed consent . no adverse events were reported during or after transfusion . besides , she was also started on steroid therapy , antibiotics and diuretics . however , she developed sudden cardiorespiratory arrest on fifth day and could not be revived . the patient was a case of coronary artery disease with off and on gastric bleed and a recipient of multiple transfusions in the past . peripheral blood smear showed dimorphic blood picture with moderate anisocytosis and poikilocytosis with mild hypochromia , microcytes , macro - ovalocytes and polychromasia . blood group was o rh - positive and two units of o rh - positive packed cells were transfused . since there was not much improvement in hemoglobin , another transfusion was requested but crossmatch was incompatible and antibody screen was positive . there was a difference in the strength of reaction at different phases and auto - control was negative . antibody identification studies suggested anti e , jka and s as the implicating antibodies ( patient e- , jka- and s- ) . strong possibility of anti e was considered on 11 cell identification panel results . meanwhile , patient improved clinically and was discharged at hemoglobin of 10.5 gm / dl with no further requirement for transfusion . subsequently , he was readmitted with another bout of hematemesis and hemoglobin of 6.4 gm / dl . patient received two transfusions by standard compatibility testing procedure since the blood bank was not informed about his previous immuno - hematological work up and hence a phenotypically matched blood was not given . however , there was a reaction with the first unit in the form of fever and mild jaundice ( serum bilirubin 2.2 mg / dl ) , which recovered subsequently . a 20-year - old female was referred to our hospital with complaints of icterus and breathlessness . she had similar complaints one year back and was treated for jaundice by a local physician . prior to her referral , she had been transfused three units of ab positive blood over one week . on general physical examination , there was mild leucocytosis and blood film showed autoagglutination with the presence of nucleated red cells ( 19/100 wbcs ) . plasma and urine hemoglobin were raised . direct antiglobulin test with poly - specific coomb 's reagent ( igg + c3d ) ( tulip diagnostics ) was positive . patient also had a positive antibody screen with all three reagent cells in the anti - human globulin test ( ortho cell panel , ortho diagnostics ) . since the patient had life - threatening anemia with urgent requirement for transfusion , detailed phenotyping was not done and crossmatching was performed with several random a rh - positive packed red cells but no compatible unit was detected . she received three  least incompatible a rh - positive non - leuco reduced packed red cell units over three days as a life - saving measure after informed consent . no adverse events were reported during or after transfusion . besides , she was also started on steroid therapy , antibiotics and diuretics . however , she developed sudden cardiorespiratory arrest on fifth day and could not be revived . the patient was a case of coronary artery disease with off and on gastric bleed and a recipient of multiple transfusions in the past . peripheral blood smear showed dimorphic blood picture with moderate anisocytosis and poikilocytosis with mild hypochromia , microcytes , macro - ovalocytes and polychromasia . blood group was o rh - positive and two units of o rh - positive packed cells were transfused . since there was not much improvement in hemoglobin , another transfusion was requested but crossmatch was incompatible and antibody screen was positive . there was a difference in the strength of reaction at different phases and auto - control was negative . antibody identification studies suggested anti e , jka and s as the implicating antibodies ( patient e- , jka- and s- ) . strong possibility of anti e was considered on 11 cell identification panel results . meanwhile , patient improved clinically and was discharged at hemoglobin of 10.5 gm / dl with no further requirement for transfusion . subsequently , he was readmitted with another bout of hematemesis and hemoglobin of 6.4 gm / dl . patient received two transfusions by standard compatibility testing procedure since the blood bank was not informed about his previous immuno - hematological work up and hence a phenotypically matched blood was not given . however , there was a reaction with the first unit in the form of fever and mild jaundice ( serum bilirubin 2.2 mg / dl ) , which recovered subsequently . autoimmune hemolytic anemia is a fairly uncommon disorder with estimates of the incidence at 13 cases per 100 000 per year . in contrast , alloimmune hemolytic anemia requires exposure to allogeneic red cells through pregnancy , transfusion or transplantation . the incidence of acute hemolytic transfusion reactions has been estimated to be 0.0030.008% , while 0.050.07% of transfused patients develop a clinically recognized delayed hemolytic transfusion reaction.[46 ] delayed serologic transfusion reactions are more common and are a frequent finding in patients who receive multiple transfusions . anemia is of variable severity and some patients present with fulminant hemolysis , jaundice , pallor , hemoglobinuria and hepatosplenomegaly . in the first case , the patient was erroneously grouped and transfused ab positive blood before referral to our center . she presented with severe life - threatening anemia , jaundice , mild hepatosplenomegaly and evidence of hemolysis . approximately 57% of patients with warm autoimmune hemolytic anemia have free serum autoantibody and a positive indirect antiglobulin test . due to pan agglutinin in the serum of patients with autoimmune hemolytic anemia , crossmatching blood is a difficult and time - consuming process since the pan agglutinin reacts with all donors red blood cells .. moreover , the most pressing problem is detection and identification of rbc alloantibodies that may be masked by the autoantibodies . in our patient , the anemia was life threatening with time constraints to perform adsorption studies with subsequent identification of underlying alloantibodies . even after thorough serological evaluation , the optimal blood for transfusion is still likely to be mismatched . clinical reluctance to administer transfusions to such patients due to serological mismatch or an incomplete workup can have devastating consequences . factors such as rate of onset of hemolysis and anemia , presence or absence of accompanying hypovolemia and the underlying health status and cardiorespiratory reserve must be taken into account to determine the transfusion trigger . when a decision to transfuse mismatched blood is taken , transfusion of small aliquots to provide relief of symptoms and avoid fluid overload has been recommended . it has also been recommended to transfuse using leucocyte - reduced blood products and pre - medication with antihistaminics and antipyretics to prevent febrile and allergic reactions , respectively , in patients with multiple antibodies . the second patient was a recipient of multiple transfusions with difficulty in finding a compatible unit . antibody screen was positive with difference in the strength of reaction in immediate spin , 37c , and in the antihuman globulin phase . the patient had multiple alloantibodies , which did not cause any clinical evidence of delayed hemolytic transfusion reaction except mild subclinical jaundice . however , in spite of repeated transfusions , there was not much improvement in the hemoglobin . the reason could be that the antibody titer was low initially but subsequent to transfusion , an anamnestic response led to rise in antibody titer and hence subsequent crossmatching did not give a compatible unit . when the patient 's sample was received in the first instance , crossmatch was compatible . the incidence of alloimmunization in random multi - transfused patients has been reported to be 034%.[1519 ] it is more in transfusion - dependent patients , such as those with sickle cell disease , aplastic anemia , myelodysplastic syndrome and other congenital or acquired anemia . in a prospective study on the incidence of red cell alloimmunization following transfusion , 8.4% of patients developed antibodies within 24 weeks of transfusion . takeuchi and coworkers have reported a delayed hemolytic transfusion reaction due to anti e , anti c and anti jka that are clinically significant antibodies . such patients present a challenge for elective transfusions particularly if multiple clinically significant alloantibodies are present . if such a situation arises , transfusion should be withheld until suitable antigen - negative donor units are located . patients with multiple alloantibodies should receive phenotypically matched red blood cells to avoid transfusion reaction and they should be given a card indicating the antibody specificities so that he can receive antigen negative blood . in either case , a good communication must be established between the clinician and the transfusion specialist to assess the clinical urgency and the complexity of serological studies . the final decision to transfuse should depend on the evaluation of the patient 's clinical status and the benefits must be weighed to the potential risks of transfusion .
the transfusion - medicine specialists and physicians are often in a difficult situation when the patient has severe worsening anemia and all the blood is mismatched . 
 this situation can arise in patients with red cell autoantibodies or alloantibodies due to previous transfusions . 
 we report two cases of immune hemolysis 
 one due to warm auto antibodies and the second due to alloimmunization from multiple transfusions .