A method for the preparation of a highly purified and heat stable oxygen carrier-containing pharmaceutical composition, the oxygen carrier-containing pharmaceutical composition including hemoglobin, the hemoglobin including cross-linked polymeric hemoglobin, the method comprising: (a) providing whole blood including at least red blood cells and plasma; (b) separating the red blood cells from the plasma in the whole blood; (c) filtering the red blood cells that were separated from the plasma to obtain a filtered red blood cell fraction; (d) lysing the red blood cells to create a solution comprising a lysate of disrupted red blood cells; (e) extracting a first hemoglobin solution from the lysate; (f) performing one or more purification processes to produce a purified hemoglobin solution; (g) heating the purified hemoglobin solution at about 60-62°C for about 10 hours; (h) cross-linking hemoglobin tetramers to create a solution including cross-linked polymeric hemoglobin, the polymeric hemoglobin including two or more cross-linked hemoglobin tetramers; (i) heat treating the solution including the cross-linked polymeric hemoglobin in a deoxygenated environment at a temperature greater than 85°C and less than or equal to approximately 95°C for a period of less than approximately 40 minutes to denature and precipitate any residual non-cross-linked tetrameric hemoglobin, any dimeric hemoglobin, and any other impurities such to form a heat stable solution including a cross-linked polymeric hemoglobin; (j) cooling the heat-treated solution to a temperature approximately less than or equal to 25 °C in approximately two minutes or less to prevent formation of met-hemoglobin; (k) removing precipitate by a centrifugation or a filtration apparatus to form a solution of purified, heat-stable hemoglobin including cross-linked polymeric hemoglobin having an undetectable concentration of dimer. (a) providing whole blood including at least red blood cells and plasma; (b) separating the red blood cells from the plasma in the whole blood; (c) filtering the red blood cells that were separated from the plasma to obtain a filtered red blood cell fraction; (d) lysing the red blood cells to create a solution comprising a lysate of disrupted red blood cells; (e) extracting a first hemoglobin solution from the lysate; (f) performing one or more purification processes to produce a purified hemoglobin solution; (g) heating the purified hemoglobin solution at about 60-62°C for about 10 hours; (h) cross-linking hemoglobin tetramers to create a solution including cross-linked polymeric hemoglobin, the polymeric hemoglobin including two or more cross-linked hemoglobin tetramers; (i) heat treating the solution including the cross-linked polymeric hemoglobin in a deoxygenated environment at a temperature greater than 85°C and less than or equal to approximately 95°C for a period of less than approximately 40 minutes to denature and precipitate any residual non-cross-linked tetrameric hemoglobin, any dimeric hemoglobin, and any other impurities such to form a heat stable solution including a cross-linked polymeric hemoglobin; (j) cooling the heat-treated solution to a temperature approximately less than or equal to 25 °C in approximately two minutes or less to prevent formation of met-hemoglobin; (k) removing precipitate by a centrifugation or a filtration apparatus to form a solution of purified, heat-stable hemoglobin including cross-linked polymeric hemoglobin having an undetectable concentration of dimer.