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HBOC-201 TREATMENT IN A JEHOVAH’S WITNESS WITH AUTO-IMMUNE HEMOLYTIC ANEMIA INTRODUCTION There are few treatment modalities for severe life-threatening anemia when blood is not an option. Hemoglobin based oxygen carriers can provide a viable alternative. RAPID CLINICAL DETERIORATION AND STABILIZATION WITH HEMOPURE DAY 1 25-year-old Jehovah’s Witness female presented with a hemoglobin concentration ([Hb]) of 5.8 g/dl that declined to 3.2 g/dl over four hours. Diagnosis: Auto-Immune Hemolytic Anemia CICU 10 hours later: Hgb 1.8 g/dl patient developed significant tachycardia, tachypnea, and hypotension – required pressors and intubated DAY 2 Consultation: Dr. Aryeh Shander recommended we pursue HBOC-201 (hemoglobin glutamer-250 [bovine], Biopure Corporation, Cambridge, MA), under 21 CRF, Part 56.104 (c); “compassionate use.” HBOC Compassionate Use: Calls to Dr. Greenberg and FDA, 2-5 minute discussion Hemopure Transport: Expected at 2000 but missed a plane connection – received 0030 and infused at 0200 Immediate Hemopure Effect: 29 hours after patient admission, three units (750 ml) HBOC-201 were infused over five hrs. Within hour one, hemodynamic stability was achieved; vasopressors were discontinued. PRIMARY DISEASE AND CRITICAL CARE MANAGEMENT DAYS 1-5 AIHA managed: Methylprednisolone, IVIG, Rituxan – No response to interventions. Hct 2-3% on days 4-15 Critical anemia management: Attention to all organ systems, FIO2 100%, PO2 250-300, Urine Output 2-2.5 liters per day, Pulse controlled 100-120, BP 110/70 Hemopure: 3 units at 0500 on day 2, then 2 units/24hours, Methemoglobin Rx’d with Methylene Blue no response, possibly worsened, increased vit C SURGERY, PANCYTOPENIA, AND CRITICAL ANEMIA MANAGEMENT DAY 10 Surgery: Embolized spleen. To OR. Intra-abdominal fluid (200- 300mls) appeared to be GI bleed type blood but was Hemopure. All organs were black. Liver massively engorged extended to left costal margin, covered spleen and GB markedly distended. Embolization of splenic artery had no effect. EBL 200-300 mls. Gently milked the spleen, but it refilled instantly. Vessels seemed somewhat more fragile DAYS 11-18 Pancytopenia: 3rd dose of Rituxan continued steroids, danazol, spleenectomy no effect on Hct, and wbc’s and plts dropped as well. Path on spleen showed reactive cells as expected. Bone Marrow obtained on day 18 Critical anemia management: Effective oxygenation of the tissues, Hemopure changed to continuous infusion of 3 units/day , Hct 3-4% END OF LIFE DAYS 18-20 GI Bleed: After 18 days of AIHA treatment, she developed a GI bleed and DIC before dying on Day 20. OBSERVATIONS AND CONCLUSIONS Hemopure demonstrated to be effective for at least 16 days in delivering oxygen to all tissues: Autopsy demonstrated no evidence of ischemia or necrosis prior to the end of life event. Hemopure augmented oxygen delivery in a patient with Hct between 1 and 4%. In the first 4 to 7 days Hct was 2% Patient was aroused at day 16 of Hemopure and followed commands and engaged family members demonstrating that the CNS was not functionally impacted by a Hct of 1-2% with Hemopure supporting oxygen delivery Nosocomial infection: HAP only infection and easily treated This in spite of 20 days of intensive care with significant immuno-modulation and eventually pancytopenia Complications: DIC – most likely this was multi-factorial Hemophagocytic Syndrome is a known but highly rare secondary event in AIHA Surgery performed with Hct of 3%: Spleenectomy performed without complications Hemopure available for replacement of any significant intravascular fluid loss Anesthesia easily managed: Vital signs were stable throughout the procedure No Hemopure was required during the procedure Hemopure may be preferred for management of AIHA: Avoid hemolysis as well as the immuno-modulation effects of allogenic blood Hemopure intended as a bridge to recovery from auto-immune response TEACHING POINTS Time critical delivery of Hemopure: Be aware of airline connections “Step by Step” printed directions for Hemopure could help expedite delivery of the first unit (Dr. Greenberg is readily available for assistance) Masimo Monitor: Inconsistent for methemoglobin monitoring in this clinical situation Specifications indicate the monitor is accurate for Methemoglobin levels from 1-15% Methemoglobin: Methylene blue may exacerbate Ferric conversion Methylene blue will work on intracellular RBC hemoglobin only Education with Consultants: Factor 7A ordered – to treat Hemopure in stool ATN misdiagnosed – due to lab alteration by Hemopure and unfamiliarity with critical anemia May not be familiar with some acute anemia management options such as surgery BONE MARROW Pancytopenia: Etiology: Hemophagocytic Syndrome DAYS 6-9 Hospital Acquired Pneumonia (HAP): LUL pneumonia by CXR, bronch washings grow serratia and pseudomonas sensitive to all antibiotics tested, PO2 drops, but improves with antibiotics and adjustments to vent, Hemopure now 1 unit q 12 hours INR Increase and Heme Positive Red Stools: Evaluate for GI bleed with EGD – Normal – received Factor 7A from consultant – red stools from Hemopure Surgery Consult: Due to hematocrit 3-4% on day 9 plan spleenectomy and trach Saint Luke's Hospital of Kansas City, Kansas City, Missouri Gary Thompson, MD 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 Admit 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 total hemoglobin 0 2 4 6 8 10 12 14 16 18 lactate g/dL Total Hb mmol/L Lactate (art) 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 Admit 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Total Hb Calculated RBC Hb Fibrin thromboembolism in myometrium Bone Marrow with Macrophages 12049
