Case 1
A 76-year-old woman with advanced ovarian cancer, iron deficiency anemia, and lower extremity chronic DVTs with extensive intraperitoneal disease and chronic ascites managed with repeated therapeutic paracentesis presented with chest pain, vomiting, abdominal tenderness, and abdominal distension. Chest CT showed bilateral pulmonary emboli. Her Hb concentration was 5.7 g/dL; she refused transfusion owing to her religious beliefs. Medications on admission included vitamin B12, ferrous sulfate, and rivaroxaban. On admission she was alert and oriented and responding appropriately, but fatigued quickly, with an inability to speak in more than brief sentences due to dyspnea, but was able to understand and participate in informed consent. Heparin infusion was started, but changed to enoxaparin because of anemia and concern for bleeding. On hospital day 2 she underwent paracentesis with removal of 4L of dark, bloody fluid, after which she reported feeling much better, with reduction of abdominal pain, and improved breathing. She expressed wishes to pursue palliative care, but noted that she would like to die in the hospital so that it would not be a burden on her family and friends.
On hospital day 3 Hb decreased to 4.4 with increasing fatigue and could speak only in short phrases, with an inability to hold a conversation. No further laboratory testing was performed. On hospital day 4 she consented to Hemopure® infusion, while competent. Later that day her mentation declined and before the
Hemopure® infusion she was somnolent and confused and could respond yes/no to questions but did not show complete understanding. Two units of Hemopure® were infused and she became lucid. After Hemopure®, she was more awake, although still easily fatigued. She showed understanding of questions and was able to participate appropriately in brief conversations. On each of days 5, 6, and 7
cognitive function decreased, and then improved after Hemopure® infusion. The family noted significant improvement in interaction.
On hospital day 9, two days after the last Hemopure® infusion she was increasingly somnolent. Hemopure® infusion was resumed. She remained mostly unresponsive with increasing tachypnea. She was transitioned to comfort care and died later that day. For the Hemopure® infusions for which we have data for blood pressure (n=7) and heart rate (n=6), or SpO2 (n=5) before and after infusion, the mean BP was 122.3 ± 7.3 / 57.9 ± 3.1 before infusion and 126.1 ± 6.7 / 60.7 ± 9.3 after infusion.
Heart rate before infusion was 109.7 ± 14.3 and after infusion was 108.2 ± 14.1.
SpO2 was 95.6 ± 1.3 before infusion and 94.8 ± 0.8 after infusion. Systolic (P=0.54) or diastolic (P=0.47) blood pressures, or heart rate (P=0.79), or SpO2 (P=0.37) did not change significantly; the maximal increase for any infusion was 1%
.
Case 2
A 42-year-old female with metastatic breast cancer and severe anemia presented for acute encephalopathy. She had extensive bony metastases with a history of prior spinal radiation with resultant bone marrow suppression complicated by severe anemia requiring multiple blood transfusions. As a result, she became extensively allo-immunized. She received "least incompatible blood" but still developed autoimmune hemolytic anemia, further complicating her clinical
course. On day 2 of admission, she was transferred to the intensive care unit with a Hb (Hb) of 2.5 g/dL, lactate 4 mmol/L, and obtundation responding only to sternal rub. On days 2-3 admission, 2 units of incompletely matched red blood cells were given. Hb increased to 3.6 g/dL and 4.7 g/dL on day 3. Subsequently, the patient
had mild improvement in mental status: she could open her eyes spontaneously, but did not respond to voice, did not track or respond to commands. On day 4: her Glasgow coma scale (GCS) was 10, Hb 4.5 g/dL, blood pressure 124/72 mmHg, heart rate 86 beats per minute (bpm), oxygen saturation (SpO2) 99%. After an eIND was obtained, 1 unit of Hemopure® was infused. After the infusion her GCS increased to 14, Hb was 6.4 g/dL, BP was 152/84 mmHg, HR 66 bpm, SpO2 97%. She began to track her eyes toward voices, made sustained eye contact. Her husband had been at her bedside continuously with no verbal response from the patient. After
Hemopure® infusion, she was asked who was at the beside and she responded "my husband," who noted this was a "dramatic improvement". On day 5 an additional 2 units of Hemopure® were infused, with resultant further increased alertness. It was noted she gradually improved to the point of swallowing and being cleared
for eating. On day 6 she was discharged to home hospice with Hb of 7.3.
Case 3
This case was reported previously for the use of Tocilizumab to treat
posttransfusion hyperhemolysis (see "case presentation" and "results").4 In brief, a 36-year old woman presented with a Hb concentration of 5.5 g/dL, with
symptomatic anemia and hyperhemolysis. She was treated with
methylprednisolone, erythropoietin, cyanocobalamin, folic acid, and later
tocilizumab. Following red cell transfusion, Hb concentration fell to 2.1 g/dL with complete obtundation (GS 8) and progressive organ dysfunction. Hemopure® was infused after obtaining an emergency IND, followed by heart rate decrease, blood pressure stability, and became fully responsive without confusion. She recovered without neurologic sequelae.
Case 4
A 70-year old female with a history of coronary artery disease presented with a massive gastro-intestinal bleed and a Hb concentration of 4.8 g/dL. With
continued bleeding she developed a Non-STEMI, leaving her with a LV ejection fraction of 10-20% (assessed by trans-thoracic echocardiography), and concomitant unconsciousness. Red cell transfusion was refused owing to religious beliefs.
Following approval of an emergency IND, she was given Hemopure® with a return of consciousness and lucidity within 20 minutes of receiving the first unit (GCS improved from 8 to 15). T-wave inversions and ST depressions observed on ECG also resolved. She remained conscious for the next 24 hours with continued
Hemopure® administration (total of 6 units). She expired approximately 30 hours from initiation of Hemopure® from complications of the myocardial infarction without resuscitation attempts, as there was a "do not resuscitate" order in place.
Case 6
An 88-year-old female living by herself fell while taking a laundry basket down a flight of stairs, suffering a non-displaced left intratrochanteric hip fracture.
She did not hit her head during the fall and was fully alert in the emergency room.
Her past medical history included hypertension, coronary artery disease,
bronchiectasis (not requiring home oxygen) and paroxysmal atrial fibrillation. She is a Jehovah’s witness and refused all blood products. On presentation her
hemoglobin was 12.2 g/dL, platelet count was 149 and her INR was 1.1.
On day 2 of her hospitalization, she underwent an open reduction and internal fixation of the hip fracture, with intra-operative blood loss of 75 mL. Following
surgery, she was given enoxaparin 30 mg twice a day for DVT prophylaxis. The post-operative day one hemoglobin fell to 9.0 g/dL. During post-operative day 1, a rapid response team was called to the patient bedside for what was diagnosed as a vasovagal episode. At their arrival, she was awake and fully oriented. On post-op day 2 her hemoglobin fell to 6.8 g/dL. On post-operative day 4, her hemoglobin fell further to a nadir of 5.2 g/dL. Vital signs at this time showed a blood pressure of 137/80, pulse of 90 and SpO2 of 97% on 2 liters/min of oxygen via a nasal cannula.
On this day, the rapid response team was called to the patient bedside twice for acute loss of consciousness. An EEG was unremarkable. At this time, she was described as delirious.
Two units of Hemopure® were administered overnight. During the
administration she became hypertensive (BP 166/87, HR 87, SpO2 95%) and was described by nursing as agitated requiring restraints. In the morning following the administration of the Hemopure®, post-operative day 6, the hemoglobin
concentration was 7.0 g/dL. Her vital signs at this time were: blood pressure
165/95, pulse rate 100 and SpO2 91% on 4 liters/minute O2 via a nasal cannula. The restraints were removed, and the patient was described as more awake, with
"better" color and described by the hospitalist as "miraculous". Twelve hours later SpO2 was 94%. Two days following the Hemopure®, hemoglobin fell to 6.0 g/dL with an unchanged mental status. During this time, aggressive erythropoietin and iron were administered. By post-op day 14 her hemoglobin had risen to 7.8 g/dL.
No further acute losses of consciousness episodes were experienced during her hospitalization. She was discharged to a skilled nursing facility on postop day 16.
