Transfusion management and hemoglobin-based oxygen carrier treatment in a patient with anti-Rh17 antibody.

BACKGROUND: A 54-year-old Hispanic OPos female with known history of anti-Rh17 antibodies was diagnosed with Philadelphia-Chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Rh17, also known as Hr0, is a high-frequency antigen composed of several epitopes on the RhCE protein. Anti-Rh17 antibodies can be made by individuals with missing or varied C/c, E/e antigens. Anti-Rh17 antibodies are clinically significant given multiple case reports of hemolytic disease of the fetus and newborn (HDFN). Finding compatible units for patients with anti-Rh17 can be particularly difficult given that only 1 in 100,000 people are Rh17 negative. STUDY DESIGN AND METHODS: Search for compatible units was conducted by the American Rare Donor Program (ARDP) with no leads. After chemotherapy induction and despite erythropoiesis stimulating agent administration, the patient's hemoglobin continued to trend down to a nadir of 2.8 g/dL. Here we report transfusion of incompatible pRBC to this patient with critically symptomatic anemia. HBOC-201 (Hemopure) was obtained and administered under an emergency compassionate/expanded access designation from the Food and Drug Administration (FDA) under an emergency Investigational New Drug (IND) application. RESULTS AND DISCUSSION: Overall difficulties in this case included the challenge of finding compatible units, dilemma of transfusing incompatible units in a patient with severe anemia and obtaining alternatives to blood products. This case report demonstrates the successful use of HBOC-21 in treating life-threatening anemia.

The utility of the dilute prothrombin time in the interpretation of antiphospholipid syndrome testing.

OBJECTIVES: To evaluate the utility of the dilute prothrombin time (DPT) in diagnosing antiphospholipid syndrome (APS), alone and when paired with the dilute Russell viper venom time (DRVVT). METHODS: Dilute prothrombin time and DRVVT testing was performed on plasma samples spiked with apixaban or rivaroxaban, or depleted of vitamin K-dependent clotting factors. A retrospective analysis of all functional APS testing results over a 44-month period at the University of Chicago Medical Center was performed. RESULTS: In spiking studies, the screening clotting time in the DPT (DPTS) is more sensitive to deficiency of vitamin K-dependent factors than is the screening clotting time in the DRVVT (DRVVTS). The converse is true for factor Xa direct oral anticoagulant (DOAC)-spiked plasma. In a 44-month retrospective analysis, only 2.6% of clinical APS panels showed isolated positivity in the DPT-based system. Comparing the DPT-based system with the DRVVT-based system showed utility in identifying false-positive DRVVT results due to anticoagulation. A DRVVTS/DPTS ratio of 0.785 or lower predicted an international normalized ratio of 1.5 or higher (sensitivity, 86.3%; specificity, 60.4%; likelihood ratio, 2.18). Conversely, a DRVVTS/DPTS ratio of 1.165 or higher was the optimal cutoff for predicting the identification of factor Xa DOAC (sensitivity, 61.8%; specificity, 77.8%; likelihood ratio, 2.78). Within the data set that had full DRVVT and DPT results, parameters were identified that could further improve identification of samples with anticoagulation interference. CONCLUSIONS: Dilute prothrombin time lupus anticoagulant assay is rarely the sole laboratory functional evidence for APS, but when combined with the DRVVT, the DPT can serve as an effective screen for common anticoagulant interference.

Embolic occlusion of internal carotid artery in conscious rats: Immediate effects of cerebral ischemia.

In most preclinical models of focal ischemic stroke, vascular occlusion is performed under general anesthesia. However, anesthetic agents exert confounding effects on mean arterial blood pressure (MABP), cerebrovascular tone, oxygen demand, and neurotransmitter receptor transduction. Moreover, the majority of studies do not use a blood clot, which more fully models embolic stroke. Here, we developed a blood clot injection model to produce large cerebral artery ischemia in unanesthetized rats. Under isoflurane anesthesia, an indwelling catheter was implanted in the internal carotid artery via a common carotid arteriotomy and preloaded with a 0.38-mm-diameter clot of 1.5, 3, or 6 cm length. After discontinuing anesthesia, the rat was returned to a home cage where it regained normal mobility, grooming, eating activity, and a stable recovery of MABP. One hour later, the clot was injected over a 10-s period and the rats were observed for 24 h. Clot injection produced a brief period of irritability, then 15-20 min of complete inactivity, followed by lethargic activity at 20-40 min, ipsilateral deviation of the head and neck at 1-2 h, and limb weakness and circling at 2-4 h. Neurologic deficits, elevated MABP, infarct volume, and increased hemisphere water content varied directly with clot size. Mortality after 6-cm clot injection (53%) was greater than that after 1.5-cm (10%) or 3-cm (20%) injection. Combined non-survivor groups had the greatest MABP, infarct volume, and water content. Among all groups, the pressor response correlated with infarct volume. The coefficient of variation of infarct volume with the 3-cm clot was less than that in published studies with the filament or standard clot models, and therefore may provide stronger statistical power for stroke translational studies. The more severe outcomes from the 6-cm clot model may be useful for the study of malignant stroke.