Marrow emboli in acute chest syndrome: artifact or etiology?

A black man with HbSC sickle cell disease (SCD) complained of severe unrelenting chest, back, and abdominal pains for 1 hour. He had experienced several sickle cell crises in the past 2 years. Initial vital signs were BP 150/100, HR 90/ min, and RR unlabored, 30/min. He was diaphoretic, but otherwise his physical examination was unremarkable. Admitting lab values wereWBCs 9.2 x 10 9 per L, PLTs 140 x 10 9 per L, Hb 9.9 g per dL, and Hct 28.4 percent. He was given morphine. Within 24 hours after admission, his WBCs had increased to 23.1 × 10 9 per L with 17 percent bands; Hb decreased to 6.8 g per dL, Hct to 19.4 percent, and PLTs to 72 x 10 9 per L; and his peripheral blood smear contained 39 nucleated RBCs per HPF. Two units of RBCs were subsequently transfused because of his increasing anemia. His blood pH decreased to 6.9 from 7.38 within 4 hours of death while being ventilated with O 2 . He died in respiratory failure 30 hours after admission. Antibody testing for parvovirus B19 was not completed until after death, but the test was positive for the presence of both IgM and IgG antibodies to the virus. A clinical hospital autopsy was performed at the local hospital. At autopsy each lung weighed 1000 g and contained large, 4- to 10-mm macroscopic fragments of necrotic marrow, nearly obstructing several pulmonary arterial branches (Fig. A, macroimage of HE Fig. B, 4x photomicrograph of marrow embolus; Fig. C, 20x photomicrograph of megakaryocyte in necrotic marrow fragment) as well as paravertebral venous plexus vessels. Multiple large areas of necrosis were present within vertebral thoracic and lumbar medullary marrow spaces. This case was evaluated on referral of the medical record and autopsy slides. Acute chest syndrome (ACS), commonly developing in patients with HbSS and occasionally in patients with HbSC, is the leading cause of death and hospitalization in patients with SCD. Although the etiology of ACS remains unclear, pulmonary fat embolism, including microscopically sized marrow emboli, have been found. Autopsy pathologists frequently regard microscopic marrow and fat emboli to be the result of vigorous cardiopulmonary resuscitation, and consequently the finding of such emboli in a patient with ACS may be inadvertently dismissed as an incidental non-pathologic finding. ACS is associated with the triad of SCD, parvovirus infection, and marrow fat embolism. The origin of pulmonary and systemic fat emboli found in ACS, and appropriate diagnostic tests for that fat, remains speculative. Large, macroscopic necrotic emboli arising from the patient's vertebral marrow, presumably caused by vascular occlusion within his hyperplastic marrow by sickled RBCs, played a significant role in the development of ACS and his subsequent respiratory demise. In patients with SCD and parvovirus infections, sudden death from ACS can be caused by obstruction of pulmonary vessels with large macroscopic fragments of marrow, which are not artifacts of vigorous cardiopulmonary resuscitation.