Keeping it in the family: Three relatives with HbSC disease and simultaneous acute pulmonary emboli

Abstract

A 30-year-old African American female (Patient #1) with Hemoglobin SC (HbSC) disease presented with a 1 week history of progressive left flank and lower extremity pain with diffuse myalgias. She had a history of multiple prior vasoocclusive episodes requiring simple and exchange transfusions. At the time of admission on physical examination, she was afebrile and hemodynamically stable with an oxygen saturation of 100% in ambient air. The only pertinent finding was mild diffuse abdominal tenderness. Laboratory studies are summarized in Table 1 and were significant for leukocytosis with a left shift, anemia worse than baseline, a depressed reticulocyte count, a normal bilirubin but a mild elevation in transaminases. Chest radiography was normal. HbSC disease is a compound heterozygous condition characterized by inheritance of one gene for ‘‘S’’ hemoglobin (Glu-Val substitution in the 6th position of the b-globin chain) and one gene for ‘‘C’’ hemoglobin (Glu-Lys substitution in the 6th position of the b-globin chain), with subsequent formation of similar levels of HbS and HbC within the erythrocyte. HbCC disease is a non-sickling disorder which results in a mild hemolytic anemia. The combination of HbS and HbC is much more clinically significant suggesting that HbS has major disease modifying effect. Population studies suggest that while patients with HbSC have less frequent complications occurring later in life than those with HbSS disease, when complications occur they can be equally severe. In contrast, there is generally milder anemia and hemolytic complications, including aplastic episodes and cholelithiasis are less severe compared to HbSS disease [1]. In our first patient, the presence of diffuse pain was suggestive of a vasoocclusive episode (VOE). There were no abnormalities on history, physical exam, or chest radiography suggestive of acute chest syndrome (ACS). In terms of anemia, this patient was noted to have approximately a 3.5 g decrease in Hb concentration with an inappropriately low reticulocyte response. This suggested a VOE complicated by an aplastic crisis. Patient #1 was admitted to the medical service and commenced on treatment for a vasoocclusive epsiode with intravenous fluids and analgesics. She was commenced on low molecular weight heparin (LMWH) for deep venous thrombosis (DVT) prophylaxis. A red blood cell transfusion was administered for treatment of symptomatic anemia. The next day, the 24-year-old brother of Patient #1 (Patient #2), was admitted to the medical service. He also had HbSC disease and lived in same household as Patient #1. He had a history of cough productive of green sputum, fever, chills, myalgia and lower back pain for one week prior to admission. On physical examination, he was afebrile and had an oxygen saturation of 100% in ambient air. The rest of his exam was unremarkable other than pain with limb and spine motion. Laboratory studies are summarized in Table 1 and were significant for a leukocytosis with a left shift, worse anemia from baseline, an abnormally reduced reticulocyte response and mild hyperbilirubinemia. Chest radiography was normal. He was treated with intravenous fluids, analgesics and was administered LMWH for DVT prophylaxis. One of the recognized complications of sickle cell disease (SCD) is a reticulocytopenic anemia, referred to as an aplastic crisis or episode. This condition can be associated with a decrease in any peripheral blood cell lines, but most commonly, there are decreased mature erythrocytes and reticulocytes, and this is referred to as transient red cell aplasia (TRCA) [2]. A number of infectious agents have been implicated as either being causative or temporally related to such an episode. The best detailed of these is Parvovirus B19 (HPV B19), the causative agent of fifth disease. This virus is the only member of the Parvoviridae family known to be pathogenic in humans, occurring worldwide endemically [3]. Most infections occur in children and young adults and are highly contagious. The association between parvovirus infection and hypoplastic episodes in sickle cell anemia was first identified in 1981, when sera from 600 children in a London hospital were analyzed for HPV B19. Six children were identified with either the presence of the B19 antigen or its acute phase antibody [4]. All six were originally from Jamaica, had SCD with worsening anemia and evidence of bone marrow erythroid hypoplasia [4]. Other viruses recognized to be associated with red cell aplasia, although not specifically in SCD, include Epstein Barr, mumps, hepatitis, and Human Herpes virus 6 [5,6].