Sickle cell disease (SCD) is the most common genetic disease in the US, affecting approximately 100,000 individuals. In SCD, genetically mutated hemoglobin (HbS) forms rigid polymers when deoxygenated, giving red blood cells a characteristic sickled shape. Increased blood viscosity and cell adhesion produce intermittent vaso-occlusion. The vaso-occlusive phenotype of SCD, which is marked by higher hemoglobin, manifests with frequent painful crises and is associated with a higher risk for developing acute chest syndrome. The hemolytic phenotype is characterized by lower baseline levels of hemoglobin and elevated markers of hemolysis. There are no reliable markers of vaso-occlusive crisis (VOC), ie, vital signs and laboratory tests are normal. After intravenous (IV) opiate titration, patient-controlled anesthesia (PCA) pumps are encouraged. Excess IV fluids have been associated with development of atelectasis, a risk factor for acute chest syndrome. Acute chest syndrome has clinical symptoms similar to pneumonia; these patients will develop progressive hypoxemia, acute respiratory distress syndrome, and death if exchange transfusion is not initiated.
In the middle of a busy evening shift, you encounter a 25-year-old man with a chief complaint of sickle cell crisis. He states that he has had an upper respiratory infection for about a week, followed by progressive pain to his lower back and legs. At home, he has been taking 4-mg tablets of hydromorphone every 3 hours, which reduces his pain score from a 10 to a 9. His vital signs are as follows: heart rate of 77, blood pressure of 115/70 mm Hg, respiratory rate of 14 breaths per minute, and temperature of 36.9°C (98.4°F). He does not appear to be uncomfortable and is sitting in bed using a cellular phone. The nurse has placed a peripheral IV, delivering a 1-L bolus of NS. You get the CBC results, and his hemoglobin is 10.2 mg/dL. You ask yourself several questions:
• Can this patient be having a crisis without a drop in hemoglobin?
• Is there a blood test I can do to confirm that he is truly having a crisis?
• Is the patient addicted to opiates or drug-seeking?
• What fluids should I administer?
• What kind of opiates should I administer?
• Should I administer supplemental oxygen?
• Should I give him IV ketorolac? Are there any other medications that might help?
You are surprised that despite many years of practice you are not sure of the answers and wonder why that is.
Sickle cell disease is the most common genetic disease in America,1 affecting approximately 100,000 individuals.2 Since the discovery of SCD 100 years ago, our understanding of the disease has changed dramatically. Research has revealed that the genetic mutations underlying SCD not only result in sickle-shaped red blood cells (RBCs) but also completely alter the rheologic properties of the blood, causing
clinical manifestations in every organ system. Despite major advances in our understanding of the disease, literature to guide clinical decisions in the treatment of SCD is sorely lacking. This issue of Emergency Medicine Practice presents a synopsis of the latest evidence regarding the pathophysiology, diagnosis, and treatment of emergent complications of SCD.
A literature search was performed using PubMed, using the search terms pain, vaso-occlusion, acute chest syndrome, stroke, avascular necrosis, priapism, sepsis, osteomyelitis, transient red cell aplasia, pulmonary hypertension, hyphema, fat embolism, splenic sequestration, hepatic sequestration, hemolysis, and iron overload. A total of 596 articles from 1964 to the present were reviewed. The Cochrane Database was searched for systematic reviews using the key term sickle cell, which identified 35 reviews. Guidelines released by the National Institutes of Health (National Heart, Lung, and Blood Institute) in 2002 and the American Pain Society (APS) in 1999 were also reviewed. Both of these guidelines represent consensus statements and are not systematic, evidence-based guidelines. Using standard evidence-level scales, the majority of clinical evidence in SCD falls into the weaker and moderately-strong categories. There are several reasons for this. First, SCD is a rare disorder, and properly designed clinical trials are often too resource-intensive to perform. Second, SCD research is severely underfunded (cystic fibrosis, a disease that is one-third as common as SCD, receives millions of dollars more in funding each year). A third and final issue is the effect of medical advances on our knowledge of the disease. For example, many observational studies of SCD were performed before the development of the pneumococcal vaccine. This and other advances in preventive medicine may call into question results of earlier observational and interventional trials. When available, recommendations
Always consider non-SCD-related conditions in your differential. For example, for right lower quadrant pain, consider appendicitis, kidney stone, and gynecological causes before presuming VOC. For chest pain, consider acute coronary syndromes, pulmonary embolism, or pneumothorax before presuming acute chest syndrome.
Consider epidural abscess and spinal osteomyelitis in the differential of midline back pain, even when fever is absent.
Never transfuse a patient simply because hemoglobin is low. Elevating the hemoglobin above baseline can cause hyperviscosity, pain, acute chest syndrome, and stroke.
When it appears that a patient has sickle cell trait on hemoglobin electrophoresis, make sure the patient did not receive a transfusion within 90 days of having the test performed. Recent transfusion renders the electrophoresis useless for diagnostic purposes.
In cases of direct eye trauma, patients with SCD and sickle cell trait should be treated the same way. Many patients do not know that they carry the trait or will fail to mention it unless prompted. Both SCD and sickle cell trait increase the risk for catastrophic ophthalmologic complications after blunt eye trauma, even if hyphema is not apparent.
Never prescribe iron for patients with SCD. These patients are usually iron-overloaded.
Assume that all patients with SCD have some degree of renal dysfunction, even if the creatinine level is normal. Supranormal proximal tubule function creates falsely low creatinine in this patient population. Take this into consideration when prescribing NSAIDs and when ordering imaging studies with IV contrast.
Using bolus normal saline to treat sickle cell crisis presents several problems. Excess IV fluid can result in atelectasis, which may precipitate acute chest syndrome. Large amounts of normal saline can produce a hyperchloremic metabolic acidosis, which may promote sickling.
Most patients with VOC will not exhibit vital sign abnormalities.
Sickle cell disease has been described in all races and should no longer be considered exclusive to black persons.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology
and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
The most informative references cited in this paper, as determined by the author, are noted by an asterisk (*) next to the number of the reference.
August 2, 2011